Cadmium exposure induces multigenerational inheritance of germ cell apoptosis and fertility suppression in Caenorhabditis elegans.

Cadmium is a significant environmental pollutant that poses a substantial health hazard to humans due to its propensity to accumulate in the body and resist excretion. We have a comprehensive understanding of the damage caused by Cd exposure and the mechanisms of tolerance, however, the intricate mechanisms underlying multigenerational effects resulting from Cd exposure remain poorly understood. In this study, Caenorhabditis elegans were used as a model organism to investigate Cd-induced multigenerational effects and its association with epigenetic modifications. The results showed that Cd exposure leads to an increase in germ cell apoptosis and a decrease in fertility, which can be passed down to subsequent generations. Further analysis revealed that transcription factors DAF-16/FOXO and SKN-1/Nrf2 play essential roles in responding to Cd exposure and in the transgenerational induction of germ cell apoptosis. Additionally, histone H3K4 trimethylation (H3K4me3) marks stress-responsive genes and enhances their transcription, ultimately triggering multigenerational germ cell apoptosis. This study provides compelling evidence that the detrimental effects of Cd on the reproductive system can be inherited across generations. These findings enhance our understanding of the multigenerational effects of environmental pollutants and may inform strategies for the prevention and control of such pollutants.

H2Se-evolving bio-heterojunctions promote cutaneous regeneration in infected wounds by inhibiting excessive cellular senescence.

Pathogenic infection leads to excessive senescent cell accumulation and stagnation of wound healing. To address these issues, we devise and develop a hydrogen selenide (H2Se)-evolving bio-heterojunction (bio-HJ) composed of graphene oxide (GO) and FeSe2 to deracinate bacterial infection, suppress cellular senescence and remedy recalcitrant infected wounds. Excited by near-infrared (NIR) laser, the bio-HJ exerts desired photothermal and photodynamic effects, resulting in rapid disinfection. The crafted bio-HJ could also evolve gaseous H2Se to inhibit cellular senescence and dampen inflammation. Mechanism studies reveal the anti-senescence effects of H2Se-evolving bio-HJ are mediated by selenium pathway and glutathione peroxidase 1 (GPX1). More critically, in vivo experiments authenticate that the H2Se-evolving bio-HJ could inhibit cellular senescence and potentiate wound regeneration in rats. As envisioned, our work not only furnishes the novel gasotransmitter-delivering bio-HJ for chronic infected wounds, but also gets insight into the development of anti-senescence biomaterials.

A new threshold selection method for species distribution models with presence-only data: Extracting the mutation point of the P/E curve by threshold regression.

Selecting thresholds to convert continuous predictions of species distribution models proves critical for many real-world applications and model assessments. Prevalent threshold selection methods for presence-only data require unproven pseudo-absence data or subjective researchers' decisions. This study proposes a new method, Boyce-Threshold Quantile Regression (BTQR), to determine thresholds objectively without pseudo-absence data. We summarize that the mutation point is a typical shape feature of the predicted-to-expected (P/E) curve after reviewing relevant articles. Analysis based on source-sink theory suggests that this mutation point may represent a transition in habitat types and serve as an appropriate threshold. Threshold regression is introduced to accurately locate the mutation point. To validate the effectiveness of BTQR, we used four virtual species of varying prevalence and a real species with reliable distribution data. Six different species distribution models were employed to generate continuous suitability predictions. BTQR and nine other traditional methods transformed these continuous outputs into binary results. Comparative experiments show that BTQR has advantages in terms of accuracy, applicability, and consistency over the existing methods.

Antibacterial and Angiogenic (2A) Bio-Heterojunctions Facilitate Infectious Ischemic Wound Regeneration via an Endogenous-Exogenous Bistimulatory Strategy.

In infectious ischemic wounds, a lack of blood perfusion significantly worsens microbe-associated infection symptoms and frequently complicates healing. To overcome this daunting issue, antibacterial and angiogenic (2A) bio-heterojunctions (bio-HJs) consisting of CuS/MXene heterojunctions and a vascular endothelial growth factor (VEGF)-mimicking peptide (VMP) are devised and developed to accelerate infectious cutaneous regeneration by boosting angiogenesis via an endogenous-exogenous bistimulatory (EEB) strategy. Assisted by near-infrared irradiation, the bio-HJ platform exhibits versatile synergistic photothermal, photodynamic, and chemodynamic effects for robust antibacterial efficacy. In addition, copper ions liberated from 2A bio-HJs elevate VEGF secretion from fibroblasts, which provokes VEGF receptors (VEGFR) activation through an endogenous pathway, whereas VMP itself promotes an exogenous pathway to facilitate endothelial cell multiplication and tube formation by directly activating the VEGFR signaling pathway. Moreover, employing an in vivo model of infectious ischemic wounds, it is confirmed that the EEB strategy can considerably boost cutaneous regeneration through pathogen elimination, angiogenesis promotion, and collagen deposition. As envisaged, this work leads to the development of a powerful 2A bio-HJ platform that can serve as an effective remedy for bacterial invasion-induced ischemic wounds through the EEB strategy.

Engineered Bio-Heterojunction Confers Extra- and Intracellular Bacterial Ferroptosis and Hunger-Triggered Cell Protection for Diabetic Wound Repair.

Nanomaterial-mediated ferroptosis has garnered considerable interest in the antibacterial field, as it invokes the disequilibrium of ion homeostasis and boosts lipid peroxidation in extra- and intracellular bacteria. However, current ferroptosis-associated antibacterial strategies indiscriminately pose damage to healthy cells, ultimately compromising their biocompatibility. To address this daunting issue, this work has designed a precise ferroptosis bio-heterojunction (F-bio-HJ) consisting of Fe2 O3 , Ti3 C2 -MXene, and glucose oxidase (GOx) to induce extra-intracellular bacteria-targeted ferroptosis for infected diabetic cutaneous regeneration. Fe2 O3 /Ti3 C2 -MXene@GOx (FMG) catalytically generates a considerable amount of ROS which assaults the membrane of extracellular bacteria, facilitating the permeation of synchronously generated Fe2+ /Fe3+ into bacteria under near-infrared (NIR) irradiation, causing planktonic bacterial death via ferroptosis, Fe2+ overload, and lipid peroxidation. Additionally, FMG facilitates intracellular bacterial ferroptosis by transporting Fe2+ into intracellular bacteria via inward ferroportin (FPN). With GOx consuming glucose, FMG creates hunger protection which helps macrophages escape cell ferroptosis by activating the adenosine 5'-monophosphate (AMP) activated protein kinase (AMPK) pathway. In vivo results authenticate that FMG boosts diabetic infectious cutaneous regeneration without triggering ferroptosis in normal cells. As envisaged, the proposed tactic provides a promising approach to combat intractable infections by precisely terminating extra-intracellular infection via steerable ferroptosis, thereby markedly elevating the biocompatibility of therapeutic ferroptosis-mediated strategies.

Higher-order sensorimotor circuit of the whole-brain functional network involved in pruritus regulation in atopic dermatitis.

BACKGROUND: Little is known about the neural mechanisms underlying pruritus regulation in Atopic dermatitis (AD). OBJECTIVE: To investigate the functional changes of the resting-state whole brain network of AD participants and the mechanisms by which they were involved in pruritus regulation. METHOD: Based on the functional magnetic resonance imaging data from 19 AD participants and 37 healthy controls (HC), a graph-theoretical measure of degree centrality (DC) conjoined with a voxel-level seed-based functional connectivity (FC) method was used to identify abnormal higher-order nodes and the functionally relevant circuit in AD participants compared to healthy controls (HC). RESULTS: Of 64 participants screened, 19 AD participants (12M/7F, median [IQR] age, 27 [14] years) and 36 HCs (13M/23F, median [IQR] age, 20 [1] years) were enrolled. DC values of the left superior frontal gyrus (LSFG) increased in AD participants and exhibited a negative correlation with the SCORAD score (r = -0.561, p = 0.012) compared with HC. In the FC analysis with LSFG as the seed, FC values of several sensory and motor regions increased in AD participants, highly overlapping with the anatomical distribution of the inferior fronto-occipital fascicle (IFOF). AD participants with severe pruritus exhibited lower levels of DC (T = -2.316, p = 0.033) and FC between the LSFG and left insula (T = -2.203, p = 0.042) than those with mild-to- moderate pruritus. CONCLUSIONS AND RELEVANCE: LSFG was involved in pruritus regulation in AD by forming a high-order sensorimotor circuit through the IFOF, a white matter fascicle that proved to provide multimodal integration in motor control and sensory information processing. These results offer more mechanism-guided treatment targets for severe pruritus in AD.

Abnormal mechanical stress induced chondrocyte senescence by YAP loss-mediated METTL3 upregulation.

OBJECTIVES: Abnormal mechanical stress is the pivotal risk factor of temporomandibular joint osteoarthritis (TMJOA). This study investigated the pathogenic mechanism by which abnormal mechanical stress induced chondrocyte senescence. MATERIALS AND METHODS: Cellular senescence was investigated in the rodent model of unilateral anterior crossbite and in the chondrocytes subjected to mechanical overloading in vitro. The effects of Yes-associated protein (YAP) in chondrocyte senescence and its correlation with methyltransferase-like 3 (METTL3) and N6 -methyladenosine (m6 A) modification were evaluated. The role of m6 A modification in chondrocyte senescence was determined. The therapeutic effects of m6 A inhibition in TMJOA were investigated. RESULTS: Senescent chondrocytes were accumulated in the mechanically induced TMJOA lesions in rats and mechanical overloading could trigger chondrocyte senescence in vitro. This mechanical stress-induced cellular senescence was revealed to be mediated by YAP deficiency that promoted METTL3-dependent m6 A modification. Moreover, inhibition of m6 A modification rescued chondrocyte senescence in vitro and in vivo, and suppressed TMJOA progression in rats. CONCLUSIONS: This study uncovered the underlying mechanism of mechanically induced senescence in TMJOA from the perspective of epitranscriptomics and revealed the therapeutic potential of m6 A inhibition in TMJOA.

Cytoplasmic Endonuclease G promotes nonalcoholic fatty liver disease via mTORC2-AKT-ACLY and endoplasmic reticulum stress.

Endonuclease G (ENDOG), a nuclear-encoded mitochondrial intermembrane space protein, is well known to be translocated into the nucleus during apoptosis. Recent studies have shown that ENDOG might enter the mitochondrial matrix to regulate mitochondrial genome cleavage and replication. However, little is known about the role of ENDOG in the cytosol. Our previous work showed that cytoplasmic ENDOG competitively binds with 14-3-3γ, which released TSC2 to repress mTORC1 signaling and induce autophagy. Here, we demonstrate that cytoplasmic ENDOG could also release Rictor from 14-3-3γ to activate the mTORC2-AKT-ACLY axis, resulting in acetyl-CoA production. Importantly, we observe that ENDOG could translocate to the ER, bind with Bip, and release IRE1a/PERK to activate the endoplasmic reticulum stress response, promoting lipid synthesis. Taken together, we demonstrate that loss of ENDOG suppresses acetyl-CoA production and lipid synthesis, along with reducing endoplasmic reticulum stress, which eventually alleviates high-fat diet-induced nonalcoholic fatty liver disease in female mice.

A 3D-printed orthopedic implant with dual-effect synergy based on MoS2 and hydroxyapatite nanoparticles for tumor therapy and bone regeneration.

Treatments for malignant bone tumors are urgently needed to be developed due to the dilemma of precise resection of tumor tissue and subsequent bone defects. Although polyether-ether-ketone (PEEK) has widely attracted attention in the orthopedic field, its bioinertness and poor osteogenic properties significantly restrict its applications in bone tumor treatment. To tackle the daunting issue, we use a hydrothermal technique to fabricate novel PEEK scaffolds modified with molybdenum disulfide (MoS2) nanosheets and hydroxyapatite (HA) nanoparticles. Our dual-effect synergistic PEEK scaffolds exhibit perfect photothermal therapeutic (PTT) property dependent on molybdous ion (Mo2+) concentration and laser power density, superior to conventional PEEK scaffolds. Under near-infrared (NIR) irradiation, the viability of MG63 osteosarcoma cells is significantly reduced by modified PEEK scaffolds, indicating a tumor-killing potential in vitro. Furthermore, the incorporation of HA nanoparticles on the surface of PEEK bolsters proliferation and adherence of MC3T3-E1 cells, boosting mineralization for further bone defect repair. The results of micro-computed tomography (micro-CT) and histological analysis of 4-week treated rat femora demonstrate the preeminent photothermal and osteogenesis capacity of 3D-printed modified scaffolds in vivo. In conclusion, the dual-effect synergistic orthopedic implant with photothermal anticancer property and osteogenic induction activity strikes a balance between tumor treatment and bone development promotion, offering a promising future therapeutic option.

Association between subclinical hypothyroidism and psychotic features in Chinese young adults with first-episode and untreated major depressive disorder.

BACKGROUND: Thyroid dysfunction is often reported in patients with major depressive disorder (MDD) and may be associated with depression severity and psychotic symptoms. We included young adults with first-episode and untreated MDD to avoid the effect of age and disease duration on thyroid dysfunction and psychotic symptoms. METHODS: 481 young patients with MDD (aged 18-24 years) were recruited. The Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), Positive and Negative Syndrome Scale (PANSS) positive subscale and Global Impression of Severity Scale (CGIS) were used to assess depression, anxiety, psychotic symptoms and disease severity, respectively. RESULTS: The prevalence rate of subclinical hypothyroidism (SCH) and thyroid antibody positivity was 56.76 % (273/481) and 26.61 % (128/481) in young MDD, respectively. A higher proportion of MDD patients with SCH displayed psychotic features (14.3 % vs. 5.3 %, OR = 2.985, p = 0.001). TSH was a risk factor for psychotic symptoms in MDD patient with SCH (B = 0.136, p = 0.017, OR = 1.384), with an AUC of 0.709, indicating acceptable discrimination. Multivariate regression analysis also showed that TSH was also independently associated with PANSS positive score (B = 0.339, t = 2.019, p = 0.045). LIMITATION: This cross-sectional study design did not demonstrate a causal relationship. Relying solely on the PANSS positive subscale as psychotic symptoms may cause bias. CONCLUSIONS: Our findings suggest that SCH is common in young patients with first-episode and untreated MDD. MDD patients with higher TSH levels may suffer from more psychotic symptoms. Regular screening of serum thyroid hormones is necessary in patients with MDD.

Fibroblast ferroptosis is involved in periodontitis-induced tissue damage and bone loss.

Periodontitis causes inflammatory destructions of tooth-supporting tissue and constitutes a significant burden on public health. Failing to reserve the tissue damage and bone loss by any of the currently available therapies has left periodontitis uncurable thus far. Understanding the molecular mechanism in the inflammatory process is crucial to elucidating the pathogenesis and enlightening new therapeutic strategies for periodontitis. This study was to investigate whether and how ferroptosis, a newly-discovered form of cell death, was involved in the pathogenesis of periodontitis. Healthy and periodontitis human gingiva samples were collected and ligature-induced periodontitis murine models were constructed to investigate the role of ferroptosis in periodontitis. Single-cell RNA sequencing data was analyzed to identify the cell type that underwent ferroptosis. The susceptibility of human gingival fibroblasts to ferroptosis was investigated by in vitro cell cultures. We found that gingival fibroblasts undergo ferroptosis in periodontitis, and that periodontitis-induced tissue damage and bone loss were alleviated by inhibition of ferroptosis. Periodontitis-induced pro-inflammatory immune responses was featured by profound elevation of fibroblast-derived Interleukin-6, which was attenuated by ferroptosis inhibition. These results indicated fibroblast ferroptosis as a new clue to unveiling the cellular and molecular basis for periodontitis-induced tissue damage. Involvement of ferroptosis/Interleukin-6 signaling in the pathogenic process suggested a potential target for immunopharmacological approaches to curing periodontitis.

Bioheterojunction-Engineered Polyetheretherketone Implants With Diabetic Infectious Micromilieu Twin-Engine Powered Disinfection for Boosted Osteogenicity.

Diabetic infectious micromilieu (DIM) leads to a critical failure rate of osseointegration by virtue of two main peculiarities: high levels of topical glucose and inevitable infection. To tackle the daunting issue, a bioheterojunction-engineered orthopedic polyetheretherketone (PEEK) implant consisting of copper sulfide/graphene oxide (CuS/GO) bioheterojunctions (bioHJs) and glucose oxidase (GOx) is conceived and developed for DIM enhanced disinfection and boosted osseointegration. Under hyperglycemic micromilieu, GOx can convert surrounding glucose into hydrogen peroxide (H2 O2 ). Then, upon infectious micromilieu, the bioHJs enable the catalyzation of H2 O2 to highly germicidal hydroxyl radical (·OH). As a result, the engineered implants massacre pathogenic bacteria through DIM twin-engine powered photo-chemodynamic therapy in vitro and in vivo. In addition, the engineered implants considerably facilitate cell viability and osteogenic activity of osteoblasts under a hyperglycemic microenvironment via synergistic induction of copper ions (Cu2+ ) and GO. In vivo studies using bone defect models of diabetic rats at 4 and 8 weeks further authenticate that bioHJ-engineering PEEK implants substantially elevate their osseointegration through biofilm elimination and vascularization, as well as macrophage reprogramming. Altogether, the present study puts forward a tactic that arms orthopedic implants with DIM twin-engine powered antibacterial and formidable osteogenic capacities for diabetic stalled osseointegration.

Gut Microbial Dysbiosis and Cognitive Impairment in Bipolar Disorder: Current Evidence.

Recent studies have reported that the gut microbiota influences mood and cognitive function through the gut-brain axis, which is involved in the pathophysiology of neurocognitive and mental disorders, including Parkinson's disease, Alzheimer's disease, and schizophrenia. These disorders have similar pathophysiology to that of cognitive dysfunction in bipolar disorder (BD), including neuroinflammation and dysregulation of various neurotransmitters (i.e., serotonin and dopamine). There is also emerging evidence of alterations in the gut microbial composition of patients with BD, suggesting that gut microbial dysbiosis contributes to disease progression and cognitive impairment in BD. Therefore, microbiota-centered treatment might be an effective adjuvant therapy for BD-related cognitive impairment. Given that studies focusing on connections between the gut microbiota and BD-related cognitive impairment are lagging behind those on other neurocognitive disorders, this review sought to explore the potential mechanisms of how gut microbial dysbiosis affects cognitive function in BD and identify potential microbiota-centered treatment.

Gene activation in Caenorhabditis elegans using the Campylobacter jejuni CRISPR-Cas9 feeding system.

Clustered regularly interspaced palindromic repeats-based activation system, a powerful genetic manipulation technology, can modulate endogenous gene transcription in various organisms through fusing nuclease-deficient Cas9 to transcriptional regulatory domains. At present, this clustered regularly interspaced palindromic repeats-based activation system has been applied to activate gene expression by microinjection manner in Caenorhabditis elegans. However, this complicated and time-consuming injection manner is not suitable for efficient and high-throughput gene regulation with clustered regularly interspaced palindromic repeats-Cas9 system. Here, we engineered a Campylobacter jejun clustered regularly interspaced palindromic repeats-Cas9-based gene activation system through bacteria feeding technique to delivering gene-specific sgRNA in C. elegans. It enables to activate various endogenous genes efficiently, as well as induce the corresponding phenotypes with a more efficient and labor-saving manner. Collectively, our results demonstrated that our novel dCjCas9-based activation feeding system holds great promise and potential in C. elegans.

The lower bow-shaped curve as a novel reference frame to determine the lateral limit of the maxillary anterior arch for smile esthetics.

INTRODUCTION: Smile analysis in horizontally angled views is indispensable for esthetic assessment and could reveal teeth-to-lip disharmony, which might escape discovery in the frontal and profile views. However, evidence is lacking on where the anterior teeth should be positioned for esthetics in angled smiles. METHODS: Based on 3-dimensional facial image processing and geometric analysis, the lip edges were projected to the horizontal plane, and the horizontal teeth-to-lip relation was simplified and represented by the distances from dental landmarks to lower bow-shaped curves (LBSC), with the distance from facial-axis (FA) point of the canine to LBSC (FA-tangent line [TL] distance) identified as the key parameter. Using photographic modification and esthetic assessment, the effect of FA-TL distances on the attractiveness of 45° angled smiles was tested, with esthetic ranges identified. A simplified method was developed to obtain the estimative LBSC and FA-TL distances using 2-dimensional photographs and geometric analysis to facilitate clinical application. RESULTS: The FA-TL distance remarkably affected the esthetics of 45° angled smiles. Smiles were attractive when the FA-TL distance ranged from -1.0 to 1.5 mm perceived by orthodontists and from -1.5 to 1.5 mm perceived by laypersons. The 2-dimensional photograph-derived estimative FA-TL distance was not significantly different from that obtained in a 3-dimensional image, validating the simplified method. CONCLUSIONS: The LBSC could serve as a reference frame to determine the lateral limit of the maxillary anterior arch for the esthetics of 45° angled smiles. The FA-TL distance, which represented the spatial relation of the maxillary canine with the lower lip, was an esthetically essential parameter. For females aged 20-30 years, the FA point of the maxillary canines should be positioned no more than 1.5 mm labial or lingual to the LBSC.

Histone H3K4me3 modification is a transgenerational epigenetic signal for lipid metabolism in Caenorhabditis elegans.

As a major risk factor to human health, obesity presents a massive burden to people and society. Interestingly, the obese status of parents can cause progeny's lipid accumulation through epigenetic inheritance in multiple species. To date, many questions remain as to how lipid accumulation leads to signals that are transmitted across generations. In this study, we establish a nematode model of C. elegans raised on a high-fat diet (HFD) that leads to measurable lipid accumulation, which can transmit the lipid accumulation signal to their multigenerational progeny. Using this model, we find that transcription factors DAF-16/FOXO and SBP-1/SREBP, nuclear receptors NHR-49 and NHR-80, and delta-9 desaturases (fat-5, fat-6, and fat-7) are required for transgenerational lipid accumulation. Additionally, histone H3K4 trimethylation (H3K4me3) marks lipid metabolism genes and increases their transcription response to multigenerational obesogenic effects. In summary, this study establishes an interaction between a network of lipid metabolic genes and chromatin modifications, which work together to achieve transgenerational epigenetic inheritance of obesogenic effects.

Shared postulations between bipolar disorder and polycystic ovary syndrome pathologies.

INTRODUCTION: Women with bipolar disorder (BD) present a high prevalence of polycystic ovary syndrome (PCOS) and other reproductive disorders even before diagnosis or treatment of the disease. Postulations on the potential molecular mechanisms of comorbid PCOS in women with BD remain limited to influence of medications and need further extension. OBJECTIVES: This review focuses on evidence suggesting that common metabolic and immune disorders may play an important role in the development of BD and PCOS. RESULTS: The literature covered in this review suggests that metabolic and immune disorders, including the dysfunction of the hypothalamic-pituitary-adrenal axis, chronic inflammatory state, gut microbial alterations, adipokine alterations and circadian rhythm disturbance, are observed in patients with BD and PCOS. Such disorders may be responsible for the increased prevalence of PCOS in the BD population and indicate a susceptibility gene overlap between the two diseases. Current evidence supports postulations of common metabolic and immune disorders as endophenotype in BD as well as in PCOS. CONCLUSIONS: Metabolic and immune disorders may be responsible for the comorbid PCOS in the BD population. The identification of hallmark metabolic and immune features common to these two diseases will contribute to the clarification of the effect of BD on the reproductive endocrine function and development of symptomatic treatments targeting the biomarkers of the two diseases.

A comprehensive analysis of the correction of alar retraction in rhinoplasty: A systematic review.

BACKGROUND: Alar retraction, as a type of alar deformity, seriously affects the esthetic perception of the nose in patients. Despite the rapid development of rhinoplasty in recent years, the treatment of alar retraction is still a challenge work in plastic surgery. This systematic review highlights the etiology, treatment, and prevention of alar retraction to further guide practitioners. METHODS: A systematic review was conducted from 1975 to 2020 through PubMed, Embase, Web of Science, and Cochrane database with the key words "alar retraction" and "rhinoplasty" or "Rhinoplasties" to investigate the surgical treatment of alar retraction. The inclusion and exclusion criteria were set to screen the literature. RESULTS: A total of 163 literatures were obtained through database retrieval. After removing the duplicate literature, reading the title and abstract, and reviewing the full text finally, 34 articles were included in the final study. Most of the articles have summarized the surgical methods to correct alar retraction by retrospective study. CONCLUSIONS: Alar retraction should be analyzed from the etiology, pathogenesis, and treatment. The diversity of surgical methods provides more options for the clinic. However, the plastic surgeons need to develop sharp analytical skills, improve clinical operational capability, and look for appropriate methods to achieve in good result.

N6-methyldeoxyadenine and histone methylation mediate transgenerational survival advantages induced by hormetic heat stress.

Environmental stress can induce survival advantages that are passed down to multiple generations, representing an evolutionarily advantageous adaptation at the species level. Using the nematode worm Caenorhabditis elegans as a model, we found that heat shock experienced in either parent could increase the longevity of themselves and up to the fifth generation of descendants. Mechanistic analyses revealed that transcription factor DAF-16/FOXO, heat shock factor HSF-1, and nuclear receptor DAF-12/FXR functioned transgenerationally to implement the hormetic stress response. Histone H3K9me3 methyltransferases SET-25 and SET-32 and DNA N6-methyl methyltransferase DAMT-1 participated in transmitting high-temperature memory across generations. H3K9me3 and N6-methyladenine could mark heat stress response genes and promote their transcription in progeny to extend life span. We dissected the mechanisms responsible for implementing and transmitting environmental memories in descendants from heat-shocked parents and demonstrated that hormetic stress caused survival benefits could be transmitted to multiple generations through H3K9me3 and N6-mA modifications.