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The COVID-19 pandemic has driven substantial evolution of the SARS-CoV-2 virus, yielding subvariants that exhibit enhanced infectiousness in humans. However, this adaptive advantage may not universally extend to zoonotic transmission. In this work, we hypothesize that viral adaptations favoring animal hosts do not necessarily correlate with increased human infectivity. In addition, we consider the potential for gain-of-function mutations that could facilitate the virus's rapid evolution in humans following adaptation in animal hosts. Specifically, we identify the SARS-CoV-2 receptor-binding domain (RBD) mutations that enhance human-animal cross-transmission. To this end, we construct a multitask deep learning model, MT-TopLap trained on multiple deep mutational scanning datasets, to accurately predict the binding free energy changes upon mutation for the RBD to ACE2 of various species, including humans, cats, bats, deer, and hamsters. By analyzing these changes, we identified key RBD mutations such as Q498H in SARS-CoV-2 and R493K in the BA.2 variant that are likely to increase the potential for human-animal cross-transmission.

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Rosa rugosa is renowned for its fragrant essential oils (EOs) including the primary volatile compounds such as terpenes (geraniol and citronellol) and 2-phenylethanol. While the role of miRNAs in plant secondary metabolism has been explored, their involvement in EOs metabolism remains largely unknown. Sequencing of the petals of R. rugosa identified 383 conserved miRNAs and 625 novel miRNAs including 53 miRNAs differentially expressed in a strong fragrance variety R. rugosa 'White Purple Branch'. Degradome sequencing predicted 1969 targets enriched in GO terms involved in the negative regulation of macromolecule metabolic process. Furthermore, 122 targets of differentially expressed miRNAs were enriched in phenylalanine metabolism and other KEGG pathways. A post-transcriptional regulation network of 52 miRNAs and 70 miRNA-transcription factor modules target terpene and 2-phenylethanol biosynthesis pathways. Six interactions including miR535f-RrHMGR, NOV146-RrNUDX1, miR166l-RrHY5 and miR156c-RrSPL2 were validated using RNA ligase-mediated RACE. Sequence alignment revealed that the NOV146-RrNUDX1 was conserved in the Rosa genus. Moreover, weaker silencing of RrNUDX1 by NOV146 contributed to the stronger fragrance of R. rugosa. These findings offer a comprehensive understanding of the post-transcriptional regulation involved in essential oil biosynthesis and identify candidate miRNAs for further genetic improvement of EO yields in R. rugosa.

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Cochlear hair cells (HCs) sense sound waves and allow us to hear. Loss of HCs will cause irreversible sensorineural hearing loss. It is well known that DNA damage repair plays a critical role in protecting cells in many organs. However, how HCs respond to DNA damage and how defective DNA damage repair contributes to hearing loss remain elusive.In this study, we showed that cisplatin induced DNA damage in outer hair cells (OHCs) and promoted OHC loss, leading to hearing loss in mice of either sex. Cisplatin induced the expression of Brca1, a DNA damage repair factor, in OHCs. Deficiency of Brca1 induced OHC and hearing loss, and further promoted cisplatin-induced DNA damage in OHCs, accelerating OHC loss. This study provides the first in vivo evidence demonstrating that cisplatin mainly induces DNA damage in OHCs and that BRCA1 promotes repair of DNA damage in OHCs and prevents hearing loss. Our findings not only demonstrate that DNA-damage inducible agent generates DNA damage in postmitotic HCs, but also suggest that DNA repair factors, like BRCA1, protect postmitotic HCs from DNA-damage induced cell death and hearing loss.Significance statement Sensorineural hearing loss is the most severe hearing loss caused by irreversible loss of cochlear hair cells. Hair cells are vulnerable to aging and ototoxic drug. Though DNA damage repair plays a critical role in protecting cells in many organs, it is poorly understood how DNA damage is repaired in hair cells. This study provides the first in vivo evidence demonstrating that cisplatin mainly induces DNA damage in outer hair cells and that BRCA1 promotes repair of DNA damage in outer hair cells and prevents outer hair cell loss as well as hearing loss.

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BACKGROUND: Total knee arthroplasty (TKA) successfully alleviates pain from knee osteoarthritis, but muscle strength and function are reduced for a long period postoperatively. Postoperative active resistance exercise may play a relevant role. PURPOSE: To systematically evaluate effects of lower-limb active resistance exercise (ARE) on mobility, physical function, muscle strength and pain intensity in patients with TKA. METHODS: A search was conducted in PubMed, EMBASE, and Cochrane Library databases from inception to September 2023. Only randomized controlled trials (RCTs) that compared the effects of ARE and no intervention or other rehabilitation program without PRE were included. The outcome variables were mobility (Maximal walking speed [MWS]/6-Minute Walk Test[6MWT]), physical function (Stair Climb Test [SCT]/Timed Up and Go [TUG]), knee extension/ flexion power(KEP/KFP), joint range of motion (ROM) and pain. Standardized Mean Differences (SMD) or Mean Differences (MD) and 95% confidence intervals (CI) were calculated and combined in meta-analyses. The Cochrane Collaboration's Handbook were used for the methodological quality assessments. GRADE was used to assess the quality of evidence. The meta-analysis was performed using the RevMan 5.4 software. RESULTS: A total of 14 randomized controlled trials, involving 880 patients, were finally included. The lower-limb ARE exhibited significantly greater improvement in MWS (MD 0.13, 95%CI 0.08-0.18, P < 0.00001), TUG(MD -0.92, 95%CI -1.55- -0.28, P = 0.005), KEP (SMD 0.58, 95%CI 0.20-0.96, P = 0.003), KFP (SMD 0.38, 95%CI 0.13-0.63, P = 0.003), ROM-flexion (MD 2.74, 95%CI 1.82-3.67, P < 0.00001) and VAS (MD - 4.65, 95% CI - 7.86- -1.44, p = 0.005) compared to conventional exercise(CE) immediately post-intervention. However, there were no statistically significant differences between both groups in regard to 6MWT (MD 7.98, 95%CI -4.60-20.56, P = 0.21), SCT (MD -0.79, 95%CI -1.69-0.10, P = 0.08) and ROM-extension (MD -0.60, 95%CI -1.23-0.03, P = 0.06). CONCLUSIONS: According to the results of meta-analysis, patients undergoing TKA who receive the lower extremity ARE show better clinical effects in terms of pain relief, strength recovery and knee ROM. Simultaneously, it may be beneficial to improve mobility and physical function of patients after TKA.

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Reproductive traits are vital economic parameters in goat production, and boosting the reproductive capacity of breeding rams is crucial for enhancing the profitability of goat farming. Currently, research on the reproductive performance of Qianbei Ma goats mainly centers on investigating mechanisms associated with prolificacy and estrous ovulation in ewes, with limited emphasis on ram reproductive aspects. This study used scanning electron microscopy and enzyme-linked immunosorbent assay (ELISA) to profile the morphology of testis and the dynamic changes of Luteinizing Hormone (LH), Follicle-Stimulating Hormone (FSH), and Testosterone (T) in serum at different developmental stages of Qianbei Ma goats. Meanwhile, transcriptome sequencing technology was used to investigate the mRNA expression patterns in testicular tissues at different developmental stages: newborn (0 M), puberty (6 M), sexual maturity (12 M), and physical maturity (18 M). The results showed that the diameter, circumference, and area of the testicular seminiferous tubules gradually increased with age. The levels of T and LH in serum significantly increased from 0 to 6 months after birth (p < 0.05), followed by a stabilization of T levels and a significant decrease in LH levels (p < 0.05). Meanwhile, FSH shows a decreasing trend between 0 and 18 months after birth. A total of 26,437 differentially expressed genes were identified in 6 comparison groups, which involve various biological processes such as immunity, growth, metabolism, development, and reproduction, and are significantly enriched in signaling pathways related to testicular development and spermatogenesis. WGCNA analysis identified 6 regions significantly associated with testicular development and spermatogenesis, and selected 320 genes for constructing a PPI network. Ten candidate genes related to testicular development and spermatogenesis were identified, including TP53, PLK4, RPS9, PFN4, ACTB, CYP17A1, GPX4, CLDN1, AMH and DHH. Of these, the CYP17A1 gene promotes interstitial cell proliferation, and promotes T synthesis. This study provides a theoretical basis and data support for promoting efficient breeding of goats and early breeding of excellent male goats.

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Although the petals of Rosa rugosa are rich in flavonoids and their bioactivity has a significant impact on human health, the flavonoid content decreases during flower development. In this study, R. rugosa 'Feng hua' was used to investigate the effects of the melatonin foliar spray on enhancing the quality of rose by focusing on major flavonoids. The results showed that the contents of total flavonoids in rose petals at the full bloom stage induced by melatonin obeyed a bell-shaped curve, with a maximum at 0.3 mM, indicating the concentration-dependent up-regulation of flavonoid biosynthesis. In the treatment with 0.3 mM melatonin, metabolomic analyses showed that the concentrations of ten main flavonoids were identified to be increased by melatonin induction, with high levels and increases observed in three flavonols and two anthocyanins. KEGG enrichment of transcriptomic analysis revealed a remarkable enrichment of DEGs in flavonoid and flavonol biosynthesis, such as Rr4CL, RrF3H, and RrANS. Furthermore, functional validation using virus-induced gene silencing technology demonstrated that Rr4CL3 is the crucial gene regulating flavonoid biosynthesis in response to the stimulant of melatonin. This study provides insights into the exogenous melatonin regulation mechanism of biosynthesis of flavonoids, thereby offering potential industrial applications.

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Basal-like breast cancer may originate from luminal epithelial or cancerous cells. Inadequately repaired DNA damage impairs luminal differentiation and promotes aberrant luminal to basal trans-differentiation in mammary epithelial cells (MECs). Ubiquitin-specific peptidase 11 (USP11), a deubiquitinase, plays a critical role in DNA damage repair. The role of USP11 in controlling mammary cell differentiation and tumorigenesis remains poorly understood. We generated Usp11 knockout mice and breast cancer cell lines expressing wild-type (WT) and mutant form of USP11. By using these mutant mice, cell lines, and human USP11-deficient and -proficient breast cancer tissues, we tested how USP11 controls mammary cell fate. We generated Usp11 knock-out mice and found that deletion of Usp11 reduced the expression of E-cadherin and promoted DNA damage in MECs. Overexpression of WT USP11, but not a deubiquitinase-inactive mutant form of USP11, promoted luminal differentiation, enhanced DNA damage repair, and suppressed tumorigenesis in mice. Mechanistically, we found that USP11 enhanced the protein expression of E-cadherin dependent on its deubiquitinase activity, and that USP11 deubiquitinated E-cadherin at K738. We discovered that USP11 bound to E-cadherin through its C-terminal region. In human breast cancers, expression of USP11 was positively correlated with that of E-cadherin, and high USP11 predicted better recurrence-free survival. Our findings provide compelling genetic and biochemical evidence that USP11 not only promotes DNA damage repair but also deubiquitinates E-cadherin and maintains the luminal feature of mammary tumor cells, thereby suppressing luminal breast cancer.

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Animals spend a considerable proportion of their life span at rest. However, resting status has often been overlooked when investigating how species respond to environmental conditions. This may induce a large bias in understanding the local adaptation of species across environmental gradients and their vulnerability to potential environmental change. Here, we conducted an empirical study on montane agamid lizards, combined with mechanistic modeling, to compare elevational variations in body temperature and metabolisms (cumulative digestion and maintenance cost) between resting and active status. Our study on three populations of an agamid lizard along an elevational gradient revealed a trend of decreasing body temperature toward higher elevations, the main contributor of which was resting status of the lizards. Using population-specific reaction norms, we predicted greater elevational variation in hourly and cumulative digestion for resting lizards than for active lizards. Climate-change impacts, estimated as the change in cumulative digestion, also show greater elevational variation when resting status is factored into the analysis. Further, our global analysis of 98 agamid species revealed that in about half of their combined distributional range, the contribution of resting status in determining the elevational variation in cumulative digestion and maintenance cost of lizards was greater than the contribution made by a lizard's active status. Our study highlights the importance of considering resting status when investigating how species respond to environmental conditions, especially for those distributed over tropical and subtropical mountain areas.

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OBJECTIVE: This study aimed to compare the gender differences in isolated mitral regurgitation (MR) repair. METHODS: Of 381 adults aged 54.8 ± 12.3 years undergoing mitral valve repair (MVP) for isolated MR from January 2019 to December 2022, the baseline and operative data, and outcomes were compared between 161 women (42.3%) and 220 men (57.7%). RESULTS: Women tended to be nonsmokers (98.1 vs. 45%, p < 0.001), and have more cerebrovascular accidents (38.5% vs. 24.1%, p = 0.004) and isolated annular dilatation (19.3 vs. 9.1%, p = 0.010), lower creatinine (70.0 ± 19.5 vs. 86.3 ± 19.9 µmol/dL, p < 0.001), and smaller left ventricular end-diastolic diameter (LVEDD; 54.4 ± 6.7 vs. 57.8 ± 6.6 mm, p < 0.001). One female died of stroke at 2 days (0.3%). Another female (0.3%) underwent mitral valve replacement for failed repair. Stroke occurred in 4 (1.0%). Two underwent reexploration for bleeding (0.5%). Women were more likely to have less 24-hour drainage (290 ± 143 vs. 385 ± 196 mL, p < 0.001). Over a mean follow-up of 2.1 ± 1.1 years (100% complete), 1 woman died and 1 man underwent a reoperation; 28 had moderate MR, and 9 had severe MR. Neither did early and late mortality and reoperation, nor freedom from late moderate or severe MR (71.6 vs. 71.4% at 5 years; p = 0.992) differ significantly between the two genders. Predictors for late moderate or severe MR were anterior leaflet prolapse (hazard ratio [HR] 4.45; 95% confidence interval [CI] 1.18-16.72; p = 0.027) and isolated annular dilation (HR 5.47, 95% CI 1.29-23.25; p = 0.021). CONCLUSION: In this series of patients undergoing isolated MR repair, despite significant differences in smoking, cerebrovascular accidents, creatinine, LVEDD, and isolated annular dilatation at baseline, and 24-hour drainage postoperatively, women and men did not show significant differences in early and late survival, reoperation, and freedom from late moderate or severe MR.

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Characterizing the nature of hydrodynamical transport properties in quantum dynamics provides valuable insights into the fundamental understanding of exotic non-equilibrium phases of matter. Experimentally simulating infinite-temperature transport on large-scale complex quantum systems is of considerable interest. Here, using a controllable and coherent superconducting quantum simulator, we experimentally realize the analog quantum circuit, which can efficiently prepare the Haar-random states, and probe spin transport at infinite temperature. We observe diffusive spin transport during the unitary evolution of the ladder-type quantum simulator with ergodic dynamics. Moreover, we explore the transport properties of the systems subjected to strong disorder or a tilted potential, revealing signatures of anomalous subdiffusion in accompany with the breakdown of thermalization. Our work demonstrates a scalable method of probing infinite-temperature spin transport on analog quantum simulators, which paves the way to study other intriguing out-of-equilibrium phenomena from the perspective of transport.

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Foxtail millet is a drought-tolerant cereal and forage crop. The basic leucine zipper (bZIP) gene family plays important roles in regulating plant development and responding to stresses. However, the roles of bZIP genes in foxtail millet remain largely uninvestigated. In this study, 92 members of the bZIP transcription factors were identified in foxtail millet and clustered into ten clades. The expression levels of four SibZIP genes (SibZIP11, SibZIP12, SibZIP41, and SibZIP67) were significantly induced after PEG treatment, and SibZIP67 was chosen for further analysis. The studies showed that ectopic overexpression of SibZIP67 in Arabidopsis enhanced the plant drought tolerance. Detached leaves of SibZIP67 overexpressing plants had lower leaf water loss rates than those of wild-type plants. SibZIP67 overexpressing plants improved survival rates under drought conditions compared to wild-type plants. Additionally, overexpressing SibZIP67 in plants displayed reduced malondialdehyde (MDA) levels and enhanced activities of antioxidant enzymes, including catalase (CAT), superoxide dismutase (SOD), and peroxidase (POD) under drought stress. Furthermore, the drought-related genes, such as AtRD29A, AtRD22, AtNCED3, AtABF3, AtABI1, and AtABI5, were found to be regulated in SibZIP67 transgenic plants than in wild-type Arabidopsis under drought conditions. These data suggested that SibZIP67 conferred drought tolerance in transgenic Arabidopsis by regulating antioxidant enzyme activities and the expression of stress-related genes. The study reveals that SibZIP67 plays a beneficial role in drought response in plants, offering a valuable genetic resource for agricultural improvement in arid environments.

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Given that many organic pollutants have been reported to facilitate the plasmid-mediated conjugative transfer of antibiotic resistance genes (ARGs), it was naturally deduced that nonylphenol (NP) can also have this kind of effect. Whereas, this study demonstrates an entirely different result that environmentally relevant concentrations of NP attenuate plasmid-mediated ARGs conjugative transfer (maximum inhibition rate 64 %), further study show that NP exposure had no significant effect on bacterial growth, cell vitality, oxidative stress response, and expression of conjugation-relevant genes, which were reported to closely relate to the conjugative transfer in numerous studies. Conclusively, it was found that the dispersant function of NP impeded the occurrence of cell mating, thus was responsible for the decline of conjugative transfer. This study shows a new perspective on understanding the effect of organic pollutants like NP on the ARGs horizontal dissemination in environment.

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AlphaFold 3 (AF3), the latest version of protein structure prediction software, goes beyond its predecessors by predicting protein-protein complexes. It could revolutionize drug discovery and protein engineering, marking a major step toward comprehensive, automated protein structure prediction. However, independent validation of AF3's predictions is necessary. In this work, we evaluate AF3 complex structures using the SKEMPI 2.0 database which involves 317 protein-protein complexes and 8338 mutations. AF3 complex structures when applied to the most advanced TDL model, MT-TopLap (MultiTask-Topological Laplacian), give rise to a very good Pearson correlation coefficient of 0.86 for predicting protein-protein binding free energy changes upon mutation, which is slightly less than the 0.88 achieved earlier with the Protein Data Bank (PDB) structures. Nonetheless, AF3 complex structures led to a 8.6% increase in the prediction RMSE compared to original PDB complex structures. Additionally, some of AF3's complex structures have large errors, which were not captured in its ipTM performance metric. Finally, it is found that AF3's complex structures are not reliable for intrinsically flexible regions or domains.

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Monoclonal antibodies targeting immune checkpoints have been widely applied in gastrointestinal cancer immunotherapy. However, systemic administration of various monoclonal antibodies does not often result in sustained effects in reversing the immunosuppressive tumor microenvironment (TME), which may be due to the spatiotemporal dynamic changes of immune checkpoints. Herein, we reported a novel immune checkpoint reprogramming strategy for gastrointestinal cancer immunotherapy. It was achieved by the sequential delivery of siPD-L1 (siRNA for programmed cell death ligand 1) and pOX40L (plasmid for OX40 ligand), which were complexed with two cationic polymer brush-grafted carbon nanotubes (dense short (DS) and dense long (DL)) designed based on the structural characteristics of nucleic acids and brush architectures. Upon administrating DL/pOX40L for the first three dosages, then followed by DS/siPD-L1 for the next three dosages to the TME, it upregulated the stimulatory checkpoint OX40L on dendritic cells (DCs) and downregulated inhibitory checkpoint PD-L1 on tumor cells and DCs in a sequential reprogramming manner. Compared with other combination treatments, this sequential strategy drastically boosted the DCs maturation, and CD8+ cytotoxic T lymphocytes infiltration in tumor site. Furthermore, it could augment the local antitumor response and improve the T cell infiltration in tumor-draining lymph nodes to reverse the peripheral immunosuppression. Our study demonstrated that sequential nucleic acid delivery strategy via personalized nanoplatforms effectively reversed the immunosuppression status in both tumor microenvironment and peripheral immune landscape, which significantly enhanced the systemic antitumor immune responses and established an optimal immunotherapy strategy against gastrointestinal cancer.

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Institutional controls, as an important measure for risk management of contaminated sites, is widely used in site management by the United States, Canada and European countries. At present, some regions in China have also begun to explore the implementation of institutional controls, but its path, safeguard mechanism, and tracking evaluation are still unclear. Based on China's unique contaminated site remediation control system and land management system, this paper proposes a framework for the whole life cycle institutional controls of China's contaminated sites: (1) evaluate the need for institutional controls; (2) establish the objectives of institutional controls; (3) identify the restrictive requirements of institutional controls; (4) establish the implementation form of institutional controls; and (5) regularly review the effectiveness of institutional controls. To demonstrate the applicability of the institutional control framework, a case demonstration study was conducted at a petrochemical contaminated site in China. By analyzing the information on residual pollutants after the implementation of risk management measures at the site, the exposure pathways and hazards in case of re-release, and the engineering facilities, we proposed eight restrictive requirements, including the prohibition of disturbing and damaging the clean and planted soil layers of the site and the protection of long-term monitoring wells. At the same time, we constructed a multi-departmental pathway to implement institutional controls in conjunction with ecological environment, natural resources and housing departments to ensure effective implementation of institutional controls. Eventually, we summarized a set of replicable and generalizable institutional controls application models, which provide valuable theoretical and practical support for China and other local governments in the implementation of institutional controls at contaminated sites.

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The MCL1 gene is frequently amplified in cancer and codes for the antiapoptotic protein myeloid cell leukemia 1 (MCL1), which confers resistance to the current standard of care. Therefore, MCL1 is an attractive anticancer target. Here we describe BRD-810 as a potent and selective MCL1 inhibitor and its key design principle of rapid systemic clearance to potentially minimize area under the curve-driven toxicities associated with MCL1 inhibition. BRD-810 induced rapid cell killing within 4 h in vitro but, in the same 4-h window, had no impact on cell viability or troponin I release in human induced pluripotent stem cell-derived cardiomyocytes, even at suprapharmacologic concentrations. In vivo BRD-810 induced efficacy in xenograft hematological and solid tumor models despite the short residence time of BRD-810 in plasma. In totality, our data support the hypothesis that short-term inhibition of MCL1 with BRD-810 can induce apoptosis in tumor cells while maintaining an acceptable safety profile. We, therefore, intend to advance BRD-810 to clinical trials.

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Breast Cancer Type 1 Susceptibility Protein (BRCA1) is a tumor-suppressor protein that regulates various cellular pathways, including those that are essential for preserving genome stability. One essential mechanism involves a BRCA1-A complex that is recruited to double-strand breaks (DSBs) by RAP80 before initiating DNA damage repair (DDR). How RAP80 itself is recruited to DNA damage sites, however, is unclear. Here, we demonstrate an intrinsic correlation between a methyltransferase DOT1L-mediated RAP80 methylation and BRCA1-A complex chromatin recruitment that occurs during cancer cell radiotherapy resistance. Mechanistically, DOT1L is quickly recruited onto chromatin and methylates RAP80 at multiple lysines in response to DNA damage. Methylated RAP80 is then indispensable for binding to ubiquitinated H2A and subsequently triggering BRCA1-A complex recruitment onto DSBs. Importantly, DOT1L-catalyzed RAP80 methylation and recruitment of BRCA1 have clinical relevance, as inhibition of DOT1L or RAP80 methylation seems to enhance the radiosensitivity of cancer cells both in vivo and in vitro. These data reveal a crucial role for DOT1L in DDR through initiating recruitment of RAP80 and BRCA1 onto chromatin and underscore a therapeutic strategy based on targeting DOT1L to overcome tumor radiotherapy resistance.

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BACKGROUND: We seek to compare the early and late outcomes of reperfusion-first versus central repair-first strategies in patients with acute type A dissection (ATAAD) complicated by mesenteric malperfusion. METHODS: Among 68 patients, reperfusion-first strategy with superior mesenteric artery (SMA) stenting was adopted in 31 and central repair-first in 37, based on rupture risk and circulatory compromise, severity, time and mechanisms of mesenteric ischemia. Early and late outcomes were compared between two strategies. Follow-up was 100% at 3.3±1.4 years. RESULTS: Mean age was 50.6±11.4 years (59 males, 86.8%). The reperfusion-first group had more celiac artery involvement (74.2% vs. 48.6%) and peritoneal irritation signs (19.4% vs. 2.7%), while central repair-first group had more tamponade (27% vs. 3.2%). Early mortality was 48.6% (18/37) with central repair-first strategy versus 19.4% (6/31) in reperfusion-first group (P=0.012). Reperfusion-first patients had fewer gastrointestinal complications (12.9% vs. 54.1%, P<0.001) and respiratory failure (3.2% vs. 24.3%, P=0.017). At 5 years, SMA stent patency was 84%, and survival was significantly higher in reperfusion-first patients (80.6% vs. 45.9%, P=0.009), with similar freedom from adverse events between two groups (74.9% vs. 76.0%, P=0.812). Tamponade (hazard ratio [HR], 3.093; P=0.023), peritoneal irritation signs (HR, 8.559; P=0.006), and lactate (mmol/L) (HR, 1.279; P<0.001) were predictors for all-cause mortality. CONCLUSIONS: In this series of ATAAD patients with mesenteric malperfusion, the reperfusion-first strategy with SMA stenting could significantly reduce the mortality risk and achieved favorable late survival and freedom from adverse events. These results argue favorably for the use of the reperfusion-first strategy in such patients.

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The fundamental role of cells in safeguarding the genome's integrity against DNA double-strand breaks (DSBs) is crucial for maintaining chromatin homeostasis and the overall genomic stability. Aberrant responses to DNA damage, known as DNA damage responses (DDRs), can result in genomic instability and contribute significantly to tumorigenesis. Unraveling the intricate mechanisms underlying DDRs following severe damage holds the key to identify therapeutic targets for cancer. Chromatin lysine acylation, encompassing diverse modifications such as acetylation, lactylation, crotonylation, succinylation, malonylation, glutarylation, propionylation, and butyrylation, has been extensively studied in the context of DDRs and chromatin homeostasis. Here, we delve into the modifying enzymes and the pivotal roles of lysine acylation and their crosstalk in maintaining chromatin homeostasis and genome integrity in response to DDRs. Moreover, we offer a comprehensive perspective and overview of the latest insights, driven primarily by chromatin acylation modification and associated regulators.