Glycosylation editing: an innovative therapeutic opportunity in precision oncology.

Cancer is still one of the most arduous challenges in the human society, even though humans have found many ways to try to conquer it. With our incremental understandings on the impact of sugar on human health, the clinical relevance of glycosylation has attracted our attention. The fact that altered glycosylation profiles reflect and define different health statuses provide novel opportunities for cancer diagnosis and therapeutics. By reviewing the mechanisms and critical enzymes involved in protein, lipid and glycosylation, as well as current use of glycosylation for cancer diagnosis and therapeutics, we identify the pivotal connection between glycosylation and cellular redox status and, correspondingly, propose the use of redox modulatory tools such as cold atmospheric plasma (CAP) in cancer control via glycosylation editing. This paper interrogates the clinical relevance of glycosylation on cancer and has the promise to provide new ideas for laboratory practice of cold atmospheric plasma (CAP) and precision oncology therapy.

The Etiology of Rapidly Progressive Dementia: A 3-Year Retrospective Study in a Tertiary Hospital in China.

Background: Rapidly progressive dementia (RPD), characterized by a rapid cognitive decline leading to dementia, comprises a diverse range of disorders. Despite advancements in diagnosis and treatment, research on RPD primarily focuses on Western populations. Objective: This study aims to explore the etiology and demographics of RPD in Chinese patients. Methods: We retrospectively analyzed 323 RPD inpatients at Huashan Hospital from May 2019 to March 2023. Data on sociodemographic factors, epidemiology, clinical presentation, and etiology were collected and analyzed. Results: The median onset age of RPD patients was 60.7 years. Two-thirds received a diagnosis within 6 months of symptom onset. Memory impairment was the most common initial symptom, followed by behavioral changes. Neurodegenerative diseases accounted for 47.4% of cases, with central nervous system inflammatory diseases at 30.96%. Autoimmune encephalitis was the leading cause (16.7%), followed by Alzheimer's disease (16.1%), neurosyphilis (11.8%), and Creutzfeldt-Jakob disease (9.0%). Alzheimer's disease, Creutzfeldt-Jakob disease, and frontotemporal dementia were the primary neurodegenerative causes, while autoimmune encephalitis, neurosyphilis, and vascular cognitive impairment were the main non-neurodegenerative causes. Conclusions: The etiology of RPD in Chinese patients is complex, with neurodegenerative and non-neurodegenerative diseases equally prevalent. Recognizing treatable conditions like autoimmune encephalitis and neurosyphilis requires careful consideration and differentiation.

A novel antimicrobial peptide S24 combats serious wound infections caused by Pseudomonas aeruginosa and Acinetobacter baumannii.

OBJECTIVES: Pseudomonas aeruginosa and Acinetobacter baumannii are ranked as top-priority organisms by WHO. Antimicrobial peptides (AMPs) are promising antimicrobial agents that are highly effective against serious bacterial infections. METHODS: In our previous study, a series of α-helical AMPs were screened using a novel multiple-descriptor strategy. The current research suggested that S24 exhibited strong antimicrobial activity against major pathogenic bacteria, and displayed minimal haemolysis, good serum stability and maintained salt resistance. RESULTS: We found that S24 exerted an antimicrobial effect by destroying outer membrane permeability and producing a strong binding effect on bacterial genomic DNA that inhibits genomic DNA migration. Furthermore, S24 exerted a strong ability to promote healing in wound infected by P. aeruginosa, A. baumannii and mixed strains in a mouse model. CONCLUSIONS: Overall, S24 showed good stability under physiological conditions and excellent antimicrobial activity, suggesting it may be a potential candidate for the development of serious bacterial infection treatment.

Calycosin inhibited MIF-mediated inflammatory chemotaxis of macrophages to ameliorate ischemia reperfusion-induced acute kidney injury.

BACKGROUND: Inflammatory macrophage infiltration plays a critical role in acute kidney disease induced by ischemia-reperfusion (IRI-AKI). Calycosin is a natural flavone with multiple bioactivities. This study aimed to investigate the therapeutic role of calycosin in IRI-AKI and its underlying mechanism. METHODS: The renoprotective and anti-inflammatory effects of calycosin were analyzed in C57BL/6 mice with IRI-AKI and lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. RNA-seq was used for mechanism investigation. The molecular target of calycosin was screened by in silico methods and validated by surface plasmon resonance (SPR). Macrophage chemotaxis was analyzed using Transwell and agarose gel spot assays. RESULTS: Calycosin treatment significantly reduced serum creatinine and urea nitrogen and attenuated tubular destruction in IRI-AKI mice. Additionally, calycosin markedly suppressed NF-κB signaling activation and the expression of inflammatory mediators IL-1ß and TNF-α in IRI-AKI kidneys and LPS-stimulated RAW 264.7 cells. Interestingly, RNA-seq revealed calycosin remarkably downregulated chemotaxis-related pathways in RAW 264.7 cells. Among the differentially expressed genes, Ccl2/MCP-1, a critical chemokine mediating macrophage inflammatory chemotaxis, was downregulated in both LPS-stimulated RAW 264.7 cells and IRI-AKI kidneys. Consistently, calycosin treatment attenuated macrophage infiltration in the IRI-AKI kidneys. Importantly, in silico target prediction, molecular docking, and SPR assay demonstrated that calycosin directly binds to macrophage migration inhibitory factor (MIF). Functionally, calycosin abrogated MIF-stimulated NF-κB signaling activation and Ccl2 expression and MIF-mediated chemotaxis in RAW 264.7 cells. CONCLUSIONS: In summary, calycosin attenuates IRI-AKI by inhibiting MIF-mediated macrophage inflammatory chemotaxis, suggesting it could be a promising therapeutic agent for the treatment of IRI-AKI.

Black rice diet alleviates colorectal cancer development through modulating tryptophan metabolism and activating AHR pathway.

Consumption of dietary fiber and anthocyanin has been linked to a lower incidence of colorectal cancer (CRC). This study scrutinizes the potential antitumorigenic attributes of a black rice diet (BRD), abundantly rich in dietary fiber and anthocyanin. Our results demonstrate notable antitumorigenic effects in mice on BRD, indicated by a reduction in both the size and number of intestinal tumors and a consequent extension in life span, compared to control diet-fed counterparts. Furthermore, fecal transplants from BRD-fed mice to germ-free mice led to a decrease in colonic cell proliferation, coupled with maintained integrity of the intestinal barrier. The BRD was associated with significant shifts in gut microbiota composition, specifically an augmentation in probiotic strains Bacteroides uniformis and Lactobacillus. Noteworthy changes in gut metabolites were also documented, including the upregulation of indole-3-lactic acid and indole. These metabolites have been identified to stimulate the intestinal aryl hydrocarbon receptor pathway, inhibiting CRC cell proliferation and colorectal tumorigenesis. In summary, these findings propose that a BRD may modulate the progression of intestinal tumors by fostering protective gut microbiota and metabolite profiles. The study accentuates the potential health advantages of whole-grain foods, emphasizing the potential utility of black rice in promoting health.

Effect of High-Flow Nasal Cannula Flow on Intrapharyngeal Pressure During Fiberoptic Bronchoscopy Under Deep Sedation.

BACKGROUND: The flow reaching the vocal folds may be lower than that at the output of high-flow nasal cannula (HFNC) system. This could be due to upper-respiratory obstruction, oxygen leakage, or other factors. The objective of this study was to observe the effect of flow through a nasopharyngeal airway on intrapharyngeal pressure (IPP) in subjects undergoing fiberoptic bronchoscopy (FOB). METHODS: Patients scheduled for FOB were invited to participate. Measurements were performed at flows of 0-60 L/min; the subjects wore WN-N95 folding medical protective masks (N95) and either underwent FOB or not. IPP at each flow was recorded following 15 s of ventilation, and the cross-sectional area (CSA) of the gastric sinus was measured before and after FOB. Hypoxemia, reflux aspiration, and other pertinent events were recorded. RESULTS: Sixty subjects undergoing FOB at the Affiliated Hospital of Jiaxing University participated in this trial from October 2022-September 2023. IPP increased significantly with an increase in flow and also increased after placing the N95 mask with the same flow (P < .001). When results from before to after FOB were compared, the difference in CSA was statistically significant 263.6 (220.7-300.5) mm2 vs 305.5 (275.4-329.5) mm2, P < .001, but the difference in the risk of reflux aspiration was not statistically significant (0% vs 6.7%, P = .13). Complication rates during treatment were 8.3% for hypoxemia, 0% for reflux aspiration, 1.7% for hypertension, 1.7% for hypotension, 6.7% for tachycardia, 5% for bradycardia, and 10% for postoperative nausea and vomiting. CONCLUSIONS: HFNC can provide effective oxygen therapy for people undergoing FOB, and increases in IPP with flow in the range of 0-60 L/min may not increase the risk of reflux aspiration.

Differential reinforcement of cGAS-STING pathway-involved immunotherapy by biomineralized bacterial outer membrane-sensitized EBRT and RNT.

Radiotherapy (RT), including external beam radiation therapy (EBRT) and radionuclide therapy (RNT), realizes physical killing of local tumors and activates systemic anti-tumor immunity. However, these effects need to be further strengthened and the difference between EBRT and RNT should be discovered. Herein, bacterial outer membrane (OM) was biomineralized with manganese oxide (MnO2) to obtain OM@MnO2-PEG nanoparticles for enhanced radio-immunotherapy via amplifying EBRT/RNT-induced immunogenic cell death (ICD) and cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) activation. OM@MnO2-PEG can react with H2O2 and then gradually produce O2, Mn2+ and OM fragments in the tumor microenvironment. The relieved tumor hypoxia improves the radio-sensitivity of tumor cells, resulting in enhanced ICD and DNA damage. Mn2+ together with the DNA fragments in the cytoplasm activate the cGAS-STING pathway, further exhibiting a positive role in various aspects of innate immunity and adaptive immunity. Besides, OM fragments promote tumor antigen presentation and anti-tumor macrophages polarization. More importantly, our study reveals that OM@MnO2-PEG-mediated RNT triggers much stronger cGAS-STING pathway-involved immunotherapy than that of EBRT, owing to the duration difference of RT. Therefore, this study develops a powerful sensitizer of radio-immunotherapy and uncovers some differences between EBRT and RNT in the activation of cGAS-STING pathway-related anti-tumor immunity.

[Effect of Xuming Decoction in Records of Proved Prescriptions, Ancient a nd Modern on cerebral ischemic injury and angiogenesis in rat model of acute cerebral infarction].

This paper aims to explore the effect of Xuming Decoction in the Records of Proved Prescriptions, Ancient and Modern on cerebral ischemic injury and angiogenesis in the rat model of acute cerebral infarction. SD rats were randomized into 6 groups: sham group, model group, low-, medium-, and high-dose(5.13, 10.26, and 20.52 g·kg~(-1), respectively) Xuming Decoction groups, and butylphthalide(0.06 g·kg~(-1)) group. After the successful establishment of the rat model by middle cerebral artery occlusion(MCAO), rats in the sham and model groups were administrated with distilled water and those in other groups with corresponding drugs for 7 consecutive days. After the neurological function was scored, all the rats were sacrificed, and the brain tissue samples were collected. The degree of cerebral ischemic injury was assessed by the neurological deficit score and staining with 2,3,5-triphenyltetrazolium chloride. Hematoxylin-eosin staining was performed to observe the pathological changes in the brain. Transmission electron microscopy was employed to observe the ultrastructures of neurons and microvascular endothelial cells(ECs) on the ischemic side of the brain tissue. Immunofluorescence assay was employed to detect the expression of von Willebrand factor(vWF) and hematopoietic progenitor cell antigen CD34(CD34) in the ischemic brain tissue. Real-time PCR and Western blot were employed to determine the mRNA and protein levels, respectively, of Runt-related transcription factor 1(RUNX1), vascular endothelial growth factor(VEGF), angiopoietin-1(Ang-1), angiopoietin-2(Ang-2), and VEGF receptor 2(VEGFR2) in the ischemic brain tissue. The results showed that compared with the sham group, the model group showed increased neurological deficit score and cerebral infarction area(P<0.01), pathological changes, and damaged ultrastructure of neurons and microvascular ECs in the ischemic brain tissue. Furthermore, the modeling up-regulated the mRNA levels of RUNX1, VEGF, Ang-1, Ang-2, and VEGFR2(P<0.01) and the protein levels of vWF, CD34, RUNX1, VEGF, Ang-1, Ang-2, and VEGFR2(P<0.05 or P<0.01). Compared with the model group, high-dose Xuming Decoction and butylphthalide decreased the neurological deficit score and cerebral infarction area(P<0.01) and alleviated the pathological changes and damage of the ultrastructure of neurons and microvascular ECs in the ischemic brain tissue. Moreover, they up-regulated the mRNA levels of RUNX1, VEGF, Ang-1, Ang-2, and VEGFR2(P<0.01) and the protein levels of vWF, CD34, RUNX1, VEGF, Ang-1, Ang-2, and VEGFR2(P<0.01). The results suggest that Xuming Decoction in the Records of Proved Prescriptions, Ancient and Modern can promote the angiogenesis and collateral circulation establishment to alleviate neurological dysfunction of the ischemic brain tissue in MCAO rats by regulating the RUNX1/VEGF pathway.

Concentration properties of biopolymers via dead-end forward osmosis.

Extracellular polymeric substances (EPSs) in excess sludge of wastewater treatment plants are valuable biopolymers that can act as recovery materials. However, effectively concentrating EPSs consumes a significant amount of energy. This study employed novel energy-saving pressure-free dead-end forward osmosis (DEFO) technology to concentrate various biopolymers, including EPSs and model biopolymers [sodium alginate (SA), bovine serum albumin (BSA), and a mixture of both (denoted as BSA-SA)]. The feasibility of the DEFO technology was proven and the largest concentration ratios for these biopolymers were 94.8 % for EPSs, 97.1 % for SA, 97.8 % for BSA, and 98.4 % for BSA-SA solutions. An evaluation model was proposed, incorporating the FO membrane's water permeability coefficient and the concentrated substances' osmotic resistance, to describe biopolymers' concentration properties. Irrespective of biopolymer type, the water permeability coefficient decreased with increasing osmotic pressure, remained constant with increasing feed solution (FS) concentration, increased with increasing crossing velocity in the draw side, and showed little dependence on draw salt type. In the EPS DEFO concentration process, osmotic resistance was minimally impacted by osmotic pressure, FS concentration, and crossing velocity, and monovalent metal salts were proposed as draw solutes. The interaction between reverse diffusion metal cations and EPSs affected the structure of the concentrated substances on the FO membrane, thus changing the osmotic resistance in the DEFO process. These findings offer insights into the efficient concentration of biopolymers using DEFO.

Stepwise Aggregation Control of PEDOT:PSS Enabled High-Conductivity, High-Resolution Printing of Polymer Electrodes for Transparent Organic Phototransistors.

Electrohydrodynamic (EHD) jet printing is a widely employed technology to create high-resolution patterns and thus has enormous potential for circuit production. However, achieving both high conductivity and high resolution in printed polymer electrodes is a challenging task. Here, by modulating the aggregation state of the conducting polymer in the solution and solid phases, a stable and continuous jetting of PEDOT:PSS is realized, and high-conductivity electrode arrays are prepared. The line width reaches less than 5 µm with a record-high conductivity of 1250 S/cm. Organic field-effect transistors (OFETs) are further developed by combining printed source/drain electrodes with ultrathin organic semiconductor crystals. These OFETs show great light sensitivity, with a specific detectivity (D*) value of 2.86 × 1014 Jones. In addition, a proof-of-concept fully transparent phototransistor is demonstrated, which opens up new pathways to multidimensional optical imaging.

Identification and analysis of differently expressed transcription factors in aristolochic acid nephropathy.

BACKGROUND: Aristolochic acid nephropathy (AAN) is a rapidly progressive interstitial nephropathy caused by Aristolochic acid (AA). AAN is associated with the development of nephropathy and urothelial carcinoma. It is estimated that more than 100 million people worldwide are at risk of developing AAN. However, the underlying mechanisms driving renal deterioration in AAN remain poorly understood, and the treatment options are limited. METHODS: We obtained GSE27168 and GSE136276 series matrix data from the Gene Expression Omnibus (GEO) related to AAN. Using the R Studio environment, we applied the limma package and WGCNA package to identify co-differently expressed genes (co-DEGs). By GO/KEGG/GSVA analysis, we revealed common biological pathways. Subsequently, co-DEGs were subjected to the String database to construct a protein-protein interaction (PPI) network. The MCC algorithms implemented in the Cytohubba plugin were employed to identify hub genes. The hub genes were cross-referenced with the transcription factor (TF) database to identify hub TFs. Immune infiltration analysis was performed to identify key immune cell groups by utilizing CIBERSORT. The expressions of AAN-associated hub TFs were verified in vivo and in vitro. Finally, siRNA intervention was performed on the two TFs to verify their regulatory effect in AAN. RESULTS: Our analysis identified 88 co-DEGs through the "limma" and "WGCNA" R packages. A PPI network comprising 53 nodes and 34 edges was constructed with a confidence level >0.4. ATF3 and c-JUN were identified as hub TFs potentially linked to AAN. Additionally, expressions of ATF3 and c-JUN positively correlated with monocytes, basophils, and vessels, and negatively correlated with eosinophils and endothelial cells. We observed a significant increase in protein and mRNA levels of these two hub TFs. Furthermore, it was found that siRNA intervention targeting ATF3, but not c-JUN, alleviated cell damage induced by AA. The knockdown of ATF3 protects against oxidative stress and inflammation in the AAN cell model. CONCLUSION: This study provides novel insights into the role of ATF3 in AAN. The comprehensive analysis sheds light on the molecular mechanisms and identifies potential biomarkers and drug targets for AAN treatment.

Utility of real-time 3D visualization system in the early stage of phacoemulsification training.

AIM: To determine the teaching effects of a real-time three dimensional (3D) visualization system in the operating room for early-stage phacoemulsification training. METHODS: A total of 10 ophthalmology residents of the first-year postgraduate were included. All the residents were novices to cataract surgery. Real-time cataract surgical observations were performed using a custom-built 3D visualization system. The training lasted 4wk (32h) in all. A modified International Council of Ophthalmology's Ophthalmology Surgical Competency Assessment Rubric (ICO-OSCAR) containing 4 specific steps of cataract surgery was applied. The self-assessment (self) and expert-assessment (expert) were performed through the microsurgical attempts in the wet lab for each participant. RESULTS: Compared with pre-training assessments (self 3.2±0.8, expert 2.5±0.6), the overall mean scores of post-training (self 5.2±0.4, expert 4.7±0.6) were significantly improved after real-time observation training of 3D visualization system (P<0.05). Scores of 4 surgical items were significantly improved both self and expert assessment after training (P<0.05). CONCLUSION: The 3D observation training provides novice ophthalmic residents with a better understanding of intraocular microsurgical techniques. It is a useful tool to improve teaching efficiency of surgical education.

Enzyme-responsive oncolytic polypeptide for tumor therapy.

Host defense peptide-mimicking cationic oncolytic polymers have attracted increasing attention for cancer treatment in recent years. However, polymers with large amounts of positive charge may cause rapid clearance and severe off-target toxicity. To facilitate in vivo application, an alkaline phosphatase (ALP)-responsive oncolytic polypeptide precursor (C12-PLL/PA) has been reported in this work. C12-PLL/PA could be hydrolyzed into the active form of the oncolytic polypeptide (C12-PLL) by the extracellular alkaline phosphatase within solid tumors, thereby resulting in the conversion of the negative charge to positive charge and restoring its membrane-lytic activity. Detailed mechanistic studies showed that C12-PLL/PA could effectively destroy cancer cell membranes and subsequently result in rapid necrosis of cancer cells. More importantly, C12-PLL/PA significantly inhibited the tumor growth in the 4T1 orthotopic breast tumor model with negligible side effects. In summary, these findings demonstrated that the shielding of the amino groups with phosphate groups represents a secure and effective strategy to develop cationic oncolytic polypeptide, which represents a valuable reference for the design of enzyme-activated oncolytic polymers. STATEMENT OF SIGNIFICANCE: Recently, there has been a growing interest in fabricating host defense peptide-mimicking cationic oncolytic polymers for cancer therapy. However, there remain concerns about the tumor selectivity and off-target toxicity of these cationic polymers. In this study, an alkaline phosphatase-responsive oncolytic polypeptide precursor (C12-PLL/PA) has been developed to selectively target cancer cells while sparing normal cells. Mechanistic investigations demonstrated that C12-PLL/PA effectively disrupted cancer cell membranes, leading to rapid necrosis. Both in vitro and in vivo experiments showed promising anticancer activity and reliable safety of C12-PLL/PA. The findings suggest that this synthetic enzyme-responsive polypeptide holds potential as a tumor-specific oncolytic polymer, paving the way for future applications in cancer therapy.

A facile and intelligent detection method for diclazuril based on a stable dual emissive Eu3+-dopped metal-organic framework.

Diclazuril (DIC) is a broad-spectrum anti-coccidiosis drug of the triazine class, widely used in poultry farming. The overuse of DIC may lead to its accumulation in animal bodies, which may enter the food chain and threaten human health. In this work, we fabricated a stable Eu3+-doped UiO-66 fluorescence sensor (EuUHIPA-30) for the sensitive detection of DIC. Among 20 veterinary drugs, the fluorescence of EuUHIPA-30 selectively responds to DIC, with a low detection limit (0.19 µM) and fast response (10 s). EuUHIPA-30 is recyclable and can detect DIC in chicken and eggs with good recoveries. Moreover, a smartphone-integrated paper-based sensor enables the instrument-free, rapid, visual, and intelligent detection of DIC in chickens and eggs. This work provides a promising candidate for practical fluorescent DIC sensing in animal-derived food to promote food safety.

Regulating Surface Dipole Moments of TiO2 for the pH-Universal Cathodic Fenton-Like Process.

Although electro-Fenton (EF) processes can avoid the safety risks raised by concentrated hydrogen peroxide (H2O2), the Fe(III) reduction has always been either unstable or inefficient at high pH, resulting in catalyst deactivation and low selectivity of H2O2 activation for producing hydroxyl radicals (•OH). Herein, we provided a strategy to regulate the surface dipole moment of TiO2 by Fe anchoring (TiO2-Fe), which, in turn, substantially increased the H2O2 activation for •OH production. The TiO2-Fe catalyst could work at pH 4-10 and maintained considerable degradation efficiency for 10 cycles. Spectroscopic analysis and a theoretical study showed that the less polar Fe-O bond on TiO2-Fe could finely tune the polarity of H2O2 to alter its empty orbital distribution, contributing to better ciprofloxacin degradation activity within a broad pH range. We further verified the critical role of the weakened polarity of H2O2 on its homolysis into •OH by theoretically and experimentally investigating Cu-, Co-, Ni-, Mn-, and Mo-anchored TiO2. This concept offers an avenue for elaborate design of green, robust, and pH-universal cathodic Fenton-like catalysts and beyond.

New G-Triplex DNA Dramatically Activates the Fluorescence of Thioflavin T and Acts as a Turn-On Fluorescent Sensor for Uracil-DNA Glycosylase Activity Detection.

G-triplexes are G-rich oligonucleotides composed of three G-tracts and have absorbed much attention due to their potential biological functions and attractive performance in biosensing. Through the optimization of loop compositions, DNA lengths, and 5'-flanking bases of G-rich sequences, a new stable G-triplex sequence with 14 bases (G3-F15) was discovered to dramatically activate the fluorescence of Thioflavin T (ThT), a water-soluble fluorogenic dye. The fluorescence enhancement of ThT after binding with G3-F15 reached 3200 times, which was the strongest one by far among all of the G-rich sequences. The conformations of G3-F15 and G3-F15/ThT were studied by circular dichroism. The thermal stability measurements indicated that G3-F15 was a highly stable G-triplex structure. The conformations of G3-F15 and G3-F15/ThT in the presence of different metal cations were studied thoroughly by fluorescent spectroscopy, circular dichroism, and nuclear magnetic resonance. Furthermore, using the G3-F15/ThT complex as a fluorescent probe, a robust and simple turn-on fluorescent sensor for uracil-DNA glycosylase activity was developed. This study proposes a new systematic strategy to explore new functional G-rich sequences and their ligands, which will promote their applications in diagnosis, therapy, and biosensing.

Human-like adrenal features in Chinese tree shrews revealed by multi-omics analysis of adrenal cell populations and steroid synthesis.

The Chinese tree shrew ( Tupaia belangeri chinensis) has emerged as a promising model for investigating adrenal steroid synthesis, but it is unclear whether the same cells produce steroid hormones and whether their production is regulated in the same way as in humans. Here, we comprehensively mapped the cell types and pathways of steroid metabolism in the adrenal gland of Chinese tree shrews using single-cell RNA sequencing, spatial transcriptome analysis, mass spectrometry, and immunohistochemistry. We compared the transcriptomes of various adrenal cell types across tree shrews, humans, macaques, and mice. Results showed that tree shrew adrenal glands expressed many of the same key enzymes for steroid synthesis as humans, including CYP11B2, CYP11B1, CYB5A, and CHGA. Biochemical analysis confirmed the production of aldosterone, cortisol, and dehydroepiandrosterone but not dehydroepiandrosterone sulfate in the tree shrew adrenal glands. Furthermore, genes in adrenal cell types in tree shrews were correlated with genetic risk factors for polycystic ovary syndrome, primary aldosteronism, hypertension, and related disorders in humans based on genome-wide association studies. Overall, this study suggests that the adrenal glands of Chinese tree shrews may consist of closely related cell populations with functional similarity to those of the human adrenal gland. Our comprehensive results (publicly available at http://gxmujyzmolab.cn:16245/scAGMap/) should facilitate the advancement of this animal model for the investigation of adrenal gland disorders.

Berberine and chlorogenic acid-assembled nanoparticles for highly efficient inhibition of multidrug-resistant Staphylococcus aureus.

Due to the bacteria resistant to various first-line antibiotics, it is urgent to develop efficient antibiotic alternatives and formulate multidimensional strategies. Herein, supramolecular Chinese medicine nanoparticles are synthesized by self-assembly of berberine (BBR) and chlorogenic acid (CGA), which exhibit higher inhibitory effect against Staphylococcus aureus and multidrug-resistant Staphylococcus aureus (MRSA) than ampicillin, oxacillin, BBR, CGA, as well as mixture of BBR and CGA (minimum inhibitory concentration, MIC = 1.5 µM). The inhibition by BBR/CGA nanoparticles (2.5 µM) reaches 99.06 % for MRSA, which is significantly higher than ampicillin (29.03 %). The nanoparticles with 1/2 MIC can also synergistically restore the antimicrobial activity of ampicillin against MRSA. Moreover, in vivo therapeutic outcome in the murine skin wound infection model suggests that the nanoparticles are able to promote wound healing. This study provides new insights in the application of Chinese medicines self-assembly for MRSA inhibition, as well as solutions for potential persistent clinical infections and drug deficiencies.