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Background. Coronavirus disease 2019 (COVID-19) has been a global threat that pushes healthcare to its limits. Hypertension is one of the most common risk factors for cardiovascular complications in COVID-19 and is strongly associated with disease severity and mortality. To date, clinical mechanisms by which hypertension leads to increased risk in COVID-19 are still unclear. Furthermore, additional factors might increase these risks, such as the consideration of age and sex, which are of interest when in search of personalized treatments for hypertensive COVID-19 patients. Methods. We conducted a retrospective cohort study of 543 COVID-19 patients in seven provinces of China to examine the epidemiological and clinical characteristics of COVID-19 in this population and to determine risk factors of hypertensive COVID-19 patients. We also used univariable and multivariable logistic regression methods to explore the risk factors associated with hypertensive COVID-19 patients in different age and sex subgroups. Results. Among the enrolled COVID-19 patients, the median age was 47 years (interquartile range (IQR) 34.0–57.0), and 99 patients (18.23%) were over 60 years old. With regard to comorbidities, 91 patients (16.75%) were diagnosed with hypertension, followed by diabetes, coronary disease, and cerebrovascular disease. Of the hypertensive COVID-19 patients, 51 (56.04%) were male. Multivariable analysis showed that old age, comorbid diabetes or coronary heart disease on admission, increased D-dimer, increased glucose, and decreased lymphocyte count were independent risk factors associated with hypertensive COVID-19 patients. Elevated total bilirubin (odds ratio [OR]: 1.014, 95% confidence interval [CI]: 0.23–1.05; p=0.043) and triglycerides (OR: 1.173, 95% CI: 0.049–1.617; p=0.007) were found to be associated with elderly hypertensive COVID-19 patients. In addition, we found that decreased lymphocytes, basophil, high-density lipoprotein, and increased fibrinogen and creatinine were related to a higher risk of disease severity in male patients. The most common abnormal clinical findings pertaining to female hypertensive COVID-19 patients were hemoglobin, total bile acid, total protein, and low-density lipoprotein. Conclusions. Factors associated with increased risk of hypertensive COVID-19 patients were identified. Results to the different age and sex subgroups in our study will allow for better possible personalized care and also provide new insights into specific risk stratification, disease management, and treatment strategies for COVID-19 patients with hypertension in the future.

To understand the distribution of aluminum （A1） under the influence of mesocale eddies in the western South China Sea （SCS）, sea level anomaly, geostrophic current, environmental parameters and reactive A1 were investigated in the western SCS in August 2013. The highest reactive A1 concentration （（180±64） nmol/L） was observed in the surface waters, indicating a substantial atmospheric input. Vertically, the reactive A1 decreased from the surface high concentration to the subsurface minima at the depth of chlorophyll a （Chl a） maxima and then increased again with depth at most of the stations. The average concentration of reactive A1 in the upper 100 m water column was significantly lower in the cyclonic eddy （（137±6） nmol/L） as compared with that in the non- eddy waters （（180±21） nmol/L）. By contrast, the average concentrations of Chl a and silicate in the upper 100 m water column were higher in the cyclonic eddy and lower in the anticyclonic eddy. There was a significant negative correlation between the average concentrations of reactive Al and Chl a in the upper 100 m water column. The vertical distribution of reactive AI and the negative correlation between reactive A1 and Chl a both suggest that the reactive A1 in the upper water column was significantly influenced by biological removal processes. Our results indicate that mesoscale eddies could regulate the distribution of reactive A1 by influencing the primary production and phytoplankton community structure in the western SCS.

Lactylation has been recently identified as a new type of posttranslational modification occurring widely on lysine residues of both histone and nonhistone proteins. The acetyltransferase p300 is thought to mediate protein lactylation, yet the cellular concentration of the proposed lactyl-donor, lactyl-coenzyme A, is about 1,000 times lower than that of acetyl-CoA, raising the question of whether p300 is a genuine lactyltransferase. Here, we report that alanyl-tRNA synthetase 1 (AARS1) moonlights as a bona fide lactyltransferase that directly uses lactate and ATP to catalyze protein lactylation. Among the candidate substrates, we focused on the Hippo pathway, which has a well-established role in tumorigenesis. Specifically, AARS1 was found to sense intracellular lactate and translocate into the nucleus to lactylate and activate the YAP-TEAD complex; and AARS1 itself was identified as a Hippo target gene that forms a positive-feedback loop with YAP-TEAD to promote gastric cancer (GC) cell proliferation. Consistently, the expression of AARS1 was found to be upregulated in GC, and elevated AARS1 expression was found to be associated with poor prognosis for patients with GC. Collectively, this work found AARS1 with lactyltransferase activity in vitro and in vivo and revealed how the metabolite lactate is translated into a signal of cell proliferation.

DNA 5-hydroxymethylcytosine (5hmC) modification is known to be associated with gene transcription and frequently used as a mark to investigate dynamic DNA methylation conversion during mammalian development and in human diseases. However, the lack of genome-wide 5hmC profiles in different human tissue types impedes drawing generalized conclusions about how 5hmC is implicated in transcription activity and tissue specificity. To meet this need, we describe the development of a 5hmC tissue map by characterizing the genomic distributions of 5hmC in 19 human tissues derived from ten organ systems. Subsequent sequencing results enabled the identification of genome-wide 5hmC distributions that uniquely separates samples by tissue type. Further comparison of the 5hmC profiles with transcriptomes and histone modifications revealed that 5hmC is preferentially enriched on tissue-specific gene bodies and enhancers. Taken together, the results provide an extensive 5hmC map across diverse human tissue types that suggests a potential role of 5hmC in tissue-specific development; as well as a resource to facilitate future studies of DNA demethylation in pathogenesis and the development of 5hmC as biomarkers. DNA 5-hydroxymethylcytosine (5hmC) modification is associated with gene transcription and used as a mark of mammalian development. Here the authors report a comprehensive 5hmC tissue map and analysis of 5hmC genomic distributions in 19 human tissues derived from 10 organ systems, thus providing insights into the role of 5hmC in tissue-specific development.

Genome editing technologies hold tremendous potential in biomedical research and drug development. Therefore, it is imperative to discover gene editing tools with superior cutting efficiency, good fidelity, and fewer genomic restrictions. Here, we report a CRISPR/Cas9 from Faecalibaculum rodentium , which is characterized by a simple PAM (5′-NNTA-3′) and a guide RNA length of 21–22 bp. We find that FrCas9 could achieve comparable efficiency and specificity to SpCas9. Interestingly, the PAM of FrCas9 presents a palindromic sequence, which greatly expands its targeting scope. Due to the PAM sequence, FrCas9 possesses double editing-windows for base editor and could directly target the TATA-box in eukaryotic promoters for TATA-box related diseases. Together, our results broaden the understanding of CRISPR/Cas-mediated genome engineering and establish FrCas9 as a safe and efficient platform for wide applications in research, biotechnology and therapeutics. Gene editing tools have tremendous potential for biomedical and basic research. Here the authors report a Cas9 from Faecalibaculum rodentium (FrCas9) that achieves efficient and specific gene editing in human cells with a NNTA palindrome PAMs for targeting optimal sites at TATA-boxes to enhance CRISPRa/i screening.

Pluripotent stem cells hold great promise in regenerative medicine and developmental biology studies. Mitochondrial metabolites, including tricarboxylic acid (TCA) cycle intermediates, have been reported to play critical roles in pluripotency. Here we show that TCA cycle enzymes including Pdha1, Pcb, Aco2, Cs, Idh3a, Ogdh, Sdha and Mdh2 are translocated to the nucleus during somatic cell reprogramming, primed-to-naive transition and totipotency acquisition. The nuclear-localized TCA cycle enzymes Pdha1, Pcb, Aco2, Cs, Idh3a promote somatic cell reprogramming and primed-to-naive transition. In addition, nuclear-localized TCA cycle enzymes, particularly nuclear-targeted Pdha1, facilitate the 2-cell program in pluripotent stem cells. Mechanistically, nuclear Pdha1 increases the acetyl-CoA and metabolite pool in the nucleus, leading to chromatin remodeling at pluripotency genes by enhancing histone H3 acetylation. Our results reveal an important role of mitochondrial TCA cycle enzymes in the epigenetic regulation of pluripotency that constitutes a mitochondria-to-nucleus retrograde signaling mode in different states of pluripotent acquisition. Cellular metabolism is important in pluripotency and cell fate regulation. Here, authors observe chromatin remodeling followed by TCA enzyme translocation from the mitochondria to the nucleus, demonstrating pluripotency regulation by mitochondria to nucleus retrograde signaling.

For over ten years, China has been the largest vehicle market in the world. In order to address energy security and air quality concerns, China issued the Dual Credit policy to improve vehicle efficiency and accelerate New Energy Vehicle adoption. In this paper, a market-penetration model is combined with a vehicle fleet model to assess implications on greenhouse gas (GHG) emissions and energy demand. Here we use this integrated modeling framework to study several scenarios, including hypothetical policy tweaks, oil price, battery cost and charging infrastructure for the Chinese passenger vehicle fleet. The model shows that the total GHGs of the Chinese passenger vehicle fleet are expected to peak in 2032 under the Dual Credit policy. A significant reduction in GHG emissions is possible if more efficient internal combustion engines continue to be part of the technology mix in the short term with more New Energy Vehicle penetration in the long term. China issued the Dual Credit policy to improve vehicle efficiency and accelerate new energy vehicle adoption. Here the authors show that the total Greenhouse gas emissions (GHGs) of the Chinese passenger vehicle fleet are expected to peak in 2032 and a significant reduction in GHG emissions is possible by optimizing the Dual Credit policy.

Aging in mammals is accompanied by an imbalance of intestinal homeostasis and accumulation of mitochondrial DNA (mtDNA) mutations. However, little is known about how accumulated mtDNA mutations modulate intestinal homeostasis. We observe the accumulation of mtDNA mutations in the small intestine of aged male mice, suggesting an association with physiological intestinal aging. Using polymerase gamma (POLG) mutator mice and wild-type mice, we generate male mice with progressive mtDNA mutation burdens. Investigation utilizing organoid technology and in vivo intestinal stem cell labeling reveals decreased colony formation efficiency of intestinal crypts and LGR5-expressing intestinal stem cells in response to a threshold mtDNA mutation burden. Mechanistically, increased mtDNA mutation burden exacerbates the aging phenotype of the small intestine through ATF5 dependent mitochondrial unfolded protein response (UPR mt ) activation. This aging phenotype is reversed by supplementation with the NAD + precursor, NMN. Thus, we uncover a NAD + dependent UPR mt triggered by mtDNA mutations that regulates the intestinal aging. How age-accumulated mtDNA mutations in the small intestine modulate intestinal homeostasis is unclear. Here, the authors show that increased mtDNA mutation burden triggers an ATF5 dependent UPRmt by NAD + depletion, and thus regulates intestinal aging through impaired Wnt/β-catenin signaling.

To examine the level and factors associated with emotional labor among pediatric nurses in Yichang, China. From December 20-25, 2024, a cross-sectional descriptive online study was conducted among 307 pediatric nurses in Yichang, China. The survey included general information, emotional labor (assessed using the Emotional Labor Scale; higher scores indicate greater emotional labor), spiritual climate, and compassion satisfaction, and the influencing factors associated with emotional labor were analyzed. Pediatric nurses in Yichang had a total emotional labor score of 69.20 ± 9.40. Regression analysis showed that nurses without children had higher emotional labor levels than those with children (P < 0.05). Higher spiritual climate and compassion satisfaction scores were both significantly associated with higher emotional labor scores (P < 0.05). The intensity of emotional labor among pediatric nurses in Yichang is high and is associated with parental status (having children), spiritual climate, and compassion satisfaction.

Gallium-nitride high-electron-mobility-transistor is an industrial leading contender for high-frequency and high-power radio-frequency applications. However, the record output-power-density has remained stagnant for nearly two decades, limited by high thermal-resistances at the nucleation layer-substrate interface and thick nitride layers. Here, we propose induced nucleation by implementing ion-implantation on silicon-carbide substrate to create nano- to microscale surface nucleation-sites. This approach suppresses conventional island-like nucleation, enabling rapid film coalescence and aggressive reduction in buffer layer thickness while maintaining low dislocation density. Therefore, a low thermal-resistance of 3.9 m²K/GW for the entire epitaxial stack is achieved, three times lower than previous reports in various high-electron-mobility-transistor epi-structures. Gallium-nitride transistors demonstrate a record Johnson’s Figure-of-Merit of 20.6 THz·V, an output-power-density of 42/20 W/mm at 8/30 GHz, representing a 30%/43% improvement over prior highest output-power-density for all X-/Ka-band transistors, respectively. This result manifests the implantation-induced nucleation strategy as a promising approach for advancing Gallium-nitride heteroepitaxy for RF electronics. Achieving high output-power-density in Gallium-nitride transistors is challenging due to high thermal resistances and thick nitride layers. Here, the authors propose ion-implantation on silicon-carbide substrates, achieving high performance and reduced thermal resistance.