A kinase-cGAS cascade to synthesize a therapeutic STING activator.

The introduction of molecular complexity in an atom- and step-efficient manner remains an outstanding goal in modern synthetic chemistry. Artificial biosynthetic pathways are uniquely able to address this challenge by using enzymes to carry out multiple synthetic steps simultaneously or in a one-pot sequence1-3. Conducting biosynthesis ex vivo further broadens its applicability by avoiding cross-talk with cellular metabolism and enabling the redesign of key biosynthetic pathways through the use of non-natural cofactors and synthetic reagents4,5. Here we describe the discovery and construction of an enzymatic cascade to MK-1454, a highly potent stimulator of interferon genes (STING) activator under study as an immuno-oncology therapeutic6,7 (ClinicalTrials.gov study NCT04220866 ). From two non-natural nucleotide monothiophosphates, MK-1454 is assembled diastereoselectively in a one-pot cascade, in which two thiotriphosphate nucleotides are simultaneously generated biocatalytically, followed by coupling and cyclization catalysed by an engineered animal cyclic guanosine-adenosine synthase (cGAS). For the thiotriphosphate synthesis, three kinase enzymes were engineered to develop a non-natural cofactor recycling system in which one thiotriphosphate serves as a cofactor in its own synthesis. This study demonstrates the substantial capacity that currently exists to use biosynthetic approaches to discover and manufacture complex, non-natural molecules.

The MksG nuclease is the executing part of the bacterial plasmid defense system MksBEFG.

Cells are continuously facing the risk of taking up foreign DNA that can compromise genomic integrity. Therefore, bacteria are in a constant arms race with mobile genetic elements such as phages, transposons and plasmids. They have developed several active strategies against invading DNA molecules that can be seen as a bacterial 'innate immune system'. Here, we investigated the molecular arrangement of the Corynebacterium glutamicum MksBEFG complex, which is homologous to the MukBEF condensin system. We show here that MksG is a nuclease that degrades plasmid DNA. The crystal structure of MksG revealed a dimeric assembly through its C-terminal domain that is homologous to the TOPRIM domain of the topoisomerase II family of enzymes and contains the corresponding ion binding site essential for DNA cleavage in topoisomerases. The MksBEF subunits exhibit an ATPase cycle in vitro and we reason that this reaction cycle, in combination with the nuclease activity provided by MksG, allows for processive degradation of invading plasmids. Super-resolution localization microscopy revealed that the Mks system is spatially regulated via the polar scaffold protein DivIVA. Introduction of plasmids results in an increase in DNA bound MksG, indicating an activation of the system in vivo.

Explosive Leidenfrost-Droplet-Mediated Synthesis of Monodispersed High-Entropy-Alloy Nanoparticles for Electrocatalysis.

High-entropy-alloy nanoparticles (HEA NPs) exhibit promising potential in various catalytic applications, yet a robust synthesis strategy has been elusive. Here, we introduce a straightforward and universal method, involving the microexplosion of Leidenfrost droplets housing carbon black and metal salt precursors, to fabricate PtRhPdIrRu HEA NPs with a size of ∼2.3 nm. The accumulated pressure within the Leidenfrost droplet triggers an intense explosion within milliseconds, propelling the carbon support and metal salt rapidly into the hot solvent through explosive force. The exceptionally quick temperature rise ensures the coreduction of metal salts, and the dilute local concentration of metal ions limits the final size of the HEA NPs. Additionally, the explosion process can be fine-tuned by selecting different solvents, enabling the harvesting of diverse HEA NPs with superior electrocatalytic activity for alcohol electrooxidation and hydrogen electrocatalysis compared to commercial Pt (Pd) unitary catalysts.

Confinement-Modulated Clusterization-Triggered Time-Dependent Phosphorescence Color from Xylan-Carbonized Polymer Dots.

Achieving time-dependent phosphorescence color (TDPC) in organic materials is attractive but extremely challenging due to the nonradiative decay and modulation puzzle of triplet state. Herein, xylan, a hemicellulose waste from the paper mill, was used to construct carbonized polymer dots (CPDs) with clusterization-triggered room-temperature phosphorescence (RTP). CPDs were endowed with tuneable triplet energy levels by through-space conjugation of heteroatom groups, which could be confined in silica to simultaneously activate surface oxide-related low-energy and cross-linked core N-related high-energy emissive centers. Thus, the blue emissive center with a lifetime of 425.6 ms and green emissive center with a longer lifetime of 1506 ms coexisted in the confined CPDs; the former was the dominant contribution to RTP at first, and the latter became dominant over time, leading to a typical TDPC evolution with large color contrast from blue to blue-green and then to green. Meanwhile, the TDPC could remain unobstructed after the confined CPDs were soaked in water for more than a month. The CPDs were successfully applied in location and deformation imaging of hydrogel and advanced dynamic information encryption and anticounterfeiting. The work may shed new light on the design of TDPC materials and broaden the high-value use of paper-mill waste xylan.

Catalyst Selection over an Electrochemical Reductive Coupling Reaction toward Direct Electrosynthesis of Oxime from NOx and Aldehyde.

Aqueous electrochemical coupling reactions, which enable the green synthesis of complex organic compounds, will be a crucial tool in synthetic chemistry. However, a lack of informed approaches for screening suitable catalysts is a major obstacle to its development. Here, we propose a pioneering electrochemical reductive coupling reaction toward direct electrosynthesis of oxime from NOx and aldehyde. Through integrating experimental and theoretical methods, we screen out the optimal catalyst, i.e., metal Fe catalyst, that facilitates the enrichment and C-N coupling of key reaction intermediates, all leading to high yields (e.g., ∼99% yield of benzaldoxime) for the direct electrosynthesis of oxime over Fe. With a divided flow reactor, we achieve a high benzaldoxime production of 22.8 g h-1 gcat-1 in ∼94% isolated yield. This work not only paves the way to the industrial mass production of oxime via electrosynthesis but also offers references for the catalyst selection of other electrochemical coupling reactions.

Facile Preparation of Full-Color Tunable Room Temperature Phosphorescence Cellulose via Click Chemistry.

Sustainable long-lived room temperature phosphorescence (RTP) materials with color-tunable afterglows are attractive but rarely reported. Here, cellulose is reconstructed by directed redox to afford ample active hydroxyl groups and water-solubility; arylboronic acids with various π conjugations can be facilely anchored to reconstructed cellulose via click chemistry within 1 min in pure water, resulting in full-color tunable RTP cellulose. The rigid environment provided by the B─O covalent bonds and hydrogen bonds can stabilize the triplet excitons, thus the target cellulose displays outstanding RTP performances with the lifetime of 2.67 s, phosphorescence quantum yield of 9.37%, and absolute afterglow luminance of 348 mcd m-2. Furthermore, due to the formation of various emissive species, the smart RTP cellulose shows excitation- and time-dependent afterglows. Taking advantages of sustainability, ultralong lifetime, and full-color tunable afterglows, et al, the environmentally friendly RTP cellulose is successfully used for nontoxic afterglow inks, delay lighting, and afterglow display.

Bifunctional Ni Foam Supported TiO2 @Ni3 S2 core@shell Nanorod Arrays for Boosting Electrocatalytic Biomass Upgrading and H2 Production Reactions.

Replacing traditional oxygen evoltion reaction (OER) with biomass oxidation reaction (BOR) is an advantageous alternative choice to obtain green hydrogen energy from electrocatalytic water splitting. Herein, a novel of extremely homogeneous Ni3 S2 nanosheets covered TiO2 nanorod arrays are in situ growth on conductive Ni foam (Ni/TiO2 @Ni3 S2 ). The Ni/TiO2 @Ni3 S2 electrode exhibits excellent electrocatalytic activity and long-term stability for both BOR and hydrogen evolution reaction (HER). Especially, taking glucose as a typical biomass, the average hydrogen production rate of the HER-glucose oxidation reaction (GOR) two-electrode system reached 984.74 µmol h-1 , about 2.7 times higher than that of in a common HER//OER two-electrode water splitting system (365.50 µmol h-1 ). The calculated power energy saving efficiency of the GOR//HER system is about 13% less than that of the OER//HER system. Meanwhile, the corresponding selectivity of the value-added formic acid produced by GOR reaches about 80%. Moreover, the Ni/TiO2 @Ni3 S2 electrode also exhibits excellent electrocatalytic activity on a diverse range of typical biomass intermediates, such as urea, sucrose, fructose, furfuryl alcohol (FFA), 5-hydroxymethylfurfural (HMF), and alcohol (EtOH). These results show that Ni/TiO2 @Ni3 S2 has great potential in electrocatalysis, especially in replacing OER reaction with BOR reaction and promoting the sustainable development of hydrogen production.

Formation of Disordered High-Entropy-Alloy Nanoparticles for Highly Efficient Hydrogen Electrocatalysis.

Nanoparticles composed of high-entropy alloys (HEA NPs) exhibit remarkable performance in electrocatalytic processes such as hydrogen evolution and oxidations. In this study, two types of quinary HEA NPs of PtRhPdIrRu, are synthesized, featuring disordered and crystallized nanostructures, both with and without a boiling mixture. The disordered HEA NPs (d-HEA NPs) with a size of 3.5 nm is synthesized under intense boiling conditions, attributed to improved heat and mass transfer during reduction of precursors and particle growth. The disordered HEA NPs displayed an exceptionally high turnover frequency of 33.1 s-1 at an overpotential of 50 mV, surpassing commercial Pt NPs in acidic electrolytes by 5.4 times. Additionally, d-HEA NPs exhibited superior stability at a constant electrolyzing current of 50 mA cm-2 compared to commercial Pt NPs. When employed as the anodic catalyst in an H2-O2 fuel cell, d-HEA NPs demonstrated a remarkable high current power density of 15.3 kW per gram of noble metal. Consequently, these findings highlight the potential of d-HEA NPs in electrochemical applications involving hydrogen.

The combination of SHOX2 and RASSF1A DNA methylation had a diagnostic value in pulmonary nodules and early lung cancer.

INTRODUCTION: The study explored the effects of SHOX2 and RASSF1A DNA methylation in lung cancer (LC). METHOD: Bronchoalveolar lavage fluid (BALF) samples as well as LC and normal adjacent tissues were collected from 72 LC patients and 35 patients with benign pulmonary nodules. Quantitative analysis of SHOX2 and RASSF1A DNA methylation was performed in benign pulmonary nodules and different stages of LC. The diagnostic value of SHOX2 and RASSF1A DNA methylation in LC and benign pulmonary nodules was determined by receiver operating characteristics analysis. Gain/loss-of-function experiments were constructed in LC cells and mouse models of xenograft and pulmonary nodule metastasis. The levels of SHOX2 and transfer-associated genes were tested through qRT-PCR and Western blot. Malignant phenotype of LC cells were assessed by functional experiment. The tumor volume and weight of mice in xenograft models were measured. Pulmonary nodule metastasis was determined through HE staining assay. 5-Azacytidine appeared as a positive control drug. RESULT: SHOX2 DNA methylation or RASSF1A DNA methylation had a diagnostic efficiency in pulmonary nodules and early LC, with the two combined had better diagnostic value. SHOX2 expression was upregulated in LC. Similar to 5-Azacytidine, SHOX2 knockdown inhibited LC cell viability, migration and invasion in vitro as well as restrained LC tumorigenesis and pulmonary nodule metastasis in vivo, whereas overexpressed SHOX2 had the opposite effects. CONCLUSION: The combination of SHOX2 and RASSF1A DNA methylation had a diagnostic value in pulmonary nodules and early LC. SHOX2 positively modulated the tumorigenesis and metastasis of LC by regulating DNA methylation processes.

Establishment of orthotopic osteosarcoma animal models in immunocompetent rats through muti-rounds of in-vivo selection.

Immunodeficient murine models are usually used as the preclinical models of osteosarcoma. Such models do not effectively simulate the process of tumorigenesis and metastasis. Establishing a suitable animal model for understanding the mechanism of osteosarcoma and the clinical translation is indispensable. The UMR-106 cell suspension was injected into the marrow cavity of Balb/C nude mice. Tumor masses were harvested from nude mice and sectioned. The tumor fragments were transplanted into the marrow cavities of SD rats immunosuppressed with cyclosporine A. Through muti-rounds selection in SD rats, we constructed orthotopic osteosarcoma animal models using rats with intact immune systems. The primary tumor cells were cultured in-vitro to obtain the immune-tolerant cell line. VX2 tumor fragments were transplanted into the distal femur and parosteal radius of New Zealand white rabbit to construct orthotopic osteosarcoma animal models in rabbits. The rate of tumor formation in SD rats (P1 generation) was 30%. After four rounds of selection and six rounds of acclimatization in SD rats with intact immune systems, we obtained immune-tolerant cell lines and established the orthotopic osteosarcoma model of the distal femur in SD rats. Micro-CT images confirmed tumor-driven osteolysis and the bone destruction process. Moreover, the orthotopic model was also established in New Zealand white rabbits by implanting VX2 tumor fragments into rabbit radii and femurs. We constructed orthotopic osteosarcoma animal models in rats with intact immune systems through muti-rounds in-vivo selection and the rabbit osteosarcoma model.

Interfacial Engineering of MoS2@CoS2 Heterostructure Electrocatalysts for Effective pH-Universal Hydrogen Evolution Reaction.

The practical utilization of the hydrogen evolution reaction (HER) necessitates the creation of electrocatalysts that are both efficient and abundant in earth elements, capable of operating effectively within a wide pH range. However, this objective continues to present itself as an arduous obstacle. In this research, we propose the incorporation of sulfur vacancies in a novel heterojunction formed by MoS2@CoS2, designed to exhibit remarkable catalytic performances. This efficacy is attributed to the advantageous combination of the low work function and space charge zone at the interface between MoS2 and CoS2 in the heterojunction. The MoS2@CoS2 heterojunction manifests outstanding hydrogen evolution activity over an extensive pH range. Remarkably, achieving a current density of 10 mA cm-2 in aqueous solutions 1.0 M KOH, 0.5 M H2SO4, and 1.0 M phosphate-buffered saline (PBS), respectively, requires only an overpotential of 48, 62, and 164 mV. The Tafel slopes for each case are 43, 32, and 62 mV dec-1, respectively. In this study, the synergistic effect of MoS2 and CoS2 is conducive to electron transfer, making the MoS2@CoS2 heterojunction show excellent electrocatalytic performance. The synergistic effects arising from the heterojunction and sulfur vacancy not only contribute to the observed catalytic prowess but also provide a valuable model and reference for the exploration of other efficient electrocatalysts. This research marks a significant stride toward overcoming the challenges associated with developing electrocatalysts for practical hydrogen evolution applications.

Hair-Derived Exposome Exploration of Cardiometabolic Health: Piloting a Bayesian Multitrait Variable Selection Approach.

Cardiometabolic health is complex and characterized by an ensemble of correlated and/or co-occurring conditions including obesity, dyslipidemia, hypertension, and diabetes mellitus. It is affected by social, lifestyle, and environmental factors, which in-turn exhibit complex correlation patterns. To account for the complexity of (i) exposure profiles and (ii) health outcomes, we propose to use a multitrait Bayesian variable selection approach and identify a sparse set of exposures jointly explanatory of the complex cardiometabolic health status. Using data from a subset (N = 941 participants) of the nutrition, environment, and cardiovascular health (NESCAV) study, we evaluated the link between measurements of the cumulative exposure to (N = 33) pollutants derived from hair and cardiometabolic health as proxied by up to nine measured traits. Our multitrait analysis showed increased statistical power, compared to single-trait analyses, to detect subtle contributions of exposures to a set of clinical phenotypes, while providing parsimonious results with improved interpretability. We identified six exposures that were jointly explanatory of cardiometabolic health as modeled by six complementary traits, of which, we identified strong associations between hexachlorobenzene and trifluralin exposure and adverse cardiometabolic health, including traits of obesity, dyslipidemia, and hypertension. This supports the use of this type of approach for the joint modeling, in an exposome context, of correlated exposures in relation to complex and multifaceted outcomes.

Research progress on intestinal microbiota regulating cognitive function through the gut-brain axis.

The intestinal microbiota community is a fundamental component of the human body and plays a significant regulatory role in maintaining overall health and in the management disease states.The intestinal microbiota-gut-brain axis represents a vital connection in the cognitive regulation of the central nervous system by the intestinal microbiota.The impact of intestinal microbiota on cognitive function is hypothesized to manifest through both the nervous system and circulatory system. Imbalances in intestinal microbiota during the perioperative period could potentially contribute to perioperative neurocognitive dysfunction. This article concentrates on a review of existing literature to explore the potential influence of intestinal microbiota on brain and cognitive functions via the nervous and circulatory systems.Additionally, it summarizes recent findings on the impact of perioperative intestinal dysbacteriosis on perioperative neurocognitive dysfunction and suggests novel approaches for prevention and treatment of this condition.

IRON MAN interacts with BRUTUS to maintain iron homeostasis in Arabidopsis.

IRON MAN (IMA) peptides, a family of small peptides, control iron (Fe) transport in plants, but their roles in Fe signaling remain unclear. BRUTUS (BTS) is a potential Fe sensor that negatively regulates Fe homeostasis by promoting the ubiquitin-mediated degradation of bHLH105 and bHLH115, two positive regulators of the Fe deficiency response. Here, we show that IMA peptides interact with BTS. The C-terminal parts of IMA peptides contain a conserved BTS interaction domain (BID) that is responsible for their interaction with the C terminus of BTS. Arabidopsis thaliana plants constitutively expressing IMA genes phenocopy the bts-2 mutant. Moreover, IMA peptides are ubiquitinated and degraded by BTS. bHLH105 and bHLH115 also share a BID, which accounts for their interaction with BTS. IMA peptides compete with bHLH105/bHLH115 for interaction with BTS, thereby inhibiting the degradation of these transcription factors by BTS. Genetic analyses suggest that bHLH105/bHLH115 and IMA3 have additive roles and function downstream of BTS. Moreover, the transcription of both BTS and IMA3 is activated directly by bHLH105 and bHLH115 under Fe-deficient conditions. Our findings provide a conceptual framework for understanding the regulation of Fe homeostasis: IMA peptides protect bHLH105/bHLH115 from degradation by sequestering BTS, thereby activating the Fe deficiency response.

Complementary Weaknesses: A Win-Win Approach for rGO/CdS to Improve the Energy Conversion Performance of Integrated Photorechargeable Li-S Batteries.

Integrating solar energy into rechargeable battery systems represents a significant advancement towards sustainable energy storage solutions. Herein, we propose a win-win solution to reduce the shuttle effect of polysulfide and improve the photocorrosion stability of CdS, thereby enhancing the energy conversion efficiency of rGO/CdS-based photorechargeable integrated lithium-sulfur batteries (PRLSBs). Experimental results show that CdS can effectively anchor polysulfide under sunlight irradiation for 20 minutes. Under a high current density (1 C), the discharge-specific capacity of the PRLSBs increased to 971.30 mAh g-1, which is 113.3 % enhancement compared to that of under dark condition (857.49 mAh g-1). Remarkably, without an electrical power supply, the PRLSBs can maintain a 21 hours discharge process following merely 1.5 hours of light irradiation, achieving a breakthrough solar-to-electrical energy conversion efficiency of up to 5.04 %. Ex situ X-ray photoelectron spectroscopy (XPS) and in situ Raman analysis corroborate the effectiveness of this complementary weakness approach in bolstering redox kinetics and curtailing polysulfide dissolution in PRLSBs. This work showcases a feasible strategy to develop PRLSBs with potential dual-functional metal sulfide photoelectrodes, which will be of great interest in future-oriented off-grid photocell systems.

Real-world clinical analysis in 190 advanced NSCLC patients with uncommon EGFR mutations: A multi-center study.

Differently from epidermal growth factor receptor (EGFR) 19Del and L858R mutations, the panoramic description of uncommon EGFR mutations is far from mature. Our understanding of its population characteristics, treatment response, and drug resistance mechanisms needs urgent expansion and deepening. Our study enrolled 437 patients with non-small-cell lung cancer from four clinical centers and who had uncommon EGFR mutations. The clinical characteristics of all patients and the treatment outcomes of 190 advanced patients who received pharmacotherapy were analyzed. Moreover, the acquired resistance mechanisms were explored based on 53 tissue or liquid re-biopsy data in 45 patients. Patients with EGFR 20ins had a shorter survival time compared with patients with non-20ins mutations. In total, 149 cases had received EGFR-tyrosine kinase inhibitors (TKI); afatinib was significantly superior to other EGFR-TKIs both in ORR and mPFS in all uncommon mutations and especially in the L861Q group. The most common acquired drug resistance mechanism was MET amplification, followed by EGFR T790M, which was significantly different from common EGFR mutations.

Collaborative Design of MgO/FeOx Nanosheets on Titanium: Combining Therapy with Regeneration.

The repair of bone defects caused by osteosarcoma resection remains a clinical challenge because of the tumor recurrence and bacterial infection. Combining tumor and bacterial therapy with bone regeneration properties in bone implants is a promising strategy for the treatment of osteosarcoma. Here, a layer of MgO/FeOx nanosheet is constructed on the Ti implant to prevent tumor recurrence and bacterial infection, while simultaneously accelerating bone formation. This MgO/FeOx double metal oxide demonstrates good peroxidase activity to catalyze H2 O2 , which is rich in tumor microenvironment, to form reactive oxygen species (ROS), and shows good photothermal conversion capacity to produce photothermal effect, thus synergistically killing tumor cells and eliminating tumor tissue. In addition, it generates a local alkaline surface microenvironment to inhibit the energy metabolism of bacteria to enhance the photothermal antibacterial effect. Furthermore, benefiting from the generation of a Mg ion-containing alkaline microenvironment, this MgO/FeOx film can promote the osteogenic differentiation of osteoblast and angiogenesis of vascular endothelial cells in vitro as well as accelerated bone formation in vivo. This study proposes a multifunctional platform for integrating tumor and bacterial therapy and bone regeneration, which has good application prospects for the treatment of osteosarcoma.

Semirational engineering of Cytophaga hutchinsonii polyphosphate kinase for developing a cost-effective, robust, and efficient adenosine 5'-triphosphate regeneration system.

IMPORTANCE: The adenosine 5'-triphosphate (ATP) regeneration system can significantly reduce the cost of many biocatalytic processes. Numerous studies have endeavored to utilize the ATP regeneration system based on Cytophaga hutchinsonii PPK (ChPPK). However, the wild-type ChPPK enzyme possesses limitations such as low enzymatic activity, poor stability, and limited substrate tolerance, impeding its application in catalytic reactions. To enhance the performance of ChPPK, we employed a semi-rational design approach to obtain the variant ChPPK/A79G/S106C/I108F/L285P. The enzymatic kinetic parameters and the catalytic performance in the synthesis of nicotinamide mononucleotide demonstrated that the variant ChPPK/A79G/S106C/I108F/L285P exhibited superior enzymatic properties than the wild-type enzyme. All data indicated that our engineered ATP regeneration system holds inherent potential for implementation in biocatalytic processes.

Comparative Analysis of Single-Path and Multipath Adrenal Venous Sampling in Primary Aldosteronism.

Objective: To evaluate the safety and efficacy of adrenal venous sampling (AVS) via the cubital vein and femoral vein synchronously. Methods: A total of 200 patients with primary aldosteronism admitted to the First Hospital of Fujian Medical University were enrolled and randomly divided into a single-path AVS group (SP, N = 108) and a multipath AVS group (MP, N = 92). We analyzed the clinical characteristics, intubation success rate, procedure cost, total fluoroscopy time, complications, contrast dosage, and the number of catheters selected during AVS. A planar quadrant system was established to mark the direction of the adrenal opening, with the intersection of the right renal vein and the inferior vena cava defined as the origin. In digital subtraction angiography images, the RAV opening located in the 0-3 o'clock direction was the first quadrant (I), and the 3-6 o'clock direction was the third quadrant (III). Results: There was no statistical difference between the two groups at baseline. Multipath AVS had a significantly higher success rate of right-sided intubation than single-path AVS (success rate of right-sided intubation/%: SP 87.96 vs MP 95.65, P = 0.043). Total fluoroscopy time was significantly reduced (fluoroscopy time/min: SP 9.80 ± 4.07 vs MP 7.42 ± 3.48, P = 0.024) and the cost of the procedure was markedly lower (cost/yuan: SP 3,900.93 ± 1,191.12 vs MP 3,378.26 ± 399.40, P < 0.001). There was no significant difference in postoperative complications between the two groups. In the group I, the procedure was completed mainly with an MPA catheter (catheter selection/%: MPA 98.19 vs TIG 17.65, P < 0.001). In the group III, TIG catheters were used more frequently (catheter selection/%: MPA 1.81 vs TIG 82.35, P < 0.001). Conclusion: Multipath AVS via the cubital vein and femoral vein improves the success rate of AVS with comparable safety compared to single-path AVS. When the RAV is opened in the III quadrant, the TIG catheter improves the cannulation success rate. The multipath AVS method provides more catheter options. Patients diagnosed with PA at the First Hospital of Fujian Medical University from December 2019 to December 2021 were included. The collection of medical records of the included population was approved by the ethics committee (approval number: [2021] 311). This was a cross-sectional study in which some patients were treated surgically and some were treated with superselective adrenal artery embolization (SAAE). We conducted a cohort study of patients treated with SAAE. ClinicalTrials.gov Protocol Registration and Results System (PRS) receipt release date: January 11, 2022. This trial is registered with NCT05188872.

Association between Environmental Exposure to Multiclass Organic Pollutants and Sex Steroid Hormone Levels in Women of Reproductive Age.

Organic pollutant exposure may alter sex steroid hormone levels in both animals and humans, but studies on mixture effects have been lacking and mainly limited to persistent organic pollutants, with few hormones being investigated. Moreover, measurements from a single blood or urine sample may not be able to reflect long-term status. Using hair analysis, here, we evaluated the relationship between multiclass organic pollutants and sex steroid hormones in 196 healthy Chinese women aged 25-45 years. Associations with nine sex steroid hormones, including progesterone, androstenedione (AD), testosterone (T), estrone (E1), and 17ß-estradiol (E2), and eight related hormone ratios were explored on 54 pollutants from polychlorinated biphenyl (PCB), pesticide, and bisphenol families using stability-based Lasso regression analysis. Our results showed that each hormone was associated with a mixture of at least 10 examined pollutants. In particular, hair E2 concentration was associated with 19 pollutants, including γ-hexachlorocyclohexane, propoxur, permethrin, fipronil, mecoprop, prochloraz, and carbendazim. There were also associations between pollutants and hormone ratios, with pentachlorophenol, dimethylthiophosphate, 3-phenoxybenzoic acid, and flusilazole being related to both E1/AD and E2/T ratios. Our results suggest that exposure to background levels of pesticides PCB180 and bisphenol S may affect sex steroid hormone homeostasis among women of reproductive age.