Network pharmacological analysis and experimental study of melatonin in chronic prostatitis/chronic pelvic pain syndrome.

This study is aimed at exploring the potential mechanisms of melatonin (MT) in treating chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) using network pharmacology and experimental study. The target genes of MT were acquired from the Swiss Target Prediction, SuperPred, SEA, and PharmMapper databases, and the CP/CPPS targets were collected based on OMIM, DisGeNET, and GeneCards databases. The intersection of MT and CP/CPPS target genes was analyzed. A PPI network was constructed using Cytoscape to identify core targets. The shared targets underwent GO and KEGG enrichment analyses by Using R software. Molecular docking of MT with core targets was performed using AutoDock and PyMOL. GROMACS software was used for molecular dynamics simulation. And using cell experiments to verify the potential effect of MT in CP/CPPS. Network pharmacology analysis reveals 284 shared targets between MT and CP/CPPS, with AKT1, SRC, HSP90AA1, PTGS2, BCL2L1, ALB, CASP3, NFKB1, HIF1A, and ESR1 identified as key targets. Enrichment analysis indicates that MT affects CP/CPPS through various biological processes, and pathway analysis emphasizes the significance of PI3K-Akt, MAPK, Ras, FoxO, HIF-1, EGFR, and apoptosis pathways. Molecular docking confirms strong binding between MT and core targets. It is worth noting that the molecular dynamics simulation showed that the average binding free energy of AKT1, PTGS2, ALB, HSP90AA1 proteins, and MT was - 26.15, - 29.48, - 18.59, and - 20.09 kcal/mol, respectively. These results indicated that AKT1, PTGS2, ALB, and HSP90AA1 proteins were strongly bound to MT. Cell experiments demonstrate that MT can inhibit the secretion of IL-1ß, IL-6, and TNF-α in LPS-induced RWPE-1 cells, alleviate inflammation, and suppress cell apoptosis and oxidative stress. Network pharmacology, molecular docking, molecular dynamics simulation, and cell experiments showed that MT could play a role in CP/CPPS by regulating multiple targets and pathways. These findings provide an important scientific basis for further exploration of the molecular mechanism and clinical application of MT in CP/CPPS treatment and are expected to provide new ideas and directions for the development of novel therapeutic strategies.

Vacancy-Driven High-Performance Metabolic Assay for Diagnosis and Therapeutic Evaluation of Depression.

Depression is one of the most common mental illnesses and is a well-known risk factor for suicide, characterized by low overall efficacy (<50%) and high relapse rate (40%). A rapid and objective approach for screening and prognosis of depression is highly desirable but still awaits further development. Herein, a high-performance metabolite-based assay to aid the diagnosis and therapeutic evaluation of depression by developing a vacancy-engineered cobalt oxide (Vo-Co3O4) assisted laser desorption/ionization mass spectrometer platform is presented. The easy-prepared nanoparticles with optimal vacancy achieve a considerable signal enhancement, characterized by favorable charge transfer and increased photothermal conversion. The optimized Vo-Co3O4 allows for a direct and robust record of plasma metabolic fingerprints (PMFs). Through machine learning of PMFs, high-performance depression diagnosis is achieved, with the areas under the curve (AUC) of 0.941-0.980 and an accuracy of over 92%. Furthermore, a simplified diagnostic panel for depression is established, with a desirable AUC value of 0.933. Finally, proline levels are quantified in a follow-up cohort of depressive patients, highlighting the potential of metabolite quantification in the therapeutic evaluation of depression. This work promotes the progression of advanced matrixes and brings insights into the management of depression.

Device-assisted intravesical chemotherapy versus bacillus Calmette-Guerin for intermediate or high-risk non-muscle invasive bladder cancer: a systematic reviewer and meta-analysis.

PURPOSE: To investigate the effectiveness and safety of device-assisted intravesical chemotherapy compared to Bacillus Calmette-Guerin (BCG) in the treatment of patients with intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC). METHODS: In February 2023, a systematic search was conducted on the PubMed, Cochrane, and Embase databases. Following the PRISMA guidelines, a systematic review and meta-analysis of the primary outcomes of interest were performed. The review was prospectively registered on PROSPERO under the registration number CRD42023398559. RESULTS: A total of 10 studies involving 1160 patients were included. The results of the meta-analysis showed that compared to BCG, device-assisted chemotherapy had a lower recurrence rate (OR: 0.63, 95% CI: 0.48-0.84, p = 0.001), longer recurrence-free survival (OR: 0.64, 95% CI: 0.47-0.88, p = 0.006), and lower incidence of fever (OR: 0.18, 95% CI: 0.08-0.44, p = 0.0002). However, no significant differences were observed between the two groups in terms of progression, overall survival, progression-free survival, disease-free survival, overall adverse events, serious adverse events, hematuria, allergy, and general discomfort. Subgroup analysis revealed that neither chemohyperthermia (CHT) nor electromotive drug administration (EMDA) showed statistically significant differences in oncological outcomes compared to BCG. Regarding adverse events, both CHT and EMDA groups showed lower rates of fever compared to the BCG group (OR: 0.26, 95% CI: 0.10-0.67, p = 0.005, and OR: 0.14, 95% CI: 0.05-0.37, p < 0.0001, respectively). No significant differences were observed in the remaining adverse events between either the CHT or EMDA group and the BCG group. CONCLUSION: Device-assisted intravesical chemotherapy appears to be a safe and viable alternative to BCG for patients with intermediate and high-risk NMIBC, showing comparable oncological outcomes and adverse events.

Designed Nanomaterials-Assisted Proteomics and Metabolomics Analysis for In Vitro Diagnosis.

In vitro diagnosis (IVD) is pivotal in modern medicine, enabling early disease detection and treatment optimization. Omics technologies, particularly proteomics and metabolomics, offer profound insights into IVD. Despite its significance, omics analyses for IVD face challenges, including low analyte concentrations and the complexity of biological environments. In addition, the direct omics analysis by mass spectrometry (MS) is often hampered by issues like large sample volume requirements and poor ionization efficiency. Through manipulating their size, surface charge, and functionalization, as well as the nanoparticle-fluid incubation conditions, nanomaterials have emerged as a promising solution to extract biomolecules and enhance the desorption/ionization efficiency in MS detection. This review delves into the last five years of nanomaterial applications in omics, focusing on their role in the enrichment, separation, and ionization analysis of proteins and metabolites for IVD. It aims to provide a comprehensive update on nanomaterial design and application in omics, highlighting their potential to revolutionize IVD.

The combination of tetracyclines effectively ameliorates liver fibrosis via inhibition of EphB1/2.

Eph receptor tyrosine kinase EphB1/2 contributes to the development of liver fibrosis, suggesting the rationale that EphB1/2 inhibitors may be effective in liver fibrosis therapy. Since tetracycline antibiotics were recently demonstrated as EphB kinase inhibitors, in present study we investigated their therapeutic potential against liver fibrosis. Our results showed that the tetracycline combination of demeclocycline (D), chlortetracycline (C), and minocycline (M) inhibited the activation of hepatic stellate cells (HSCs) in vitro and alleviated CCl4-induced animal model of liver fibrosis in vivo. Mechanistically, DCM combination inhibited EphB1/2 phosphorylation and subsequent activation of the MAPK signaling. Moreover, we found that short-term and low-dose DCM combination treatment decreased tissue inflammation and improved liver fibrosis in mice. Thus, our study indicates that tetracyclines may be repurposed for the treatment of liver fibrosis.

Biological control of Magnaporthe oryzae using natively isolated Bacillus subtilis G5 from Oryza officinalis roots.

Rice blast, caused by Magnaporthe oryzae, is a major threat to global rice production causing significant crop losses and impacting grain quality. The annual loss of rice production due to this disease ranges from 10% to 30%. The use of biologically controlled strains, instead of chemical pesticides, to control plant diseases has become a research hotspot. In this study, an antagonistic endophytic bacterial strain was isolated from the roots of Oryza officinalis using the traditional isolation and culture methods. A phylogenetic tree based on 16S RNA and whole-genome sequencing identified isolate G5 as a strain of Bacillus subtilis. This isolate displayed strong antagonistic effects against different physiological strains of M. oryzae. After co-culture in LB medium for 7 days, the inhibition rates of the mycelial growth of four strains of M. oryzae, ZB15, WH97, Guy11, and T-39800E were 98.07 ± 0.0034%, 98.59 ± 0.0051%, 99.16 ± 0.0012%, and 98.69 ± 0.0065%, respectively. Isolate G5 significantly inhibited the formation of conidia of M. oryzae, with an inhibition rate of 97% at an OD600 of 2. Isolate G5 was able to provide 66.81% protection against rice blast under potted conditions. Whole-genome sequencing revealed that the genome size of isolate G5 was 4,065,878 bp, including 4,182 coding genes. Using the anti-SMASH software, 14 secondary metabolite synthesis gene clusters were predicted to encode antifungal substances, such as fengycin, surfactin, and bacilysin. The G5 isolate also contained genes related to plant growth promotion. These findings provide a theoretical basis for expounding the biocontrol mechanisms of this strain and suggest further development of biogenic agents that could effectively inhibit rice blast pathogen growth and reduce crop damage, while being environmentally friendly, conducive to ecological development, and a sustainable alternative to chemical pesticides. This study also enriches the relevant research on endophytes of wild rice, which proves that wild rice is a valuable microbial resource bank.

Hollow multishelled heterostructures with enhanced performance for laser desorption/ionization mass spectrometry based metabolic diagnosis.

High-performance metabolic diagnosis-based laser desorption/ionization mass spectrometry (LDI-MS) improves the precision diagnosis of diseases and subsequent treatment. Inorganic matrices are promising for the detection of metabolites by LDI-MS, while the structure and component impacts of the matrices on the LDI process are still under investigation. Here, we designed a multiple-shelled ZnMn2O4/(Co, Mn)(Co, Mn)2O4 (ZMO/CMO) as the matrix from calcined MOF-on-MOF for detecting metabolites in LDI-MS and clarified the synergistic impacts of multiple-shells and the heterostructure on LDI efficiency. The ZMO/CMO heterostructure allowed 3-5 fold signal enhancement compared with ZMO and CMO with the same morphology. Furthermore, the ZMO/CMO heterostructure with a triple-shelled hollow structure displayed a 3-fold signal enhancement compared to its nanoparticle counterpart. Taken together, the triple-shelled hollow ZMO/CMO exhibits 102-fold signal enhancement compared to the commercial matrix products (e.g., DHB and DHAP), allowing for sensitive metabolic profiling in bio-detection. We directly extracted metabolic patterns by the optimized triple-shelled hollow ZMO/CMO particle-assisted LDI-MS within 1 s using 100 nL of serum and used machine learning as the readout to distinguish hepatocellular carcinoma from healthy controls with the area under the curve value of 0.984. Our approach guides us in matrix design for LDI-MS metabolic analysis and drives the development of a nanomaterial-based LDI-MS platform toward precision diagnosis.

Construction of a ternary component chip with enhanced desorption efficiency for laser desorption/ionization mass spectrometry based metabolic fingerprinting.

Introduction: In vitro metabolic fingerprinting encodes diverse diseases for clinical practice, while tedious sample pretreatment in bio-samples has largely hindered its universal application. Designed materials are highly demanded to construct diagnostic tools for high-throughput metabolic information extraction. Results: Herein, a ternary component chip composed of mesoporous silica substrate, plasmonic matrix, and perfluoroalkyl initiator is constructed for direct metabolic fingerprinting of biofluids by laser desorption/ionization mass spectrometry. Method: The performance of the designed chip is optimized in terms of silica pore size, gold sputtering time, and initiator loading parameter. The optimized chip can be coupled with microarrays to realize fast, high-throughput (∼second/sample), and microscaled (∼1 µL) sample analysis in human urine without any enrichment or purification. On-chip urine fingerprints further allow for differentiation between kidney stone patients and healthy controls. Discussion: Given the fast, high throughput, and easy operation, our approach brings a new dimension to designing nano-material-based chips for high-performance metabolic analysis and large-scale diagnostic use.

Neddylation of EphB1 Regulates Its Activity and Associates with Liver Fibrosis.

Liver fibrosis is a pathological process characterized by the excessive synthesis and accumulation of extracellular matrix proteins (ECMs) contributed mainly by the activated hepatic stellate cells (HSCs). Currently, no direct and effective anti-fibrotic agents have been approved for clinical use worldwide. Although the dysregulation of Eph receptor tyrosine kinase EphB2 has been reported to associate with the development of liver fibrosis, the involvement of other Eph family members in liver fibrosis remains underexplored. In this study, we found that the expression of EphB1 is significantly increased accompanying remarkable neddylation in activated HSCs. Mechanistically, this neddylation enhanced the kinase activity of EphB1 by the prevention of its degradation, thereby promoting the proliferation, migration, and activation of HSCs. Our findings revealed the involvement of EphB1 in the development of liver fibrosis through its neddylation, which provides new insights into the Eph receptor signaling and a potential target for the treatment of liver fibrosis.

Designed Concave Octahedron Heterostructures Decode Distinct Metabolic Patterns of Epithelial Ovarian Tumors.

Epithelial ovarian cancer (EOC) is a polyfactorial process associated with alterations in metabolic pathways. A high-performance screening tool for EOC is in high demand to improve prognostic outcome but is still missing. Here, a concave octahedron Mn2 O3 /(Co,Mn)(Co,Mn)2 O4 (MO/CMO) composite with a heterojunction, rough surface, hollow interior, and sharp corners is developed to record metabolic patterns of ovarian tumors by laser desorption/ionization mass spectrometry (LDI-MS). The MO/CMO composites with multiple physical effects induce enhanced light absorption, preferred charge transfer, increased photothermal conversion, and selective trapping of small molecules. The MO/CMO shows ≈2-5-fold signal enhancement compared to mono- or dual-enhancement counterparts, and ≈10-48-fold compared to the commercialized products. Subsequently, serum metabolic fingerprints of ovarian tumors are revealed by MO/CMO-assisted LDI-MS, achieving high reproducibility of direct serum detection without treatment. Furthermore, machine learning of the metabolic fingerprints distinguishes malignant ovarian tumors from benign controls with the area under the curve value of 0.987. Finally, seven metabolites associated with the progression of ovarian tumors are screened as potential biomarkers. The approach guides the future depiction of the state-of-the-art matrix for intensive MS detection and accelerates the growth of nanomaterials-based platforms toward precision diagnosis scenarios.

Enhanced spin-orbit torque and field-free switching in Au/TMDs/Ni hybrid structures.

Spin-orbit torque (SOT) plays a significant role in spintronic logic and memory devices. However, due to the limited spin Hall angle and SOT symmetry in a heavy-metal-ferromagnet bilayer, further improving SOT efficiency and all-electric magnetization manipulation remain a challenge. Here we report enhanced SOT efficiency and all-electric switching in Au based magnetic structures, by inserting two-dimensional transition metal dichalcogenides (2D TMDs) with large spin-orbit coupling. With the TMD spacer insert, both damping-like and field-like SOTs are improved, and an unconventional out-of-plane damping-like SOT is induced, due to the interface orbital hybridization, modified spin-mixing conductance and orbital current. Moreover, current induced field-free magnetization switching is demonstrated in Au/WTe2/Ni and Au/MoS2/Ni devices, and it shows multiple intermediate states and can be efficiently controlled by an electric current. Our results open a path for increasing torques and expand the application of 2D TMDs in spintronic devices for neuromorphic computing.

Probing the Interaction Between Supercarrier RBC Membrane and Nanoparticles for Optimal Drug Delivery.

Red blood cell (RBC) membrane-hitchhiking nanoparticles (NPs) have been an increasingly popular supercarrier for targeted drug delivery. However, the kinetic details of the shear-induced NP detachment process from RBC in blood flow remain unclear. Here, we perform detailed computational simulations of the traversal dynamics of an RBC-NP composite supercarrier with tunable properties. We show that the detachment of NPs from RBC occurs in a shear-dependent manner which is consistent with previous experiment results. We quantify the NP detachment rate in the microcapillary flow, and our simulation results suggest that there may be an optimal adhesion strength span of 25-40 µJ/m2 for rigid spherical NPs to improve the supercarrier performance and targeting efficiency. In addition, we find that the stiffness and the shape of NPs alter the detachment efficiency by changing the RBC-NP contact areas. Together, these findings provide unique insights into the shear-dependent NP release from the RBC surface, facilitating the clinical utility of RBC-NP composite supercarriers in targeted and localized drug delivery with high precision and efficiency.

Effects of Low-intensity Extracorporeal Shockwave Therapy on Erectile Dysfunction: A Systematic Review and Meta-analysis.

This present systemic review and meta-analysis was conducted to assess the effectiveness of low-intensity extracorporeal shockwave therapy (Li-ESWT) on erectile dysfunction (ED) based on the relevant randomised controlled trials (RCTs). A comprehensive search of databases, including Medline and Embase databases, from 1st January 2012 to 31st July 2020, that investigated the efficacy of Li-ESWT for ED, was searched. All the trials were divided into two groups: the experimental group received a different shockwave treatment, and the control group received the same treatment as the corresponding experimental group vibration, sound, etc) but no energy transmission. The primary endpoint was the International Index of Erectile Function-Erectile Function domain (IIEF-EF) score/questionnaire or erectile hardness score (EHS). The average IIEF-EF score was increased with statistical significance in the Li-ESWT group relative to the control group (p<0.001). Besides, the Li-ESWT group had evidently elevated changes in IIEF-EF score (p<0.001). Altogether seven articles reported the remarkably elevated EHS score with different total pulses (p<0.001). The favourable outcomes in terms of the average IIEF scores were observed in the cases developing mild or moderate ED (p<0.001). Compared with placebo treatment, Li-ESWT alleviates ED symptoms in patients, particularly those who have mild or moderate ED. Taken together, these results suggest that the Li-ESWT may hold promise for patients with ED. Key Words: Erectile dysfunction, Low-intensity extracorporeal shockwave therapy, Meta-analysis, Randomised controlled trials.

Demethylzeylasteral attenuates hepatic stellate cell activation and liver fibrosis by inhibiting AGAP2 mediated signaling.

BACKGROUND: Liver fibrosis is a common cause of chronic liver disease. If left untreated, it can ultimately develop into liver cirrhosis or hepatocellular carcinoma. However, a direct antifibrotic therapy is currently unavailable. A re-examination of existing chemicals might be a potential strategy for finding more lead compounds against liver fibrosis. Demethylzeylasteral (T-96), a naturally occurring bioactive compound found in Tripterygium wilfordii Hook. f. (TwHf) possesses multiple pharmacological properties. However, its antifibrotic potential has not yet been fully evaluated. PURPOSE: This study aimed to investigate the antifibrotic properties of T-96 and its underlying molecular mechanisms. METHODS: The antifibrotic properties of T-96 were investigated in three types of hepatic stellate cells (HSCs) and in a CCl4-induced liver fibrosis mouse model. The effect of T-96 on the proliferation, migration, and activation of HSCs was detected using CCK-8 and scratch/wound healing assays. Hepatic inflammation and fibrosis were evaluated by H&E, Masson's trichrome stain, and Sirius Red staining. The expression of inflammatory and fibrogenic genes was detected by quantitative real-time PCR (qRT-PCR) and western blotting. RNA sequencing (RNA-seq) was performed to explore the potential molecular mechanisms mediating the antifibrotic effect of T-96, which was verified by dual-luciferase reporter assay, qRT-PCR, western blotting, immunofluorescence, and immunoprecipitation analysis. RESULTS: The T-96 treatment significantly suppressed the proliferation, migration, and activation of HSCs in vitro. The administration of T-96 attenuated hepatic injury, inflammation, and fibrosis progression in mice with CCl4-induced liver fibrosis. In addition, the RNA-seq of fibrotic liver tissues and subsequent functional verification indicated that the key mechanisms of the antifibrotic effect of T-96 were mediated by suppressing the expression of AGAP2 (Arf GAP with GTPase-like domain, ankyrin repeat and PH domain 2), inhibiting the subsequent phosphorylation of focal adhesion kinase (FAK) and protein kinase B (AKT), and finally reducing the expression of fibrosis-related genes. CONCLUSION: Our results provide the first insight that T-96 exerts potent antifibrotic effects both in vitro and in vivo by inhibiting the AGAP2 mediated FAK/AKT signaling axis, and that T-96 may serve as a potential therapeutic candidate for the treatment of liver fibrosis.

Dendrimer-Modified Silica Nanoparticles for Efficient Enrichment of Low-Concentration Peptides.

Peptide profiling based on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is of particular interest as it can provide physiologically and pathologically related information of the bio-samples. Due to the complexity of real biological samples, MALDI-TOF MS-based peptide mapping methods rely strongly on particular enrichment methods to improve the signal intensity. This paper introduces third-generation dendrimer-modified SBA-15 with the surface functionalization of amino and carboxyl group, respectively (denoted as SBA-15/G3-NH2 and SBA-15/G3-COOH), for the efficient capture of low-abundance peptides. The enrichment ability of the nanocomposites was evaluated by standard peptides digests and real biological samples. The synthesized nanocomposites incorporated the benefit of dendrimers and mesoporous silica nanomaterial SBA-15, showing enhanced peptide enrichment ability. Therefore, this work may provide a new class of nanomaterials for peptide mapping from biological samples.

Self-assembly of Peptide dendrimers and their bio-applications in theranostics.

Nanotechnology has brought revolutionized advances in disease diagnosis and therapy. Self-assembled peptide dendrimers own novel physicochemical properties through the synergistic effects of the polypeptide chain, dendrimer and nano-structure, exhibiting great potential in theranostic. This review provides comprehensive insights into various peptide dendrimers for self-assembly. Their nanosize, morphology and composition are presented to understand self-assembly behaviors precisely. We further introduce the emerging theranostic applications based on specific imaging and efficient delivery recently.

Hollow Cobalt Oxide/Carbon Hybrids Aid Metabolic Encoding for Active Systemic Lupus Erythematosus during Pregnancy.

A noninvasive, easy operation, and accurate diagnostic protocol is highly demanded to assess systemic lupus erythematosus (SLE) activity during pregnancy, promising real-time activity monitoring during the whole gestational period to reduce adverse pregnancy outcomes. Here, machine learning of serum metabolic fingerprints (SMFs) is developed to assess the SLE activity for pregnant women. The SMFs are directly extracted through a hollow-cobalt oxide/carbon (Co3 O4 /C)-composite-assisted laser desorption/ionization mass spectrometer (LDI MS) platform. The Co3 O4 /C composite owns enhanced light absorption, size-selective trapping, and better charge-hole separation, enabling improved ionization efficiency and selectivity for LDI MS detection toward small molecules. Metabolic fingerprints are collected from ≈0.1 µL serum within 1 s without enrichment and encoded by the optimized elastic net algorithm. The averaged area under the curve (AUC) value in the differentiation of active SLE from inactive SLE and healthy controls reaches 0.985 and 0.990, respectively. Further, a simplified panel based on four identified metabolites is built to distinguish SLE flares in pregnant women with the highest AUC value of 0.875 for the blind test. This work sets an accurate and practical protocol for SLE activity assessment during pregnancy, promoting precision diagnosis of disease status transitions in clinics.

Association Between Alcohol Consumption and Risk of Bladder Cancer: A Dose-Response Meta-Analysis of Prospective Cohort Studies.

BACKGROUND: Controversial results of the association between alcohol consumption and risk of bladder cancer were reported by the previous meta-analyses. OBJECTIVE: To quantitatively investigate the association between alcohol consumption and risk of bladder cancer based on prospective cohort studies, and explore whether there is potential dose-response relation. METHOD: PubMed, EMBASE, the Cochrane Library databases, China Biology Medicine disc (CBM), and Chinese National Knowledge Infrastructure (CNKI) were searched for relevant studies. Categorical meta-analysis was performed for risk estimates of any alcohol consumers versus non-drinkers as well as different drinking degrees (light, moderate, and heavy) versus none. And two-stage generalized least-squares regression and restricted cubic spline, as well as fixed-effects dose-response models, were used for linear and nonlinear dose-response relation exploration. RESULTS: 9 prospective cohort studies including 1,971,396 individuals were finally included. We did not observe a significant association between alcohol intake and the risk of bladder cancer in the entire population. Linear association was detected in those who consumed alcohol from liquor or spirits (P linear=0.02). One drink increment each day of alcohol could elevate the risk of bladder cancer by 9% (RR=1.09; 95%CI: 1.01-1.17). Alcohol was a risk factor of bladder cancer for male drinkers (RR=1.23; 95%CI: 1.13-1.35; I2=3.7%), while none linear or nonlinear relation was found. CONCLUSION: No significant association between alcohol consumption and bladder cancer risk was found in the entire population, but there was a linear dose-response relation in those who consume alcohol from liquor or spirits. Alcohol may elevate the risk of bladder cancer in males in a dose-independent way. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, PROSPERO (CRD42020216195).

Experimental Research on the Effect of Ultrasonic Waves on the Adsorption, Desorption, and Seepage Characteristics of Shale Gas.

Shale gas reservoirs are tight reservoirs with ultralow porosity and ultralow permeability, and their matrix pores are mostly nanoscale. In addition, matrix particles and organic pore surfaces adsorb shale gas. These problems cause the production per well of shale gas to be lower than that of conventional natural gas. The use of hydraulic fracturing technology to exploit shale gas can achieve a good production increase effect. However, using this technology has some limitations caused by technical characteristics and geological conditions. Therefore, new technologies for shale gas exploitation need to be explored. In this study, we propose a method to improve the flow characteristics of shale gas by using ultrasonic waves to increase shale gas production and perform experimental tests to research the actual effect of this method. The lithology, mineral composition, pore structure, specific surface area, and pore size distribution of shale samples are tested. Then, the attenuation characteristics of ultrasonic waves propagating in shale are analyzed. Finally, the effect of ultrasonic waves on the adsorption, desorption, and seepage of shale gas is explored. Results show that the Langmuir adsorption isotherm can describe the adsorption characteristics of shale gas under the action of ultrasonic waves. The gas adsorption constant decreases with increasing ultrasonic wave power. The ultrasonic waves accelerate the gas desorption rate, significantly increase the desorption volume, and prolong the time taken to reach desorption equilibrium. They also increase the permeability of shale gas, and the growth is proportional to the power of the ultrasonic waves. These results indicate that the permeability of shale gas has a power function relationship with the effective stress under ultrasonic waves.