The RhWRKY33a-RhPLATZ9 regulatory module delays petal senescence by suppressing rapid reactive oxygen species accumulation in rose flowers.

Redox homeostasis in plant cells is critical for maintaining normal growth and development because reactive oxygen species (ROS) can function as signaling molecules or toxic compounds. However, how plants fine-tune redox homeostasis during natural or stress-induced senescence remains unclear. Cut roses (Rosa hybrida), an economically important ornamental product worldwide, often undergo stress-induced precocious senescence at the post-harvest bud stage. Here, we identified RhPLATZ9, an age- and dehydration-induced PLATZ (plant AT-rich sequence and zinc-binding) protein, and determined that it functions as a transcriptional repressor in rose flowers during senescence. We also showed that RhWRKY33a regulates RhPLATZ9 expression during flower senescence. RhPLATZ9-silenced flowers and RhWRKY33a-silenced flowers showed accelerated senescence, with higher ROS contents than the control. By contrast, overexpression of RhWRKY33a or RhPLATZ9 delayed flower senescence, and overexpression in rose calli showed lower ROS accumulation than the control. RNA-sequencing analysis revealed that apoplastic NADPH oxidase genes (RhRbohs) were enriched among the upregulated differentially expressed genes in RhPLATZ9-silenced flowers compared to wild-type flowers. Yeast one-hybrid assays, electrophoretic mobility shift assays, dual luciferase assays and chromatin immunoprecipitation quantitative PCR confirmed that the RhRbohD gene is a direct target of RhPLATZ9. These findings suggest that the RhWRKY33a-RhPLATZ9-RhRbohD regulatory module acts as a brake to help maintain ROS homeostasis in petals and thus antagonize age- and stress-induced precocious senescence in rose flowers.

NHC-CDI Ligands Boost Multicarbon Production in Electrocatalytic CO2 Reduction by Increasing Accumulated Charged Intermediates and Promoting *CO Dimerization on Cu.

Copper-based materials exhibit significant potential as catalysts for electrochemical CO2 reduction, owing to their capacity to generate multicarbon hydrocarbons. The molecular functionalization of Cu electrodes represents a simple yet powerful strategy for improving the intrinsic activity of these materials by favoring specific reaction pathways through the creation of tailored microenvironments around the surface active sites. However, despite its success, comprehensive mechanistic insights derived from experimental techniques are often limited, leaving the active role of surface modifiers inconclusive. In this work, we show that N-heterocyclic carbene-carbodiimide-functionalized Cu catalysts display a remarkable activity for multicarbon product formation, surpassing bare Cu electrodes by more than an order of magnitude. These hybrid catalysts operate efficiently using an electrolyzer equipped with a gas diffusion electrode, achieving a multicarbon product selectivity of 58% with a partial current density of ca. -80 mA cm-2. We found that the activity for multicarbon product formation is closely linked to the surface charge that accumulates during electrocatalysis, stemming from surface intermediate buildup. Through X-ray photoelectron spectroscopy, we elucidated the role of the molecular additives in altering the electronic structure of the Cu electrodes, promoting the stabilization of surface CO. Additionally, in situ Raman measurements established the identity of the reaction intermediates that accumulate during electrocatalysis, indicating preferential CO binding on Cu step sites, known for facilitating C-C coupling. This study underscores the significant potential of molecular surface modifications in developing efficient electrocatalysts for CO2 reduction, highlighting surface charge as a pivotal descriptor of multicarbon product activity.

Proteomic Profiling of Colorectal Adenomas Identifies a Predictive Risk Signature for Development of Metachronous Advanced Colorectal Neoplasia.

BACKGROUND & AIMS: Colonic adenomatous polyps, or adenomas, are frequent precancerous lesions and the origin of most cases of colorectal adenocarcinoma. However, we know from epidemiologic studies that although most colorectal cancers (CRCs) originate from adenomas, only a small fraction of adenomas (3%-5%) ever progress to cancer. At present, there are no molecular markers to guide follow-up surveillance programs. METHODS: We profiled, by mass spectrometry-based proteomics combined with machine learning analysis, a selected cohort of formalin-fixed, paraffin-embedded high-grade (HG) adenomas with long clinical follow-up, collected as part of the Danish national screening program. We grouped subjects in the cohort according to their subsequent history of findings: a nonmetachronous advanced neoplasia group (G0), with no new HG adenomas or CRCs up to 10 years after polypectomy, and a metachronous advanced neoplasia group (G1) where individuals developed a new HG adenoma or CRC within 5 years of diagnosis. RESULTS: We generated a proteome dataset from 98 selected HG adenoma samples, including 20 technical replicates, of which 45 samples belonged to the nonmetachronous advanced neoplasia group and 53 to the metachronous advanced neoplasia group. The clear distinction of these 2 groups seen in a uniform manifold approximation and projection plot indicated that the information contained within the abundance of the ∼5000 proteins was sufficient to predict the future occurrence of HG adenomas or development of CRC. CONCLUSIONS: We performed an in-depth analysis of quantitative proteomic data from 98 resected adenoma samples using various novel algorithms and statistical packages and found that their proteome can predict development of metachronous advanced lesions and progression several years in advance.

The contrast-free diffusion MRI multiple index for the early prediction of pathological response to neoadjuvant chemotherapy in breast cancer.

Early tumor response prediction can help avoid overtreatment with unnecessary chemotherapy sessions. It is important to determine whether multiple apparent diffusion coefficient indices (S index, ADC-diff) are effective in the early prediction of pathological response to neoadjuvant chemotherapy (NAC) in breast cancer (BC). Patients with stage II and III BCs who underwent T1WI, diffusion-weighted imaging (DWI), and dynamic contrast-enhanced MRI using a 3 T system were included. They were divided into two groups: major histological responders (MHRs, Miller-Payne G4/5) and nonmajor histological responders (nMHRs, Miller-Payne G1-3). Three b values were used for DWI to derive the S index; ADC-diff values were obtained using b = 0 and 1000 s/mm2. The different interquartile ranges of percentile S-index and ADC-diff values after treatment were calculated and compared. The assessment was performed at baseline and after two and four NAC cycles. A total of 59 patients were evaluated. There are some correlations of interquartile ranges of S-index parameters and ADC-diff values with histopathological prognostic factors (such as estrogen receptor and human epidermal growth factor receptor 2 expression, all p < 0.05), but no significant differences were found in some other interquartile ranges of S-index parameters or ADC-diff values between progesterone receptor positive and negative or for Ki-67 tumors (all P > 0.05). No differences were found in the dynamic contrast-enhanced MRI characteristics between the two groups. HER-2 expression and kurtosis of the S-index distribution were screened out as independent risk factors for predicting MHR group (p < 0.05, area under the curve (AUC) = 0.811) before NAC. After early NAC (two cycles), only the 10th percentile S index was statistically significant between the two groups (p < 0.05, AUC = 0.714). No significant differences were found in ADC-diff value at any time point of NAC between the two groups (P > 0.1). These findings demonstrate that the S-index value may be used as an early predictor of pathological response to NAC in BC; the value of ADC-diff as an imaging biomarker of NAC needs to be further confirmed by ongoing multicenter prospective trials.

Effects on peripheral and central nervous system of key inflammatory intercellular signalling peptides and proteins in psoriasis.

Psoriasis is a chronic systemic inflammatory cutaneous disease. Where the immune system plays an important role in its pathogenesis, with key inflammatory intercellular signalling peptides and proteins including IL-17 and IL-23. The psychoneurological system also figures prominently in development of psoriasis. There is a high prevalence of comorbidity between psoriasis and mental health disorders such as depression, anxiety and mania. Patients with psoriasis often suffer from pathological pain in the lesions, and their neurological accidents could improve the lesions in innervated areas. The immune system and the psychoneurological system interact closely in the pathogenesis of psoriasis. Patients with psoriasis exhibit abnormal levels of neuropeptides both in circulating and localized lesion, acting as immunomodulators involved in the inflammatory response. Moreover, receptors for inflammatory factors are expressed in both peripheral and central nervous systems (CNSs), suggesting that nervous system can receive and be influenced by signals from immune system. Key inflammatory intercellular signalling peptides and proteins in psoriasis, such as IL-17 and IL-23, can be involved in sensory signalling and may affect synaptic plasticity and the blood-brain barrier of CNS through the circulation. This review provides an overview of the multiple effects on the peripheral and CNS under conditions of systemic inflammation in psoriasis, providing a framework and inspiration for in-depth studies of neuroimmunomodulation in psoriasis.

Association of peritumoral region features assessed on breast MRI and prognosis of breast cancer: a systematic review and meta-analysis.

BACKGROUND: Increasing attention has been given to the peritumoral region. However, conflicting findings have been reported regarding the relationship between peritumoral region features on MRI and the prognosis of breast cancer. PURPOSE: To evaluate the relationship between peritumoral region features on MRI and prognosis of breast cancer. MATERIALS AND METHODS: A retrospective meta-analysis of observational studies comparing either qualitative or quantitative assessments of peritumoral MRI features on breast cancer with poor prognosis and control subjects was performed for studies published till October 2022. Pooled odds ratios (ORs) or standardized mean differences and 95% confidence intervals (CIs) were estimated by using random-effects models. The heterogeneity across the studies was measured using the statistic I2. Sensitivity analyses were conducted to test this association according to different study characteristics. RESULTS: Twenty-four studies comprising 1853 breast cancers of poor prognosis and 2590 control participants were included in the analysis. Peritumoral edema was associated with non-luminal breast cancers (OR=3.56; 95%CI: 2.17, 5.83; p=.000), high expression of the Ki-67 index (OR=3.70; 95%CI: 2.41, 5.70; p =.000), high histological grade (OR=5.85; 95%CI: 3.89, 8.80; p=.000), lymph node metastasis (OR=2.83; 95%CI: 1.71, 4.67; p=.000), negative expression of HR (OR=3.15; 95%CI: 2.03, 4.88; p=.000), and lymphovascular invasion (OR=1.72; 95%CI: 1.28, 2.30; p=.000). The adjacent vessel sign was associated with greater odds of breast cancer with poor prognosis (OR=2.02; 95%CI: 1.68, 2.44; p=.000). Additionally, breast cancers with poor prognosis had higher peritumor-tumor ADC ratio (SMD=0.67; 95%CI: 0.54, 0.79; p=.000) and peritumoral ADCmean (SMD=0.29; 95%CI: 0.15, 0.42; p=.000). A peritumoral region of 2-20 mm away from the margin of the tumor is recommended. CONCLUSION: The presence of peritumoral edema and adjacent vessel signs, higher peritumor-tumor ADC ratio, and peritumoral ADCmean were significantly correlated with poor prognosis of breast cancer. CLINICAL RELEVANCE STATEMENT: MRI features of the peritumoral region can be used as a non-invasive index for the prognostic evaluation of invasive breast cancer. KEY POINTS: • Peritumoral edema was positively associated with non-luminal breast cancer, high expression of the Ki-67 index, high histological grade, lymph node metastasis, negative expression of HR, and lymphovascular invasion. • The adjacent vessel sign was associated with greater odds of breast cancers with poor prognosis. • Breast cancers with poor prognosis had higher peritumor-tumor ADC ratio and peritumoral ADCmean.

Genetic insights into the gut microbiota and risk of facial skin aging: A Mendelian randomization study.

BACKGROUND: A growing number of experimental studies have shown an association between the gut microbiota (GM) and facial skin aging. However, the causal relationship between GM and facial skin aging remains unclear to date. METHODS: We conducted a two-sample Mendelian randomization (MR) analysis to investigate the potential causal relationship between GM and facial skin aging. MR analysis was mainly performed using the inverse-variance weighting (IVW) method, complemented by the weighted median (MW) method, MR-Egger regression, and weighted mode, and sensitivity analysis was used to test the reliability of MR analysis results. RESULTS: Eleven GM taxa associated with facial skin aging were identified by IVW method analysis, Family Victivallaceae (p = 0.010), Genus Eubacterium coprostanoligenes group (p = 0.038), and Genus Parasutterella (p = 0.011) were negatively associated with facial skin aging, while Phylum Verrucomicrobia (p = 0.034), Family Lactobacillaceae (p = 0.017) and its subgroups Genus Lactobacillus (p = 0.038), Genus Parabacteroides (p = 0.040), Genus Eggerthella (p = 0.049), Genus Family XIII UCG001 (p = 0.036), Genus Phascolarctobacterium (p = 0.027), and Genus Ruminococcaceae UCG005 (p = 0.012) were positively associated with facial skin aging. At Class and Order levels, we did not find a causal relationship between GM and facial skin aging. Results of sensitivity analyses did not show evidence of pleiotropy and heterogeneity. CONCLUSION: Our findings confirm the causal relationship between GM and facial skin aging, providing a new perspective on delaying facial aging.

Tetramethylpyrazine Antagonizes the Subchronic Cadmium Exposure-Induced Oxidative Damage in Mouse Livers via the Nrf2/HO-1 Pathway.

Hepatic oxidative stress is an important mechanism of Cd-induced hepatotoxicity, and it is ameliorated by TMP. However, this underlying mechanism remains to be elucidated. To investigate the mechanism of the protective effect of TMP on liver injuries in mice induced by subchronic cadmium exposure, 60 healthy male ICR mice were randomly divided into five groups of 12 mice each, namely, control (CON), Cd (2 mg/kg of CdCl2), Cd + 100 mg/kg of TMP, Cd + 150 mg/kg of TMP, and Cd + 200 mg/kg of TMP, and were acclimatized and fed for 7 d. The five groups of mice were gavaged for 28 consecutive days with a maximum dose of 0.2 mL/10 g/day. Except for the control group, all groups were given fluoride (35 mg/kg) by an intraperitoneal injection on the last day of the experiment. The results of this study show that compared with the Cd group, TMP attenuated CdCl2-induced pathological changes in the liver and improved the ultrastructure of liver cells, and TMP significantly decreased the MDA level (p < 0.05) and increased the levels of T-AOC, T-SOD, and GSH (p < 0.05). The results of mRNA detection show that TMP significantly increased the levels of Nrf2 in the liver compared with the Cd group as well as the HO-1 and mRNA expression levels in the liver (p < 0.05). In conclusion, TMP could inhibit oxidative stress and attenuate Cd group-induced liver injuries by activating the Nrf2 pathway.

Selective recovery of lithium from spent lithium iron phosphate batteries.

The recovery of lithium from spent lithium iron phosphate (LiFePO4) batteries is of great significance to prevent resource depletion and environmental pollution. In this study, through active ingredient separation, selective leaching and stepwise chemical precipitation develop a new method for the selective recovery of lithium from spent LiFePO4 batteries by using sodium persulphate (Na2S2O8) to oxidize LiFePO4 to FePO4. The impact of various variables on the efficiency of lithium leaching was investigated. Moreover, a combination of thermodynamic analysis and characterization techniques such as X-ray diffraction and X-ray photoelectron spectroscopy was employed to elucidate the leaching mechanism. It was found that 98.65% of lithium could be selectively leached in just 35 minutes at 60°C with only 0.2 times excess of Na2S2O8. This high leaching efficiency can be attributed to the stability and lack of structural damage during the oxidation leaching process. The proposed process is economically viable and environmentally friendly, thus showing great potential for the large-scale recycling of spent LiFePO4 batteries.

A network analysis of subjective well-being in Chinese high school students.

BACKGROUND: The psychological situation of high school students during adolescence is not promising, and the most obvious manifestation is the lack of subjective well-being (SWB). This network analysis presents a model of the interaction and correlation between different items of SWB, identifying the most central items for high school students. METHODS: Through offline and online surveys, 4,378 questionnaires were sent out and finally 4,282 Chinese high school students were available. The response rate was 97.807%. The study used the eLASSO method to estimate the network structure and centrality measures. This algorithm used the EBIC to select the best neighbor factor for each node. RESULTS: The average age for high school students was 16.320 years old and the average SWB score was 76.680. The distribution of SWB between male and female students was significant different (P < 0.001). S8 (Have you been anxious, worried, or upset) was the node with the highest strength and expected influence. The network structure and centrality remained stable after discarding 75% of the sample at random. Except for S15 (How concerned or worried about your health have you been), all nodes were positively correlated with each other (P < 0.01). The network structure of SWB was similar for female and male students (network strength: 8.482 for male participants; 8.323 for female participants; P = 0.159), as well as for rural and urban students (network strength: 8.500 for rural students; 8.315 for urban students; P = 0.140). CONCLUSION: Targeting S8 (Have you been anxious, worried, or upset) as a potential intervention target may increase high school students' SWB effectively.

The acquisition of the gender-brilliance stereotype: Age trajectory, relation to parents' stereotypes, and intersections with race/ethnicity.

Past research has explored children's gender stereotypes about specific intellectual domains, such as mathematics and science, but less is known about the acquisition of domain-general stereotypes about the intellectual abilities of women and men. During 2017 and 2018, the authors administered Implicit Association Tests to Chinese Singaporean adults and 8- to 12-year-olds (N = 731; 58% female) to examine the gender stereotype that portrays exceptional intellectual ability (e.g., genius, brilliance) as a male attribute. This gender-brilliance stereotype was present among adults and children and for both Chinese and White stereotype targets. It also was stronger among older children and among children whose parents also showed it. This early-emerging stereotype may be an obstacle to gender equity in many prestigious employment sectors.

Cost-effectiveness of comprehensive preventive measures for coal workers' pneumoconiosis in China.

BACKGROUND: Coal workers' pneumoconiosis (CWP) remains one of the most severe occupational diseases in China. Despite the implementation of CWP comprehensive preventive measures, the unreasonable allocation of investment by coal enterprises limits the effect of preventing CWP, especially when the health resources are inadequate. This study aims to evaluate the cost-effectiveness of comprehensive measures for CWP from the perspective of coal enterprises. METHODS: Comprehensive measures and two primary interventions (engineering controls and individual protective equipment) were selected. A time-dependent Markov model was developed to evaluate cost and quality-adjusted life-years (QALYs). The input data were collected from the survey and literature. A hypothetical null situation, in which the currently implemented interventions were eliminated, was used as a comparator based on the generalised cost-effectiveness analysis (GCEA) recommended by the World Health Organization (WHO). The primary outcomes of the model were reported in terms of incremental cost-effectiveness ratios (ICERs). Uncertainty was verified using one-way and probabilistic sensitivity analyses. RESULTS: The QALYs of the comprehensive measures, engineering controls, and individual protective equipment were 17.60, 17.50, and 16.85 years, respectively. Compared with null, the ICERs of the interventions were 65,044.73, 30,865.15, and 86,952.41 RMB/QALY, respectively. Individual protective equipment was dominated by an ICER of -11,416.02 RMB/QALY compared to engineering controls. Sensitivity analysis suggested the robustness of the results. CONCLUSIONS: The comprehensive preventive measures for CWP that are currently implemented in Chinese state-owned mines are cost-effective. In comprehensive measures, engineering controls are more cost-effective than individual protective equipment. Investment in engineering controls should be increased to improve the cost-effectiveness of preventing CWP.

Challenges and Prospects in the Catalytic Conversion of Carbon Dioxide to Formaldehyde.

Formaldehyde (HCHO) is a crucial C1 building block for daily-life commodities in a wide range of industrial processes. Industrial production of HCHO today is based on energy- and cost-intensive gas-phase catalytic oxidation of methanol, which calls for exploring other and more sustainable ways of carrying out this process. Utilization of carbon dioxide (CO2 ) as precursor presents a promising strategy to simultaneously mitigate the carbon footprint and alleviate environmental issues. This Minireview summarizes recent progress in CO2 -to-HCHO conversion using hydrogenation, hydroboration/hydrosilylation as well as photochemical, electrochemical, photoelectrochemical, and enzymatic approaches. The active species, reaction intermediates, and mechanistic pathways are discussed to deepen the understanding of HCHO selectivity issues. Finally, shortcomings and prospects of the various strategies for sustainable reduction of CO2 to HCHO are discussed.

Association among starch storage, metabolism, related genes and growth of Moso bamboo (Phyllostachys heterocycla) shoots.

BACKGROUND: Both underground rhizomes/buds and above-ground Moso bamboo (Phyllostachys heterocycla) shoots/culms/branches are connected together into a close inter-connecting system in which nutrients are transported and shared among each organ. However, the starch storage and utilization mechanisms during bamboo shoot growth remain unclear. This study aimed to reveal in which organs starch was stored, how carbohydrates were transformed among each organ, and how the expression of key genes was regulated during bamboo shoot growth and developmental stages which should lay a foundation for developing new theoretical techniques for bamboo cultivation. RESULTS: Based on changes of the NSC content, starch metabolism-related enzyme activity and gene expression from S0 to S3, we observed that starch grains were mainly elliptical in shape and proliferated through budding and constriction. Content of both soluble sugar and starch in bamboo shoot peaked at S0, in which the former decreased gradually, and the latter initially decreased and then increased as shoots grew. Starch synthesis-related enzymes (AGPase, GBSS and SBE) and starch hydrolase (α-amylase and ß-amylase) activities exhibited the same dynamic change patterns as those of the starch content. From S0 to S3, the activity of starch synthesis-related enzyme and starch amylase in bamboo rhizome was significantly higher than that in bamboo shoot, while the NSC content in rhizomes was obviously lower than that in bamboo shoots. It was revealed by the comparative transcriptome analysis that the expression of starch synthesis-related enzyme-encoding genes were increased at S0, but reduced thereafter, with almost the same dynamic change tendency as the starch content and metabolism-related enzymes, especially during S0 and S1. It was revealed by the gene interaction analysis that AGPase and SBE were core genes for the starch and sucrose metabolism pathway. CONCLUSIONS: Bamboo shoots were the main organ in which starch was stored, while bamboo rhizome should be mainly functioned as a carbohydrate transportation channel and the second carbohydrate sink. Starch metabolism-related genes were expressed at the transcriptional level during underground growth, but at the post-transcriptional level during above-ground growth. It may be possible to enhance edible bamboo shoot quality for an alternative starch source through genetic engineering.

Tuning transmission properties of 3D printed metal rod arrays by breaking the structural symmetry.

In this work, one metallic photonic crystal waveguide composed of periodic metal rod arrays (MRAs) is experimentally and numerically demonstrated in terahertz frequencies. Such waveguides fabricated by 3D printers exhibit two resonant modes: the fundamental mode and the high-order mode, separating by a broad bandgap. Compared to the fundamental mode, the high-order mode shows higher field confinement and more sensitive to the geometry changes. By breaking the structure parameter, i.e., increasing or decreasing the metal rod interspace, the spectral positions, bandwidths, as well as the transmittances of high-order modes can be optimized. With broken symmetry in MRAs, the third resonant mode having high transmittance has emerged in the transmission spectrum. Results showing that fine-tuning in the alignment of metal rods leads to a great change in the transmission of high-order modes. These findings suggest that the transportation efficiency of THz waves through an MRA is tunable by breaking the structural symmetry.

The Prevalence of Mild Cognitive Impairment among Chinese People: A Meta-Analysis.

BACKGROUND: Mild cognitive impairment (MCI) induced the majority number of dementia patients. The prevalence of MCI in China varied across studies with different screening tools and diagnostic criteria. OBJECTIVE: A systematic review and meta-analysis was conducted to estimate the pooled MCI prevalence among the population aged 55 years and older in China. METHODS: PubMed, EMBASE, CNKI, Wanfang, CQVIP, and CBMdisc were searched for studies on prevalence of MCI among Chinese elderly between January 1, 1980, and February 10, 2020. The quality assessment was conducted via external validity, internal validity, and informativity, the pooled prevalence was calculated through the random-effect model, and the homogeneity was evaluated by Cochran's Q test and I2. RESULTS: Fifty-three studies with 123,766 subjects were included. The pooled prevalence of MCI among Chinese elderly was 15.4% (95% CI: 13.5-17.4%). Subgroup analyses indicated that the prevalence calculated with different screening tools was 20.2% (95% CI: 15.1-25.9%) for Montreal Cognitive Assessment (MoCA) and 13.0% (95% CI: 10.7-15.5%) for Mini-Mental State Examination (MMSE). According to different diagnostic criteria, the prevalence was 14.8% (95% CI: 12.2-17.6%) for Petersen criteria, 15.0% (95% CI: 12.7-17.5%) for DSM-IV, and 21.2% (95% CI: 17.5-25.2%) for Chinese Expert Consensus on Cognitive Impairment (CECCI). Besides, women, older adults, illiterate people, rural residents, and those who lived with unhealthy lifestyles and morbidity showed higher prevalence. CONCLUSIONS: The prevalence of MCI in China was 15.4%, which varied by demographics, lifestyles, morbidity, screening tools, and diagnostic criteria. In further studies, screening tools and diagnosis criteria should be considered when estimating MCI prevalence.

XAB2 depletion induces intron retention in POLR2A to impair global transcription and promote cellular senescence.

XAB2 is a multi-functional protein participating processes including transcription, splicing, DNA repair and mRNA export. Here, we report POLR2A, the largest catalytic subunit of RNA polymerase II, as a major target gene down-regulated after XAB2 depletion. XAB2 depletion led to severe splicing defects of POLR2A with significant intron retention. Such defects resulted in substantial loss of POLR2A at RNA and protein levels, which further impaired global transcription. Treatment of splicing inhibitor madrasin induced similar reduction of POLR2A. Screen using TMT-based quantitative proteomics identified several proteins involved in mRNA surveillance including Dom34 with elevated expression. Inhibition of translation or depletion of Dom34 rescued the expression of POLR2A by stabilizing its mRNA. Immuno-precipitation further confirmed that XAB2 associated with spliceosome components important to POLR2A expression. Domain mapping revealed that TPR motifs 2-4 and 11 of XAB2 were critical for POLR2A expression by interacting with SNW1. Finally, we showed POLR2A mediated cell senescence caused by XAB2 deficiency. Depletion of XAB2 or POLR2A induced cell senescence by up-regulation of p53 and p21, re-expression of POLR2A after XAB2 depletion alleviated cellular senescence. These data together support that XAB2 serves as a guardian of POLR2A expression to ensure global gene expression and antagonize cell senescence.

Impacts of multimorbidity on medication treatment, primary healthcare and hospitalization among middle-aged and older adults in China: evidence from a nationwide longitudinal study.

BACKGROUND: Multimorbidity is a significant contributor to inequalities in healthcare and has become a major unaddressed challenge for the health system in China. The aim of this study is to assess the socio-demographic distribution of multimorbidity and the relationships between multimorbidity, primary healthcare, hospitalization and healthcare spending. METHODS: We conducted this nationwide population-based panel data study in China. Study participants included 12,306 residents aged ≥45 years from the China Health and Retirement Longitudinal Study in 2011, 2013 and 2015. Random-effects logistic regression models were applied to estimate the association between multimorbidity and primary healthcare as well as admission to the hospital. We used log-linear regression models to investigate the association between multimorbidity and health spending. RESULTS: Overall, 46.2% of total interviewees reported multimorbidity. Random-effects logistic regression analyses showed that multimorbidity was associated with a higher likelihood of medication use (Adjusted odds ratio (AOR) =19.19, 95% CI = 17.60, 20.93), health check (AOR = 1.51, 95% CI = 1.43, 1.59), outpatient care (AOR = 2.39, 95% CI = 2.23, 2.56) and admission to hospital (AOR = 2.94, 95% CI = 2.68, 3.21). Log-linear regression models showed that multimorbidity was also positively associated with spending for outpatient care (coefficient = 0.64, 95% CI = 0.59, 0.68) and hospitalization (coefficient = 0.65, 95% CI = 0.60, 0.71). CONCLUSIONS: Multimorbidity is associated with higher levels of primary care, hospitalization and greater financial burden to individuals in China. Health systems need to shift from single-disease models to new financing and service delivery models to more effectively manage multimorbidity.

Tobin's q and corporate investment with a pandemic shock.

We analyze the impact of COVID-19 on investment by incorporating a stochastic transmission shock into the standard q theoretical framework. Our model suggests that the adjustment cost amplifies the negative pandemic shock to investment and decreases firm value. In particular, when the infection rate is low, the reduction in investment is higher for firms with low adjustment costs in that they are more sensitive to the infection rate. An optimistic expectation of the arrival rate of a vaccine reduces the probability of executing mitigation policy. Moreover, the uncertainty of the pandemic increases investment and enhances firm value during the pandemic regime.

Low-Valence Znδ+ (0<δ<2) Single-Atom Material as Highly Efficient Electrocatalyst for CO2 Reduction.

A nitrogen-stabilized single-atom catalyst containing low-valence zinc atoms (Znδ+ -NC) is reported. It contains saturated four-coordinate (Zn-N4 ) and unsaturated three-coordinate (Zn-N3 ) sites. The latter makes Zn a low-valence state, as deduced from X-ray photoelectron spectroscopy, X-ray absorption spectroscopy, electron paramagnetic resonance, and density functional theory. Znδ+ -NC catalyzes electrochemical reduction of CO2 to CO with near-unity selectivity in water at an overpotential as low as 310 mV. A current density up to 1 A cm-2 can be achieved together with high CO selectivity of >95 % using Znδ+ -NC in a flow cell. Calculations suggest that the unsaturated Zn-N3 could dramatically reduce the energy barrier by stabilizing the COOH* intermediate owing to the electron-rich environment of Zn. This work sheds light on the relationship among coordination number, valence state, and catalytic performance and achieves high current densities relevant for industrial applications.