Late Quaternary dynamics of Arctic biota from ancient environmental genomics.

During the last glacial-interglacial cycle, Arctic biotas experienced substantial climatic changes, yet the nature, extent and rate of their responses are not fully understood1-8. Here we report a large-scale environmental DNA metagenomic study of ancient plant and mammal communities, analysing 535 permafrost and lake sediment samples from across the Arctic spanning the past 50,000 years. Furthermore, we present 1,541 contemporary plant genome assemblies that were generated as reference sequences. Our study provides several insights into the long-term dynamics of the Arctic biota at the circumpolar and regional scales. Our key findings include: (1) a relatively homogeneous steppe-tundra flora dominated the Arctic during the Last Glacial Maximum, followed by regional divergence of vegetation during the Holocene epoch; (2) certain grazing animals consistently co-occurred in space and time; (3) humans appear to have been a minor factor in driving animal distributions; (4) higher effective precipitation, as well as an increase in the proportion of wetland plants, show negative effects on animal diversity; (5) the persistence of the steppe-tundra vegetation in northern Siberia enabled the late survival of several now-extinct megafauna species, including the woolly mammoth until 3.9 ± 0.2 thousand years ago (ka) and the woolly rhinoceros until 9.8 ± 0.2 ka; and (6) phylogenetic analysis of mammoth environmental DNA reveals a previously unsampled mitochondrial lineage. Our findings highlight the power of ancient environmental metagenomics analyses to advance understanding of population histories and long-term ecological dynamics.

FAP expression in adipose tissue macrophages promotes obesity and metabolic inflammation.

Adipose tissue macrophages (ATM) are key players in the development of obesity and associated metabolic inflammation which contributes to systemic metabolic dysfunction. We here found that fibroblast activation protein α (FAP), a well-known marker of cancer-associated fibroblast, is selectively expressed in murine and human ATM among adipose tissue-infiltrating leukocytes. Macrophage FAP deficiency protects mice against diet-induced obesity and proinflammatory macrophage infiltration in obese adipose tissues, thereby alleviating hepatic steatosis and insulin resistance. Mechanistically, FAP specifically mediates monocyte chemokine protein CCL8 expression by ATM, which is further upregulated upon high-fat-diet (HFD) feeding, contributing to the recruitment of monocyte-derived proinflammatory macrophages with no effect on their classical inflammatory activation. CCL8 overexpression restores HFD-induced metabolic phenotypes in the absence of FAP. Moreover, macrophage FAP deficiency enhances energy expenditure and oxygen consumption preceding differential body weight after HFD feeding. Such enhanced energy expenditure is associated with increased levels of norepinephrine (NE) and lipolysis in white adipose tissues, likely due to decreased expression of monoamine oxidase, a NE degradation enzyme, by Fap-/- ATM. Collectively, our study identifies FAP as a previously unrecognized regulator of ATM function contributing to diet-induced obesity and metabolic inflammation and suggests FAP as a potential immunotherapeutic target against metabolic disorders.

Transcriptomic analysis reveals molecular characterization and immune landscape of PANoptosis-related genes in atherosclerosis.

BACKGROUND: Atherosclerosis is a chronic inflammatory disease characterized by abnormal lipid deposition in the arteries. Programmed cell death is involved in the inflammatory response of atherosclerosis, but PANoptosis, as a new form of programmed cell death, is still unclear in atherosclerosis. This study explored the key PANoptosis-related genes involved in atherosclerosis and their potential mechanisms through bioinformatics analysis. METHODS: We evaluated differentially expressed genes (DEGs) and immune infiltration landscape in atherosclerosis using microarray datasets and bioinformatics analysis. By intersecting PANoptosis-related genes from the GeneCards database with DEGs, we obtained a set of PANoptosis-related genes in atherosclerosis (PANoDEGs). Functional enrichment analysis of PANoDEGs was performed and protein-protein interaction (PPI) network of PANoDEGs was established. The machine learning algorithms were used to identify the key PANoDEGs closely linked to atherosclerosis. Receiver operating characteristic (ROC) analysis was used to assess the diagnostic potency of key PANoDEGs. CIBERSORT was used to analyze the immune infiltration patterns in atherosclerosis, and the Spearman method was used to study the relationship between key PANoDEGs and immune infiltration abundance. The single gene enrichment analysis of key PANoDEGs was investigated by GSEA. The transcription factors and target miRNAs of key PANoDEGs were predicted by Cytoscape and online database, respectively. The expression of key PANoDEGs was validated through animal and cell experiments. RESULTS: PANoDEGs in atherosclerosis were significantly enriched in apoptotic process, pyroptosis, necroptosis, cytosolic DNA-sensing pathway, NOD-like receptor signaling pathway, lipid and atherosclerosis. Four key PANoDEGs (ZBP1, SNHG6, DNM1L, and AIM2) were found to be closely related to atherosclerosis. The ROC curve analysis demonstrated that the key PANoDEGs had a strong diagnostic potential in distinguishing atherosclerotic samples from control samples. Immune cell infiltration analysis revealed that the proportion of initial B cells, plasma cells, CD4 memory resting T cells, and M1 macrophages was significantly higher in atherosclerotic tissues compared to normal tissues. Spearman analysis showed that key PANoDEGs showed strong correlations with immune cells such as T cells, macrophages, plasma cells, and mast cells. The regulatory networks of the four key PANoDEGs were established. The expression of key PANoDEGs was verified in further cell and animal experiments. CONCLUSIONS: This study evaluated the expression changes of PANoptosis-related genes in atherosclerosis, providing a reference direction for the study of PANoptosis in atherosclerosis and offering potential new avenues for further understanding the pathogenesis and treatment strategies of atherosclerosis.

Disinfection Byproducts of Haloacetaldehydes Disrupt Hepatic Lipid Metabolism and Induce Lipotoxicity in High-Fat Culture Conditions.

Unhealthy lifestyles, obesity, and environmental pollutants are strongly correlated with the development of nonalcoholic fatty liver disease (NAFLD). Haloacetaldehyde-associated disinfection byproducts (HAL-DBPs) at various multiples of concentrations found in finished drinking water together with high-fat (HF) were examined to gauge their mixed effects on hepatic lipid metabolism. Using new alternative methods (NAMs), studying effects in human cells in vitro for risk assessment, we investigated the combined effects of HF and HAL-DBPs on hepatic lipid metabolism and lipotoxicity in immortalized LO-2 human hepatocytes. Coexposure of HAL-DBPs at various multiples of environmental exposure levels with HF increased the levels of triglycerides, interfered with de novo lipogenesis, enhanced fatty acid oxidation, and inhibited the secretion of very low-density lipoproteins. Lipid accumulation caused by the coexposure of HAL-DBPs and HF also resulted in more severe lipotoxicity in these cells. Our results using an in vitro NAM-based method provide novel insights into metabolic reprogramming in hepatocytes due to coexposure of HF and HAL-DBPs and strongly suggest that the risk of NAFLD in sensitive populations due to HAL-DBPs and poor lifestyle deserves further investigation both with laboratory and epidemiological tools. We also discuss how results from our studies could be used in health risk assessments for HAL-DBPs.

Effect of simethicone for the management of early abdominal distension after laparoscopic cholecystectomy: a multicenter retrospective propensity score matching study.

OBJECTIVE: To investigate whether simethicone expediates the remission of abdominal distension after laparoscopic cholecystectomy (LC). METHODS: This retrospective study involved LC patients who either received perioperative simethicone treatment or not. Propensity score matching (PSM) was employed to minimize bias. The primary endpoint was the remission rate of abdominal distension within 24 h after LC. Univariable and multivariable logistic regression analyses were conducted to identify independent risk factors affecting the early remission of abdominal distension after LC. Subsequently, a prediction model was established and validated. RESULTS: A total of 1,286 patients were divided into simethicone (n = 811) and non-simethicone groups (n = 475) as 2:1 PSM. The patients receiving simethicone had better remission rates of abdominal distension at both 24 h and 48 h after LC (49.2% vs. 34.7%, 83.9% vs. 74.8%, respectively), along with shorter time to the first flatus (14.6 ± 11.1 h vs. 17.2 ± 9.1 h, P < 0.001) compared to those without. Multiple logistic regression identified gallstone (OR = 0.33, P = 0.001), cholecystic polyp (OR = 0.53, P = 0.050), preoperative abdominal distention (OR = 0.63, P = 0.002) and simethicone use (OR = 1.89, P < 0.001) as independent factors contributing to the early remission of abdominal distension following LC. The prognosis model developed for predicting remission rates of abdominal distension within 24 h after LC yielded an area under the curve of 0.643 and internal validation a value of 0.644. CONCLUSIONS: Simethicone administration significantly enhanced the early remission of post-LC abdominal distension, particularly for patients who had gallstones, cholecystic polyp, prolonged anesthesia or preoperative abdominal distention. TRIAL REGISTRATION: ChiCTR2200064964 (24/10/2022).

Characterization of Pt-coated twin paraboloidal laboratory capillary high energy X-ray optics.

Novel focusing optics composed of twin paraboloidal capillaries coated with Pt, for laboratory X-ray sources are presented and characterized. The optics are designed to focus the X-rays, resulting in an achromatic focused beam with photon energies up to 40 keV. The performance of the optics under different operational conditions is studied by comparing the energy-photon count spectra of the direct and focused beams. Based on these analyses, the optics gain and efficiency as a function of photon energy are determined. A focal spot of 8.5 µm with a divergence angle of 0.59° is observed. The obtained characteristics are discussed and related to theoretical considerations. Moreover, the suitability and advantages of the present optics for X-ray microdiffraction is demonstrated using polycrystalline aluminium. Finally, possibilities for further developments are suggested.

Machine learning for image-based multi-omics analysis of leaf veins.

Veins are a critical component of the plant growth and development system, playing an integral role in supporting and protecting leaves, as well as transporting water, nutrients, and photosynthetic products. A comprehensive understanding of the form and function of veins requires a dual approach that combines plant physiology with cutting-edge image recognition technology. The latest advancements in computer vision and machine learning have facilitated the creation of algorithms that can identify vein networks and explore their developmental progression. Here, we review the functional, environmental, and genetic factors associated with vein networks, along with the current status of research on image analysis. In addition, we discuss the methods of venous phenotype extraction and multi-omics association analysis using machine learning technology, which could provide a theoretical basis for improving crop productivity by optimizing the vein network architecture.

Akt2 deficiency alleviates oxidative stress in the heart and liver via up-regulating SIRT6 during high-fat diet-induced obesity.

The present study aims to investigate the role of AKT2 in the pathogenesis of hepatic and cardiac lipotoxicity induced by lipid overload-induced obesity and identify its downstream targets. WT and Akt2 KO mice were fed either normal diet, or high-fat diet (HFD) to induce obesity model in vivo. Human hepatic cell line (L02 cells) and neonatal rat cardiomyocytes (NRCMs) were used as in vitro models. We observed that during HFD-induced obesity, Akt2 loss-of-function mitigated lipid accumulation and oxidative stress in the liver and heart tissue. Mechanistically, down-regulation of Akt2 promotes SIRT6 expression in L02 cells and NRCMs, the latter deacetylates SOD2, which promotes SOD2 activity and therefore alleviates oxidative stress-induced injury of hepatocytes and cardiomyocytes. Furthermore, we also proved that AKT2 inhibitor protects hepatocytes and cardiomyocytes from HFD-induced oxidative stress. Therefore, our work prove that AKT2 plays an important role in the regulation of obesity-induced lipid metabolic disorder in the liver and heart. Our study also indicates AKT2 inhibitor as a potential therapy for obesity-induced hepatic and cardiac injury.

Demethyleneberberine alleviates Pseudomonas aeruginosa-induced acute pneumonia by inhibiting the AIM2 inflammasome and oxidative stress.

BACKGROUND: Acute pneumonia induced by Pseudomonas aeruginosa is characterized by massive infiltration of inflammatory cell and the production of reactive oxygen species (ROS), which lead to severe and transient pulmonary inflammation and acute lung injury. However, P.aeruginosa infection is resistant to multiple antibiotics and causes high mortality in clinic, the search for alternative prophylactic and therapeutic strategies is imperative. PURPOSE: This study was aimed to investigate the anti-inflammatory and antioxidant effects of DMB, a novel derivative of berberine, and explore the role of AIM2 inflammasome in P. aeruginosa-induced acute pneumonia. METHODS: Acute pneumonia mice were established by tracheal injection of P. aeruginosa suspension. Pathological changes of lung tissue were observed by its appearance and H&E staining. The lung coefficient ratio was measured to evaluate pulmonary edema. Inflammatory factors were detected by qRT-PCR, western blotting and immunohistochemistry. ROS and other indicators of oxidative damage were analyzed by flow cytometry and specific kit. Proteins related to AIM2 inflammasome were detected by western blotting. RESULTS: Compared with the P. aeruginosa-induced group, DMB ameliorated pulmonary edema, hyperemia, and pathological damage based on its appearance and H&E staining in DMB groups. First, DMB attenuated the inflammatory response induced by P.aeruginosa. Compared with the P. aeruginosa-induced group, the lung coefficient ratio was decreased by 31.5%, the MPO activity of lung tissue was decreased by 44.0%, the mRNA expression levels of TNF-α, IL-1ß and IL-6 were decreased by 64.8%, 51.2% and 64.0% respectively, and those protein expression levels were decreased by 40.1%, 42.8% and 47.8% respectively, and the number of white blood cells, neutrophils and monocytes were decreased by 53.5%, 29.4% and 13.7% in high dose (200 mg/kg) DMB group. Second, DMB alleviates oxidative stress in the lung tissue during P. aeruginosa-induced acute pneumonia. Compared with the P. aeruginosa-induced group, the level of GSH was increased by 42.5% and MDA was decreased by 49.5% in high dose DMB group. Moreover, the western blotting results showed that DMB markedly suppressed the expression of AIM2, ASC, Cleaved caspase1 and decreased the secretion of IL-1ß. Additionally, these results were also confirmed by in vitro experiments using MH-S and BEAS-2B cell lines. CONCLUSIONS: Taken together, these results indicated that DMB ameliorates P. aeruginosa-induced acute pneumonia through anti-inflammatory, antioxidant effects, and inhibition of AIM2 inflammasome activation.

SIRT6 regulates obesity-induced oxidative stress via ENDOG/SOD2 signaling in the heart.

The sirtuin 6 (SIRT6) participates in regulating glucose and lipid homeostasis. However, the function of SIRT6 in the process of cardiac pathogenesis caused by obesity-associated lipotoxicity remains to be unveiled. This study was designed to elucidate the role of SIRT6 in the pathogenesis of cardiac injury due to nutrition overload-induced obesity and explore the downstream signaling pathways affecting oxidative stress in the heart. In this study, we used Sirt6 cardiac-specific knockout murine models treated with a high-fat diet (HFD) feeding to explore the function and mechanism of SIRT6 in the heart tissue during HFD-induced obesity. We also took advantage of neonatal cardiomyocytes to study the role and downstream molecules of SIRT6 during HFD-induced injury in vitro, in which intracellular oxidative stress and mitochondrial content were assessed. We observed that during HFD-induced obesity, Sirt6 loss-of-function aggravated cardiac injury including left ventricular hypertrophy and lipid accumulation. Our results evidenced that upon increased fatty acid uptake, SIRT6 positively regulated the expression of endonuclease G (ENDOG), which is a mitochondrial-resident molecule that plays an important role in mitochondrial biogenesis and redox homeostasis. Our results also showed that SIRT6 positively regulated superoxide dismutase 2 (SOD2) expression post-transcriptionally via ENDOG. Our study gives a new sight into SIRT6 beneficial role in mitochondrial biogenesis of cardiomyocytes. Our data also show that SIRT6 is required to reduce intracellular oxidative stress in the heart triggered by high-fat diet-induced obesity, involving the control of ENDOG/SOD2.

Early application of metagenomics next-generation sequencing may significantly reduce unnecessary consumption of antibiotics in patients with fever of unknown origin.

BACKGROUND: Metagenomic next-generation sequencing (mNGS) is a novel nucleic acid method for the detection of unknown and difficult pathogenic microorganisms, and its application in the etiological diagnosis of fever of unknown origin (FUO) is less reported. We aimed to comprehensively assess the value of mNGS in the etiologic diagnosis of FUO by the pathogen spectrum and diagnostic performance, and to investigate whether it is different in the time to diagnosis, length of hospitalization, antibiotic consumption and cost between FUO patients with and without early application of mNGS. METHODS: A total of 149 FUO inpatients underwent both mNGS and routine pathogen detection was retrospectively analyzed. The diagnostic performance of mNGS, culture and CMTs for the final clinical diagnosis was evaluated by using sensitivity, specificity, positive predictive value, negative predictive value and total conforming rate. Patients were furtherly divided into two groups: the earlier mNGS detection group (sampling time: 0 to 3 days of the admission) and the later mNGS detection group (sampling time: after 3 days of the admission). The length of hospital stay, time spent on diagnosis, cost and consumption of antibiotics were compared between the two groups. RESULTS: Compared with the conventional microbiological methods, mNGS detected much more species and had the higher negative predictive (67.6%) and total conforming rate (65.1%). Patients with mNGS sampled earlier had a significantly shorter time to diagnosis (6.05+/-6.23 vs. 10.5+/-6.4 days, P < 0.001) and days of hospital stay (13.7+/-20.0 vs. 30.3 +/-26.9, P < 0.001), as well as a significantly less consumption (13.3+/-7.8 vs. 19.5+/-8.0, P < 0.001) and cost (4543+/-7326 vs. 9873 +/- 9958 China Yuan [CNY], P = 0.001) of antibiotics compared with the patients sampled later. CONCLUSIONS: mNGS could significantly improve the detected pathogen spectrum, clinical conforming rate of pathogens while having good negative predictive value for ruling out infections. Early mNGS detection may shorten the diagnosis time and hospitalization days and reduce unnecessary consumption of antibiotics.

Recurrent pacemaker-mediated arrhythmia with a right bundle branch block pattern in a patient with a cardiac resynchronization therapy device.

Under certain conditions, cardiovascular implantable electronic devices can be directly involved in initiating and sustaining pacemaker-mediated arrhythmias (PMA), of which repetitive reentrant ventriculoatrial synchrony (RRVAS) is the most well-known and common type. RRVAS, also known as pacemaker-mediated tachycardia, was commonly secondary to atrioventricular (AV) dissociation and subsequent ventriculoatrial (VA) conduction. RRVAS in a biventricular system is rare due to its less predisposition to the appearance of AV dissociation and subsequent VA conduction, but urgent in its adverse impact on cardiac resynchronization therapy (CRT), which may predispose to exacerbated heart failure. We present a rare case of recurrent PMA manifested as a right bundle branch block pattern in a patient with a CRT device. Notably, most episodes of PMA were triggered by a premature atrial contraction accompanied by the appearance of VA conduction with no prolongation of AV delay. In this study, we have demonstrated the impact of the appearance of VA conduction due to the loss of capture of right ventricular lead and its potential risk for inducing RRVAS in a CRT device.

Characterization of the interaction between allicin and soy protein isolate and functional properties of the adducts.

BACKGROUND: Soybean meal, a by-product of the soybean oil production industry, has a high protein content but the compact globular structure of the protein from soybean meal limits its wide application in food processing. Allicin has been found to have numerous functional properties. In this study, allicin was interacted with soy protein isolate (SPI). The functional properties of the adducts were investigated. RESULTS: Binding with allicin significantly quenched the fluorescence intensity of SPI. Static quenching was the main quenching mechanism. The stability of adducts decreased with increasing temperature. The greatest extent of binding between allicin and sulfhydryl groups (SH) of SPI was obtained at an allicin/SH molar ratio of 1:2. The amino groups of SPI did not bind with allicin covalently. Soy protein isolate was modified by allicin through covalent and non-covalent interactions. Compared with SPI, the emulsifying activity index and foaming capacity of adducts with a ratio of 3:1 were improved by 39.91% and 64.29%, respectively. Soy protein isolate-allicin adducts also exhibited obvious antibacterial effects. The minimum inhibitory concentrations (MICs) of SPI-allicin adducts on Escherichia coli and Staphylococcus aureus were 200 and 160 µg mL-1 , respectively. CONCLUSION: The interaction of allicin with SPI is beneficial for the functional properties of SPI. These adducts can be used in different food formulations as emulsifiers, foamers, and transport carriers. © 2023 Society of Chemical Industry.

Metformin alleviates HFD-induced oxidative stress in hepatocyte via activating SIRT6/PGC-1α/ENDOG signaling.

Metformin is accepted as a first-line drug for the therapy of Type 2 diabetes (T2D), while its mechanism is still controversial. In the present study, by taking advantage of mouse model of high-fat-diet (HFD)-induced obesity and primary mouse hepatocytes (PMHCs) as well as human hepatocyte L02 cell line, we aimed to investigate the involvement of SIRTs during the application of metformin for the therapy of T2D. Our data evidenced that during HFD-induced obesity, there was elevation of nucleus protein acetylation. Analysis of liver tissue showed that among all SIRT members, SIRT6 expression was significantly down-regulated during HFD feeding, which was sustained to regular level with metformin administration. Our result also showed that SIRT6 suppressed intracellular oxidative stress upon FAs stimulation in PMHCs and L02 cells. Mechanistically, SIRT6, but not SIRT1 promoted PGC-1α expression. We further prove that ENDOG is downstream of PGC-1α. In addition, we evidenced that ENDOG protects hepatocytes from lipid-induced oxidative stress, and down-regulation of Endog blunted the protective role of metformin in defending against FAs-induced oxidative stress. Our study established a novel mechanism of metformin in counteracting lipid-induced hepatic injury via activating SIRT6/PGC-1α/ENDOG signaling, thus providing novel targets of metformin in the therapy of T2D.

Imbalanced GSH/ROS and sequential cell death.

Reactive oxygen species (ROS) are produced in cells during metabolic processes. Excessive intracellular ROS may react with large biomolecules, such as DNA, RNA, proteins, and small biomolecules, that is, glutathione (GSH) and unsaturated fatty acids. GSH has physiological functions, including free radical scavenging, anti-oxidation, and electrophile elimination. The disruption of ROS/GSH balance results in the deleterious oxidation and chemical modification of biomacromolecules, which eventually leads to cell-cycle arrest and proliferation inhibition, and even induces cell death. Imbalanced ROS/GSH may result from a direct increase of ROS, consumption of GSH, intracellular oxidoreductase interference, or thioredoxin activity reduction. Some chemicals including arsenic trioxide (ATO), pyrogallol (PG), and carbobenzoxy-Leu-Leu-leucinal (MG132) could also disrupt the balance of GSH and ROS. This article reviews the occurrence and consequences of the imbalance between GSH and ROS and introduces factors responsible for the disruption of cellular ROS and GSH balance, resulting in cell death. "GSH" and "ROS" were used as keywords to search the relevant literaturess.

A sudden change in pacing rate: Normal or malfunction?

A woman with a dual-chamber pacemaker was examined for recurrent chest discomfort and palpitations at our hospital. The Holter monitor test recorded recurrent episodes of a sudden increase in pacing rate from 60 to 105 bpm, which corresponded to the symptoms. Orthodromic pacemaker-mediated arrhythmia (OPMA), caused by ventricular lead dislodgement and atrial far-field sensing, caused the recurrent episodes of a sudden change in pacing rate. The occurrence of OPMA may represent a rare but noteworthy pacemaker problem. To our knowledge, our study reports the first case of PMA that only occurs, and is maintained, in the DDI mode.

Cadmium exposure reprograms energy metabolism of hematopoietic stem cells to promote myelopoiesis at the expense of lymphopoiesis in mice.

Cadmium (Cd) is a highly toxic heavy metal in our living environment. Hematopoietic stem cells (HSC) are ancestors for all blood cells. Therefore understanding the impact of Cd on HSC is significant for public health. The aim of this study was to investigate the impact of Cd2+ on energy metabolism of HSC and its involvement in hematopoiesis. Wild-type C57BL/6 mice were treated with 10 ppm of Cd2+ via drinking water for 3 months, and thereafter glycolysis and mitochondrial (MT) oxidative phosphorylation (OXPHOS) of HSC in the bone marrow (BM) and their impact on hematopoiesis were evaluated. After Cd2+ treatment, HSC had reduced lactate dehydrogenase (LDH) activity and lactate production while having increased pyruvate dehydrogenase (PDH) activity, MT membrane potential, ATP production, oxygen (O2) consumption and reactive oxygen species (ROS), indicating that Cd2+ switched the pattern of energy metabolism from glycolysis to OXPHOS in HSC. Moreover, Cd2+ switch of HSC energy metabolism was critically dependent on Wnt5a/Cdc42/calcium (Ca2+) signaling triggered by a direct action of Cd2+ on HSC. To test the biological significance of Cd2+ impact on HSC energy metabolism, HSC were intervened for Ca2+, OXPHOS, or ROS in vitro, and thereafter the HSC were transplanted into lethally irradiated recipients to reconstitute the immune system; the transplantation assay indicated that Ca2+-dependent MT OXPHOS dominated the skewed myelopoiesis of HSC by Cd2+ exposure. Collectively, we revealed that Cd2+ exposure activated Wnt5a/Cdc42/Ca2+ signaling to reprogram the energy metabolism of HSC to drive myelopoiesis at the expense of lymphopoiesis.