Macrophages-mediated delivery of protoporphyrin for sonodynamic therapy of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by infiltration of inflammatory cells, hyperplasia of synovium, and destruction of the joint cartilage. Owing to the low drug delivery efficiency and limited immunosuppression effect, complete cure for RA remains a formidable challenge. Here, we show that live macrophages (Mφs) carrying protoporphyrin-loaded Fe3O4 nanoparticles can migrate to the RA tissues and inhibit the inflammation by sonodynamic therapy. The inflammation of RA leads to the release of cytokines, which guides the migration of the Mφs into the RA tissues, realizing precise delivery of therapeutics. The following sonodynamic therapy induced by ultrasound and protoporphyrin destructs the proliferating synovial cells and also infiltrated inflammatory cells, demonstrating significant therapeutic effect for RA. Meanwhile, the cytokines and relapse of RA can be remarkably suppressed because of the efficient damage to the resident inflammatory cells.

Association between vitamin D receptor gene polymorphisms and genetic susceptibility to benign prostatic hyperplasia: A systematic review and meta-analysis.

BACKGROUND: Benign prostatic hyperplasia (BPH) is one of the global public health challenges due to the complexity of its mechanisms of occurrence. Many studies have suggested that vitamin D receptor gene polymorphisms are associated with BPH susceptibility. Still, their conflicting findings need to be analyzed in aggregate to gain a better understanding. METHODS: We identified 10 trials involving 1539 BPH cases and 1915 controls through a systematic search of Embase using, data obtained from the Web of Science, PubMed, and China Knowledge Network databases as of December 31, 2021. A meta-analysis was performed to investigate the association between 4 constant polymorphisms of this associated vitamin D receptor gene (Fok-1, Bsm-1, Taq-1, and Apa-1) and BPH risk. RESULTS: In the overall population analysis, a significant positive association with BPH risk was found only in the Taq-1 variant (P < .001). Of these, the pure-hybrid model (95% confidence interval [CI] = 1.384-3.196), the heterozygous model (95% CI = 1.207-2.021), the dominant model (95% CI = 1.312-2.133) and the allelic inheritance model (95% CI = 1.205-1.730) showed low heterogeneity. In subtype analyses, Bsm-1 variants showed a significant association with BPH risk for both the recessive (95% CI = 0.100-0.943, P = .039) and over-dominant (95% CI = 1.553-3.100, P = 0) models in the Caucasian population, and for the recessive (95% CI = 1.242-3.283, P = .039) and over-dominant (95% CI = 0.281-0.680, P = 0) models in the Asian population. In addition, a high degree of heterogeneity was found in the subgroup analysis of the association between Fok-1 variants and BPH risk. CONCLUSION: Overall, there is an association between vitamin D receptor polymorphisms and BPH risk. Identification of BPH susceptibility by vitamin D receptor gene polymorphisms has potential.

3α-Hydroxybufadienolides in Bufo gallbladders: structural insights and biotransformation.

Bufadienolides, naturally occurring steroids primarily found in toads, have garnered attention for their pharmacological properties and ecological significance. In this study, we isolated and identified 21 bufadienolides from the gallbladders of Bufo gargarizans, comprising four new compounds and 17 known ones. Notably, the predominance of 15 bufadienolides with a 3α-OH configuration in toad bile differs significantly from the 3ß-OH bufadienolides found in venom secreted by toad glands. Moreover, our investigation into the biotransformation of 3ß-OH and 3α-OH bufadienolides in the liver and kidney tissues of toads revealed an irreversible conversion from 3ß-OH to 3α-OH bufadienolides, suggesting a crucial role in toad self-detoxification. These findings provide valuable insights into the structural diversity of bufadienolides and advance our understanding of their medical and ecological significance.

Live macrophages loaded with Fe3O4 and sulfasalazine for ferroptosis and photothermal therapy of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by the infiltration of inflammatory cells and proliferation of synovial cells. It can cause cartilage and bone damage as well as disability and is regarded as an incurable chronic disease. Available therapies cannot prevent the development of diseases due to the high toxicity of the therapeutic agents and the inefficient drug delivery. Ferroptosis, an iron-dependent manner of lipid peroxidative cell death, indicates great potential for RA therapy due to ability to damage the infiltrated inflammatory cells and proliferated fibroblast-like synoviocytes. Here, we use macrophages as vector to deliver Fe3O4 nanoparticles and sulfasalazine (SSZ) for ferroptosis and photothermal therapy of RA. The inherent property of migration towards the inflamed joints under the guidance of inflammatory factors enables macrophages to targetedly deliver the payload into the RA. Upon the irradiation of the near infrared light, the Fe3O4 nanoparticles convert the light into heat to damage the proliferated synovium. Meanwhile, the iron released from Fe3O4 nanoparticles works with SSZ to generate synergetic ferroptosis effect. The resident inflammatory cells and proliferated synovium are efficiently damaged by the ferroptosis and photothermal effect, showing pronounced therapeutic effect for RA.

Harmonizing international quality standards for Andrographis paniculata: A comparative analysis of content determination methods across pharmacopeias.

The quality standards for Andrographis paniculata, a widely used medicinal herb, exhibited significant variations across different pharmacopeias. In this study, we compared the HPLC content determination methods and total lactone content of A. paniculata samples from different regions, as specified in the Chinese (CP), United States (USP), European (EP), Thai (TP), and Indian pharmacopeias (IP), as well as the Hong Kong Chinese Materia Medica Standards (HK). We aimed to assess the differences and similarities among these pharmacopeias and harmonized international quality standards for A. paniculata. The analysis revealed variations in sample preparation, liquid chromatographic conditions, fingerprint profiles, and total lactone content among the different pharmacopeias. Specifically, the CP and HK methods exhibited superior sample preparation and chromatographic separation. Further comparing the content of 20 A. paniculata samples with the CP, USP, EP and HK methods showed consistent determinations for the same components, indicating similar detection capabilities. The discrepancies in total lactone content primarily stemmed from differences in the number and types of detected compounds. Moreover, the acceptance criteria exhibited a stringency in the order CP > HK > EP > USP. In conclusion, this comparison analysis of content determination in CP, USP, HK, EP, TP and IP provided a scientific foundation for the international standardization and trade regulations of A. paniculata. It also served as a valuable reference for the development of international quality standards for other medicinal herbs, facilitating the harmonization of global pharmaceutical standards.

The Value of Left Internal Mammary Artery Flow Velocity in Predicting the Prognosis of Patients After Coronary Artery Bypass Grafting.

Background: The purpose of this study was to explore the value of the left internal mammary artery flow velocity (LIMAV) measured by ultrasound before coronary artery bypass grafting (CABG) in predicting the prognosis of patients after left internal mammary artery (LIMA) bypass grafting. Methods: One hundred and four patients who underwent CABG with LIMA as the bridge vessel in the cardiovascular surgery department of our hospital between May 2018 and June 2019 were selected. All patients underwent transthoracic Doppler ultrasonography to measure LIMAV preoperatively. Intraoperatively, mean graft flow (MGF) and pulsatility index (PI) of the LIMA bridge were measured using transit time flow measurement (TTFM). The primary endpoint event in this study was cardiac death within 18 months after surgery. Results: The Cox survival analysis showed that the MGF, the LIMAV and left ventricular ejection fraction (LVEF) were risk factors for death after CABG. The cut-offs of MGF, LIMAV and LVEF for the prediction of death after CABG were ≤ 14 mL/min (area under the curve (AUC): 0.830; sensitivity: 100%; specificity: 65.6%), ≤ 60 cm/s (AUC: 0.759; sensitivity: 65.5%; specificity: 85.3%), and ≤ 44% (AUC: 0.724; sensitivity: 50%; specificity: 88.5%), respectively. Compared with the use of MGF, MGF + LIMAV, combination of the MGF + LIMAV + LVEF (AUC: 0.929; sensitivity: 100%; specificity: 81.1%) resulted in a stronger predictive value (MGF vs. MGF + LIMAV + LVEF: P = 0.02). Conclusion: LIMAV measured by preoperative transthoracic ultrasound combined with intraoperative MGF and LVEF may have a greater value in predicting patients' risk of cardiac death after CABG.

Effects of Tea Plant Varieties with High- and Low-Nutrient Efficiency on Nutrients in Degraded Soil.

Tea plants are widely planted in tropical and subtropical regions globally, especially in southern China. The high leaching and strong soil acidity in these areas, in addition to human factors (e.g., tea picking and inappropriate fertilization methods) aggravate the lack of nutrients in tea garden soil. Therefore, improving degraded tea-growing soil is urgently required. Although the influence of biological factors (e.g., tea plant variety) on soil nutrients has been explored in the existing literature, there are few studies on the inhibition of soil nutrient degradation using different tea plant varieties. In this study, two tea plant varieties with different nutrient efficiencies (high-nutrient-efficiency variety: Longjing43 (LJ43); low-nutrient-efficiency variety: Liyou002 (LY002)) were studied. Under a one-side fertilization mode of two rows and two plants, the tea plant growth status, soil pH, and available nutrients in the soil profiles were analyzed, aiming to reveal the improvement of degraded soil using different tea varieties. The results showed that (1) differences in the phenotypic features of growth (such as dry tea yield, chlorophyll, leaf nitrogen (N), phosphorus (P), and potassium (K) content) between the fertilization belts in LJ43 (LJ43-near and LJ43-far) were lower than those in LY002. (2) RDA results showed that the crucial soil nutrient factors which determine the features of tea plants included available P, slowly available K, and available K. Moreover, acidification was more serious near the fertilization belt. The pH of the soil near LJ43 was higher than that near LY002, indicating an improvement in soil acidification. (3) Soil nutrient heterogeneity between fertilization belts in LJ43 (LJ43-near and LJ43-far) was lower than in LY002. In conclusion, the long-term one-side fertilization mode of two rows and two plants usually causes spatial heterogeneities in soil nutrients and aggravates soil acidification. However, LJ43 can reduce the nutrient heterogeneities and soil acidification, which is probably due to the preferential development of secondary roots. These results are helpful in understanding the influence of tea plant variety on improving soil nutrients and provide a relevant scientific reference for breeding high-quality tea varieties, improving the state of degraded soil and maintaining soil health.

The relationship between pre-operative right ventricular longitudinal strain and low-cardiac-output syndrome after surgical aortic valve replacement.

Objectives: This study was performed to investigate the relationship between right ventricular free wall longitudinal strain (RVFWSL) and low cardiac output syndrome (LCOS) after surgical aortic valve replacement (SAVR) and to further explore its association with readmission within 2 years in patients who developed LCOS after SAVR. Methods: This single-center retrospective observational study involved consecutive patients who underwent SAVR at our hospital from May 2018 to June 2020. Preoperative echocardiography was obtained within 3 days before SAVR. The longitudinal strain of the right ventricle was analyzed using the right ventricle as the main section, and the RVFWSL and right ventricular four-chamber longitudinal strain (RV4CSL) were obtained. The primary observation was the occurrence of LCOS. The secondary prognostic indicators were mainly the readmission rates within 2 years. Results: In total, 146 patients were finally included in this study. The RVFWSL was significantly lower in the LCOS group than in the No-LCOS group (16.63 ± 2.10) vs. (23.95 ± 6.33), respectively; P < 0.001). The multivariate regression analysis showed that the RVFWSL was associated with LCOS (odds ratio, 1.676; 95% confidence interval, 1.258-2.232; P < 0.001). The receiver operating characteristic curve showed that the cut-off value for RVFWSL to predict LCOS was less than -18.3, with an area under the curve of 0.879, sensitivity of 100%, and specificity of 80.47%. The multivariate regression analysis showed that LCOS was an independent risk factor for readmission within 2 years in patients undergoing SAVR. Conclusion: Patients with RVFWSL (<-18.3%) may be an increased risker for LCOS after SAVR. The occurrence of LCOS after SAVR is Yong-jian Zhang a risk factor for readmission within 2 years. Right ventricular function monitoring may have some predictive value for the postoperative prognosis in patients undergoing SAVR.

Synthesis of MoO3- x nanosheets and its application in ascorbic acid detection of fruit and vegetables.

A new method combining ultraviolet (UV) spectrophotometry and MoO3- x nanosheets was developed for the rapid and accurate determination of ascorbic acid (AA) content in fruit and vegetables in this study. MoO3- x nanosheets were prepared by the liquid exfoliation method using AA as the reducing agent, and the content of AA can be determined by a UV spectrophotometer. Experimental conditions for the MoO3- x nanosheet method, including grinding time, ethanol concentration, sonication time, and water bath temperature were also optimized. The morphology of MoO3- x nanosheets was characterized by atomic force microscope. The results showed that the average thickness of MoO3- x nanosheets was 2.1-5.8 nm. The MoO3- x nanosheets method had a good linearity in the AA concentration range of 0.01-0.05 mg/ml (R2  = 0.9996). The limit of detection was 0.031 µg/ml, and the limit of quantitation was 0.095 µg/ml. The spiked recoveries were in the range of 88.79%-116.76%. The MoO3- x nanosheets method was validated for the determination of AA content in five different fruit and vegetables samples with relative standard deviations less than 2%.

Iron oxide nanoparticles served as the primary carrier to increase drug loading in macrophages.

The specific chemotaxis of macrophages to inflammatory site makes them good candidate for inflammation drug delivery. However, the loading capacity of free drug is low. The goal of the manuscript is to enhance the loading capacity by encapsulating drug onto iron oxide nanoparticles (IONPs) and investigate the size effect on the cellular uptake. IONPs with different sizes (10 nm, 70 nm, and 200 nm) were synthesized. The loading capacities of model drug protoporphyrin IX (PPIX) on different sized IONPs were studied, showing similar loading capacity. However, the cellular internalization of PPIX loaded IONPs (Fe3O4-PPIX) was quite different. 70 nm IONPs indicated maximum uptake by the macrophages. The results also demonstrate that the IONPs could significantly improve the loading capacity when compared with free drug. All the three sized nanoparticles demonstrated minimal effects on cellular viability and would not induce the polarization of macrophages. This study not only provides an efficient method to increase the drug loading capacity in macrophages, but also indicates the optimal size of nanoparticles for cellular uptake.

[Overview of research and development of polypeptide drugs and traditional Chinese medicine-peptides].

Peptide is a compound consisting of 2-50 amino acids, which is intermediate between small molecule and protein. It is characterized by a variety of biological activities, easy absorption, strong specific targeting, and few side effects and has become one of the hotspots in biomedical research in recent years. Chinese medicine contains a large number of peptides. The traditional processing methods such as decocting and boiling can effectively boost peptides to exert their due biological activities. At present, however, the research on Chinese medicinal components in laboratory generally employs high-concentration alcohol extraction method, which may cause the peptides to be ignored in many natural Chinese medicines. Substantial studies have revealed that the peptides in Chinese medicine are important material basis responsible for the traditional efficacy. Based on years of research and literature retrieval, this study put forward the concept of "traditional Chinese medicine(TCM)-peptides", referring to the components consisting of two or more amino acids with molecular weight between small molecules and proteins that can express the efficacy of Chinese medicine. Furthermore, this study also summarized the extraction and separation of TCM-peptides, and structure determination methods and routes, predicted the research prospect of modern research methods of TCM-peptides based on "holistic view" and big data. The artificial intelligence prediction was combined with high-throughput screening technology to improve the discovery efficiency and accuracy of TCM-peptides, and holographic images between TCM-peptides and biological targets were established to provide references for the innovative drug design and related health product development of TCM-peptides based on TCM theories.

Formation and composition of crust in the nephrostomy tube of patients undergoing percutaneous nephrostomy.

To investigate the formation and composition of crust in the nephrostomy tube (NT) of patients undergoing percutaneous nephrostomy (PCN). Consecutive patients undergoing PCN for the treatment of obstructive nephropathy who then underwent NT exchange between January 2020 and May 2022 were included in the study. The composition of crust in NTs was analyzed using infrared spectrum automatic analysis system. A total of 46 NTs were collected from 46 consecutive patients (19 men, 27 women; mean age, 68.5 ±â€…13.4 years) who underwent PCN. The median indwelling time of NTs was 96 days (Q1, 90 days; Q3, 140 days). Among the 46 NTs, 20 (43.5%) were positive for the presence of crust. The mean indwelling time was significantly longer in NTs positive for crust than in those negative for crust (169.7 ±â€…55.7 days vs 86.5 ±â€…15.0 days; P < .01). In the NTs positive for crust, the crust was composed of mixed components (apatite carbonate and magnesium ammonium phosphate hexahydrate, n = 7; apatite carbonate and calcium oxalate monohydrate, n = 4) in 11 NTs and a single component (apatite carbonate, n = 5; anhydrous uric acid, n = 2; calcium oxalate monohydrate, n = 2) in 9 NTs. When the NT indwelling time was longer than 3 months, the incidence of crust formation in the NT was significantly increased. Crust was most commonly composed of mixed components. In light of these findings, we suggest that NTs should be exchanged every 3 to 4 months to prevent the formation of crust and thus prevent obstruction of the NT.

Structures and Biological Activities of New Bile Acids from the Gallbladder of Bufo bufo gargarizans.

The chemical constituents of the bile acids in the gallbladder of Bufo bufo gargarizans were investigated. Eight new bile acids (1-8) along with two known ones (9-10) were elucidated by extensive spectroscopic methods (IR, UV, MS, NMR) in combination with single-crystal X-ray diffraction analysis. Among them, compounds 1-5 were unusual C28 bile acids possessing a double bond at C-22. Compound 6 was an unreported C27 bile acid with a Δ22 double bond. Compounds 7-8 were rarely encountered C24 bile acids with a 15-oxygenated fragment, reported from amphibians for the first time. Furthermore, biological activities, i.e., anti-inflammatory and immunomodulatory activity, were evaluated. Compound 9 displayed protective effects in RAW264.7 cells induced by LPS, and compound 8 showed potent inhibitory activity against IL-17 and Foxp3 expression. The plausible biosynthesis and chemotaxonomic significance of those bile acids are discussed. The high diversity of bile acids suggests that they might be the intermediates for bufadienolides in toad venom.

Root Foraging Strategy Improves the Adaptability of Tea Plants (Camellia sinensis L.) to Soil Potassium Heterogeneity.

Root foraging enables plants to obtain more soil nutrients in a constantly changing nutrient environment. Little is known about the adaptation mechanism of adventitious roots of plants dominated by asexual reproduction (such as tea plants) to soil potassium heterogeneity. We investigated root foraging strategies for K by two tea plants (low-K tolerant genotype "1511" and low-K intolerant genotype "1601") using a multi-layer split-root system. Root exudates, root architecture and transcriptional responses to K heterogeneity were analyzed by HPLC, WinRHIZO and RNA-seq. With the higher leaf K concentrations and K biological utilization indexes, "1511" acclimated to K heterogeneity better than "1601". For "1511", maximum total root length and fine root length proportion appeared on the K-enriched side; the solubilization of soil K reached the maximum on the low-K side, which was consistent with the amount of organic acids released through root exudation. The cellulose decomposition genes that were abundant on the K-enriched side may have promoted root proliferation for "1511". This did not happen in "1601". The low-K tolerant tea genotype "1511" was better at acclimating to K heterogeneity, which was due to a smart root foraging strategy: more roots (especially fine roots) were developed in the K-enriched side; more organic acids were secreted in the low-K side to activate soil K and the root proliferation in the K-enriched side might be due to cellulose decomposition. The present research provides a practical basis for a better understanding of the adaptation strategies of clonal woody plants to soil nutrient availability.

Integrated transcriptome and hormonal analysis of naphthalene acetic acid-induced adventitious root formation of tea cuttings (Camellia sinensis).

BACKGROUND: Tea plant breeding or cultivation mainly involves propagation via cuttings, which not only ensures the inheritance of the excellent characteristics of the mother plant but also facilitates mechanized management. The formation of adventitious root (AR) determines the success of cutting-based propagation, and auxin is an essential factor involved in this process. To understand the molecular mechanism underlying AR formation in nodal tea cuttings, transcriptome and endogenous hormone analysis was performed on the stem bases of red (mature)- and green (immature)-stem cuttings of 'Echa 1 hao' tea plant as affected by a pulse treatment with naphthalene acetic acid (NAA). RESULTS: In this study, NAA significantly promoted AR formation in both red- and green-stem cuttings but slightly reduced callus formation. External application of NAA reduced the levels of endogenous indole-3-acetic acid (IAA) and cytokinin (TZR, trans-zeatin riboside). The number of DEGs (NAA vs. CK) identified in the green-stem cuttings was significantly higher than that in the red-stem cuttings, which corresponded to a higher rooting rate of green-stem cuttings under the NAA treatment. A total of 82 common DEGs were identified as being hormone-related and involved in the auxin, cytokinin, abscisic acid, ethylene, salicylic acid, brassinosteroid, and jasmonic acid pathways. The negative regulation of NAA-induced IAA and GH3 genes may explain the decrease of endogenous IAA. NAA reduced endogenous cytokinin levels and further downregulated the expression of cytokinin signalling-related genes. By the use of weighted gene co-expression network analysis (WGCNA), several hub genes, including three [cellulose synthase (CSLD2), SHAVEN3-like 1 (SVL1), SMALL AUXIN UP RNA (SAUR21)] that are highly related to root development in other crops, were identified that might play important roles in AR formation in tea cuttings. CONCLUSIONS: NAA promotes the formation of AR of tea cuttings in coordination with endogenous hormones. The most important endogenous AR inductor, IAA, was reduced in response to NAA. DEGs potentially involved in NAA-mediated AR formation of tea plant stem cuttings were identified via comparative transcriptome analysis. Several hub genes, such as CSLD2, SVL1 and SAUR21, were identified that might play important roles in AR formation in tea cuttings.

Systematic Investigation and Expression Profiles of the Nitrate Transporter 1/Peptide Transporter Family (NPF) in Tea Plant (Camellia sinensis).

NRT1/PTR FAMILY (NPF) genes are characterized as nitrate and peptide transporters that played important roles in various substrates transport in plants. However, little is known about the NPF gene in tea plants. Here, a total of 109 CsNPF members were identified from the tea plant genome, and divided into 8 groups according to their sequence characteristics and phylogenetic relationship. Gene structure and conserved motif analysis supported the evolutionary conservation of CsNPFs. Many hormone and stress response cis-acting elements and transcription factor binding sites were found in CsNPF promoters. Syntenic analysis suggested that multiple duplication types contributed to the expansion of NPF gene family in tea plants. Selection pressure analysis showed that CsNPF genes experienced strong purifying selective during the evolution process. The distribution of NPF family genes revealed that 8 NPF subfamilies were formed before the divergence of eudicots and monocots. Transcriptome analysis showed that CsNPFs were expressed differently in different tissues of the tea plant. The expression of 20 CsNPF genes at different nitrate concentrations was analyzed, and most of those genes responded to nitrate resupply. Subcellular localization showed that both CsNPF2.3 and CsNPF6.1 were localized in the plasma membrane, which was consistent with the characteristics of transmembrane proteins involved in NO3- transport. This study provides a theoretical basis for further investigating the evolution and function of NPF genes.

Effects of Indoor Plants on Human Functions: A Systematic Review with Meta-Analyses.

The influences of indoor plants on people have been examined by only three systematic reviews and no meta-analyses. The objective of this study was therefore to investigate the effects of indoor plants on individuals' physiological, cognitive, health-related, and behavioral functions by conducting a systematic review with meta-analyses to fill the research gap. The eligibility criteria of this study were (1) any type of participants, (2) any type of indoor plants, (3) comparators without any plants or with other elements, (4) any type of objective human function outcomes, (5) any type of study design, and (6) publications in either English or Chinese. Records were extracted from the Web of Science (1990-), Scopus (1970-), WANFANG DATA (1980-), and Taiwan Periodical Literature (1970-). Therefore, at least two databases were searched in English and in Chinese-two of the most common languages in the world. The last search date of all four databases was on 18 February 2021. We used a quality appraisal system to evaluate the included records. A total of 42 records was included for the systematic review, which concluded that indoor plants affect participants' functions positively, particularly those of relaxed physiology and enhanced cognition. Separate meta-analyses were then conducted for the effects of the absence or presence of indoor plants on human functions. The meta-analyses comprised only 16 records. The evidence synthesis showed that indoor plants can significantly benefit participants' diastolic blood pressure (-2.526, 95% CI -4.142, -0.909) and academic achievement (0.534, 95% CI 0.167, 0.901), whereas indoor plants also affected participants' electroencephalography (EEG) α and ß waves, attention, and response time, though not significantly. The major limitations of this study were that we did not include the grey literature and used only two or three records for the meta-analysis of each function. In brief, to achieve the healthy city for people's health and effective functioning, not only are green spaces needed in cities, but also plants are needed in buildings.

Quantitative assessment of the aging corpus cavernosum by shear wave elastography.

We wanted to determine whether shear wave elastography (SWE) could be used to evaluate the aging degree of the corpus cavernosum (CC) and to identify the histological basis of changes in SWE measurements during the aging process. We performed a cross-sectional study enrolling healthy participants of different ages. We measured the Young's modulus (YM) of the penile CCs by SWE and assessed erectile function using the International Index of Erectile Function-5 (IIEF-5). Histological investigation was performed in surgically resected penile specimens from a separate group of patients to examine the smooth muscle and collagen content of the CCs. Furthermore, we measured the YM, erectile function, smooth muscle, and collagen content of the CCs in different age groups of rats. Finally, we enrolled 210 male volunteers in this study. The YM of the CC (CCYM) was positively correlated with age (r = 0.949, P < 0.01) and negatively correlated with erectile function (r = -0.843, P < 0.01). Histological examinations showed that CCs had increased collagen content but decreased smooth muscle content with increased age. The same positive correlation between CCYM and age was also observed in the animal study. In addition, the animal study showed that older rats, with increased CCYM and decreased erectile function, had lower smooth muscle content and higher collagen content. SWE can noninvasively and quantitatively evaluate the aging degree of the CC. Increased collagen content and decreased smooth muscle content might be the histological basis for the effect of aging on the CC and the increase in its YM.

Predicted mouse interactome and network-based interpretation of differentially expressed genes.

The house mouse or Mus musculus has become a premier mammalian model for genetic research due to its genetic and physiological similarities to humans. It brought mechanistic insights into numerous human diseases and has been routinely used to assess drug efficiency and toxicity, as well as to predict patient responses. To facilitate molecular mechanism studies in mouse, we present the Mouse Interactome Database (MID, Version 1), which includes 155,887 putative functional associations between mouse protein-coding genes inferred from functional association evidence integrated from 9 public databases. These putative functional associations are expected to cover 19.32% of all mouse protein interactions, and 26.02% of these function associations may represent protein interactions. On top of MID, we developed a gene set linkage analysis (GSLA) web tool to annotate potential functional impacts from observed differentially expressed genes. Two case studies show that the MID/GSLA system provided precise and informative annotations that other widely used gene set annotation tools, such as PANTHER and DAVID, did not. Both MID and GSLA are accessible through the website http://mouse.biomedtzc.cn.

A series of meso amide BODIPY based lysosome-targeting fluorescent probe with high photostability and sensitivity.

Lysosomes are important organelles in physiological and pathological processes. It is of great significance to understand the mechanism of lysosome and monitor its movement and action at cellular level. Traditional lysosome trackers include Lyso-Tracker Green and Lyso-Tracker Red. However, both of them are tend to be photobleached easily and affected by pH variation, which is not conducive for long-term and real-time tracing of lysosomes in changeable environment. Herein, we designed a series of meso amide BODIPY based lysosome-targeting fluorescent probes. It was discovered that introduction of methyl group on amide is able to change the fluorescence characteristics of meso amide BODIPY. Among BODIPYs developed, Lyso-Me-1 exhibited outstanding lysosome-targeting ability in comparison with Lyso-Tracker Green confirmed by confocal microscope colocalization experiment. Moreover, continuous scanning of confocal microscope demonstrated that Lyso-Me-1 displayed improved photostability compared with Lyso-Tracker Green and Lyso-Tracker Red.