Molecular mechanism of de novo replication by the Ebola virus polymerase.

Non-segmented negative-strand RNA viruses, including Ebola virus (EBOV), rabies virus, human respiratory syncytial virus and pneumoviruses, can cause respiratory infections, haemorrhagic fever and encephalitis in humans and animals, and are considered a substantial health and economic burden worldwide1. Replication and transcription of the viral genome are executed by the large (L) polymerase, which is a promising target for the development of antiviral drugs. Here, using the L polymerase of EBOV as a representative, we show that de novo replication of L polymerase is controlled by the specific 3' leader sequence of the EBOV genome in an enzymatic assay, and that formation of at least three base pairs can effectively drive the elongation process of RNA synthesis independent of the specific RNA sequence. We present the high-resolution structures of the EBOV L-VP35-RNA complex and show that the 3' leader RNA binds in the template entry channel with a distinctive stable bend conformation. Using mutagenesis assays, we confirm that the bend conformation of the RNA is required for the de novo replication activity and reveal the key residues of the L protein that stabilize the RNA conformation. These findings provide a new mechanistic understanding of RNA synthesis for polymerases of non-segmented negative-strand RNA viruses, and reveal important targets for the development of antiviral drugs.

Identification of a role for TRIM29 in the control of innate immunity in the respiratory tract.

The respiratory tract is heavily populated with innate immune cells, but the mechanisms that control such cells are poorly defined. Here we found that the E3 ubiquitin ligase TRIM29 was a selective regulator of the activation of alveolar macrophages, the expression of type I interferons and the production of proinflammatory cytokines in the lungs. We found that deletion of TRIM29 enhanced macrophage production of type I interferons and protected mice from infection with influenza virus, while challenge of Trim29-/- mice with Haemophilus influenzae resulted in lethal lung inflammation due to massive production of proinflammatory cytokines by macrophages. Mechanistically, we demonstrated that TRIM29 inhibited interferon-regulatory factors and signaling via the transcription factor NF-κB by degrading the adaptor NEMO and that TRIM29 directly bound NEMO and subsequently induced its ubiquitination and proteolytic degradation. These data identify TRIM29 as a key negative regulator of alveolar macrophages and might have important clinical implications for local immunity and immunopathology.

Structure of the Ebola virus polymerase complex.

Filoviruses, including Ebola virus, pose an increasing threat to the public health. Although two therapeutic monoclonal antibodies have been approved to treat the Ebola virus disease1,2, there are no approved broadly reactive drugs to control diverse filovirus infection. Filovirus has a large polymerase (L) protein and the cofactor viral protein 35 (VP35), which constitute the basic functional unit responsible for virus genome RNA synthesis3. Owing to its conservation, the L-VP35 polymerase complex is a promising target for broadly reactive antiviral drugs. Here we determined the structure of Ebola virus L protein in complex with tetrameric VP35 using cryo-electron microscopy (state 1). Structural analysis revealed that Ebola virus L possesses a filovirus-specific insertion element that is essential for RNA synthesis, and that VP35 interacts extensively with the N-terminal region of L by three protomers of the VP35 tetramer. Notably, we captured the complex structure in a second conformation with the unambiguous priming loop and supporting helix away from polymerase active site (state 2). Moreover, we demonstrated that the century-old drug suramin could inhibit the activity of the Ebola virus polymerase in an enzymatic assay. The structure of the L-VP35-suramin complex reveals that suramin can bind at the highly conserved NTP entry channel to prevent substrates from entering the active site. These findings reveal the mechanism of Ebola virus replication and may guide the development of more powerful anti-filovirus drugs.

Inhibition of ASGR1 decreases lipid levels by promoting cholesterol excretion.

High cholesterol is a major risk factor for cardiovascular disease1. Currently, no drug lowers cholesterol through directly promoting cholesterol excretion. Human genetic studies have identified that the loss-of-function Asialoglycoprotein receptor 1 (ASGR1) variants associate with low cholesterol and a reduced risk of cardiovascular disease2. ASGR1 is exclusively expressed in liver and mediates internalization and lysosomal degradation of blood asialoglycoproteins3. The mechanism by which ASGR1 affects cholesterol metabolism is unknown. Here, we find that Asgr1 deficiency decreases lipid levels in serum and liver by stabilizing LXRα. LXRα upregulates ABCA1 and ABCG5/G8, which promotes cholesterol transport to high-density lipoprotein and excretion to bile and faeces4, respectively. ASGR1 deficiency blocks endocytosis and lysosomal degradation of glycoproteins, reduces amino-acid levels in lysosomes, and thereby inhibits mTORC1 and activates AMPK. On one hand, AMPK increases LXRα by decreasing its ubiquitin ligases BRCA1/BARD1. On the other hand, AMPK suppresses SREBP1 that controls lipogenesis. Anti-ASGR1 neutralizing antibody lowers lipid levels by increasing cholesterol excretion, and shows synergistic beneficial effects with atorvastatin or ezetimibe, two widely used hypocholesterolaemic drugs. In summary, this study demonstrates that targeting ASGR1 upregulates LXRα, ABCA1 and ABCG5/G8, inhibits SREBP1 and lipogenesis, and therefore promotes cholesterol excretion and decreases lipid levels.

GRAMD1/ASTER-mediated cholesterol transport promotes Smoothened cholesterylation at the endoplasmic reticulum.

Hedgehog (Hh) signaling pathway plays a pivotal role in embryonic development. Hh binding to Patched1 (PTCH1) derepresses Smoothened (SMO), thereby activating the downstream signal transduction. Covalent SMO modification by cholesterol in its cysteine-rich domain (CRD) is essential for SMO function. SMO cholesterylation is a calcium-accelerated autoprocessing reaction, and STIM1-ORAI1-mediated store-operated calcium entry promotes cholesterylation and activation of endosome-localized SMO. However, it is unknown whether the Hh-PTCH1 interplay regulates the activity of the endoplasmic reticulum (ER)-localized SMO. Here, we found that PTCH1 inhibited the COPII-dependent export of SMO from the ER, whereas Hh promoted this process. The RRxWxR amino acid motif in the cytosolic tail of SMO was essential for COPII recognition, ciliary localization, and signal transduction activity. Hh and PTCH1 regulated cholesterol modification of the ER-localized SMO, and SMO cholesterylation accelerated its exit from ER. The GRAMD1/ASTER sterol transport proteins facilitated cholesterol transfer to ER from PM, resulting in increased SMO cholesterylation and enhanced Hh signaling. Collectively, we reveal a regulatory role of GRAMD-mediated cholesterol transport in ER-resident SMO maturation and Hh signaling.

Single-cell landscape of idiopathic multicentric Castleman disease in identical twins.

ABSTRACT: Idiopathic multicentric Castleman disease (iMCD) is a rare cytokine-driven disorder characterized by systemic inflammation, generalized lymphadenopathy, and organ dysfunction. Here, we present an unusual occurrence of iMCD in identical twins and examined the immune milieu within the affected lymphoid organs and the host circulation using multiomic high-dimensional profiling. Using spatial enhanced resolution omics sequencing (Stereo-seq) transcriptomic profiling, we performed unsupervised spatially constrained clustering to identify different anatomic structures, mapping the follicles and interfollicular regions. After a cell segmentation approach, interleukin 6 (IL-6) pathway genes significantly colocalized with endothelial cells and fibroblastic reticular cells, confirming observations using a single-cell sequencing approach (10× Chromium). Furthermore, single-cell sequencing of peripheral blood mononuclear cells revealed an "inflammatory" peripheral monocytosis enriched for the expression of S100A family genes in both twins. In summary, we provided evidence of the putative cell-of-origin of IL-6 signals in iMCD and described a distinct monocytic host immune response phenotype through a unique identical twin model.

The E3 ubiquitin ligase TRIM21 negatively regulates the innate immune response to intracellular double-stranded DNA.

DDX41 is a sensor of intracellular double-stranded DNA (dsDNA) in myeloid dendritic cells (mDCs) that triggers a type I interferon response via the signaling adaptor STING. We identified the E3 ligase TRIM21 as a DDX41-interacting protein and found that knockdown of or deficiency in TRIM21 resulted in enhanced type I interferon responses to intracellular dsDNA and DNA viruses. Overexpression of TRIM21 resulted in more degradation of DDX41 and less production of interferon-ß (IFN-ß) in response to intracellular dsDNA. The SPRY-PRY domain of TRIM21 interacted with the DEADc domain of DDX41. Lys9 and Lys115 of DDX41 were the targets of TRIM21-mediated ubiquitination. TRIM21 is therefore an interferon-inducible E3 ligase that induces the Lys48 (K48)-linked ubiquitination and degradation of DDX41 and negatively regulates the innate immune response to intracellular dsDNA.

Thermal-Responsive Gel-Based Overheat Limiter Enabled Intelligent Photothermal Therapy.

Uncontrolled and excessive photothermal heating in photothermal therapy (PTT) inevitably causes thermal damage to surrounding normal tissues, severely limiting the universality and safety of PTT. To address this issue, an intelligent cooling thermal-responsive (ICTR) gel containing poly(N-isopropylacrylamide-co-acrylamide) (P(NIPAM-AM))microgel is applied onto the skin to realize intelligent PTT, which can avoid excessive heating and accidental injury. The high near-infrared (NIR) light transmittance (> 95%) of the ICTR gel ensures effective light delivery at low temperatures, while the refractive index of the P(NIPAM-AM) microgel increases remarkably when the temperature exceeds a predetermined threshold, resulting in progressively enhanced light scattering and weakened photothermal conversion. In animal studies, the negative feedback regulation of ICTR gel on light transmittance and photothermal heating allows the photothermal temperature in the lesion site to be stabilized within the effective therapeutic range (45 °C) while ensuring that the skin surface temperature does not exceed 35 °C. Compared with the severe skin thermal damage found in the histological staining of mice skin receiving conventional PTT, the mice skin receiving the ICTR gel-enabled intelligent PTT remains in good condition. This study establishes an intelligent and universal paradigm for PTT thermal regulation, which is of great significance for achieving safe and effective PTT.

Revealing the Subzero-Temperature Electrochemical Kinetics Behaviors in Ni-Rich Cathode.

The sluggish kinetics in Ni-rich cathodes at subzero temperatures causes decreased specific capacity and poor rate capability, resulting in slow and unstable charge storage. So far, the driving force of this phenomenon remains a mystery. Herein, with the help of in-situ X-ray diffraction and time of flight secondary ion mass spectrometry techniques, the continuous accumulation of both the cathode electrolyte interphase (CEI) film formation and the incomplete structure evolution during cycling under subzero temperature are proposed. It is presented that excessively uniform and thick CEI film generated at subzero temperatures would block the diffusion of Li+ -ions, resulting in incomplete phase evolution and clear charge potential delay. The incomplete phase evolution throughout the Li+ -ion intercalation/de-intercalation processes would further cause low depth of discharge and poor electrochemical reversibility with low initial Coulombic efficiency, as well. In addition, the formation of the thick and uniform CEI film would also consume Li+ -ions during the charging process. This discovery highlights the effects of the CEI film formation behavior and incomplete phase evolution in restricting electrochemical kinetics under subzero temperatures, which the authors believe would promote the further application of the Ni-rich cathodes.

Progress of Polymer Electrolytes Worked in Solid-State Lithium Batteries for Wide-Temperature Application.

Solid-state Li-ion batteries have emerged as the most promising next-generation energy storage systems, offering theoretical advantages such as superior safety and higher energy density. However, polymer-based solid-state Li-ion batteries face challenges across wide temperature ranges. The primary issue lies in the fact that most polymer electrolytes exhibit relatively low ionic conductivity at or below room temperature. This sensitivity to temperature variations poses challenges in operating solid-state lithium batteries at sub-zero temperatures. Moreover, elevated working temperatures lead to polymer shrinkage and deformation, ultimately resulting in battery failure. To address this challenge of polymer-based solid-state batteries, this review presents an overview of various promising polymer electrolyte systems. The review provides insights into the temperature-dependent physical and electrochemical properties of polymers, aiming to expand the temperature range of operation. The review also further summarizes modification strategies for polymer electrolytes suited to diverse temperatures. The final section summarizes the performance of various polymer-based solid-state batteries at different temperatures. Valuable insights and potential future research directions for designing wide-temperature polymer electrolytes are presented based on the differences in battery performance. This information is intended to inspire practical applications of wide-temperature polymer-based solid-state batteries.

Evidence supporting a role for the immune checkpoint protein B7-H3 in NK cell-mediated cytotoxicity against AML.

We observed that the immune checkpoint protein B7-H3 is overexpressed in acute myeloid leukemia (AML) patients with poor treatment outcomes. Inhibition of B7-H3 expression or blocking of its activity using a novel monoclonal antibody (T-1A5) in AML cells significantly enhanced natural killer (NK) cell-mediated cytotoxicity in AML cells in vitro and in vivo. Moreover, a human-mouse chimera of this antibody (ChT-1A5) induced antibody-dependent cell-mediated cytotoxicity (ADCC) in B7-H3+ primary AML cells, but not in normal hematopoietic cells, suggesting the specify of this antibody for AML cells. Epitope mapping studies identified that both T-1A5 and ChT-1A5 antibodies bind to the FG-loop region of B7-H3, which is known to regulate the immunosuppressive function of B7-H3. Furthermore, treatment with ChT-1A5 in combination with human NK cells significantly prolonged survival in AML patient-derived xenograft (PDX) models. Our results suggest that the ChT-1A5 antibody can inhibit the immunosuppressive function of B7-H3 protein as well as induce ADCC in B7-H3+ AML.

Deepened Photodynamic Therapy through Skin Optical Clearing Technology in the Visible Light Window.

The trade-off that shorter wavelength light facilitates the efficient generation of reactive oxygen species (ROS) from photosensitizer (PS) while facing the drawback of limited penetration depth through skin tissue restricts the further development of photodynamic therapy (PDT). Here, we address this contradiction and achieve visible-light-tailored deep PDT combined with the skin optical clearing technology. With the help of the prepared skin optical clearing gel, the refractive index inhomogeneity between skin tissue components is greatly attenuated, and the light scattering effect within the skin tissue is remarkably reduced. As a consequence, the transmittance of visible light at 600 nm through in vitro porcine skin and in vivo mouse skin after treatment increases from approximately 10 and 40 to 70 and 70%, respectively. Furthermore, in the tumor cell eradication experiment, the local ROS generation efficiency in the experimental group is several times higher than that in the control group owing to improved visible transmittance, which is thus responsible for the complete eradication of tumor cells, even when shaded by skin tissue. The results suggest that this strategy may serve as a valuable supplement to the current deep PDT strategies.

Factors Associated With Radiological Lung Growth Rate After Lobectomy in Patients With Lung Cancer.

INTRODUCTION: This study is a retrospective study. This study aims to explore the association between lobectomy in lung cancer patients and subsequent compensatory lung growth (CLG), and to identify factors that may be associated with variations in CLG. METHODS: 207 lung cancer patients who underwent lobectomy at Yunnan Cancer Hospital between January 2020 and December 2020. All patients had stage IA primary lung cancer and were performed by the same surgical team. And computed tomography examinations were performed before and 1 y postoperatively. Based on computed tomography images, the volume of each lung lobe was measured using computer software and manual, the radiological lung weight was calculated. And multiple linear regressions were used to analyze the factors related to the increase in postoperative lung weight. RESULTS: One year after lobectomy, the radiological lung weight increased by an average of 112.4 ± 20.8%. Smoking history, number of resected lung segments, preoperative low attenuation volume, intraoperative arterial oxygen partial pressure/fraction of inspired oxygen ratio and postoperative visual analog scale scores at 48 h were significantly associated with postoperative radiological lung weight gain. CONCLUSIONS: Our results suggest that CLG have occurred after lobectomy in adults. In addition, anesthetists should maintain high arterial oxygen partial pressure/fraction of inspired oxygen ratio during one-lung ventilation and improve acute postoperative pain to benefit CLG.

Seizure control and adverse outcomes of lamotrigine use during pregnancy: A systematic review and meta-analysis.

OBJECTIVE: This review aims to summarize existing evidence on the adverse pregnancy outcomes and seizure control effects of using lamotrigine (LTG) monotherapy in pregnancy women with epilepsy (WWE) during pregnancy. METHODS: A comprehensive search was conducted in various databases including Cochrane, Web of Science, CBM, PubMed, Embase, CNKI, and Pregnancy Registration Center databases to identify relevant studies. The search was concluded up to January 2024. Studies comparing LTG with other antiseizure medications (ASMs) for treating epilepsy in pregnant women were included, with no language or regional restrictions. RESULTS: A total of 19 studies were included for analysis, with 16 studies reporting adverse pregnancy outcomes and 6 studies reporting seizure control outcomes. Meta-analysis showed that compared to monotherapy with carbamazepine (CBZ), sodium valproate (VPA), and levetiracetam (LEV), LTG monotherapy had a slightly weaker ability to control seizures during pregnancy, with ORs and 95 %CIs of 0.65 (0.57-0.75; CBZ), 0.50 (0.32-0.79; VPA), and 0.55 (0.36-0.84; LEV). Regarding adverse pregnancy outcomes, the occurrence rate of LTG monotherapy was significantly lower than that of CBZ, VPA, phenytoin (PHT), and phenobarbital (PHB), with ORs and 95 %CIs ranging from 0.30 (0.25-0.35; VPA) to 0.68 (0.56-0.81; CBZ). CONCLUSION: Based on meta-analysis, LTG and LEV appear to be preferred medications for controlling seizures during pregnancy. This review provides further support for the use of LTG monotherapy in pregnant WWE, building upon existing evidence for clinical practitioners.

Breastfeeding and risk of food allergy and allergic rhinitis in offspring: a systematic review and meta-analysis of cohort studies.

The association between breastfeeding and the occurrence of allergic rhinitis (AR) and food allergy (FA) in offspring remains inconclusive. This review aims to comprehensively explore the potential relationships between various patterns and durations of breastfeeding and allergic diseases in offspring. We systematically searched PubMed, EMBASE, Cochrane, WOS databases, and Google Scholar for observational studies published up to March 30, 2023, that investigated the link between breastfeeding and allergies in offspring. The quality of the studies was assessed using the Newcastle-Ottawa Scale (NOS) and Joanna Briggs Institute (JBI). Pooled odds ratios (OR) and 95% confidence intervals (95% CI) were calculated employing an appropriate model based on the degree of heterogeneity. A total of 68 studies, encompassing 772,142 children, were ultimately included. The findings indicated that breastfeeding for more than 6 months was associated with a reduced risk of AR (OR = 0.88, 95% CI: 0.79 to 0.98) but posed a risk for FA (OR = 1.69, 95% CI: 1.27 to 2.25). Exclusive breastfeeding exhibited a protective effect against AR (OR = 0.94, 95% CI: 0.90 to 0.97), whereas non-breastfeeding was identified as a risk factor for AR (OR = 1.48; 95% CI: 1.03 to 2.12). No significant association was observed between breastfeeding patterns and FA. CONCLUSION: Breastfeeding for more than 6 months proves to be an effective preventive measure against AR. However, large prospective high-quality studies are needed to investigate the potential risk of FA in children with prolonged breastfeeding. WHAT IS KNOWN: • The impact of breastfeeding on allergic rhinitis and food allergy in offspring is controversial. • Previous meta-analyses fail to prove the effect of breastfeeding on food allergy in offspring of all ages. WHAT IS NEW: • Breastfeeding for more than 6 months proves to be an effective preventive measure against AR. However, it potentially elevates the risk of FA in children. Non-breastfeeding is linked to an increased risk of AR in children, but there is no evidence of an association between breastfeeding patterns and FA in children. • The impact of breastfeeding on allergic rhinitis and food allergy in offspring may vary with the time and pattern of breastfeeding.

Marine Prostanoids with Cytotoxic Activity from Octocoral Clavularia spp.

Octocoral of the genus Clavularia is a kind of marine invertebrate possessing abundant cytotoxic secondary metabolites, such as prostanoids and dolabellanes. In our continuous natural product study of C. spp., two previously undescribed prostanoids [clavulone I-15-one (1) and 12-O-deacetylclavulone I (2)] and eleven known analogs (3-13) were identified. The structures of these new compounds were elucidated based on analysis of their 1D and 2D NMR, HRESIMS, and IR data. Additionally, all tested prostanoids (1 and 3-13) showed potent cytotoxic activities against the human oral cancer cell line (Ca9-22). The major compound 3 showed cytotoxic activity against the Ca9-22 cells with the IC50 value of 2.11 ± 0.03 µg/mL, which echoes the cytotoxic effect of the coral extract. In addition, in silico tools were used to predict the possible effects of isolated compounds on human tumor cell lines and nitric oxide production, as well as the pharmacological potentials.

Evidence for root adaptation to a spatially discontinuous water availability in the absence of external water potential gradients.

We hereby show that root systems adapt to a spatially discontinuous pattern of water availability even when the gradients of water potential across them are vanishingly small. A paper microfluidic approach allowed us to expose the entire root system of Brassica rapa plants to a square array of water sources, separated by dry areas. Gradients in the concentration of water vapor across the root system were as small as 10-4⋅mM⋅m-1 (∼4 orders of magnitude smaller than in conventional hydrotropism assays). Despite such minuscule gradients (which greatly limit the possible influence of the well-understood gradient-driven hydrotropic response), our results show that 1) individual roots as well as the root system as a whole adapt to the pattern of water availability to maximize access to water, and that 2) this adaptation increases as water sources become more rare. These results suggest that either plant roots are more sensitive to water gradients than humanmade water sensors by 3-5 orders of magnitude, or they might have developed, like other organisms, mechanisms for water foraging that allow them to find water in the absence of an external gradient in water potential.

MicroRNA 98-5p Overexpression Contributes to Delayed Fracture Healing via Targeting BMP-2.

MicroRNAs (miRNAs) are related to the regulation of bone metabolism. Delayed fracture healing (DFH) is a common complication after fracture surgery. The study attempted to examine the role of miR-98-5p and bone morphogenetic protein (BMP)-2 with the onset of DFH. A total of 140 patients with femoral neck fracture were recruited, including 80 cases with normal fracture healing (NFH) and 60 cases with DFH. MC3T3-E1 cells were induced cell differentiation for cell function experiments. Real-time quantitative polymerase chain reaction (RT-qPCR) was carried out to test mRNA levels. Cell proliferation and apoptosis were determined via CCK-8 and flow cytometry assay. Luciferase reporter assay was done to verify the targeted regulatory relationship of miR-98-5p with BMP-2. In comparison with NFH cases, DFH patients owned high levels of serum miR-98-5p and low concentration of BMP-2, and the levels of the two indexes are significantly negatively correlated. Both miR-98-5p and BMP-2 had the ability to predict DFH, while their combined diagnostic value is the highest. BMP-2 was demonstrated to be the target gene of miR-98-5p. Overexpression of BMP-2 reversed the role of miR-98-5p in MC3T3-E1 cell proliferation, apoptosis and differentiation. Increased miR-98-5p and decreased BMP-2 serve as potential biomarkers for the diagnosis of DFH. MiR-98-5p overexpression inhibits osteoblast proliferation and differentiation via targeting BMP-2.

Fecal calprotectin is a novel biomarker to predict the clinical outcomes of patients with ruptured intracranial aneurysm.

BACKGROUND: Intracranial aneurysm (IA) is a common cerebrovascular disease and the leading cause of spontaneous subarachnoid hemorrhage. Recent evidence suggests that gut microbiota is involved in the pathophysiological process of IA through the gut-brain axis. However, the role of gut inflammation in the development of IA has yet to be clarified. Our study aimed to investigate whether fecal calprotectin (FC) level, a sensitive marker of gut inflammation, is correlated with the development of IA and the prognosis of patients with ruptured IA (RIA). METHODS: 182 patients were collected from January 2022 to January 2023, including 151 patients with IA and 31 healthy individuals. 151 IA patients included 109 patients with unruptured IA (UIA) and 42 patients with RIA. The FC level was measured by enzyme-linked immunosorbent assay. Other detailed information was obtained from an electronic medical record system. RESULTS: Compared with healthy controls, the FC levels in patients with IA were increased (P < 0.0001). Patients with RIA had significantly higher FC levels than UIA patients (P < 0.0001). Moreover, the FC level in RIA patients with unfavorable outcomes was higher than in RIA patients with favorable outcomes. Logistic regression analysis showed that the elevated FC level was an independent risk factor for a 3-month poor prognosis in patients with RIA (OR=1.005, 95% CI = 1.000 -1.009, P = 0.044). CONCLUSION: Fecal calprotectin level is significantly elevated in IA patients, especially those with RIA. FC is a novel biomarker of 3-month poor outcomes in RIA patients.

The degree of population aging and living carbon emissions: Evidence from China.

Population aging and global warming have become everyday concerns of all countries. Based on the panel data of 30 provinces in China from 2003 to 2019, this paper uses the panel fixed effect model and two-stage least square method to analyze the effect of population aging on domestic energy carbon emissions of urban and rural residents. On this basis, the threshold regression model is introduced to explore the heterogeneity of the effect under different aging levels. The results show that (1) the progress of population aging at the overall level will significantly increase the level of carbon emissions from household energy consumption. At the regional level, the effect of population aging on carbon emissions from household energy consumption in rural areas is higher than in urban areas. (2) Population aging has a nonlinear effect on the carbon emissions of residential energy consumption. For urban areas, when the level of population aging crosses the threshold, its marginal impact on living carbon emissions in urban areas is further enhanced. In contrast, the opposite is true in rural areas. (3) Heterogeneity analysis results show that the impact of population aging on residential energy carbon emissions differs in different regions at the national and rural levels but does not show regional heterogeneity at the urban level.