Achieving Dendrite-Free and By-Product-Free Aqueous Zn-Ion Battery Anode via Nicotinic Acid Electrolyte Additive with Molecule-Ion Conversion Mechanism.

The widespread adoption of aqueous Zn ion batteries is hindered by the instability of the Zn anode. Herein, an elegant strategy is proposed to enhance the stability of Zn anode by incorporating nicotinic acid (NA), an additive with a unique molecule-ion conversion mechanism, to optimize the anode/electrolyte interface and the typical ZnSO4 electrolyte system. Experimental characterization and theoretical calculations demonstrate that the NA additive preferentially replaces H2O in the original solvation shell and adsorbs onto the Zn anode surface upon conversion from molecule to ion in the electrolyte environment, thereby suppressing side reactions arising from activated H2O decomposition and stochastic growth of Zn dendrites. Simultaneously, such a molecule-to-ion conversion mechanism may induce preferential deposition of Zn along the (002) plane. Benefiting from it, the Zn||Zn symmetric battery cycles stably for 2500 h at 1 mA cm-2, 1 mAh cm-2. More encouragingly, the Zn||AC full batteries and the Zn||AC full batteries using NA electrolyte and Zn||VO2 full batteries also exhibit excellent performance improvements. This work emphasizes the role of variation in the form of additives (especially weak acid-based additives) in fine-tuning the solvation structure and the anode/electrolyte interface, hopefully enhancing the performance of various aqueous metal batteries.

Frontiers and hotspots evolution in cytokine storm: A bibliometric analysis from 2004 to 2022.

Background: As a fatal disease, cytokine storm has garnered research attention in recent years. Nonetheless, as the body of related studies expands, a thorough and impartial evaluation of the current status of research on cytokine storms remains absent. Consequently, this study aimed to thoroughly explore the research landscape and evolution of cytokine storm utilizing bibliometric and knowledge graph approaches. Methods: Research articles and reviews centered on cytokine storms were retrieved from the Web of Science Core Collection database. For bibliometric analysis, tools such as Excel 365, CiteSpace, VOSviewer, and the Bibliometrix R package were utilized. Results: This bibliometric analysis encompassed 6647 articles published between 2004 and 2022. The quantity of pertinent articles and citation frequency exhibited a yearly upward trend, with a sharp increase starting in 2020. Network analysis of collaborations reveals that the United States holds a dominant position in this area, boasting the largest publication count and leading institutions. Frontiers in Immunology ranks as the leading journal for the largest publication count in this area. Stephan A. Grupp, a prominent researcher in this area, has authored the largest publication count and has the second-highest citation frequency. Research trends and keyword evaluations show that the connection between cytokine storm and COVID-19, as well as cytokine storm treatment, are hot topics in research. Furthermore, research on cytokine storm and COVID-19 sits at the forefront in this area. Conclusion: This study employed bibliometric analysis to create a visual representation of cytokine storm research, revealing current trends and burgeoning topics in this area for the first time. It will provide valuable insights, helping scholars pinpoint critical research areas and potential collaborators.

Research on the method of determining the block size for an open-pit mine integrating mining parameters and shovel-truck's operation efficiency.

The production plan of an open-pit mine depends on the block model, so it's crucial to determine the appropriate method and size for partitioning it. This study proposes a new method based on a closed shell three-dimensional geological model for determining block model size in open-pit mines. Instead of using regular block models, the shell model is directly cut, and the discrete geological body is referred to as the "mining model." Mining parameters and the shovel-truck's performance are integrated into the method. Bench height determines the Z-axis size, bench slope angle determines the inclination angle, and shovel width determines the X-axis size of the block model. The operation efficiency of the shovel-truck considers the probability distribution of simultaneous operations, allowing the determination of the Y-axis size of block models for different types of shovels. The developed "Mining Model" module in the software "Life Cycle Mining System" is used for practical implementation. By comparing the results with traditional block models, the superiority of the proposed method is demonstrated. This study provides a more accurate model for optimizing the production plan of open-pit mines throughout their life cycle.

Case report: Decreased hemoglobin and multiple organ failure caused by ceftizoxime-induced immune hemolytic anemia in a Chinese patient with malignant rectal cancer.

Background: Drug-induced immune hemolytic anemia (DIIHA) is a rare but serious condition, with an estimated incidence of one in 100,000 cases, associated with various antibiotics. This study reports on a case of ceftizoxime-induced hemolysis observed in a patient in China. Case description: A Chinese patient diagnosed with malignant rectal cancer underwent antimicrobial therapy after laparoscopic partial recto-sigmoid resection (L-Dixon). After receiving four doses of ceftizoxime, the patient developed symptoms including rash, itchy skin, and chest distress, followed by a rapid decline in hemoglobin levels, the presence of hemoglobin in the urine (hemoglobinuria), renal failure, and disseminated intravascular coagulation. Laboratory analysis revealed high-titer antibodies against ceftizoxime and red blood cells (RBCs) in the patient's serum, including immunoglobulin M (IgM) (1:128) antibodies and immunoglobulin G (IgG) (1:8) antibodies, with noted crossreactivity to ceftriaxone. Significant improvement in the patient's hemolytic symptoms was observed following immediate discontinuation of the drug, two plasma exchanges, and extensive RBC transfusion. Conclusion: This case, together with previous reports, underscores the importance of considering DIIHA in patients who exhibit unexplained decreases in hemoglobin levels following antibiotic therapy. A thorough examination of the patient's medical history can provide crucial insights for diagnosing DIIHA. The effective management of DIIHA includes immediate cessation of the implicated drug, plasma exchange, and transfusion support based on the identification of specific drug-dependent antibodies through serological testing.

No genetic causal associations between periodontitis and brain atrophy or cognitive impairment: evidence from a comprehensive bidirectional Mendelian randomization study.

BACKGROUND: Observational studies have explored the relationships of periodontitis with brain atrophy and cognitive impairment, but these findings are limited by reverse causation, confounders and have reported conflicting results. Our study aimed to investigate the causal associations of periodontitis with brain atrophy and cognitive impairment through a comprehensive bidirectional Mendelian randomization (MR) research. METHODS: We incorporated two distinct genome-wide association study (GWAS) summary datasets as an exploration cohort and a replication cohort for periodontitis. Four and eight metrics were selected for the insightful evaluation of brain atrophy and cognitive impairment, respectively. The former involved cortical thickness and surface area, left and right hippocampal volumes, with the latter covering assessments of cognitive performance, fluid intelligence scores, prospective memory, and reaction time for mild cognitive impairment to Alzheimer's disease (AD), Lewy body dementia, vascular dementia and frontotemporal dementia for severe situations. Furthermore, supplementary analyses were conducted to examine the associations between the longitudinal rates of change in brain atrophy and cognitive function metrics with periodontitis. The main analysis utilized the inverse variance weighting (IVW) method and evaluated the robustness of the results through a series of sensitivity analyses. For multiple tests, associations with p-values < 0.0021 were considered statistically significant, while p-values ≥ 0.0021 and < 0.05 were regarded as suggestive of significance. RESULTS: In the exploration cohort, forward and reverse MR results revealed no causal associations between periodontitis and brain atrophy or cognitive impairment, and only a potential causal association was found between AD and periodontitis (IVW: OR = 0.917, 95% CI from 0.845 to 0.995, P = 0.038). Results from the replication cohort similarly corroborated the absence of a causal relationship. In the supplementary analyses, the longitudinal rates of change in brain atrophy and cognitive function were also not found to have causal relationships with periodontitis. CONCLUSIONS: The MR analyses indicated a lack of substantial evidence for a causal connection between periodontitis and both brain atrophy and cognitive impairment.

A psychobiographical analysis of Empress Dowager Cixi: exploring the femininity castrated complex.

In Chinese culture, there is a widely circulated phrase, 'A hen crows in the morning'. This phrase is used to humiliate women who steal power and engage in the political field. It demonstrates the complicated relationship between women and power in the context of Chinese culture. Women are not completely excluded from the politics, but women in power are often stigmatised. This study explores the life of Empress Dowager Cixi (1835-1908), the last female dominator in Chinese history, takes psychobiography as the research method, and attempts to understand the complicated relationship between women and power in Chinese culture through analysing Cixi's life from the perspective of complex and cultural complex theory which originated with C.G. Jung and analytical theory. The research findings show that humiliating and suppressing women with political talent can trigger their complexes, both personal and cultural. This study attempts to propose the femininity castrated complex to better describe the conscious and unconscious psychological dynamics impacting on women within patriarchal, political Chinese culture. This complex further relates to (1) denying her biological sex in order to avoid accusations of superego and, (2) the relationship with her son who is not only her son, but also her enemy regarding (political) power.

A multicomponent reaction for modular assembly of indole-fused heterocycles.

Indoles are privileged chemical entities in natural products and drug discovery. Indole-fused heterocycles, particularly seven-membered ones, have received increasing attention due to their distinctive chemical characteristics and wide spectrum of bioactivities. However, the synthetic access to these compounds is highly limited. Herein, we report a unique multicomponent reaction (MCR) for modular assembly of indole-fused seven-membered heterocycles. In this process, indole, formaldehyde and amino hydrochloride could assemble rapidly to yield indole-fused oxadiazepines, and another addition of sodium thiosulphate would furnish indole-fused thiadiazepines. The biological evaluation disclosed the promising anticancer activity of these compounds. Furthermore, this MCR could be applicable in the late-stage and selective modifications of peptides. Therefore, this work provides a powerful strategy for indole functionalization and valuable tool for construction of seven-membered heterocycles.

Responses of physiological, microbiome and lipid metabolism to lignocellulose wastes in gut of yellow mealworm (Tenebrio molitor).

There is limited research on physiological and degradation mechanisms of yellow mealworm, a novel organic waste converter, in processing lignocellulosic wastes. This study has selected two types of lignocellulosic wastes, distillers' grains (DG) and maize straw (MS), to feed yellow mealworms. This study investigated the effects of lignocellulosic wastes on the growth, antioxidant system, microbiome, and lipidome of yellow mealworms. The relative growth of lignocellulosic waste group was not significantly different from wheat bran. The antioxidant level was elevated in DG. MS was significantly enriched in cellulose-degrading bacteria in the gut and was accompanied by disturbances in lipid metabolism. The correlation coefficients were used to construct a network connecting diet, microbiota, and lipids. The correlation analysis indicated that two sphingolipids, hexylglyceramide and dihydroglyceramide, were strongly and positively linked with the dominating species. This study provides comprehensive information on physiological and mechanism of mealworms in process of treating lignocellulosic waste.

Effect of Health Service Area on Primary Care Physician Provision of Low-Value Cancer Screening.

BACKGROUND: Using a health systems approach to investigate low-value care (LVC) may provide insights into structural drivers of this pervasive problem. OBJECTIVE: To evaluate the influence of service area practice patterns on low-value mammography and prostate-specific antigen (PSA) testing. DESIGN: Retrospective study analyzing LVC rates between 2008 and 2018, leveraging physician relocation in 3-year intervals of matched physician and patient groups. SETTING: U.S. Medicare claims data. PARTICIPANTS: 8254 physicians and 56 467 patients aged 75 years or older. MEASUREMENTS: LVC rates for physicians staying in their original service area and those relocating to new areas. RESULTS: Physicians relocating from higher-LVC areas to low-LVC areas were more likely to provide lower rates of LVC. For mammography, physicians staying in high-LVC areas (LVC rate, 10.1% [95% CI, 8.8% to 12.2%]) or medium-LVC areas (LVC rate, 10.3% [CI, 9.0% to 12.4%]) provided LVC at a higher rate than physicians relocating from those areas to low-LVC areas (LVC rates, 6.0% [CI, 4.4% to 7.5%] [difference, -4.1 percentage points {CI, -6.7 to -2.3 percentage points}] and 5.9% [CI, 4.6% to 7.8%] [difference, -4.4 percentage points {CI, -6.7 to -2.4 percentage points}], respectively). For PSA testing, physicians staying in high- or moderate-LVC service areas provided LVC at a rate of 17.5% (CI, 14.9% to 20.7%) or 10.6% (CI, 9.6% to 13.2%), respectively, compared with those relocating from those areas to low-LVC areas (LVC rates, 9.9% [CI, 7.5% to 13.2%] [difference, -7.6 percentage points {CI, -10.9 to -3.8 percentage points}] and 6.2% [CI, 3.5% to 9.8%] [difference, -4.4 percentage points {CI, -7.6 to -2.2 percentage points}], respectively). Physicians relocating from lower- to higher-LVC service areas were not more likely to provide LVC at a higher rate. LIMITATION: Use of retrospective observational data, possible unmeasured confounding, and potential for relocating physicians to practice differently from those who stay. CONCLUSION: Physicians relocating to service areas with lower rates of LVC provided less LVC than physicians who stayed in areas with higher rates of LVC. Systemic structures may contribute to LVC. Understanding which factors are contributing may present opportunities for policy and interventions to broadly improve care. PRIMARY FUNDING SOURCE: National Cancer Institute of the National Institutes of Health.

The impacts of national centralized drug procurement policy on drug utilization of medical institutions: an empirical study in a county-level hospital in China.

PURPOSE: Under the background of the regular implementation of the National Centralized Drug Procurement (NCDP) policy, this study aimed to assess the impacts of the NCDP policy on drug utilization of county-level medical institutions, and probe into the influencing factors of the changes in drug utilization. METHOD: A pre-post study was applied using inpatient data from a county-level medical institution in Nanjing. Drug utilization behavior of medical institutions of 88 most commonly used policy-related drugs (by generic name, including bid-winning and bid-non-winning brands) was analyzed, and the substitution of bid-winning brands for brand-name drugs after policy intervention was evaluated. RESULTS: After policy intervention, 43.18% of policy-related drugs realized the substitution of bid-winning brands for bid-non-winning brands (6.82% of complete substitution, 36.36% of partial substitution). Meanwhile, 40.90% of policy-related drugs failed to realize brand substitution. Multiple factors affected brand substitution, including: (1) Policy effect: brand substitution was more obvious after the intervention of the first and third round of NCDP. (2) Drug market competition: the greater the price reduction of bid-non-winning brands, the more the drugs for the same indication, the more likely that medical institutions keep using the same brands as they did before policy intervention. (3) Previous drug utilization of medical institutions: brand substitution was more obvious in drugs with large number of prescriptions and weak preference for brand-name drugs. CONCLUSION: The NCDP policy promoted the substitution of bid-winning brands for bid-non-winning brands. However, the NCDP policy remained to be further implemented in county-level medical institutions. Policy implememtation efforts, drug market competition and drug utilization of medical institutions would affect the implementation of the NCDP policy.

Increased DNA methylation contributes to the early ripening of pear fruits during domestication and improvement.

BACKGROUND: DNA methylation is an essential epigenetic modification. However, its contribution to trait changes and diversity in the domestication of perennial fruit trees remains unknown. RESULTS: Here, we investigate the variation in DNA methylation during pear domestication and improvement using whole-genome bisulfite sequencing in 41 pear accessions. Contrary to the significant decrease during rice domestication, we detect a global increase in DNA methylation during pear domestication and improvement. We find this specific increase in pear is significantly correlated with the downregulation of Demeter-like1 (DML1, encoding DNA demethylase) due to human selection. We identify a total of 5591 differentially methylated regions (DMRs). Methylation in the CG and CHG contexts undergoes co-evolution during pear domestication and improvement. DMRs have higher genetic diversity than selection sweep regions, especially in the introns. Approximately 97% of DMRs are not associated with any SNPs, and these DMRs are associated with starch and sucrose metabolism and phenylpropanoid biosynthesis. We also perform correlation analysis between DNA methylation and gene expression. We find genes close to the hypermethylated DMRs that are significantly associated with fruit ripening. We further verify the function of a hyper-DMR-associated gene, CAMTA2, and demonstrate that overexpression of CAMTA2 in tomato and pear callus inhibits fruit ripening. CONCLUSIONS: Our study describes a specific pattern of DNA methylation in the domestication and improvement of a perennial pear tree and suggests that increased DNA methylation plays an essential role in the early ripening of pear fruits.

Cocreation of photogenerated electron and hole collectors on polymeric carbon nitride synergistically promotes carrier separation and reaction kinetics towards propelling photocatalytic hydrogen evolution.

It is a challenging issue for the creation of photogenerated carrier collectors on the photocatalyst to drive charge separation and promote reaction kinetics in the photocatalytic reaction. Herein, based on one-step dual-modulation strategy, IrO2 nanodots are modified at the edge of polymeric carbon nitride (PCN) nanosheets and atomically dispersed Ir atoms are implanted in the skeleton of PCN to obtain a unique Ir-PCN/IrO2 photocatalyst. IrO2 nanodots and atomically dispersed Ir atoms act as hole and electron collectors to synergistically promote the carrier separation and reaction kinetics, respectively, thereby greatly improving the photocatalytic hydrogen evolution (PHE) performance. As a result, without adding additional cocatalyst, the PHE rate over the optimal Ir-PCN/IrO2-2% sample reaches up to 1564.4 µmol h-1 g-1 under the visible light irradiation, with achieving an apparent quantum yield (AQY) of 15.7% at 420 nm.

Synthetic Knockout Protein Standard for Evaluating Interference in Tandem Mass Tag-Based Proteomics.

Isobaric labeling is widely used for unbiased, proteome-wide studies, and it provides several advantages, such as fewer missing values among samples and higher quantitative precision. However, ion interference may lead to compressed or distorted observed ratios due to the coelution and coanalysis of peptides. Here, we introduced a synthetic KnockOut standard (sKO) for evaluating interference in tandem mass tags-based proteomics. sKO is made by mixing TMTpro-labeled tryptic peptides derived from four nonhuman proteins and a whole human proteome as background at different proportions. We showcased the utility of the sKO standard by exploring ion interference at different peptide concentrations (up to a 30-fold change in abundance) and using a variety of mass spectrometer data acquisition strategies. We also demonstrated that the sKO standard could provide valuable information for the rational design of acquisition strategies to achieve optimal data quality and discussed its potential applications for high-throughput proteomics workflows development.

Metabolomic Profiling Reveals the Quality Variations in Citri Reticulatae Pericarpium (Citrus reticulata Blanco cv. Chachiensis) with Different Storage Ages in Response to "Candidatus Liberibacter Asiaticus" Infection.

Citri Reticulatae Pericarpium, especially the pericarp of Citrus reticulata Blanco cv. Chachiensis (PCRC), is an important edible and medicinal ingredient for health and pharmacological properties. Citrus Huanglongbing, a devastating disease that currently threatens the citrus industry worldwide, is caused by a phloem-limited alpha-proteobacterium, "Candidatus Liberibacter asiaticus" (CLas). The industry of cultivar Chachiensis has been suffering from HLB. Although HLB affected the quality of citrus fruit, whether the quality of PCRC was affected by HLB remains unclear. In this study, we compared the metabolite profiles between HLB-affected and healthy PCRC from three sources: fresh, 6-month-old, and 9-year-old PCRC, through the untargeted LC-MS method. Compared to healthy controls, various types of bioactive compounds, mainly flavonoids, terpenoids, alkaloids, coumarins, polysaccharides, and phenolic acids, accumulated in HLB-affected PCRC, especially in the HLB-affected 9-year PCRC. In particular, isorhamnetin, isoliquiritigenin, luteolin 7-O-beta-D-glucoside, limonin, geniposide, pyrimidodiazepine, scoparone, chitobiose, m-coumaric acid, malonate, and pantothenic acid, which contributed to the pharmacological activity and health care effects of PCRC, were highly accumulated in HLB-affected 9-year-old PCRC compared to the healthy control. Multibioassay analyses revealed that HLB-affected 9-year-old PCRC had a higher content of total flavonoids and total polyphenols and exhibited similar antioxidant capacity as compared to healthy controls. The results of this study provided detailed information on the quality of HLB-affected PCRC.

Simultaneous Pore Detection and Morphological Features Extraction in Laser Powder Bed Fusion with Image Processing.

Internal pore defects are inevitable during laser powder bed fusion (LPBF), which have a significant impact on the mechanical properties of the parts. Therefore, detecting pores and obtaining their morphology will contribute to the quality of LPBF parts. Currently, supervised models are used for defect image detection, which requires a large amount of LPBF sample data, image labeling, and computing power equipment during the training process, resulting in high detection costs. This study extensively collected LPBF sample data and proposed a method for pore defect classification by obtaining its morphological features while detecting pore defects in optical microscopy (OM) images under various conditions. Compared with other advanced models, the proposed method achieves better detection accuracy on pore defect datasets with limited data. In addition, quickly detecting pore defects in a large number of labeling ground truth images will also contribute to the development of deep learning. In terms of image segmentation, the average accuracy scores of this method in the test images exceed 85%. The research results indicate that the algorithm proposed in this paper is suitable for quickly and accurately identifying pore defects from optical microscopy images.

S-scheme NiO/C3N5 heterojunctions with enhanced interfacial electric field for boosting photothermal-assisted photocatalytic H2 and H2O2 production.

Heterostructured visible-light-responsive photocatalysts represent a prospective approach to achieve efficient solar-to-chemical energy conversion. Herein, we propose a facile self-assembly technique to synthesize NiO nanoparticles/C3N5 nanosheets (NOCN) heterojunctions for hydrogen (H2) evolution catalysis and hydrogen peroxide (H2O2) production under visible light. In this regard, the black NiO nanoparticles (NPs) were tightly anchored on the surface of C3N5 nanosheets (CNNS) to construct S-scheme NOCN heterojunction, enabling efficient charge separation and high redox capability. Obtained results elucidated that the incorporated NiO NPs significantly promote light-harvesting efficiency and photo-to-thermal capacity over the NOCN composites. The enhanced photothermal effect facilitates the charge carrier transfer rate across the heterojunction and boosts the surface reaction kinetics. Accordingly, the photocatalytic performances of CNNS for H2 release and H2O2 production can be manipulated by introducing NiO NPs. The modified photocatalytic properties of NOCN composites are ascribed to the synergistic effects of all integrated components and the S-scheme heterojunction formation. Impressively, the high H2 evolution photocatalysis efficiency of NOCN nano-catalysts in seawater certifies their potential environmental applicability. Among all, the 12-NOCN nano-catalyst exhibits a higher photocatalytic efficiency for H2 release (112.2 µmol∙g-1∙h-1) and H2O2 production (91.2 µmol∙L-1∙h-1). Besides, the 12-NOCN nano-catalyst reveals excellent recyclability and structural stability. Additionally, the possible mechanism for photothermal-assisted photocatalysis is proposed. This work affords a feasible pathway to design photothermal-assisted S-scheme heterojunctions for diverse photocatalytic applications.

FOXM1 promotes the progression of non-small cell lung cancer by inhibiting miR-509-5p expression via binding to the miR-509-5p promoter region.

Background: Forkhead box M1 (FOXM1) functions as a transcription factor and is consistently overexpressed in various cancers, including non-small-cell lung-, breast-, cervical-, and colorectal cancer. Its overexpression is associated with poor prognosis in patients with non-small-cell lung cancer, although the detailed mechanisms by which FOXM1 promotes the development of non-small-cell lung cancer remain unclear. Objective: The mechanism of FOXM1 in migration, invasion, apoptosis, and viability of lung cancer cells was investigated. Methods: Transwell assay, scratch test, and flow cytometry were employed to study the effects of FOXM1 on migration, invasion, and apoptosis in A549 cells. A quantitative polymerase chain reaction was used to determine the impact of FOXM1 on miR-509-5p expression in A549 cells. Dual-luciferase reporter gene assay and chromatin immunoprecipitation were adopted to investigate the molecular mechanisms of FOXM1 on miR-509-5p expression. Results: FDI-6 (a FOXM1 inhibitor) reduced the protein abundance of FOXM1, thereby increasing the expression of miR-509-5p in A549 cells. Moreover, FDI-6 treatment significantly reduced migration, invasion, and viability of A549 cells while promoting cell apoptosis. Furthermore, miR-509-5p inhibitor obviously alleviated the biological effects of FDI-6 on A549 cells, suggesting that FOXM1 primarily exerted its cancer promoting effect by regulating miR-509-5p. Mechanistically, FOXM1 directly bound to the miR-509-5p promoter to inhibit miR-509-5p expression. Conclusion: FOXM1 directly binds to the promoter region of miR-509-5p to form a negative feedback loop, thereby inhibiting miR-509-5p expression and promoting the development of non-small-cell lung cancer. This study is expected to complement research on the pathogenesis of non-small-cell lung cancer and promote the development of novel therapeutic targets for this disease.

Aging induces region-specific dysregulation of hormone synthesis in the primate adrenal gland.

Adrenal glands, vital for steroid secretion and the regulation of metabolism, stress responses and immune activation, experience age-related decline, impacting systemic health. However, the regulatory mechanisms underlying adrenal aging remain largely uninvestigated. Here we established a single-nucleus transcriptomic atlas of both young and aged primate suprarenal glands, identifying lipid metabolism and steroidogenic pathways as core processes impacted by aging. We found dysregulation in centripetal adrenocortical differentiation in aged adrenal tissues and cells in the zona reticularis region, responsible for producing dehydroepiandrosterone sulfate (DHEA-S), were highly susceptible to aging, reflected by senescence, exhaustion and disturbed hormone production. Remarkably, LDLR was downregulated in all cell types of the outer cortex, and its targeted inactivation in human adrenal cells compromised cholesterol uptake and secretion of dehydroepiandrosterone sulfate, as observed in aged primate adrenal glands. Our study provides crucial insights into endocrine physiology, holding therapeutic promise for addressing aging-related adrenal insufficiency and delaying systemic aging.