Chronic prostatitis/chronic pelvic pain syndrome induces metabolomic changes in expressed prostatic secretions and plasma.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a complex disease that is often accompanied by mental health disorders. However, the potential mechanisms underlying the heterogeneous clinical presentation of CP/CPPS remain uncertain. This study analyzed widely targeted metabolomic data of expressed prostatic secretions (EPS) and plasma to reveal the underlying pathological mechanisms of CP/CPPS. A total of 24 CP/CPPS patients from The Second Nanning People's Hospital (Nanning, China), and 35 asymptomatic control individuals from First Affiliated Hospital of Guangxi Medical University (Nanning, China) were enrolled. The indicators related to CP/CPPS and psychiatric symptoms were recorded. Differential analysis, coexpression network analysis, and correlation analysis were performed to identify metabolites that were specifically altered in patients and associated with various phenotypes of CP/CPPS. The crucial links between EPS and plasma were further investigated. The metabolomic data of EPS from CP/CPPS patients were significantly different from those from control individuals. Pathway analysis revealed dysregulation of amino acid metabolism, lipid metabolism, and the citrate cycle in EPS. The tryptophan metabolic pathway was found to be the most significantly altered pathway associated with distinct CP/CPPS phenotypes. Moreover, the dysregulation of tryptophan and tyrosine metabolism and elevation of oxidative stress-related metabolites in plasma were found to effectively elucidate the development of depression in CP/CPPS. Overall, metabolomic alterations in the EPS and plasma of patients were primarily associated with oxidative damage, energy metabolism abnormalities, neurological impairment, and immune dysregulation. These alterations may be associated with chronic pain, voiding symptoms, reduced fertility, and depression in CP/CPPS. This study provides a local-global perspective for understanding the pathological mechanisms of CP/CPPS and offers potential diagnostic and therapeutic targets.

Mechanical, physical and thermal properties of composite materials produced with the basidiomycete Fomes fomentarius.

BACKGROUND: To achieve climate neutrality, fundamentally new concepts of circularity need to be implemented by the building sector as it contributes to 40% of anthropogenic CO2 emission. Fungal biotechnology can make a significant contribution here and help eliminate fossil dependency for building material production. Recently, we have shown that the medicinal polypore Fomes fomentarius feeds well on renewable lignocellulosic biomass and produces composite materials that could potentially replace fossil fuel-based expanded polystyrene as insulation material. RESULTS: In this study, we explored the mechanical, physical, and thermal properties of F. fomentarius-based composite materials in more detail and determined key performance parameters that are important to evaluate the usability of F. fomentarius-based composite materials in the construction sector. These parameters were determined according to European standards and included compressive strength, modulus of elasticity, thermal conductivity, water vapour permeability, and flammability of uncompressed composites as well as flexural strength, transverse tensile strength, and water absorption capacity of heat-pressed composites, among others. We could show that uncompressed composites obtained from F. fomentarius and hemp shives display a thermal conductivity of 0.044 W (m K)-1 which is in the range of natural organic fibres. A water vapour permeability of 1.72 and classification into flammability class B1 clearly surpasses fossil-based insulation materials including expanded polystyrene and polyurethane. We could furthermore show that heat-pressing can be used to reliably generate stiff and firm particleboards that have the potential to replace current wood-based particleboards that contain synthetic additives. X-ray microcomputed tomography finally visualized for the first time the growth of hyphae of F. fomentarius on and into the hemp shive substrates and generated high-resolution images of the microstructure of F. fomentarius-based composites. CONCLUSION: This study demonstrates that fungal-based composites produced with F. fomentarius partially meet or even exceed key performance parameters of currently used fossil fuel-based insulation materials and can also be used to replace particleboards.

Circulating exosomal mRNA signatures for the early diagnosis of clear cell renal cell carcinoma.

BACKGROUND: There are no proven tumor biomarkers for the early diagnosis of clear cell renal cell carcinoma (ccRCC) thus far. This study aimed to identify novel biomarkers of ccRCC based on exosomal mRNA (emRNA) profiling and develop emRNA-based signatures for the early detection of ccRCC. METHODS: Four hundred eighty-eight participants, including 226 localized ccRCCs, 73 patients with benign renal masses, and 189 healthy controls, were recruited. Circulating emRNA sequencing was performed in 12 ccRCCs and 22 healthy controls in the discovery phase. The candidate emRNAs were evaluated with 108 ccRCCs and 70 healthy controls in the test and training phases. The emRNA-based signatures were developed by logistic regression analysis and validated with additional cohorts of 106 ccRCCs, 97 healthy controls, and 73 benign individuals. RESULTS: Five emRNAs, CUL9, KMT2D, PBRM1, PREX2, and SETD2, were identified as novel potential biomarkers of ccRCC. We further developed an early diagnostic signature that comprised KMT2D and PREX2 and a differential diagnostic signature that comprised CUL9, KMT2D, and PREX2 for RCC detection. The early diagnostic signature displayed high accuracy in distinguishing ccRCCs from healthy controls, with areas under the receiver operating characteristic curve (AUCs) of 0.836 and 0.830 in the training and validation cohorts, respectively. The differential diagnostic signature also showed great performance in distinguishing ccRCCs from benign renal masses (AUC = 0.816), including solid masses (AUC = 0.810) and cystic masses (AUC = 0.832). CONCLUSIONS: We established and validated novel emRNA-based signatures for the early detection of ccRCC and differential diagnosis of uncertain renal masses. These signatures could be promising and noninvasive biomarkers for ccRCC detection and thus improve the prognosis of ccRCC patients.

Effects of different potassium-lowering regimens on acute hyperkalemia in hemodialysis patients: a real-world, retrospective study.

BACKGROUND: Hyperkalemia is a common and potentially life-threatening electrolyte disorder in maintenance hemodialysis (MHD) patients. This study aimed to evaluate the efficacy and safety of potassium-lowering regimens during treatment of acute hyperkalemia in MHD patients. METHODS: This retrospective real-world study (RWS) was conducted among 139 MHD patients. They were given different potassium-lowering regimens, viz. the insulin and glucose (IG) intravenous administration group (IG, 46 patients), the sodium polystyrene sulfonate group (SPS, 33 patients), the sodium zirconium cyclosilicate group (SZC, 38 patients), the IG + SZC group (22 patients). The primary efficacy end point was the rate of serum potassium decline at 2 h. The rates of adverse events were also compared. RESULTS: At 2 h, the mean ± SE change of serum potassium level was - 0.71 ± 0.32 mmol per liter (mmol/L) in IG group, - 0.43 ± 0.38 mmol/L in SPS group, - 0.64 ± 0.36 mmol/L in SZC group, - 1.43 ± 0.38 mmol/L in IG + SZC group (P < 0.01). The serum potassium level in IG + SZC group decreased more than that in the other three groups (P < 0.01), while the serum potassium level in SPS group decreased less than that in the other three groups (P < 0.05). There was no significant difference on the decrease of the serum potassium level between IG group and the SZC group (P = 0.374). The IG group and the IG + SZC group had higher rates of symptomatic hypoglycemia. The SPS group had significant decreases of serum calcium and serum magnesium after treatment. CONCLUSIONS: Among MHD patients with acute hyperkalemia, SZC had similar potassium-lowering efficacy with IG intravenous administration at 2 h and superior on convenience and side-effects.

Single-cell transcriptomics reveals cell type diversity of human prostate.

Extensive studies have been performed to describe the phenotypic changes occurring during malignant transformation of the prostate. However, the cell types and associated changes that contribute to the development of prostate diseases and cancer remain elusive, largely due to the heterogeneous composition of prostatic tissues. Here, we conduct a comprehensive evaluation of four human prostate tissues by single-cell RNA sequencing (scRNA-seq) to analyze their cellular compositions. We identify 18 clusters of cell types, each with distinct gene expression profiles and unique features; of these, one cluster of epithelial cells (Ep) is found to be associated with immune function. In addition, we characterize a special cluster of fibroblasts and aberrant signaling changes associated with prostate cancer (PCa). Moreover, we provide insights into the epithelial changes that occur during the cellular senescence and aging. These results expand our understanding of the unique functional associations between the diverse prostatic cell types and the contributions of specific cell clusters to the malignant transformation of prostate tissues and PCa development.

Single-cell transcriptomes reveal characteristic features of cell types within the human adrenal microenvironment.

Various cells within the adrenal microenvironment are important in maintaining the body homeostasis. However, our understanding of adrenal disease pathogenesis is limited by an incomplete molecular characterization of the cell types responsible for the organ's multiple homeostatic functions. We report a cellular landscape of the human adrenal gland using single-cell RNA sequencing. We reveal characteristic features of cell types within the human adrenal microenvironment and found immune activation of nonimmune cells in the adrenal endothelial cells. We also reveal that abundant immune cells occupied a lot of space in adrenal gland. Additionally, Sex-related diversity in the adrenocortical cells and different gene expression profiles between the left and right adrenal gland are also observed at single-cell resolution. Together, at single-cell resolution, the transcriptomic map presents a comprehensive view of the human adrenal gland, which serves as a fundamental baseline description of this organ and paves a way for the further studies of adrenal diseases.

The Endogenous Alterations of the Gut Microbiota and Feces Metabolites Alleviate Oxidative Damage in the Brain of LanCL1 Knockout Mice.

Altered composition of the gut microbiota has been observed in many neurodegenerative diseases. LanCL1 has been proven to protect neurons and reduce oxidative stress. The present study was designed to investigate alterations of the gut microbiota in LanCL1 knockout mice and to study the interactions between gut bacteria and the brain. Wild-type and LanCL1 knockout mice on a normal chow diet were evaluated at 4 and 8-9 weeks of age. 16s rRNA sequence and untargeted metabolomics analyses were performed to investigate changes in the gut microbiota and feces metabolites. Real-time polymerase chain reaction analysis, AB-PAS staining, and a TUNEL assay were performed to detect alterations in the gut and brain of knockout mice. The serum cytokines of 9-week-old knockout mice, which were detected by a multiplex cytokine assay, were significantly increased. In the central nervous system, there was no increase of antioxidant defense genes even though there was only low activity of glutathione S-transferase in the brain of 8-week-old knockout mice. Interestingly, the gut tight junctions, zonula occludens-1 and occludin, also displayed a downregulated expression level in 8-week-old knockout mice. On the contrary, the production of mucus increased in 8-week-old knockout mice. Moreover, the compositions of the gut microbiota and feces metabolites markedly changed in 8-week-old knockout mice but not in 4-week-old mice. Linear discriminant analysis and t-tests identified Akkermansia as a specific abundant bacteria in knockout mice. Quite a few feces metabolites that have protective effects on the brain were reduced in 8-week-old knockout mice. However, N-acetylsphingosine was the most significant downregulated feces metabolite, which may cause the postponement of neuronal apoptosis. To further investigate the effect of the gut microbiota, antibiotics treatment was given to both types of mice from 5 to 11 weeks of age. After treatment, a significant increase of oxidative damage in the brain of knockout mice was observed, which may have been alleviated by the gut microbiota before. In conclusion, alterations of the gut microbiota and feces metabolites alleviated oxidative damage to the brain of LanCL1 knockout mice, revealing that an endogenous feedback loop mechanism of the microbiota-gut-brain axis maintains systemic homeostasis.

Synthetic Anti-PT Symmetry in a Single Microcavity.

Non-Hermitian systems based on parity-time (PT) and anti-PT symmetry reveal rich physics beyond the Hermitian regime. So far, realizations of such symmetric systems have been limited to the spatial domain. Here we theoretically and experimentally demonstrate synthetic anti-PT symmetry in a spectral dimension induced by nonlinear Brillouin scattering in a single optical microcavity, where Brillouin scattering induced transparency or absorption in two spectral resonances provides the optical gain and loss to observe a phase transition between two symmetry regimes. This scheme provides a new paradigm towards the investigation of non-Hermitian physics in a synthetic photonic dimension for all-optical signal processing and quantum information science.

Coherent control of acoustic phonons by seeded Brillouin scattering in polarization-maintaining fibers.

Coherent excitation of phonons by optical waves, one of the most important channels for light-matter interactions, provides a promising route for optical manipulation of microscopic acoustic phonons for quantum opto-mechanic and phononic devices. Prior research, such as stimulated Brillouin scattering (SBS) in fibers, mainly emphasized phonon amplitude modulation; however, coherent phase control of these phonons has not yet been well explored. Here we experimentally demonstrate a new mechanism to coherently control acoustic phonon phases by a seeded SBS scheme in an optical fiber. Interference between acoustic phonons enables either nearly total transmission or enhanced reflection of optical waves, effectively controlled by phase modulation. This new technique addresses the crucial problem of phase-controlled phonon generation, paving the way for important applications in quantum opto-mechanic and phononic devices.

VDR Activation Reduces Proteinuria and High-Glucose-Induced Injury of Kidneys and Podocytes by Regulating Wnt Signaling Pathway.

BACKGROUND: Diabetic nephropathy (DN) is a major cause of end-stage renal disease and proteinuria is one of the most prominent clinical manifestations. The expression of Vitamin D receptor (VDR) in patients with chronic kidney diseases was decreased, while VDR agonists could partially alleviate the proteinuria of DN in animal models. The present study was designed to determine the expression of VDR in renal tissues and its relationship with proteinuria the diabetic model db/db mice. METHODS: The regulation effects of VDR on the Wnt signaling pathway were analyzed using RNA interference and VDR agonist paricalcitol. RESULTS: With the increase in age of the db/db mice, the VDR protein and mRNA levels in renal tissues were decreased, proteinuria increased, and the protein and mRNA levels of GSK-3ß of and ß-catenin increased. Paricalcitol treatment resulted in the up-regulation of VDR and down-regulation of GSK-3ß and ß-catenin, indicating that VDR had a regulatory effect on the Wnt signaling pathway. CONCLUSION: VDR activation could reduce proteinuria of DN mice and alleviate high-glucose-induced injury of kidneys and podocytes by regulating the key molecules of Wnt signaling pathway.

Ultra-low temperature silicon nitride photonic integration platform.

High-quality SiNx films with controllable low stress and low optical loss are deposited at ultra-low temperature (75 °C) using inductively coupled plasma chemical vapor deposition (ICP-CVD). Two kinds of integrated photonic structures have been demonstrated that exemplify its viability as a photonic integration platform. A microcavity consists of two distributed Bragg reflectors (DBR) formed by alternating a total of 49 layers of SiNx and SiO2 with a total thickness of about 11.5 µm is grown without any cracks, confirming the excellent stress control in the process. Microring resonators are also fabricated in as-deposited planar SiNx waveguide layer using electron-beam lithography (EBL) and plasma etching. Average waveguide loss of 0.79 ± 0.22 dB/cm has been achieved in the range of 1550-1600 nm for ring radii larger than 40 µm. The ultra-low temperature grown SiNx with properties of low loss and low stress is therefore a promising photonic integration platform for various photonic integration applications.

[Dinggui Oil Capsule in treating irritable bowel syndrome with stagnation of qi and cold: a prospective, multi-center, randomized, placebo-controlled, double-blind trial].

OBJECTIVE: To evaluate the efficacy and safety of Dinggui Oil Capsule in treating irritable bowel syndrome (IBS) with stagnation of qi and cold. METHODS: A prospective, randomized, placebo-controlled, double-blind clinical study was undertaken. One hundred and ninety-eight patients with IBS and syndrome of stagnation of qi and cold were randomly divided into high-dose Dinggui Oil group (DGO-H, 1.2 g, 3 times daily; n=66), low-dose Dinggui Oil group (DGO-L, 0.8 g, 3 times daily, n=66), and placebo group (placebo, 5.0 g, 3 times daily, n=66). Patients in the three groups were all treated for 2 weeks. RESULTS: The total significant effective rates for IBS were 54.1%, 28.8% and 21.9% in the DGO-H, DGO-L, and placebo groups, and the total effective rates for the syndrome of stagnation of qi and cold were 54.1%, 25.8% and 23.4% in the three groups, respectively. Dinggui Oil Capsule showed a higher efficacy than the placebo in relieving the abdominal pain (P<0.01). No adverse effects were found in this trial. CONCLUSION: Dinggui Oil Capsule is effective and safe in relieving abdominal pain due to IBS with stagnation of qi and cold.