Thermosensitive hydrogel with emodin-loaded triple-targeted nanoparticles for a rectal drug delivery system in the treatment of chronic non-bacterial prostatitis.

BACKGROUND: The complex etiology and pathogenesis underlying Chronic Non-Bacterial Prostatitis (CNP), coupled with the existence of a Blood Prostate Barrier (BPB), contribute to a lack of specificity and poor penetration of most drugs. Emodin (EMO), a potential natural compound for CNP treatment, exhibits commendable anti-inflammatory, anti-oxidant, and anti-fibrosis properties but suffers from the same problems as other drugs. METHODS: By exploiting the recognition properties of lactoferrin (LF) receptors that target intestinal epithelial cells (NCM-460) and prostate epithelial cells (RWPE-1), a pathway is established for the transrectal absorption of EMO to effectively reach the prostate. Additionally, hyaluronic acid (HA) is employed, recognizing CD44 receptors which target macrophages within the inflamed prostate. This interaction facilitates the intraprostatic delivery of EMO, leading to its pronounced anti-inflammatory effects. A thermosensitive hydrogel (CS-Gel) prepared from chitosan (CS) and ß-glycerophosphate disodium salt (ß-GP) was used for rectal drug delivery with strong adhesion to achieve effective drug retention and sustained slow release. Thus, we developed a triple-targeted nanoparticle (NPs)/thermosensitive hydrogel (Gel) rectal drug delivery system. In this process, LF, with its positive charge, was utilized to load EMO through dialysis, producing LF@EMO-NPs. Subsequently, HA was employed to encapsulate EMO-loaded LF nanoparticles via electrostatic adsorption, yielding HA/LF@EMO-NPs. Finally, HA/LF@EMO-NPs lyophilized powder was added to CS-Gel (HA/LF@EMO-NPs Gel). RESULTS: Cellular assays indicated that NCM-460 and RWPE-1 cells showed high uptake of both LF@EMO-NPs and HA/LF@EMO-NPs, while Raw 264.7 cells exhibited substantial uptake of HA/LF@EMO-NPs. For LPS-induced Raw 264.7 cells, HA/LF@EMO-NPs can reduce the inflammatory responses by modulating TLR4/NF-κB signaling pathways. Tissue imaging corroborated the capacity of HA/LF-modified formulations to breach the BPB, accumulating within the gland's lumen. Animal experiments showed that rectal administration of HA/LF@EMO-NPs Gel significantly reduced inflammatory cytokine expression, oxidative stress levels and fibrosis in the CNP rats, in addition to exerting anti-inflammatory effects by inhibiting the NF-κB signaling pathway without obvious toxicity. CONCLUSION: This triple-targeted NPs/Gel rectal delivery system with slow-release anti-inflammatory, anti-oxidant, and anti-fibrosis properties shows great potential for the effective treatment of CNP.

Does joint-sparing tumor resection jeopardize oncologic and functional outcomes in non-metastatic high-grade osteosarcoma around the knee?

BACKGROUND: We previously reported joint-sparing tumor resection for osteosarcoma with epiphyseal involvement in which transepiphyseal osteotomy went through the in situ ablated epiphysis. However, we do not know whether this is a safe approach when compared with joint-sacrificed tumor resection. Our objective was to compare oncologic and functional outcomes between patients who underwent joint preservation (JP) and joint replacement (JR) tumor resection. Furthermore, we identified the risk factors of local recurrence, metastasis and survival. METHODS: Eighty-nine patients with non-metastatic high-grade osteosarcoma around the knee were treated with limb-salvage surgery (JP in 47 and JR in 42). Age, gender, tumor location, pathologic fracture, plain radiographic pattern, limb diameter change, perivascular space alteration, surgical margin, local recurrence, metastasis, death, and the Musculoskeletal Tumor Society (MSTS)-93 scores were extracted from the records. Univariate analysis was performed to compare oncologic and functional outcomes. Binary logistic and cox regression models were used to identify predicted factors for local recurrence, metastasis, and survival. RESULTS: Local recurrence, metastasis and overall survival were similar in the JP and JR group (p = 0.3; p = 0.211; p = 0.143). Major complications and limb survival were also similar in the JR and JP group (p = 0.14; p = 0.181). The MSTS score of 27.06 ± 1.77 in the JP group was higher than that of 25.88 ± 1.79 in the JR group (p = 0.005). The marginal margin of soft tissue compared with a wide margin was the only independent predictor of local recurrence (p = 0.006). Limb diameter increase and perivascular fat plane disappearance during neoadjuvant chemotherapy were independent predictors for metastasis (p = 0.002; p = 0.000) and worse survival (p = 0.000; p = 0.001). CONCLUSIONS: Joint-sparing tumor resection with the ablative bone margin offers advantage of native joint preservation with favorable functional outcomes while not jeopardizing oncologic outcomes compared with joint-sacrificed tumor resection. Surgeon should strive to obtain adequate soft tissue surgical margin decreasing risk of local recurrence. Novel drug regimens might be reasonable options for patients with obvious limb diameter increase and perivascular fat disappearance during chemotherapy.

Qiangjing tablets ameliorate asthenozoospermia via mitochondrial ubiquitination and mitophagy mediated by LKB1/AMPK/ULK1 signaling.

CONTEXT: Therapeutic effects of Qiangjing tablets (QJT) on sperm vitality and asthenozoospermia (AZS) have been confirmed. However, the mechanism of action remains unclear. OBJECTIVE: This study investigates the effects of QJT on AZS and the underlying mechanism of action. MATERIALS AND METHODS: Sixty Sprague-Dawley rats were randomly divided into six groups: Control, ORN (ornidazole; 200 mg/kg), ORN + QJT-low (0.17 g/mL), ORN + QJT-middle (0.33 g/mL), ORN + QJT-high (0.67 g/mL), and ORN + QJT + Radicicol (0.67 g/mL QJT and 20 mg/kg radicicol) groups. Pathological evaluation and analysis of mitophagy were conducted by H&E staining and transmission electron microscopy, respectively. Reactive oxygen species were detected by flow cytometry. Protein expression was determined by Western blotting. RESULTS: QJT significantly improved ORN-treated sperm motility and kinematic parameters, as well as the pathological symptoms of testicular and epididymal tissues. In particular, QJT mitigated impaired mitochondrial morphology, and increased the PHB, Beclin-1, LC3-II protein, and ROS levels (p < 0.05), and reduced the protein expression levels of LC3-I and p62 (p < 0.05). Mechanistically, QJT antagonized the downregulation of SCF and Parkin protein levels (p < 0.05). Furthermore, QJT significantly increased the protein expressions levels of LKB1, AMPKα, p-AMPKα, ULK1 and p-ULK1 (p < 0.05). The ameliorative effect of QJT on pathological manifestations, mitochondrial morphology, and the expressions of mitophagy and mitochondrial ubiquitination-related proteins was counteracted by radicicol. DISCUSSION AND CONCLUSIONS: QJT improved AZS via mitochondrial ubiquitination and mitophagy mediated by the LKB1/AMPK/ULK1 signaling pathway. Our study provides a theoretical basis for the treatment of AZS and male infertility.

Feature-weighted ordinal classification for predicting drug response in multiple myeloma.

MOTIVATION: Ordinal classification problems arise in a variety of real-world applications, in which samples need to be classified into categories with a natural ordering. An example of classifying high-dimensional ordinal data is to use gene expressions to predict the ordinal drug response, which has been increasingly studied in pharmacogenetics. Classical ordinal classification methods are typically not able to tackle high-dimensional data and standard high-dimensional classification methods discard the ordering information among the classes. Existing work of high-dimensional ordinal classification approaches usually assume a linear ordinality among the classes. We argue that manually labeled ordinal classes may not be linearly arranged in the data space, especially in high-dimensional complex problems. RESULTS: We propose a new approach that can project high-dimensional data into a lower discriminating subspace, where the innate ordinal structure of the classes is uncovered. The proposed method weights the features based on their rank correlations with the class labels and incorporates the weights into the framework of linear discriminant analysis. We apply the method to predict the response to two types of drugs for patients with multiple myeloma, respectively. A comparative analysis with both ordinal and nominal existing methods demonstrates that the proposed method can achieve a competitive predictive performance while honoring the intrinsic ordinal structure of the classes. We provide interpretations on the genes that are selected by the proposed approach to understand their drug-specific response mechanisms. AVAILABILITY AND IMPLEMENTATION: The data underlying this article are available in the Gene Expression Omnibus Database at https://www.ncbi.nlm.nih.gov/geo/ and can be accessed with accession number GSE9782 and GSE68871. The source code for FWOC can be accessed at https://github.com/pisuduo/Feature-Weighted-Ordinal-Classification-FWOC. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Physical secure key distribution based on chaotic self-carrier phase modulation and time-delayed shift keying of synchronized optical chaos.

High speed physical secure key distribution in a classical optical fiber channel is unprecedentedly desired for modern secure communication, but it still remains a worldwide technical challenge. In this paper, we propose and experimentally demonstrate a novel high-speed physical secure key distribution scheme based on chaotic optical signal processing and private hardware modules, which employs chaotic self-carrier phase modulation for chaotic bandwidth expansion and time-delayed shift keying of commonly driven synchronized optical chaos for physical layer security. In this scheme, the entropy source rate of synchronized chaos output from two remote response lasers is greatly expanded by chaotic self-carrier delayed nonlinear phase disturbance, which facilitates high speed key extraction from the entropy source with guaranteed randomness. Moreover, a synchronization recovery time of sub-nanosecond is achieved by dynamic keying of the chaotic delay time after chaos synchronization to accelerate the key distribution rate. Based on the proposed scheme, a high physical key distribution rate of 2.1 Gb/s over 40 km is successfully demonstrated in the experiment. The proposed solution provides a promising strategy for future high-speed key distribution based on chaotic optical signal processing and classical fiber channel.

Consistency and synchronization of AMPK-glycogen in endometrial epithelial cells are critical to the embryo implantation.

Uterine receptivity to the embryo is crucial for successful implantation. The establishment of uterine receptivity requires a large amount of energy, and abnormal energy regulation causes implantation failure. Glucose metabolism in the endometrium is tissue specific. Glucose is largely stored in the form of glycogen, which is the main energy source for the endometrium. AMP-activated protein kinase (AMPK), an important energy-sensing molecule, is a key player in the regulation of glucose metabolism and its regulation is also tissue specific. However, the mechanism of energy regulation in the endometrium for the establishment of uterine receptivity remains to be elucidated. In this study, we aimed to investigate the energy regulation mechanism of mouse uterine receptivity and its significance in embryo implantation. The results showed that the AMPK, p-AMPK, glycogen synthase 1, and glycogen phosphorylase M levels and the glycogen content in mouse endometrial epithelium varied in a periodic manner under regulation by the ovarian hormone. Specifically, progesterone significantly activated AMPK, promoted glycogenolysis, and upregulated glycogen phosphorylase M expression. AMPK regulated glycogen phosphorylase M expression and promoted glycogenolysis. AMPK was also found to be activated by changes in the energy or glycogen of the endometrial epithelial cells. The inhibition of AMPK activity or glycogenolysis altered the uterine receptivity markers during the window of implantation and ultimately interfered with implantation. In summary, consistency and synchronization of AMPK and glycogen metabolism constitute the core regulatory mechanism in mouse endometrial epithelial cells involved in the establishment of uterine receptivity.

Lelliottia steviae sp. nov. isolated from Stevia rebaudiana Bertoni.

A Gram-negative, aerobic, chemoheterotrophic, rod-shaped, and motile bacterium, designated as LST-1T, was isolated from wild Stevia rebaudiana Bertoni and subjected to a polyphasic taxonomic analysis. The LST-1 strain grew optimally at 37 °C and pH 6.0-7.0 in the presence of 0.5% (w/v) NaCl. Phylogenetic analysis based on the 16S rDNA sequence indicated that LST-1 is closely related to Lelliottia jeotgali PFL01T (99.85%), Lelliottia nimipressuralis LMG10245T (98.82%), and Lelliottia amnigena LMG2784T (98.54%). Multi-locus sequence typing of concatenated partial atpD, infB, gyrB, and rpoB genes was performed to improve the resolution, and clear distinctions between the closest related type strains were observed. The results of average nucleotide identify analyses and DNA-DNA hybridization with four species (16S rDNA similarity > 98.65%) were less than 90 and 40%, respectively, verifying the distinct characteristics from other species of Lelliottia. The cellular fatty acid profile of the strain consisted of C16:0, Summed Feature3, and Summed Feature8 (possibly 16:1 w6c/16:1 w7c and 18:1 w6c) as major components. The major polar lipids included phosphatidylethanolamine, phosphatidylglycerol, an aminophospholipid, three non-characteristic phospholipids, and a non-characteristic lipid. The genome of LST-1T was 4,611,055 bp in size, with a G + C content of 55.02%. The unique combination of several phenotypic, chemotaxonomic, and genomic characteristics proved that strain LST-1T belongs to a novel species, for which the name Lelliottia steviae sp. nov. is proposed. The type strain is LST-1T (= CGMCC 1.19175T = JCM 34938T).Repositories: The genbank accession numbers for the 16S rRNA gene and genome sequences of strain LST-1T are MZ497264 and CP063663, respectively.

Directional bioconversion and optimization of stevioside into rubusoside by Lelliottia sp. LST-1.

AIMS: The present study aimed to specifically transform stevioside (ST) into rubusoside (RS) through bioconversion with high efficiency, seeking to endow steviol glycosides (SGs) with subtle flavours for commercial acceptability. METHODS AND RESULTS: An endophytic bacterium named Lelliottia LST-1 was screened and confirmed to specifically convert ST into RS, reaching a conversion rate of 75.4% after response surface optimization. Phylogenetic analysis combined with complete genome sequencing demonstrated that LST-1 was also presumed to be a new species. To further explore the principle and process of biological transformation, the potential beta-glucosidases GH3-1, GH3-2, GH3-3 and GH3-4 were expressed, purified and reacted with SGs. High-performance liquid chromatography revealed that all enzymes hydrolysed ST and generated RS, but substrate specificity analysis indicated that GH3-2 had the highest substrate specificity towards STs and the highest enzyme activity. CONCLUSION: The potential ß-glucosidase GH3-2 in Lelliottia sp. LST-1 was found to specifically and efficiently convert ST to RS. SIGNIFICANCE AND IMPACT OF STUDY: The efficient biotransformation of ST into RS will be beneficial to its large-scale production and extensive application in the food and pharmaceutical industries.

Investigation on the thermal blooming effect in a high power spectral beam combining fiber laser system.

We demonstrate the influence of the thermal blooming effect on the far-field beam quality in a seven-channel spectral beam combining system. Stimulated Raman scattering in the incident narrow-linewidth fiber amplifier is verified to be the dominant factor that induces thermal blooming in the beam combining system. When the power density of Raman light reaches only 180W/cm2, the peak intensity of the far-field beam reduces severely and the beam distribution profile spreads. We reveal that H2O content in the atmosphere has a positive relationship with the thermal blooming effect and study the influence of the humidity on the thermal blooming effect. The influence of the optical path length on the thermal blooming effect is also revealed. The result shows that the focusing property of the far-field beam degrades gradually as the optical path length increases from 100 to 450 mm. The results are conducive to optimize the beam quality of spectral beam combining.

[Neuroprotective mechanism of traditional Chinese medicine extracts in the treatment of diabetic ED by inhibiting the ferroptosis pathway].

Diabetic ED (DMED) is a sexual dysfunction disease accompanied by poor blood sugar control, which is a most common organic ED clinically, with the lesions of the nervous system as the most important pathological mechanism in the process of its occurrence. Ferroptosis is a new form of autophagy-dependent cell death involved in the development and progression of a variety of diseases and closely related to the death of nerve cells. The ferroptosis pathway has been conformed to be involved in the mechanism of neuromodulation of DMED, which can be used as an important basis for the treatment of the disease. Studies have shown that some herbal extracts can inhibit the ferroptosis pathway of nerve cells. This review summarizes the neuroprotective mechanism of traditional Chinese medicine extracts in the treatment of DMED by inhibiting the ferroptosis pathway of nerve cells, and provides a theoretical foundation for future clinical treatment of the disease.

Microfluidic Fabrication of Hierarchical-Ordered ZIF-L(Zn)@Ti3 C2 Tx Core-Sheath Fibers for High-Performance Asymmetric Supercapacitors.

We report hierarchical-ordered ZIF-L(Zn)@Ti3 C2 Tx MXene core-sheath fibers, in which a ZIF-L(Zn) nanowall array sheath is grown vertically on an anisotropic Ti3 C2 Tx core by Ti-O-Zn/Ti-F-Zn chemical bonds. Through highly efficient microfluidic assembly and microchannel reactions, ZIF-L(Zn)@Ti3 C2 Tx exhibits well-developed micro-/mesoporosity, ordered ionic pathways, fast interfacial electron conduction and large-scale fabrication, significantly boosting charges dynamic transport and intercalation. The resultant ZIF-L(Zn)@Ti3 C2 Tx fiber presents large capacitance (1700 F cm-3 ) and outstanding rate performance in a 1 M H2 SO4 electrolyte. Additionally, ZIF-L(Zn)@Ti3 C2 Tx fiber-based solid-state asymmetric supercapacitors deliver high energy density (19.0 mWh cm-3 ), excellent capacitance (854 F cm-3 ), large deformable/wearable capabilities and long-time cyclic stability (20 000 cycles), which realize natural sunlight-induced self-powered applications to drive water level/earthquake alarm devices.

Interfacial Polymetallic Oxides and Hierarchical Porous Core-Shell Fibres for High Energy-Density Electrochemical Supercapacitors.

Realizing high energy-density and actual applications of fibre-based electrochemical supercapacitors (FESCs) are pivotal but challenging, as the ability to construct advanced fibres for accelerating charges kinetic diffusion and Faradaic storage remain key bottlenecks. Here, we demonstrate high-performance FESCs based on hetero-structured polymetallic oxides/porous graphene core-sheath fibres, where the large pseudo-active polymetallic oxide (PMO) sheath is uniformly loaded on a hierarchical porous graphene fibre (PGF) core. Due to the abundant micro-/mesoporous pathways, large accessible surface, excellent redox activity and good interface electron conduction, the PMO-PGF possesses high areal capacitance (2959.78 mF cm-2 ) and manageable Faradaic reversibility in a 6 M KOH electrolyte. Furthermore, the PMO-PGF-based solid-state FESCs present high energy-density (187.22 µ Wh cm-2 ), long-life cycles (95.8 % capacitive retention after 20 000 cycles), diverse-powered capabilities and actual energy-supply applications.

A Covalent Black Phosphorus/Metal-Organic Framework Hetero-nanostructure for High-Performance Flexible Supercapacitors.

We develop hetero-nanostructured black phosphorus/metal-organic framework hybrids formed by P-O-Co covalent bonding based on a designed droplet microfluidic strategy consisting of confined and ultrafast microdroplet reactions. The resulting hybrid exhibits large capacitance (1347 F g-1 ) in KOH electrolytes due to its large specific-surface-area (632.47 m2 g-1 ), well-developed micro-porosity (0.38 cm3 g-1 ), and engineered electroactivity. Furthermore, the proposed 3D printing method allows to construct all-integrated solid-state supercapacitor, which maintains interconnected porous network, good interfacial adhesion, and robust flexibility for short-path diffusion and excessive accommodation of ions. Consequently, the fabricated flexible supercapacitor delivers ultrahigh volumetric energy density of 109.8 mWh cm-3 , large capacitance of 506 F cm-3 , and good long-term stability of 12000 cycles.

[Alterations of regional homogeneity in patients with psychogenic erectile dysfunction: A study by resting-state functional MRI].

OBJECTIVE: To study the correlation between the brain regional homogeneity (ReHo) features and the clinical characteristics of the patients with psychogenic erectile dysfunction (pED). METHODS: Using IIEF-5 and the Self-Esteem and Relationship (SEAR) questionnaire, we evaluated the erectile function and psychosocial status of 32 pED patients and 28 healthy male subjects. Then, we compared the regional brain activity between the patients and healthy controls by resting-state functional magnetic resonance imaging (RS-fMRI) and the ReHo method, analyzed the correlation of the ReHo value of the altered brain regions with the results of IIEF-5 and SEAR questionnaire investigation, and explored the relationship between the ReHo features and the symptoms of the pED patients. RESULTS: Compared with the healthy male subjects, the pED patients obtained significantly lower IIEF-5 scores (22.21 ± 0.98 vs 13.97 ± 3.60, P < 0.01) and SEAR scores (61.92 ± 3.73 vs 37.58 ± 7.96, P < 0.01), a higher ReHo value of the left lateral cerebellum, and a lower ReHo value of the right precentral gyrus. The ReHo value of the left lateral cerebellum was correlated negatively with the IIEF-5 scores (r= －0.51, P < 0.01) and SEAR scores (r = －0.54, P < 0.01), while that of the right precentral gyrus positively with the IIEF-5 scores (r = 0.57, P < 0.01) and SEAR scores (r = 0.66, P < 0.01). CONCLUSIONS: Patients with pED had lateral cerebellum-mediated abnormal sensory integration and precentral gyrus-related dysfunction of motor imagery and motor execution.

Positional behavior and substrate use in wild adult bearded capuchin monkeys (Sapajus libidinosus).

Natural selection for positional behavior (posture and locomotion) has at least partially driven the evolution of anatomical form and function in the order Primates. Examination of bipedal behaviors associated with daily activity patterns, foraging, and terrestrial habitat use in nonhuman primates, particularly those that adopt bipedal postures and use bipedal locomotion, allows us to refine hypotheses concerning the evolution of bipedalism in humans. This study describes the positional behavior of wild bearded capuchins (Sapajus libidinosus), a species that is known for its use of terrestrial substrates and its habitual use of stones as tools. Here, we test the association of terrestrial substrate use with bipedal posture and locomotion, and the influence of sex (which co-varies with body mass in adults of this species) on positional behavior and substrate use. Behavior and location of 16 wild adult bearded capuchins from two groups were sampled systematically at 15 s intervals for 2 min periods for 1 year (10,244 samples). Despite their different body masses, adult males (average 3.5 kg) and females (average 2.1 kg) in this study did not differ substantially in their positional behaviors, postures, or use of substrates for particular activities. The monkeys used terrestrial substrates in 27% of samples. Bipedal postures and behaviors, while not a prominent feature of their behavior, occurred in different forms on the two substrates. The monkeys crouched bipedally in trees, but did not use other bipedal postures in trees. While on terrestrial substrates, they also crouched bipedally but occasionally stood upright and moved bipedally with orthograde posture. Bearded capuchin monkeys' behavior supports the suggestion from anatomical analysis that S. libidinosus is morphologically better adapted than its congeners to adopt orthograde postures.

Drugtamer-PROTAC Conjugation Strategy for Targeted PROTAC Delivery and Synergistic Antitumor Therapy.

Proteolysis-targeting chimeras (PROTACs) have emerged as a promising strategy for targeted protein degradation and drug discovery. To overcome the inherent limitations of conventional PROTACs, an innovative drugtamer-PROTAC conjugation approach is developed to enhance tumor targeting and antitumor potency. Specifically, a smart prodrug is designed by conjugating "drugtamer" to a nicotinamide phosphoribosyltransferase (NAMPT) PROTAC using a tumor microenvironment responsible linker. The "drugtamer" consists of fluorouridine nucleotide and DNA-like oligomer. Compared to NAMPT PROTAC and the combination of PROTAC + fluorouracil, the designed prodrug AS-2F-NP demonstrates superior tumor targeting, efficient cellular uptake, improved in vivo potency and reduced side effects. This study provides a promising strategy for the precise delivery of PROTAC and synergistic antitumor agents.

The 100 most-cited publications on Peyronie's disease: a bibliometric analysis and visualization study.

This study aimed to summarize the characteristics of the top 100 most-cited publications on Peyronie's disease (PD) research and to analyse past and current research hotspots and trends. The SCI-E database of the Web of Science Core Collection (WoSCC) provided us with the top 100 most-cited publications in PD research, from which we took the following information: general trend of publication, year of publication, nation/region, institution, journal, author, and keywords. VOSviewer (version 1.6.18) and Excel (version 2016) were used for information analysis. Through a standardized search, we ultimately found 1019 papers in the field of PD research, from which we extracted the 100 articles that had received the highest citations. The articles were published between 1949 and 2016. The United States is a major contributor to PD research (n = 67). The University of California, Los Angeles, was the institution with the largest number of articles (n = 11). These articles were published in 16 journals, with the largest number appearing in the Journal of Urology (n = 47). The author with the most articles was Levine LA (n = 9). Gelbard MK's articles had the highest citation frequency (n = 1158). Erectile dysfunction (n = 19) was the keyword with the highest frequency, indicating that PD-related erectile dysfunction was the leading focus of research in this field. Most of the keywords that have appeared in the past decade are related to the clinical treatment of PD. Therefore, we believe that improving patients' erectile function to the greatest extent in clinical treatment is the frontier and hot spot of future research.

Silencing DOCK2 Attenuates Cardiac Fibrosis Following Myocardial Infarction in Mice Via Targeting PI3K/Akt and Wnt/ß-Catenin Pathways.

Cardiac fibrosis following myocardial infarction (MI) seriously affects the prognosis and survival rate of patients. This study aimed to determine the effect and regulation mechanism of the dedicator of cytokinesis 2 (DOCK2) during this process. Experiments were carried out in mice in vivo, and in Ang II treated cardiac fibroblasts (CFs) in vitro. DOCK2 was increased in mouse myocardial tissues after MI and Ang II-treated CFs. In MI mice, DOCK2 silencing improved cardiac function, and ameliorated cardiac fibrosis. DOCK2 knockdown suppressed the activation of CFs and decreased the expression of α-SMA, collagen I, and collagen III. Suppression of DOCK2 mitigated Ang II induced migration of CFs. DOCK2 inhibition reduced the activity of the PI3K/Akt and Wnt/ß-catenin pathways, while this change could be reversed by the pathway activators, SC79 and SKL2001. In summary, DOCK2 suppression improves cardiac dysfunction and attenuates cardiac fibrosis after MI via attenuating PI3K/Akt and Wnt/ß-catenin pathways.

l-Theanine Prevents Colonic Damage via NF-κB/MAPK Signaling Pathways Induced by a High-Fat Diet in Rats.

SCOPE: l-Theanine (l-Thea) is an amino acid which is naturally present in tea leaves. It has been associated with possible health advantages, including obesity prevention, but the underlying molecular mechanisms have not been elucidated. METHODS AND RESULTS: A multiomics approach is utilized to examine the mechanism by which l-Thea exerts its antiobesity effects. This study reveals that l-Thea administration significantly ameliorates high-fat diet (HFD)-induced obesity in rats by improving body weight and hyperlipidemia. l-Thea mitigates HFD-induced inflammation and reverses hepatic and colonic damage, and intestinal barrier. This research verifies that the preventive effect of l-Thea on obesity in rats induced by an HFD with colitis is accomplished by suppressing the phosphorylation of important proteins in the NF-κB/mitogen-activated protein kinase (MAPK) pathways. Metabolome analysis reveals that l-Thea regulates HFD-induced metabolic disorders, specifically through modulation of steroid hormone biosynthesis. Microbiome analysis reveals that l-Thea mitigates HFD-induced dysbiosis by increasing the relative abundance of obesity-associated probiotic bacteria, including Blautia coccoides and Lactobacillus murinus, while simultaneously suppressing the abundance of pathogenic bacteria. CONCLUSIONS: l-Thea alleviates colitis generated by an HFD by restoring the integrity of the intestinal barrier, suppressing inflammation through regulation of MAPK/NF-κB signaling pathways, and enhancing microbial metabolism in colon.