Unintentional emissions of polychlorinated naphthalenes in China: Sources, composition, and historical trends.

Polychlorinated naphthalenes (PCNs) are detrimental to human health and the environment. With the commercial production of PCNs banned, unintentional releases have emerged as a significant environmental source. However, relevant information is still scarce. In this study, provincial emissions for eight PCNs homologues from 37 sources in the Chinese mainland during the period of 1960-2019 were estimated based on a source-specific and time-varying emission factor database. The results showed that the total PCNs emissions in 2019 reached 757.0 kg with Hebei ranked at the top among all the provinces and iron & steel industry as the biggest source. Low-chlorinated PCNs comprised 90% of emissions by mass, while highly chlorinated PCNs dominated in terms of toxicity, highlighting divergent priorities for mitigating emissions and safeguarding human health. The emissions showed an overall upward trend from 1960 to 2019 driven by emission increase from iron & steel industry in terms of source, and from North China and East China in terms of geographic area. Per-capita emissions followed an inverted U-shaped environmental Kuznets curve while emission intensities decreased with increasing per-capita Gross Domestic Product (GDP) following a nearly linear pattern when log-transformed.

Identification of the effects of alkalinity exposure on the gills of oriental river prawns, Macrobrachium nipponense.

Macrobrachium nipponense is an important commercial freshwater species in China. However, the ability of alkali tolerance of M. nipponense is insufficient to culture in the major saline-alkali water source in China. Thus, it is urgently needed to perform the genetic improvement of alkali tolerance in this species. In the present study, we aimed to analyse the effects of alkali treatment on gills in this species after 96 h alkalinity exposure under the alkali concentrations of 0 mmol/L, 4 mmol/L, 8 mmol/L, and 12 mmol/L through performing the histological observations, measurement of antioxidant enzymes, metabolic profiling analysis, and transcriptome profiling analysis. The results of the present study revealed that alkali treatment stimulated the contents of malondialdehyde, glutathione, glutathione peroxidase in gills, indicating these antioxidant enzymes plays essential roles in the protection of body from the damage, caused by the alkali treatment. In addition, high concentration of alkali treatment (> 8 mmol/L) resulted in the damage of gill membrane and haemolymph vessel, affecting the normal respiratory function of gill. Metabolic profiling analysis revealed that Metabolic pathways, Biosynthesis of secondary metabolites, Biosynthesis of plant secondary metabolites, Microbial metabolism in diverse environments, Biosynthesis of amino acids were identified as the main enriched metabolic pathways of differentially expressed metabolites, which are consistent with the previous publications, treated by the various environmental factors. Transcriptome profiling analyses revealed that the alkali concentration of 12 mmol/L has more regulatory effects on the changes of gene expression than the other alkali concentrations. KEGG analysis revealed that Phagosome, Lysosome, Glycolysis/Gluconeogenesis, Purine Metabolism, Amino sugar and nucleotide sugar metabolism, and Endocytosis were identified as the main enriched metabolic pathways in the present study, predicting these metabolic pathways may be involved in the adaption of alkali treatment in M. nipponense. Phagosome, Lysosome, Purine Metabolism, and Endocytosis are immune-related metabolic pathways, while Glycolysis/Gluconeogenesis, and Amino sugar and nucleotide sugar metabolism are energy metabolism-related metabolic pathways. Quantitative PCR analyses of differentially expressed genes (DEGs) verified the accuracy of the RNA-Seq. Alkali treatment significantly stimulated the expressions of DEGs from the metabolic pathways of Phagosome and Lysosome, suggesting Phagosome and Lysosome play essential roles in the regulation of alkali tolerance in this species, as well as the genes from these metabolic pathways. The present study identified the effects of alkali treatment on gills, providing valuable evidences for the genetic improvement of alkali tolerance in M. nipponense.

Combination of radiotherapy and PD-L1 blockade induces abscopal responses in EGFR-mutated lung cancer through activating CD8+ T cells.

Patients with EGFR-mutated non-small cell lung cancer (NSCLC) respond poorly to immune checkpoint inhibitors (ICIs). It has been reported that the number of CD8+T cells is reduced in EGFR-mutated NSCLC. However, the extent of heterogeneity and effector function of distinct populations of CD8+T cells has not been investigated intensively. In addition, studies investigating whether a combination of radiotherapy and ICIs can improve the efficacy of ICIs in EGFR-mutated lung cancer are lacking. Single-cell RNA sequencing (scRNA-seq) was used to investigate the heterogeneity of CD8+T cell populations in EGFR-mutated NSCLC. The STING pathway was explored after hypofractionated radiation of EGFR-mutated and wild-type cells. Mice bearing LLC-19del and LLC-EGFR tumors were treated with radiotherapy plus anti-PD-L1. The scRNA-seq data showed the percentage of progenitor exhausted CD8+T cells was lower in EGFR-mutated NSCLC. In addition, CD8+T cells in EGFR-mutated NSCLC were enriched in oxidative phosphorylation. In EGFR-mutated and wild-type cells, 8 Gy × 3 increased the expression of chemokines that recruit T cells and activate the cGAS-STING pathway. In the LLC-19del and LLC-EGFR mouse model, the combination of radiation and anti-PD-L1 significantly inhibited the growth of abscopal tumors. The enhanced abscopal effect was associated with systemic CD8+T cell infiltration. This study provided an intensive understanding of the heterogeneity and effector functions of CD8+T cells in EGFR-mutated NSCLC. We showed that the combination of hypofractionated radiation and anti-PD-L1 significantly enhanced the abscopal responses in both EGFR-mutated and wild-type lung cancer by activating CD8+T cells in mice.

NRF2-HIF2α Signaling Attenuates Endothelial Cell Senescence and Maintains Intercellular Junctions in Diabetes.

In the context of diabetes, endothelial cells frequently exhibit compromised intercellular junctions and accelerated cellular senescence simultaneously. The precise mechanisms underlying these issues and the identification of effective treatments remain largely undefined. Our findings reveal that human umbilical vein endothelial cells (HUVECs) can counteract senescence and uphold the integrity of intercellular junctions under mildly to moderately elevated glucose levels (10 mM and 15 mM) via two primary mechanisms: i) The acetylation of NRF2 at lysine residues K56, K68, and K52 prevents its ubiquitination, enhancing the transcription of antioxidant genes GST, SOD1, and GPX1. This activity diminishes cytoplasmic oxidative stress, thereby mitigating endothelial cell senescence. ii) The interaction between the Neh2 domain of NRF2 and the PAS-B domain of HIF-2α within the nucleus curtails the attachment of HIF-2α to the NOX4/p22phox promoter. This action lessens oxidative stress near the cell membrane, maintaining intercellular junctions by safeguarding the disulfide bonds in occludin and E-cadherin from disruption. However, these protective strategies prove insufficient under severe hyperglycemic conditions (25 mM). Further investigation has identified Oltipraz, an activator of NRF2, as also promoting the degradation of HIF-2α. Through its simultaneous modulation of NRF2 and HIF-2α, Oltipraz significantly reduces cellular senescence and prevents the deterioration of intercellular junctions in HUVECs subjected to high glucose concentrations (25 mM). Our research positions Oltipraz as a promising therapeutic candidate for mitigating diabetes-induced vascular endothelial damage, potentially offering benefits against diabetes-related atherosclerosis and valvular calcification.

A thalamic nucleus reuniens-lateral septum-lateral hypothalamus circuit for comorbid anxiety-like behaviors in chronic itch.

Chronic itch often clinically coexists with anxiety symptoms, creating a vicious cycle of itch-anxiety comorbidities that are difficult to treat. However, the neuronal circuit mechanisms underlying the comorbidity of anxiety in chronic itch remain elusive. Here, we report anxiety-like behaviors in mouse models of chronic itch and identify γ-aminobutyric acid-releasing (GABAergic) neurons in the lateral septum (LS) as the key player in chronic itch-induced anxiety. In addition, chronic itch is accompanied with enhanced activity and synaptic plasticity of excitatory projections from the thalamic nucleus reuniens (Re) onto LS GABAergic neurons. Selective chemogenetic inhibition of the Re → LS circuit notably alleviated chronic itch-induced anxiety, with no impact on anxiety induced by restraint stress. Last, GABAergic neurons in lateral hypothalamus (LH) receive monosynaptic inhibition from LS GABAergic neurons to mediate chronic itch-induced anxiety. These findings underscore the potential significance of the Re → LS → LH pathway in regulating anxiety-like comorbid symptoms associated with chronic itch.

Spliceosomal GTPase Eftud2 deficiency-triggered ferroptosis leads to Purkinje cell degeneration.

Spliceosomal GTPase elongation factor Tu GTP binding domain containing 2 (EFTUD2) is a causative gene for mandibulofacial dysostosis with microcephaly (MFDM) syndrome comprising cerebellar hypoplasia and motor dysfunction. How EFTUD2 deficiency contributes to these symptoms remains elusive. Here, we demonstrate that specific ablation of Eftud2 in cerebellar Purkinje cells (PCs) in mice results in severe ferroptosis, PC degeneration, dyskinesia, and cerebellar atrophy, which recapitulates phenotypes observed in patients with MFDM. Mechanistically, Eftud2 promotes Scd1 and Gch1 expression, upregulates monounsaturated fatty acid phospholipids, and enhances antioxidant activity, thereby suppressing PC ferroptosis. Importantly, we identified transcription factor Atf4 as a downstream target to regulate anti-ferroptosis effects in PCs in a p53-independent manner. Inhibiting ferroptosis efficiently rescued cerebellar deficits in Eftud2 cKO mice. Our data reveal an important role of Eftud2 in maintaining PC survival, showing that pharmacologically or genetically inhibiting ferroptosis may be a promising therapeutic strategy for EFTUD2 deficiency-induced disorders.

Examining Diabetes Status by the Social Determinants of Health Among Adults in Hawai'i.

The social determinants of health (SDoH) influence health outcomes based on conditions from birth, growth, living, and age factors. Diabetes is a chronic condition, impacted by race, education, and income, which may lead to serious health consequences. In Hawai'i, approximately 11.2% of adults have been diagnosed with diabetes. The objective of this secondary cross-sectional study is to assess the relationship between the prevalence of diabetes and the social determinants of health among Hawai'i adults who participated in the Behavioral Risk Factor Surveillance System between 2018-2020. The prevalence of diabetes among adults was 11.0% (CI: 10.4-11.5%). Filipino, Japanese and Native Hawaiian adults had the highest prevalence of diabetes at 14.4% (CI: 12.7-16.2%), 14.2% (CI: 12.7-15.7%), and 13.2% (CI: 12.0-14.4%), respectively. Poverty level and education were significantly associated with diabetes status. Within employment categories, the adjusted odds ratio (AOR) for retired and unable to work adults were large at AOR: 1.51 (CI: 1.26-1.81) and AOR: 2.91 (CI: 2.28-3.72), respectively. SDoH can impact the development and management of diabetes. Understanding the role SDoH plays on diabetes status is crucial for promoting health equity, building community capacity, and improving diabetes management.

Decline in carbon emission intensity of global agriculture has stagnated recently.

Using global data for around 180 countries and territories and 170 food/feed types primarily derived from FAOSTAT, we have systematically analyzed the changes in greenhouse gas (GHG) emission intensity (GHGi) (kg CO2eq per kg protein production) over the past six decades. We found that, with large spatial heterogeneity, emission intensity decreased by nearly two-thirds from 1961 to 2019, predominantly in the earlier years due to agronomic improvement in productivity. However, in the most recent decade, emission intensity has become stagnant, and in a few countries even showed an increase, due to the rapid increase in livestock production and land use changes. The trade of final produced protein between countries has potentially reduced the global GHGi, especially for countries that are net importers with high GHGi, such as many in Africa and South Asia. Overall, a continuous decline of emission intensity in the future relies on countries with higher emission intensity to increase agricultural productivity and minimize land use changes. Countries with lower emission intensity should reduce livestock production and increase the free trade of agricultural products and improve the trade optimality.

Study on needle stick injuries during surgery and blunt needle use for reducing occupational exposure and hygiene benefits.

BACKGROUND: The conventional round suture needle poses a significant risk of needle stick injuries among surgical physicians, identified as a global occupational hazard by the World Health Organization, increasing hospital costs and exposure to bloodborne pathogens. While novel blunt suture needles have shown promise in reducing these risks, their adoption is limited domestically, prompting a study to compare their efficacy against traditional sharp needles in reducing needle stick injuries among surgical physicians. OBJECTIVE: To investigate suture needle stick injuries among surgical doctors during operations and assess the application effectiveness of a novel blunt suture needle. METHODS: A total of 106 surgical department physicians from March 2021 to February 2023 participated in the study. After completing a questionnaire survey on suture needle injuries during surgery, the participants were divided into two groups. Over a 6-month intervention period, the control group used regular round needles while the study group utilized novel blunt suture needles. Subsequently, suture needle injury incidence rates and economic hygiene benefits were compared between the two groups. RESULTS: The suture needle injury questionnaire survey showed that over the past 6 months, among 106 surgical department physicians, 20 needle stick injuries occurred, yielding an incidence rate of 18.87%. The highest incidence (65.00%) was during suturing incisions longer than 10 cm, primarily when visibility was poor (70.00%). Surgeons linked most injuries (60.00%) to prolonged surgical duration causing fatigue. Although 85.00% detected injuries within 1 minute, only 40.00% were reported, often due to perceived reporting complexity. Following intervention, the study group had significantly fewer injuries per surgery and lower occupational exposure costs compared to the control group (p< 0.05). CONCLUSION: Surgical department physicians commonly sustain suture needle injuries while suturing incisions of 5-10 cm length under poor visibility, exacerbated by prolonged surgical duration. Despite detecting most injuries within 1 minute, only 40% are reported. The implementation of novel blunt suture needles significantly decreases injury rates, resulting in reduced occupational exposure costs and favorable safety and economic hygiene outcomes.

Protective effects of degraded Bletilla striata polysaccharides against UVB-induced oxidative stress in skin.

The Bletilla striata polysaccharides (BSP) extracted through alkali-assisted method exhibit significant antioxidant activity, but its bioaccessibility was inadequate due to its tightly filamentous reticulation structure and high molecular weight. The anti-photoaging and anti-melanogenesis effects of degraded BSP (DBSPs) against UVB-induced oxidative stress on the skin were investigated. The molecular weights of the DBSPs were reduced to 153.94 kDa, 66.96 kDa, and 15.54 kDa from an initial value of 298.82 kDa. The degradation treatment altered the branched chain structure of the DBSPs, while the backbone structure, triple-helix structure, and crystallinity remained. DBSPs with a lower molecular weight exhibit better in vitro antioxidant activity. DBSPs did not show cytotoxicity to HSF cells but inhibited B16F10 cell proliferation. The addition of DBSPs protected HSF and B16F10 cells from oxidative stress and reduced ROS levels, B16F10 melanin content, and B16F10 tyrosinase activity after UVB damage, but DBSP-10 particles were slightly less effective due to aggregation. In contrast, DBSP-5 demonstrated effectiveness in reducing MDA levels in cells stressed by oxidative stress, increased total antioxidant capacity, and inhibited melanogenesis in B16F10, suggesting that DBSP-5 has potential as a topical therapeutic agent for the treatment of skin diseases associated with oxidative stress.

Covalent organic framework-hybridized Ag nanoparticles as SERS substrate for highly sensitive detection of DNA bases.

Currently, research in the development of high-performance sensing platforms has increased to fulfill the needs of analysis and detection. In this study, we developed a novel type of surface-enhanced Raman scattering (SERS) chip composed of a covalent organic framework (COF)-silver nanoparticles (AgNPs) nanocomposite, and this nanocomposite was fabricated by a one-step method of ultrasonically mixing the obtained COF and AgNPs. The fabricated chip exhibited high sensitivity and repeatable SERS effects. Practical application results showed that the chip was highly sensitive and reliable and capable of detecting DNA bases (adenine) to fit an equation in the range from 0.01 pM to 1 nM, with an R-square of 0.97253 and a detection limit of ~0.026 pM (signal-to-noise ratio (S/N) = 3). Therefore, the proposed SERS system has potential applications in biological assays.

Transcriptomic decoding of regional cortical vulnerability to major depressive disorder.

Previous studies in small samples have identified inconsistent cortical abnormalities in major depressive disorder (MDD). Despite genetic influences on MDD and the brain, it is unclear how genetic risk for MDD is translated into spatially patterned cortical vulnerability. Here, we initially examined voxel-wise differences in cortical function and structure using the largest multi-modal MRI data from 1660 MDD patients and 1341 controls. Combined with the Allen Human Brain Atlas, we then adopted transcription-neuroimaging spatial correlation and the newly developed ensemble-based gene category enrichment analysis to identify gene categories with expression related to cortical changes in MDD. Results showed that patients had relatively circumscribed impairments in local functional properties and broadly distributed disruptions in global functional connectivity, consistently characterized by hyper-function in associative areas and hypo-function in primary regions. Moreover, the local functional alterations were correlated with genes enriched for biological functions related to MDD in general (e.g., endoplasmic reticulum stress, mitogen-activated protein kinase, histone acetylation, and DNA methylation); and the global functional connectivity changes were associated with not only MDD-general, but also brain-relevant genes (e.g., neuron, synapse, axon, glial cell, and neurotransmitters). Our findings may provide important insights into the transcriptomic signatures of regional cortical vulnerability to MDD.

Hippocampal subfield morphology from first episodes of bipolar disorder type II and major depressive disorder in a drug naïve Chinese cohort.

Introduction: Symptoms during the onset of major depressive disorder [MDD] and bipolar disorder type II [BD-II] are similar. The difference of hippocampus subregion could be a biological marker to distinguish MDD from BD-II. Methods: We recruited 61 drug-naïve patients with a first-episode MDD and BD-II episode and 30 healthy controls (HC) to participate in a magnetic resonance imaging [MRI] study. We built a general linear model (one-way analysis of covariance) with 22 hippocampal subfields and two total hippocampal volumes as dependent variables, and the diagnosis of MDD, BD-II, and HC as independent variables. We performed pair-wise comparisons of hippocampal subfield volumes between MDD and HC, BD-II and MDD, BD-II and HC with post hoc for primary analysis. Results: We identified three regions that differed significantly in size between patients and controls. The left hippocampal fissure, the hippocampal-amygdaloid transition area (HATA), and the right subiculum body were all significantly larger in patients with MDD compared with the HC. In the onset of first-episode of MDD, the hippocampal volume increased significantly, especially on the left side comparing to HC. However, we found differences between MDD and BD-II were not statistically significant. The volume of the left HATA and right subiculum body in BD-II was larger. Conclusions: The sample size of this study is relatively small, as it is a cross-sectional comparative study. In both MDD and BD-II groups, the volume of more left subregions appeared to increase. The left subregions were severely injured in the development of depressive disorder.

Concordance of phenotypic characteristics among patients with familial Crohn's disease in China.

OBJECTIVES: Familial Crohn's disease (CD) accounts for approximately 1.5%-22.5% of all CD cases worldwide. We aimed to assess the concordance in disease subtype and phenotypic features among patients with CD and their relatives based on data from a large, well-characterized, referral center-based cohort in China. METHODS: A retrospective study was conducted on patients with familial CD who were admitted to the Sixth Affiliated Hospital of Sun Yat-sen University between January 2012 and June 2022. We analyzed the disease characteristics and performed a concordance analysis within the same family among patients with familial CD. RESULTS: Among 5150 patients, 70 (1.4%) had a family history of Crohn's disease. The median age of the patients at initial diagnosis did not differ significantly between the probands and successors of family members with CD (p = 0.25). At the initial diagnosis, 54 first-degree relatives showed moderate concordance in age (κ = 0.50) and disease location (κ = 0.44). At the last follow-up visit, all family members and first-degree relatives showed good concordance in upper gastrointestinal involvement (κ = 0.67 and 0.62) and stricturing or penetrating behavior (κ = 0.69 and 0.77), respectively. Patients with familial CD within the same family showed moderate agreement regarding anti-tumor necrosis factor α monoclonal antibody use and treatment efficacy (κ = 0.44 and 0.42) and mild agreement regarding the efficacy and adverse reactions of thiopurine (κ = 0.26 and 0.35). CONCLUSIONS: The proportion of patients with familial CD in China may be relatively low. The consistency of certain disease features in familial CD may be associated with the degree of kinship and convergence with longer follow-up duration.

Enhancing Swimming Performance of Magnetic Helical Microswimmers by Surface Microstructure.

Artificial bacterial flagella (ABF), also known as a magnetic helical microswimmer, has demonstrated enormous potential in various future biomedical applications (e.g., targeted drug delivery and minimally invasive surgery). Nevertheless, when used for in vivo/in vitro treatment applications, it is essential to achieve the high motion efficiency of the microswimmers for rapid therapy. In this paper, inspired by microorganisms, the surface microstructure was introduced into ABFs to investigate its effect on the swimming behavior. It was confirmed that compared with smooth counterparts, the ABF with surface microstructure reveals a smaller forward velocity below the step-out frequency (i.e., the frequency corresponding to the maximum velocity) but a larger maximum forward velocity and higher step-out frequency. A hydrodynamic model of microstructured ABF is employed to reveal the underlying movement mechanism, demonstrating that the interfacial slippage and the interaction between the fluid and the microstructure are essential to the swimming behavior. Furthermore, the effect of surface wettability and solid fraction of microstructure on the swimming performance of ABFs was investigated experimentally and analytically, which further reveals the influence of surface microstructure on the movement mechanism. The results present an effective approach for designing fast microrobots for in vivo/in vitro biomedical applications.

Phospholipid peroxidation in macrophage confers tumor resistance by suppressing phagocytic capability towards ferroptotic cells.

Ferroptosis holds significant potential for application in cancer therapy. However, ferroptosis inducers are not cell-specific and can cause phospholipid peroxidation in both tumor and non-tumor cells. This limitation greatly restricts the use of ferroptosis therapy as a safe and effective anticancer strategy. Our previous study demonstrated that macrophages can engulf ferroptotic cells through Toll-like receptor 2 (TLR2). Despite this advancement, the precise mechanism by which phospholipid peroxidation in macrophages affects their phagocytotic capability during treatment of tumors with ferroptotic agents is still unknown. Here, we utilized flow sorting combined with redox phospholipidomics to determine that phospholipid peroxidation in tumor microenvironment (TME) macrophages impaired the macrophages ability to eliminate ferroptotic tumor cells by phagocytosis, ultimately fostering tumor resistance to ferroptosis therapy. Mechanistically, the accumulation of phospholipid peroxidation in the macrophage endoplasmic reticulum (ER) repressed TLR2 trafficking to the plasma membrane and caused its retention in the ER by disrupting the interaction between TLR2 and its chaperone CNPY3. Subsequently, this ER-retained TLR2 recruited E3 ligase MARCH6 and initiated the proteasome-dependent degradation. Using redox phospholipidomics, we identified 1-steaoryl-2-15-HpETE-sn-glycero-3-phosphatidylethanolamine (SAPE-OOH) as the crucial mediator of these effects. Conclusively, our discovery elucidates a novel molecular mechanism underlying macrophage phospholipid peroxidation-induced tumor resistance to ferroptosis therapy and highlights the TLR2-MARCH6 axis as a potential therapeutic target for cancer therapy.

M2 macrophage-derived extracellular vesicles ameliorate Benzalkonium Chloride-induced dry eye.

Dry eye disease (DED) is a common ocular condition affecting a significant portion of the global population, yet effective treatment options remain elusive. This study investigates the therapeutic potential of M2 macrophage-derived extracellular vesicles (M2-EVs) in a mouse model of DED. The DED model was established using 0.2% benzalkonium chloride (BAC) eye drops, applied twice daily for a week. Post induction, the mice were categorized into 5 groups: PBS, Sodium Hyaluronate (HA, 0.1%), Fluoromethalone (FM, 0.1%), M0-EVs, and M2-EVs. The efficacy of M2-EVs was assessed through tear production, corneal fluorescein staining and HE staining. RNA sequencing (RNA-seq) was employed to investigate the mechanisms underlying the therapeutic effects of M2-EVs in DED. Notably, the M2-EVs treated group exhibited the highest tear secretion, indicating improved tear film stability and reduced corneal surface damage. Histological analysis revealed better corneal structure organization in the M2-EVs group, suggesting enhanced ocular surface repair and corneal preservation. Furthermore, M2-EVs treatment significantly decreased pro-inflammatory cytokine levels and showed unique enrichment of genes related to retinal development. These findings suggest that M2-EVs could serve as a promising noninvasive therapeutic approach for human DED, targeting ocular surface inflammation.

Identification of Blood Biomarkers Related to Energy Metabolism and Construction of Diagnostic Prediction Model Based on Three Independent Alzheimer's Disease Cohorts.

Background: Blood biomarkers are crucial for the diagnosis and therapy of Alzheimer's disease (AD). Energy metabolism disturbances are closely related to AD. However, research on blood biomarkers related to energy metabolism is still insufficient. Objective: This study aims to explore the diagnostic and therapeutic significance of energy metabolism-related genes in AD. Methods: AD cohorts were obtained from GEO database and single center. Machine learning algorithms were used to identify key genes. GSEA was used for functional analysis. Six algorithms were utilized to establish and evaluate diagnostic models. Key gene-related drugs were screened through network pharmacology. Results: We identified 4 energy metabolism genes, NDUFA1, MECOM, RPL26, and RPS27. These genes have been confirmed to be closely related to multiple energy metabolic pathways and different types of T cell immune infiltration. Additionally, the transcription factors INSM2 and 4 lncRNAs were involved in regulating 4 genes. Further analysis showed that all biomarkers were downregulated in the AD cohorts and not affected by aging and gender. More importantly, we constructed a diagnostic prediction model of 4 biomarkers, which has been validated by various algorithms for its diagnostic performance. Furthermore, we found that valproic acid mainly interacted with these biomarkers through hydrogen bonding, salt bonding, and hydrophobic interaction. Conclusions: We constructed a predictive model based on 4 energy metabolism genes, which may be helpful for the diagnosis of AD. The 4 validated genes could serve as promising blood biomarkers for AD. Their interaction with valproic acid may play a crucial role in the therapy of AD.