HCN channels in the lateral habenula regulate pain and comorbid depressive-like behaviors in mice.

AIMS: Comorbid anxiodepressive-like symptoms (CADS) in chronic pain are closely related to the overactivation of the lateral habenula (LHb). Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels have been implicated to play a key role in regulating neuronal excitability. However, the role of HCN channels in the LHb during CADS has not yet been characterized. This study aimed to investigate the effect of HCN channels in the LHb on CADS during chronic pain. METHODS: After chronic neuropathic pain induction by spared nerve injury (SNI), mice underwent a sucrose preference test, forced swimming test, tail suspension test, open-field test, and elevated plus maze test to evaluate their anxiodepressive-like behaviors. Electrophysiological recordings, immunohistochemistry, Western blotting, pharmacological experiments, and virus knockdown strategies were used to investigate the underlying mechanisms. RESULTS: Evident anxiodepressive-like behaviors were observed 6w after the SNI surgery, accompanied by increased neuronal excitability, enhanced HCN channel function, and increased expression of HCN2 isoforms in the LHb. Either pharmacological inhibition or virus knockdown of HCN2 channels significantly reduced LHb neuronal excitability and ameliorated both pain and depressive-like behaviors. CONCLUSION: Our results indicated that the LHb neurons were hyperactive under CADS in chronic pain, and this hyperactivation possibly resulted from the enhanced function of HCN channels and up-regulation of HCN2 isoforms.

Membrane P-glycoprotein expression in lymphocytes from adult patients with refractory glomerulonephritis.

OBJECTIVES: To investigate the expression of P-glycoprotein in T-cell subpopulations of lymphocytes from adult patients with refractory glomerulonephritis (GN). MATERIALS AND METHODS: Flow cytometry was used to analyze the T-cell subpopulations of lymphocytes from adult patients with refractory GN and healthy individuals. The CD243 antibody marked the membrane P-glycoprotein of immune cells. RESULTS: The mean ± standard deviation (SD) values of percentages of CD3+, CD3+CD4+, CD3+CD8+ cells in lymphocytes from patients with refractory GN were 63.94 ± 26.98, 55.16 ± 4.78, and 37.79 ± 6.01%, respectively. These values in healthy individuals were 74.88 ± 3.75, 56.60 ± 9.22, and 34.20 ± 5.21%, respectively. No significant differences were observed between the patients with refractory GN and healthy individuals. The mean ± SD values of percentages of CD3+CD4+CD243+ and CD3+CD8+CD243+ cells in the lymphocytes of patients with refractory GN were 0.14 ± 0.11 and 0.11 ± 0.07%, respectively. These values in healthy individuals were 0.05 ± 0.02 and 0.04 ± 0.02%, respectively. The difference in CD3+CD8+CD243+ percentage between patients with refractory GN and healthy individuals was significant (p = 0.0216). CONCLUSION: These findings suggest that P-glycoprotein expression on CD3+CD8+ T cells is a promising marker and a suitable target of drug resistance in patients with refractory GN.

Pharmacology of hydrogen sulfide and its donors in cardiometabolic diseases.

Cardiometabolic diseases (CMDs) are major contributors to global mortality, emphasizing the critical need for novel therapeutic interventions. Hydrogen sulfide (H2S) has garnered enormous attention as a significant gasotransmitter with various physiological, pathophysiological, and pharmacological impacts within mammalian cardiometabolic systems. In addition to its roles in attenuating oxidative stress and inflammatory response, burgeoning research emphasizes the significance of H2S in regulating proteins via persulfidation, a well-known modification intricately associated with the pathogenesis of CMDs This review seeks to investigate recent updates on the physiological actions of endogenous H2S and the pharmacological roles of various H2S donors in addressing diverse aspects of CMDs across cellular, animal, and clinical studies. Of note, advanced methodologies including multi-omics, intestinal microflora analysis, organoid and single-cell sequencing techniques are gaining traction due to their ability to offer comprehensive insights into biomedical research. These emerging approaches hold promise in characterizing the pharmacological roles of H2S in health and diseases. We will critically assesse the current literatures to clarify the roles of H2S in diseases while also delineating the opportunities and challenges they present in H2S-based pharmacotherapy for CMDs. Significance Statement The comprehensive review covers recent developments in H2S biology and pharmacology in CMDs. Endogenous H2S and its donors show great promise for the management of CMDs by regulating numerous proteins and signaling pathways. The emergence of new technologies will considerably advance the pharmacological research and clinical translation of H2S.

Vaccarin alleviates septic cardiomyopathy by potentiating NLRP3 palmitoylation and inactivation.

BACKGROUND: Sepsis often leads to significant morbidity and mortality due to severe myocardial injury. As is known, the activation of NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome crucially contributes to septic cardiomyopathy (SCM) by facilitating the secretion of interleukin (IL)-1ß and IL-18. The removal of palmitoyl groups from NLRP3 is a crucial step in the activation of the NLRP3 inflammasome. Thus, the potential inhibitors that regulate the palmitoylation and inactivation of NLRP3 may significantly diminish sepsis-induced cardiac dysfunction. PURPOSE: The present study sought to explore the effects of the prospective flavonoid compounds targeting NLRP3 on SCM and to elucidate the associated underlying mechanisms. STUDY DESIGN: The palmitoylation and activation of NLRP3 were detected in H9c2 cells and C57BL/6 J mice. METHODS/RESULTS: Echocardiography, histological staining, western blotting, co-immunoprecipitation, qPCR, ELISA and network pharmacology were used to assess the impact of vaccarin (VAC) on SCM in mice subjected to lipopolysaccharide (LPS) injection. From the collection of 74 compounds, we identified that VAC had the strongest capability to suppress NLRP3 luciferase report gene activity in cardiomyocytes, and the anti-inflammatory characteristics of VAC were further ascertained by the network pharmacology. Exposure of LPS triggered apoptosis, inflammation, oxidative stress, mitochondrial disorder in cardiomyocytes. The detrimental alterations were significantly reversed upon VAC treatment in both septic mice and H9c2 cells exposed to LPS. In vivo experiments demonstrated that VAC treatment alleviated septic myocardial injury, indicated by enhanced cardiac function parameters, preserved cardiac structure, and reduced inflammation/oxidative response. Mechanistically, VAC induced NLRP3 palmitoylation to inactivate NLRP3 inflammasome by acting on zDHHC12. In support, the NLRP3 agonist ATP and the acylation inhibitor 2-bromopalmitate (2-BP) prevented the effects of VAC. CONCLUSION: Our findings suggest that VAC holds promise in protecting against SCM by mitigating cardiac oxidative stress and inflammation via priming NLRP3 palmitoylation and inactivation. These results lay the solid basis for further assessment of the therapeutic potential of VAC against SCM.

Improved multi-layer wavelet transform and blind source separation based ECG artifacts removal algorithm from the sEMG signal: in the case of upper limbs.

Introduction: Surface electromyogram (sEMG) signals have been widely used in human upper limb force estimation and motion intention recognition. However, the electrocardiogram(ECG) artifact generated by the beating of the heart is a major factor that reduces the quality of the EMG signal when recording the sEMG signal from the muscle close to the heart. sEMG signals contaminated by ECG artifacts are difficult to be understood correctly. The objective of this paper is to effectively remove ECG artifacts from sEMG signals by a novel method. Methods: In this paper, sEMG and ECG signals of the biceps brachii, brachialis, and triceps muscle of the human upper limb will be collected respectively. Firstly, an improved multi-layer wavelet transform algorithm is used to preprocess the raw sEMG signal to remove the background noise and power frequency interference in the raw signal. Then, based on the theory of blind source separation analysis, an improved Fast-ICA algorithm was constructed to separate the denoising signals. Finally, an ECG discrimination algorithm was used to find and eliminate ECG signals in sEMG signals. This method consists of the following steps: 1) Acquisition of raw sEMG and ECG signals; 2) Decoupling the raw sEMG signal; 3) Fast-ICA-based signal component separation; 4) ECG artifact recognition and elimination. Results and discussion: The experimental results show that our method has a good effect on removing ECG artifacts from contaminated EMG signals. It can further improve the quality of EMG signals, which is of great significance for improving the accuracy of force estimation and motion intention recognition tasks. Compared with other state-of-the-art methods, our method can also provide the guiding significance for other biological signals.

Current Applications of Colorectal Cancer Organoids: A Review.

Colorectal cancer is a prevalent malignancy, with advanced and metastatic forms exhibiting poor treatment outcomes and high relapse rates. To enhance patient outcomes, a comprehensive understanding of the pathophysiological processes and the development of targeted therapies are imperative. The high heterogeneity of colorectal cancer demands precise and personalized treatment strategies. Colorectal cancer organoids, a three-dimensional in vitro model, have emerged as a valuable tool for replicating tumor biology and exhibit promise in scientific research, disease modeling, drug screening, and personalized medicine. In this review, we present an overview of colorectal cancer organoids and explore their applications in research and personalized medicine, while also discussing potential future developments in this field.

A Novel Classification System of Renal Hilar Tumors for Surgical Guidance: Technique, Outcome, and Safety.

BACKGROUND: This study was designed to develop an innovative classification and guidance system for renal hilar tumors and to assess the safety and effectiveness of robot-assisted partial nephrectomy (RAPN) for managing such tumors. METHODS: A total of 179 patients undergoing RAPN for renal hilar tumors were retrospectively reviewed. A novel classification system with surgical techniques was introduced and the perioperative features, tumor characteristics, and the efficacy and safety of RAPN were compared within subgroups. RESULTS: We classified the tumors according to our novel system as follows: 131 Type I, 35 Type II, and 13 Type III. However, Type III had higher median R.E.N.A.L., PADUA, and ROADS scores compared with the others (all p < 0.001), indicating increased operative complexity and higher estimated blood loss [180.00 (115.00-215.00) ml]. Operative outcomes revealed significant disparities between Type III and the others, with longer operative times [165.00 (145.00-200.50) min], warm ischemia times [24.00 (21.50-30.50) min], tumor resection times [13.00 (12.00-15.50) min], and incision closure times [22.00 (20.00-23.50) min] (all p < 0.005). Postoperative outcomes also showed significant differences, with longer durations of drain removal (77.08 ± 18.16 h) and hospitalization for Type III [5.00 (5.00-6.00) d] (all p < 0.05). Additionally, Type I had a larger tumor diameter than the others (p = 0.009) and pT stage differed significantly between the subtypes (p = 0.020). CONCLUSIONS: The novel renal hilar tumor classification system is capable of differentiating the surgical difficulty of RAPN and further offers personalized surgical steps tailored to each specific classification. It provides a meaningful tool for clinical practice.

Downregulation of Serum PTEN Expression in Mercury-Exposed Population and PI3K/AKT Pathway-Induced Inflammation.

Objective: This study investigated the impact of occupational mercury (Hg) exposure on human gene transcription and expression, and its potential biological mechanisms. Methods: Differentially expressed genes related to Hg exposure were identified and validated using gene expression microarray analysis and extended validation. Hg-exposed cell models and PTEN low-expression models were established in vitro using 293T cells. PTEN gene expression was assessed using qRT-PCR, and Western blotting was used to measure PTEN, AKT, and PI3K protein levels. IL-6 expression was determined by ELISA. Results: Combined findings from gene expression microarray analysis, bioinformatics, and population expansion validation indicated significant downregulation of the PTEN gene in the high-concentration Hg exposure group. In the Hg-exposed cell model (25 and 10 µmol/L), a significant decrease in PTEN expression was observed, accompanied by a significant increase in PI3K, AKT, and IL-6 expression. Similarly, a low-expression cell model demonstrated that PTEN gene knockdown led to a significant decrease in PTEN protein expression and a substantial increase in PI3K, AKT, and IL-6 levels. Conclusion: This is the first study to report that Hg exposure downregulates the PTEN gene, activates the PI3K/AKT regulatory pathway, and increases the expression of inflammatory factors, ultimately resulting in kidney inflammation.

Cichoric acid ameliorates sepsis-induced acute kidney injury by inhibiting M1 macrophage polarization.

Cichoric acid (CA), a widely utilized polyphenolic compound in medicine, has garnered significant attention due to its potential health benefits. Sepsis-induced acute kidney disease (AKI) is related with an elevated risk of end-stage kidney disease (ESKD). However, it remains unclear whether CA provides protection against septic AKI. The aim of this study is to investigated the protective effect and possible mechanisms of CA against LPS-induced septic AKI. Sepsis-induced AKI was induced in mice through intraperitoneal injection of lipopolysaccharide (LPS), and RAW264.7 macrophages were incubated with LPS. LPS exposure significantly increased the levels of M1 macrophage biomarkers while reducing the levels of M2 macrophage indicators. This was accompanied by the release of inflammatory factors, superoxide anion production, mitochondrial dysfunction, activation of succinate dehydrogenase (SDH), and subsequent succinate formation. Conversely, pretreatment with CA mitigated these abnormalities. CA attenuated hypoxia-inducible factor-1α (HIF-1α)-induced glycolysis by lifting the NAD+/NADH ratio in macrophages. Additionally, CA disrupted the K (lysine) acetyltransferase 2A (KAT2A)/α-tubulin complex, thereby reducing α-tubulin acetylation and subsequently inactivating the NLRP3 inflammasome. Importantly, administration of CA ameliorated LPS-induced renal pathological damage, apoptosis, inflammation, oxidative stress, and disturbances in mitochondrial function in mice. Overall, CA restrained HIF-1α-mediated glycolysis via inactivation of SDH, leading to NLRP3 inflammasome inactivation and the amelioration of sepsis-induced AKI.

Oxidative stress mediated decrement of spinal endomorphin-2 contributes to lumbar disc herniation sciatica in rats.

Increasing evidence supported that oxidative stress induced by herniated lumbar disc played important role in the formation of lumbar disc herniation sciatica (LDHS), however, the neural mechanisms underlying LDHS need further clarification. Endomorphin-2 (EM2) is the endogenous ligand for mu-opioid receptor (MOR), and there is increasing evidence implicating the involvement of spinal EM2 in neuropathic pain. In this study, using an nucleus pulposus implantation induced LDHS rat model that displayed obvious mechanical allodynia, it was found that the expression of EM2 in dorsal root ganglion (DRG) and spinal cord was significantly decreased. It was further found that oxidative stress in DRG and spinal cord was significantly increased in LDHS rats, and the reduction of EM2 in DRG and spinal cord was determined by oxidative stress dominated increment of dipeptidylpeptidase IV activity. A systemic treatment with antioxidant could prevent the forming of mechanical allodynia in LDHS rats. In addition, MOR expression in DRG and spinal cord remained unchanged in LDHS rats. Intrathecal injection of MOR antagonist promoted pain behavior in LDHS rats, and the analgesic effect of intrathecal injection of EM2 was stronger than that of endomorphin-1 and morphine. Taken together, our findings suggest that oxidative stress mediated decrement of EM2 in DRG and spinal cord causes the loss of endogenous analgesic effects and enhances the pain sensation of LDHS.

Revealing the potential of solute carrier family 31 (copper transporters), member 1: Insights into its role in bladder cancer progression and therapeutic implications.

Introduction: Bladder cancer represents a significant public health concern with diverse genetic alterations influencing disease onset, progression, and therapy response. In this study, we explore the multifaceted role of Solute Carrier Family 31 Member 1 (SLC31A1) in bladder cancer, a pivotal gene involved in copper homeostasis. Methods: Our research involved analyzing the SLC31A1 gene expression via RT-qPCR, promoter methylation via targeted bisulfite sequencing, and mutational status via Next Generation Sequencing (NGS) using the clinical samples sourced by the local bladder cancer patients. Later on, The Cancer Genome Atlas (TCGA) datasets were utilized for validation purposes. Moreover, prognostic significance, gene enrichment terms, and therapeutic drugs of SLC31A1 were also explored using KM Plotter, DAVID, and DrugBank databases. Results: We observed that SLC31A1 was significantly up-regulated at both the mRNA and protein levels in bladder cancer tissue samples, suggesting its potential involvement in bladder cancer development and progression. Furthermore, our investigation into the methylation status revealed that SLC31A1 was significantly hypomethylated in bladder cancer tissues, which may contribute to its overexpression. The ROC analysis of the SLC31A1 gene indicated promising diagnostic potential, emphasizing its relevance in distinguishing bladder cancer patients from normal individuals. However, it is crucial to consider other factors such as cancer stage, metastasis, and recurrence for a more accurate evaluation in the clinical context. Interestingly, mutational analysis of SLC31A1 demonstrated only benign mutations, indicating their unknown role in the SLC31A1 disruption. In addition to its diagnostic value, high SLC31A1 expression was associated with poorer overall survival (OS) in bladder cancer patients, shedding light on its prognostic relevance. Gene enrichment analysis indicated that SLC31A1 could influence metabolic and copper-related processes, further underscoring its role in bladder cancer. Lastly, we explored the DrugBank database to identify potential therapeutic agents capable of reducing SLC31A1 expression. Our findings unveiled six important drugs with the potential to target SLC31A1 as a treatment strategy. Conclusion: Our comprehensive investigation highlights SLC31A1 as a promising biomarker for bladder cancer development, progression, and therapy.

Circ_TMCO3 Inhibits the Progression of Cervical Cancer by Activating FRMD6 Expression by Restraining miR-1291.

Cervical cancer (CC) is one of the most common cancers that threaten the life of women. More and more circular RNAs (circRNAs) have been found to be maladjusted in tumor tissues. However, the mechanism of circ_TMCO3 in CC needs to be studied. In this study, quantitative real-time polymerase chain reaction (qRT-PCR), western blot, and immunohistochemistry (IHC) were used to detect the expressions of circ_TMCO3, miR-1291, and FERM domain-containing protein 6 (FRMD6). Cell viability, proliferation, apoptosis, migration, invasion, and protein level were detected via 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT), 5-Ethynyl-2'-deoxyuridine (EdU), flow cytometry, transwell and western blot, respectively. The glycolysis level was detected via specific kits. Dual-luciferase activity assay was used to analyze the targeted relationship between miR-1291 and circ_TMCO3 or FRMD6. Xenograft models were used to analyze the effect of circ_TMCO3 on the growth of CC tumors in vivo. Circ_TMCO3 and FRMD6 were low expressed in tumor tissues, and miR-1291 was conspicuously upregulated in tumor tissues. Upregulation of circ_TMCO3 dramatically curbed cell viability, proliferation, migration, and invasion, and enhanced cell apoptosis, while those effects were attenuated after the overexpression of miR-1291. MiR-1291 could directly target FRMD6, and knockdown of FRMD6 could restore the inhibitory effect of miR-1291 silencing on tumor cell growth. In terms of mechanism, circ_TMCO3 was confirmed as a miR-1291 sponge to regulate the expression of FRMD6. Tumor growth was markedly retarded with the overexpression of circ_TMCO3. In conclusion, circ_TMCO3 inhibited tumorigenicity of CC via miR-1291/FRMD6 axis, providing a potential therapeutic strategy for CC patients.

Ophiocordyceps sinensis preparations combined with the renin-angiotensin system inhibitor for diabetic kidney disease treatment: an umbrella review of systematic reviews and network meta-analysis.

Aims: This study aimed to synthesize the evidence of the comparative effectiveness and safety of Ophiocordyceps sinensis (OS) preparations combined with renin-angiotensin system inhibitors (RASi) for diabetic kidney disease (DKD). Methods: Eight databases were searched from their inception to May 2023. Systematic reviews (SRs) of OS preparations combined with RASi for DKD were identified. Randomized controlled trials (RCTs) from the included SRs and additional searching were performed for data pooling. Cochrane risk-of-bias 2 (RoB 2) tool and AMSTAR 2 were used to evaluate the methodological quality of RCTs and SRs, respectively. A Bayesian network meta-analysis was performed to compare the add-on effect and safety of OS preparations for DKD. The certainty of evidence was graded using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Results: Fourteen SRs were included, whose methodological quality was assessed as high (1/14) or critically low (13/14). After combining additional searching, 157 RCTs were included, involving 13,143 participants. The quality of the RCTs showed some concerns (155/157) or high risk (2/157). Jinshuibao capsules and tablets, Bailing capsules and tablets, and Zhiling capsules were evaluated. Compared to RASi, adding either of the OS capsular preparations resulted in a decreased 24-h urinary total protein levels. OS preparations ranked differently in each outcome. Jinshuibao capsules plus RASi were beneficial in reducing urinary protein, serum creatinine, serum urea nitrogen, and blood glucose levels, with moderate-certainty evidence. No serious adverse events were observed after adding OS to RASi. Conclusion: Combining OS capsular preparations with RASi appeared to be associated with decreased urinary total protein levels in DKD patients. Further high-quality studies are needed to confirm. Systematic Review Registration: INPASY202350066.

Association of Overweight and Inflammatory Indicators with Breast Cancer: A Cross-Sectional Study in Chinese Women.

Objective: This cross-sectional study aimed to explore the association of overweight and inflammatory indicators with breast cancer risk in Chinese patients. Methods: Weight, height, and peripheral blood inflammatory indicators, including white blood cell count (WBC), neutrophil count (NE), lymphocyte count (LY), platelet count (PLT) and the concentration of hypersensitivity C-reactive protein (hsCRP), were collected in 383 patients with benign breast lumps (non-cancer) and 358 patients with malignant breast tumors (cancer) at the First Affiliated Hospital of Soochow University, China, from March 2018 to July 2020. Body mass index (BMI), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII) were determined according to the ratio equation. The correlations among overweight, inflammatory indicators, and the proportion of non-cancer or cancer cases were analyzed. Results: BMI is associated with an increased breast cancer risk. Compared with non-cancer patients, the average WBC count, NE count, NLR, and level of hsCRP were significantly higher in cancer patients. The level of hsCRP was closely associated with the size of malignant breast tumors. Conclusion: We conclude that overweight and high levels of hsCRP may serve as putative risk factors for malignant breast tumors in Chinese women.

Deficiency of neutral cholesterol ester hydrolase 1 (NCEH1) impairs endothelial function in diet-induced diabetic mice.

BACKGROUND: Neutral cholesterol ester hydrolase 1 (NCEH1) plays a critical role in the regulation of cholesterol ester metabolism. Deficiency of NCHE1 accelerated atherosclerotic lesion formation in mice. Nonetheless, the role of NCEH1 in endothelial dysfunction associated with diabetes has not been explored. The present study sought to investigate whether NCEH1 improved endothelial function in diabetes, and the underlying mechanisms were explored. METHODS: The expression and activity of NCEH1 were determined in obese mice with high-fat diet (HFD) feeding, high glucose (HG)-induced mouse aortae or primary endothelial cells (ECs). Endothelium-dependent relaxation (EDR) in aortae response to acetylcholine (Ach) was measured. RESULTS: Results showed that the expression and activity of NCEH1 were lower in HFD-induced mouse aortae, HG-exposed mouse aortae ex vivo, and HG-incubated primary ECs. HG exposure reduced EDR in mouse aortae, which was exaggerated by endothelial-specific deficiency of NCEH1, whereas NCEH1 overexpression restored the impaired EDR. Similar results were observed in HFD mice. Mechanically, NCEH1 ameliorated the disrupted EDR by dissociating endothelial nitric oxide synthase (eNOS) from caveolin-1 (Cav-1), leading to eNOS activation and nitric oxide (NO) release. Moreover, interaction of NCEH1 with the E3 ubiquitin-protein ligase ZNRF1 led to the degradation of Cav-1 through the ubiquitination pathway. Silencing Cav-1 and upregulating ZNRF1 were sufficient to improve EDR of diabetic aortas, while overexpression of Cav-1 and downregulation of ZNRF1 abolished the effects of NCEH1 on endothelial function in diabetes. Thus, NCEH1 preserves endothelial function through increasing NO bioavailability secondary to the disruption of the Cav-1/eNOS complex in the endothelium of diabetic mice, depending on ZNRF1-induced ubiquitination of Cav-1. CONCLUSIONS: NCEH1 may be a promising candidate for the prevention and treatment of vascular complications of diabetes.

The application strategy of liposomes in organ targeting therapy.

Liposomes-microscopic phospholipid bubbles with bilayered membrane structure-have been a focal point in drug delivery research for the past 30 years. Current liposomes possess a blend of biocompatibility, drug loading efficiency, prolonged circulation and targeted delivery. Tailored liposomes, varying in size, charge, lipid composition, and ratio, have been developed to address diseases in specific organs, thereby enhancing drug circulation, accumulation at lesion sites, intracellular delivery, and treatment efficacy for various organ-specific diseases. For further successful development of this field, this review summarized liposomal strategies for targeting different organs in series of major human diseases, including widely studied cardiovascular diseases, liver and spleen immune diseases, chronic or acute kidney injury, neurodegenerative diseases, and organ-specific tumors. It highlights recent advances of liposome-mediated therapeutic agent delivery for disease intervention and organ rehabilitation, offering practical guidelines for designing organ-targeted liposomes. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Biology-Inspired Nanomaterials > Lipid-Based Structures.

Species distribution modeling combined with environmental DNA analysis to explore distribution of invasive alien mosquitofish (Gambusia affinis) in China.

China has become one of the most serious countries suffering from biological invasions in the world. In the context of global climate change, invasive alien species (IAS) are likely to invade a wider area, posing greater ecological and economic threats in China. Western mosquitofish (Gambusia affinis), which is known as one of the 100 most invasive alien species, has distributed widely in southern China and is gradually spreading to the north, causing serious ecological damage and economic losses. However, its distribution in China is still unclear. Hence, there is an urgent need for a more convenient way to detect and monitor the distribution of G. affinis to put forward specific management. Therefore, we detected the distribution of G. affinis in China under current and future climate change by combing Maxent modeling prediction and eDNA verification, which is a more time-saving and reliable method to estimate the distribution of species. The Maxent modeling showed that G. affinis has a broad habitat suitability in China (especially in southern China) and would continue to spread in the future with ongoing climate change. However, eDNA monitoring showed that occurrences can already be detected in regions that Maxent still categorized as unsuitable. Besides temperature, precipitation and human influence were the most important environmental factors affecting the distribution of G. affinis in China. In addition, by environmental DNA analysis, we verified the presence of G. affinis predicted by Maxent in the Qinling Mountains where the presence of G. affinis had not been previously recorded.

Distinguishing benign and malignant thyroid nodules using plasma trimethylamine N-oxide, carnitine, choline and betaine.

PURPOSE: Trimethylamine N-oxide (TMAO), a gut microbiome-derived metabolite, and its precursors (carnitine, choline, betaine) have not been fully examined in relation to thyroid cancer (TC) risk. The aim of this study was to assess the value of TMAO and its precursors in diagnosis of benign and malignant thyroid nodules. METHODS: In this study, high-performance liquid chromatography-tandem mass spectrometry was utilized to measure the levels of plasma TMAO and its precursors (choline, carnitine, and betaine) in 215 TC patients, 63 benign thyroid nodules (BTN) patients and 148 healthy controls (HC). The distribution of levels of TMAO and its precursors among the three groups were compared by the Kruskal-Wallis test. Receiver operating characteristic curve (ROC) analysis was performed to evaluate the sensitivity, specificity, and the predictive accuracy of single and combined biomarkers. RESULTS: In comparison to HC, TC showed higher levels of TMAO and lower levels of its precursors (carnitine, choline, and betaine) (all P < 0.001). Plasma choline (P < 0.01) and betaine (P < 0.05) were declined in BTN than HC. The levels of carnitine (P < 0.001) and choline (P < 0.05) were significantly higher in BTN than that in TC group. Plasma TMAO showed lower levels in TC with lymph node metastasis (101.5 (73.1-144.5) ng/ml) than those without lymph node metastasis (131 (84.8-201) ng/ml, P < 0.05). Combinations of these four metabolites achieved good performance in the differential diagnosis, with the area under the ROC curve of 0.703, 0.741, 0.793 when discriminating between TC and BTN, BTN and HC, TC and HC, respectively. CONCLUSION: Plasma TMAO, along with its precursors could serve as new biomarkers for the diagnosis of benign and malignant thyroid nodules.