PLA2G2D promotes immune escape in non-small cell lung cancer by regulating T cell immune function through PD-L1-expressing extracellular vesicles.

It is urgent to explore factors affecting immunotherapy efficacy to benefit non-small cell lung cancer (NSCLC) patient survival. Bioinformatics predicted genes associated with programmed cell death ligand 1 (PD-L1) expression and analysed phospholipase A2 group IID (PLA2G2D) expression in NSCLC. BODIPY 493/503 dye staining and kits detected lipids, triglycerides, and phospholipids in H1299 cells, respectively. Extracellular vesicles (EVs) were extracted for morphology and size assessment using electron microscopy. Western blot assayed CD9, CD63, HSP90, EVs-PD-L1, PD-L1, and PLA2G2D expression. CCK-8, LDH, and ELISA tested proliferation and toxicity of CD8+ T cells, interleukin-2, and interferon-gamma secretion, respectively. PLA2G2D, PD-L1, and Ki67 expression was detected by immunohistochemistry. Immunofluorescence assayed PLA2G2D localisation and CD8+ T cell content. Flow cytometry assessed PD-L1 and CD8 expression. In NSCLC, upregulated EVs-PD-L1 and clinical characteristics showed a strong correlation. H1299 cells with overexpression PD-L1 significantly reduced proliferation, toxicity of CD8+ T cells, and interleukin-2 and interferon-gamma levels. Bioinformatics revealed positive correlations between PLA2G2D and overexpressed PD-L1. PLA2G2D was expressed in macrophages and dendritic cells in NSCLC tissue. Overexpression PLA2G2D (oe-PLA2G2D) increased lipids, triglycerides, and phospholipids contents in H1299 cells. oe-PLA2G2D significantly reduced proliferation, toxicity of CD8+ T cells, and interleukin-2 and interferon-gamma levels. si-PD-L1 restored inhibition of oe-PLA2G2D on CD8+ T cells. oe-PLA2G2D significantly increased mice tumour volume and weight, upregulated expression of blood EVs-PD-L1 and tissue PD-L1, PLA2G2D, Ki67, and decreased CD8+ T cell content. PLA2G2D facilitated immune escape in NSCLC by regulating CD8+ T cell immune function by upregulating EVs-PD-L1.

N6-methyladenosine-modified circ_104797 sustains cisplatin resistance in bladder cancer through acting as RNA sponges.

BACKGROUND: Bladder cancer (BCa) ranks among the predominant malignancies affecting the urinary system. Cisplatin (CDDP) remains a cornerstone therapeutic agent for BCa management. Recent insights suggest pivotal roles of circular RNA (circRNA) and N6-methyladenosine (m6A) in modulating CDDP resistance in BCa, emphasizing the importance of elucidating these pathways to optimize cisplatin-based treatments. METHODS: Comprehensive bioinformatics assessments were undertaken to discern circ_104797 expression patterns, its specific interaction domains, and m6A motifs. These findings were subsequently corroborated through experimental validations. To ascertain the functional implications of circ_104797 in BCa metastasis, in vivo assays employing CRISPR/dCas13b-ALKBH5 were conducted. Techniques, such as RNA immunoprecipitation, biotin pull-down, RNA pull-down, luciferase reporter assays, and western blotting, were employed to delineate the underlying molecular intricacies. RESULTS: Our investigations revealed an elevated expression of circ_104797 in CDDP-resistant BCa cells, underscoring its pivotal role in sustaining cisplatin resistance. Remarkably, demethylation of circ_104797 markedly augmented the potency of cisplatin-mediated apoptosis. The amplification of circ_104797 in CDDP-resistant cells was attributed to enhanced RNA stability, stemming from an augmented m6A level at a distinct adenosine within circ_104797. Delving deeper, we discerned that circ_104797 functioned as a microRNA reservoir, specifically sequestering miR-103a and miR-660-3p, thereby potentiating cisplatin resistance. CONCLUSIONS: Our findings unveil a previously uncharted mechanism underpinning cisplatin resistance and advocate the potential therapeutic targeting of circ_104797 in cisplatin-administered patients with BCa, offering a promising avenue for advanced BCa management.

Stability of a calibrant as certified reference material for determination of trans-zearalenone by high performance liquid chromatography-diode array detection-triple quadrupole tandem mass spectrometry.

In this study, a trans-zearalenone (trans-ZEN) calibrant in acetonitrile as certified reference material (CRM) was prepared and intensively investigated the stability by high performance liquid chromatography coupled diode array detection and triple quadrupole tandem mass spectrometry (HPLC-DAD-MS/MS). The photoisomerization and degradation of main component and related impurities in trans-ZEN calibrant CRM was studied in detail under different light conditions such as UV light (254 nm), sunlight, and visible light. Trans-ZEN in acetonitrile was confirmed a significant shift toward cis-ZEN up to a 52% cis-isomerization rate after exposing to UV light (254 nm) in transparent ampule for 1 day. The unsaturated double bond photosensitive groups of trans-ZEN and cis-ZEN will further undergo photoreaction to generate more isomers and related products with the increase of UV irradiation time. The calibrant in amber ampules was relatively stable after exposing to sunlight for 28 days, with only 0.35% cis-isomer observed. The results indicated that trans-ZEN solution calibrant should be packed in amber ampules to avoid UV rays. Thermal stability test exhibited this calibrant was stable over 6 weeks even at 60 °C. Trans-ZEN was found to be more stable in acetonitrile than in methanol since an unknown impurity was observed in methanol after 6 weeks placed at 25 °C. The stability study of trans-ZEN calibrant provided a basis for the usage, storage, and transportation of the CRM. A concentration and expanded uncertainty of the trans-ZEN calibrant CRM of 11.01 ± 0.18 µg/mL was developed.

LncRNA H19 Regulates Proliferation, Apoptosis and ECM Degradation of Aortic Smooth Muscle Cells Via miR-1-3p/ADAM10 Axis in Thoracic Aortic Aneurysm.

Thoracic aortic aneurysm (TAA) is a prevalent health problem worldwide. Long non-coding RNA H19was highly expressed in TAA patients, but the function and mechanism of H19 in TAA remain unknown. The expression levels of H19, microRNA-1-3p (miR-1-3p), and a disintegrin and metalloproteinase 10 (ADAM10) were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Receiver operating characteristic (ROS) cure was performed to evaluate the diagnostic value of H19 on TAA patients. Proliferation and apoptosis were detected by Cell Counting Kit-8 (CCK-8), colony formation, and flow cytometry. Protein levels of proliferating cell nuclear antigen (PCNA), Cleaved-caspase 3 (Cleaved-cas3), Cleaved-caspase 9 (Cleaved-cas9), Collagen I, Collagen III, and ADAM10 were tested by western blot assay. The binding relationship between miR-1-3p and H19 or ADAM10 was predicted by LncBase Predicted v.2 or Starbase, and verified by the dual-luciferase reporter, RNA pull-down assay, and RNA Immunoprecipitation (RIP) assays. H19 was increased in TAA aorta tissues and serum and vascular smooth muscle cell (VSMC), and hindered proliferation as well as promoted apoptosis and extracellular matrix (ECM) degradation of VSMC. Moreover, miR-1-3p was decreased, and ADAM10 was upregulated in TAA aorta tissues and VSMC. The mechanical analysis confirmed that H19 affected ADAM10 expression by targeting miR-1-3p. Our results indicated that H19 inhibited proliferation, and accelerated apoptosis and ECM degradation of VSMC, providing an underlying lncRNA-targeted therapy for TAA treatment.

Construction of Decision Trees Based on Gene Expression Omnibus Data to Classify Bladder Cancer and Its Subtypes.

BACKGROUND Bladder cancer is a malignant tumor of the genitourinary system. Different subtypes of bladder cancer have different treatment methods and prognoses. Therefore, identifying hub genes affecting other genes is of great significance for the treatment of bladder cancer. MATERIAL AND METHODS We obtained expression profiles from the GSE13507 and GSE77952 datasets from the Gene Expression Omnibus database. First, principal component analysis was used to identify the difference in gene expression in different types of tissues. Differential expression analysis was used to find the differentially expressed genes between normal and tumor tissues, and between tumors with and without muscle infiltration. Further, based on differentially expressed genes, we constructed 2 decision trees for differentiating between tumor and normal tissues, and between muscle-infiltrating and non-muscle-infiltrating tumor tissues. A receiver operating characteristic curve was used to evaluate the prediction effect of the decision trees. RESULTS FAM107A and C8orf4 showed significantly lower expression in bladder cancer tissues than in normal tissues. Regarding muscle infiltration, CTHRC1 showed lower expression and HMGCS2 showed higher expression in non-muscle-infiltrating samples than in those with muscle infiltration. We constructed 2 decision trees for differentiating between tumor and normal tissue, and between tissues with and without muscle infiltration. Both decision trees showed good prediction results. CONCLUSIONS These newly discovered hub genes will be helpful in understanding the occurrence and development of different subtypes of bladder cancer, and will provide new therapeutic targets and biomarkers for bladder cancer.

LSD1 deletion represses gastric cancer migration by upregulating a novel miR-142-5p target protein CD9.

LSD1 (histone lysine specific demethylase 1) takes part in the physiological process of cell differentiation, EMT (epithelial-mesenchymal transition) and immune response. In this study, we found LSD1 expression in metastatic gastric cancer tissues was significantly higher than that in normal tissues. Furthermore, LSD1 deletion was found to suppress gastric cancer migration by decreasing intracellular miR-142-5p, which further led to the upregulation of migration suppressor CD9, a newly identified target of miR-142-5p. While LSD1 was reported as a demethylase of H3K4me1/2, H3K9me1/2 and several non-histone proteins, this is a new evidence for LSD1 as a functional regulator of miRNA. On the other hand, our data suggested that promoting the secretion of miR-142-5p using small extracellular vesicles as vehicles is a new mechanism for LSD1 abrogation to down-regulate intracellular miR-142-5p. Taken together, this study uncovered a new mechanism for LSD1 that can contribute to gastric cancer migration by facilitating miR-142-5p to target CD9.

Long non-coding RNA HOXA-AS2 promotes the migration, invasion and stemness of bladder cancer via regulating miR-125b/Smad2 axis.

Long non-coding RNA HOXA-AS2 (HOXA cluster antisense RNA 2) has been reported to function as an oncogene in different types of cancers including breast cancer, liver cancer, gastric cancer and colorectal cancer, etc. However, its role in the development and progression of bladder cancer remains unknown. This study aimed to examine the expression of HOXA-AS2 in bladder cancer, to explore its role in the migration, invasion and stemness of bladder cancer cells and to further identify the potential downstream target miRNAs of HOXA-AS2 in this type of cancer. Our results firstly demonstrated the upregulation of HOXA-AS2 in both bladder cancer cells and clinical bladder tumors. Such upregulation was also positively correlated with the advanced stage, invasion and lymph node metastasis of bladder cancer as well as the expression of cancer stem cell marker OCT4 in patients. After knockdown of HOXA-AS2 in bladder cancer 5637 and T24 cells, the migration, invasion and stemness of cancer cells were significantly inhibited, indicating the capability of HOXA-AS2 to promote the migration, invasion and stemness of bladder cancer cells. Knockdown of HOXA-AS2 also suppressed in vivo tumor growth in the nude mice. Furthermore, this study also identified miR-125b as a downstream target of HOXA-AS2 and revealed the downregulation of miR-125b by HOXA-AS2 as well as the involvement of HOXA-AS2/miR-125b/Smad2 interactions in the functional role of HOXA-AS2 in mediating the migration, invasion and stemness of bladder cancer cells. Together, our findings suggest that HOXA-AS2 might be a potential biomarker and target for the diagnosis, monitoring and treatment of bladder cancer.

Sanggenon O induced apoptosis of A549 cells is counterbalanced by protective autophagy.

Sanggenon O (SO) is a Diels-Alder type adduct extracted fromMorus alba, which has been used for its anti-inflammatory action in the Oriental medicine. However, whether it has regulatory effect on human cancer cell proliferation and what the underlying mechanism remains unknown. Here, we found that SO could significantly inhibit the growth and proliferation of A549 cells and induce its pro-apoptotic action through a caspase-dependent pathway. It could also impair the mitochondria which can be reflected by mitochondrial membrane permeabilization. Besides, SQSTM1 up-regulation and autophagic flux measurement demonstrated that exposure to SO led to autophagosome accumulation, which plays a protective role in SO-treated cells. In addition, knocking down of LC3B increased SO triggered apoptotic cell rates. These results indicated that SO has great potential as a promising candidate combined with autophagy inhibitor for the treatment of NSCLC. In conclusion, our results identified a novel mechanism by which SO exerts potent anticancer activity.

Asymmetric Synthesis of the Antiviral Diterpene Wickerol A.

Wickerol A (1) is an unusual diterpene with remarkable activity against the H1N1 influenza virus. Its tetracyclic skeleton contains three quaternary carbons and is marked by several syn-pentane interactions which force a six-membered ring into a twist-boat conformation. We present an asymmetric synthesis of wickerol A (1) that is based on a Jung Diels-Alder reaction, an intramolecular alkylation to complete the 6-5-6-6 ring system, and a conjugate addition, all of which overcome considerable steric strain. During the synthesis, we isolated an unexpected cyclopropane that presumably stems from a carbonium ion intermediate.

Expression patterns of miR-146a and miR-146b in mastitis infected dairy cattle.

This study reports a significant up-regulation of bta-miR-146a and bta-miR-146b expression levels in bovine mammary tissues infected with subclinical, clinical and experimental mastitis. Potential target genes are involved in multiple immunological pathways. These results suggest a regulatory function of both miRNAs for the bovine inflammatory response in mammary tissue.

Electro-catalytic degradation of sulfisoxazole by using graphene anode.

Graphite and graphene electrodes were prepared by using pure graphite as precursor. The electrode materials were characterized by a scanning electron microscope (SEM), X-ray diffraction (XRD) and cyclic voltammetry (CV) measurements. The electro-catalytic activity for degradation of sulfisoxazole (SIZ) was investigated by using prepared graphene or graphite anode. The results showed that the degradation of SIZ was much more rapid on the graphene than that on the graphite electrode. Moreover, the graphene electrode exhibited good stability and recyclability. The analysis on the intermediate products and the measurement of active species during the SIZ degradation demonstrated that indirect oxidation is the dominant mechanism, involving the electro-catalytic generation of OH and O2(-) as the main active oxygen species. This study implies that graphene is a promising potential electrode material for long-term application to electro-catalytic degradation of organic pollutants.

Meta-analysis of elastic versus rigid fixation in the treatment of acute tibiofibular syndesmosis injury.

OBJECTIVE: The objective of this study was to conduct a meta-analysis by synthesizing multiple literature sources to explore whether there are any differences between elastic fixation and rigid fixation in the treatment of acute tibiofibular syndesmosis injuries. The aim was to provide effective guidance for clinical treatment. METHODS: We conducted a comprehensive search across seven databases, including both Chinese and English, to include all studies related to the treatment of acute tibiofibular syndesmosis injuries with elastic fixation and rigid fixation published between January 1, 2013, and November 15, 2022. Following the PRISMA guidelines, we rigorously screened, assessed, and extracted data from the included studies. The outcome measures included AOFAS scores at 3, 6, and 12 months postoperatively; tibiofibular clear space (TBCS) and tibiofibular overlap distance (TBOL) at the early postoperative and 12-month follow-up; intraoperative blood loss; operative time; time to full weight-bearing postoperatively; and postoperative complications. Meta-analysis was performed using Review Manager 5.4. RESULTS: A total of 35 studies were included, comprising 16 randomized controlled trials and 19 retrospective cohort studies. The study population included 2120 cases, with 1044 cases in the elastic fixation group and 1076 cases in the rigid fixation group. The elastic fixation group had higher AOFAS scores at 3, 6, and 12 months postoperatively compared to the rigid fixation group. Although the elastic fixation group had a slightly larger TBCS than the rigid fixation group in the early postoperative period, the difference between the two groups became statistically insignificant at 12 months postoperatively. There was no statistically significant difference in TBOL between the two groups in the early postoperative period, but at 12 months, the elastic fixation group had a greater TBOL than the rigid fixation group. Additionally, the elastic fixation group had lower rates of postoperative local irritation, wound infection, and postoperative internal fixation loosening or rupture compared to the rigid fixation group. The rate of postoperative tibiofibular redislocation did not differ statistically between the two groups. The time to full weight-bearing was shorter in the elastic fixation group than in the rigid fixation group. Although the elastic fixation group had a slightly longer operative time, there was no statistically significant difference in intraoperative blood loss between the two groups. CONCLUSION: Compared to rigid fixation, elastic fixation in the treatment of acute tibiofibular syndesmosis injuries offers several advantages, including better postoperative ankle joint function recovery, more precise anatomical reduction of the syndesmosis postoperatively, a lower incidence of postoperative complications, and shorter time to full weight-bearing postoperatively. These findings provide robust guidance for clinical treatment.

Assessing Spatial Representativeness of Global Flux Tower Eddy-Covariance Measurements Using Data from FLUXNET2015.

Large datasets of carbon dioxide, energy, and water fluxes were measured with the eddy-covariance (EC) technique, such as FLUXNET2015. These datasets are widely used to validate remote-sensing products and benchmark models. One of the major challenges in utilizing EC-flux data is determining the spatial extent to which measurements taken at individual EC towers reflect model-grid or remote sensing pixels. To minimize the potential biases caused by the footprint-to-target area mismatch, it is important to use flux datasets with awareness of the footprint. This study analyze the spatial representativeness of global EC measurements based on the open-source FLUXNET2015 data, using the published flux footprint model (SAFE-f). The calculated annual cumulative footprint climatology (ACFC) was overlaid on land cover and vegetation index maps to create a spatial representativeness dataset of global flux towers. The dataset includes the following components: (1) the ACFC contour (ACFCC) data and areas representing 50%, 60%, 70%, and 80% ACFCC of each site, (2) the proportion of each land cover type weighted by the 80% ACFC (ACFCW), (3) the semivariogram calculated using Normalized Difference Vegetation Index (NDVI) considering the 80% ACFCW, and (4) the sensor location bias (SLB) between the 80% ACFCW and designated areas (e.g. 80% ACFCC and window sizes) proxied by NDVI. Finally, we conducted a comprehensive evaluation of the representativeness of each site from three aspects: (1) the underlying surface cover, (2) the semivariogram, and (3) the SLB between 80% ACFCW and 80% ACFCC, and categorized them into 3 levels. The goal of creating this dataset is to provide data quality guidance for international researchers to effectively utilize the FLUXNET2015 dataset in the future.

Differences of microplastics and nanoplastics in urban waters: Environmental behaviors, hazards, and removal.

Microplastics (MPs) and nanoplastics (NPs) are ubiquitous in the aquatic environment and have caused widespread concerns globally due to their potential hazards to humans. Especially, NPs have smaller sizes and higher penetrability, and therefore can penetrate the human barrier more easily and may pose potentially higher risks than MPs. Currently, most reviews have overlooked the differences between MPs and NPs and conflated them in the discussions. This review compared the differences in physicochemical properties and environmental behaviors of MPs and NPs. Commonly used techniques for removing MPs and NPs currently employed by wastewater treatment plants and drinking water treatment plants were summarized, and their weaknesses were analyzed. We further comprehensively reviewed the latest technological advances (e.g., emerging coagulants, new filters, novel membrane materials, photocatalysis, Fenton, ozone, and persulfate oxidation) for the separation and degradation of MPs and NPs. Microplastics are more easily removed than NPs through separation processes, while NPs are more easily degraded than MPs through advanced oxidation processes. The operational parameters, efficiency, and potential governing mechanisms of various technologies as well as their advantages and disadvantages were also analyzed in detail. Appropriate technology should be selected based on environmental conditions and plastic size and type. Finally, current challenges and prospects in the detection, toxicity assessment, and removal of MPs and NPs were proposed. This review intends to clarify the differences between MPs and NPs and provide guidance for removing MPs and NPs from urban water systems.

Integrin α2 promotes immune escape in non-small-cell lung cancer by enhancing PD-L1 expression in exosomes to inhibit CD8 + T-cell activity.

This study intended to delineate the mechanism and functional role of integrin α2 (ITGA2) in non-small-cell lung cancer (NSCLC) cell immune escape. Bioinformatics analysis was utilized to analyze ITGA2 expression in NSCLC tissues, and correlations between ITGA2 expression and patient survival time, ITGA2 expression and programmed cell death ligand 1 (PD-L1; CD274) expression, and ITGA2 expression and CD8+ T-cell infiltration. Quantitative real-time polymerase chain reaction detected ITGA2 expression. Transmission electron microscopy was applied to examine the morphology of exosomes, and western blot measured CD9, CD63, and PD-L1 levels. CCK-8 measured cell viability. Cell toxicity experiment measured the killing effect of CD8+ T cells on cancer cells. Enzyme-linked immunosorbent assay assessed secretion levels of interleukin-2, interferon-gamma, tumor necrosis factor-alpha, and PD-L1 expression in exosomes. Immunohistochemistry detected ITGA2, CD8, and PD-L1 expression in patient tissue samples. ITGA2 was highly expressed in NSCLC, and Pearson correlation analysis showed a negative correlation of ITGA2 with CD8+ T-cell infiltration and a positive correlation of ITGA2 with PD-L1 expression. Cell experiments showed that silencing ITGA2 hindered NSCLC cell progression and increased levels of CD8+ T-cell secretory factors. Further mechanism studies found that ITGA2 reduced CD8+ T-cell-mediated antitumor immunity via the increase in PD-L1 expression. Clinical sample testing unveiled that ITGA2 was upregulated in NSCLC tissues. PD-L1 upregulation was seen in exosomes separated from patient blood, and correlation analysis showed a positive correlation of exosomal PD-L1 expression in blood with ITGA2 expression in tissues. This study displays a novel mechanism and role of ITGA2 in NSCLC immune escape, providing directions for the clinical therapy of NSCLC patients.

Role of iron in host-microbiota interaction and its effects on intestinal mucosal growth and immune plasticity in a piglet model.

Iron is an essential trace element for both the host and resident microbes in the gut. In this study, iron was administered orally and parenterally to anemic piglets to investigate the role of iron in host-microbiota interaction and its effects on intestinal mucosal growth and immune plasticity. We found that oral iron administration easily increased the abundance of Proteobacteria and Escherichia-Shigella, and decreased the abundance of Lactobacillus in the ileum. Furthermore, similar bacterial changes, namely an increase in Proteobacteria, Escherichia-Shigella, and Fusobacterium and a reduction in the Christensenellaceae_R-7_group, were observed in the colon of both iron-supplemented groups. Spearman's correlation analysis indicated that the changed Fusobacterium, Fusobacteria and Proteobacteria in the colon were positively correlated with hemoglobin, colon and spleen iron levels. Nevertheless, it was found that activated mTOR1 signaling, improved villous height and crypt depth in the ileum, enhanced immune communication, and increased protein expression of IL-22 and IL-10 in the colon of both iron-supplemented groups. In conclusion, the benefits of improved host iron outweigh the risks of altered gut microbiota for intestinal mucosal growth and immune regulation in treating iron deficiency anemia.

Efficacy and safety evaluation of complete intrafascial prostatectomy in suspected prostate cancer patients with dysuria: a retrospective cohort study.

Background: Suspected localized prostate cancer (PCa) patients with dysuria Complete intrafascial prostatectomy (CIP) can remove the whole prostate gland with the maximal retain of adjacent normal tissues around the prostate, and can be applied in some suspected localized prostate cancer (PCa) patients with dysuria. However, precious few studies have assessed the efficacy and safety of CIP in these patients without preoperative needle biopsies. Methods: In this retrospective single-arm cohort study, all 22 suspected PCa patients with dysuria who underwent CIP at our hospital were enrolled. The clinical data including age, prostate-specific antigen (PSA), free-serum PSA, prostate volume, perioperative and postoperative complications were collected. The PSA level at 6 weeks after CIP and recoveries of urinary continence and erectile function were acquired in the follow-up procedures, and were used as the main measurements of efficacy and safety for CIP respectively. Results: The patients had an average age of 71.91±8.29 years and an average preoperative PSA level of 10.75±4.25 ng/mL. The operations for all 22 patients were successfully completed. The average operation time was 135.20±41.44 min (range, 40.0-215.0 min), and the average blood loss volume was 128.64±145.09 mL. In total, 17 patients (77.27%) had PCa confirmed by postoperative pathology, and 5 patients (22.73%) had benign prostatic hyperplasia. The PSA level dropped to 0.010±0.004 ng/mL at 6 weeks after surgery. According to the loose criteria to assess urinary incontinence, the patients achieved continence rates of 63.6% immediately after the operation, 95.5% at 1 month, and 100% at 3 months. According to the strict criteria, the continence rates immediately, and at 1, 3, 6, and 9 months after surgery were 27.3%, 63.6%, 90.9%, 95.5%, and 100%, respectively. None of the patients complained of urinary obstruction symptoms after surgery. Before CIP, all the patients had erectile dysfunction and an International Index of Erectile Function 5 (IIEF-5) score of 9.64±5.91. After surgery, the patients had IIEF-5 scores at 3, 6, and 12 months of 5.45±4.43, 6.95±5.30, and 7.57±5.69, respectively. Conclusions: Although the study had some limitations, CIP may be a prudent option for patients with suspected localized PCa who also present with dysuria.

The potential risks posed by micro-nanoplastics to the safety of disinfected drinking water.

Micro-nanoplastics (M-NPs) have become an emerging critical issue in the environment because they migrate easily, can bioaccumulate with toxic effects, and are difficult to degrade. Unfortunately, the current technologies for removing or degrading M-NPs in drinking water are insufficient to eliminate them completely, and residual M-NPs in drinking water may pose a threat to human health by impairing human immunity and metabolism. In addition to their intrinsic toxic effects, M-NPs may be even more harmful after drinking water disinfection than before disinfection. Herein, this paper comprehensively summarizes the negative impacts of several commonly used disinfection processes (ozone, chlorine, and UV) on M-NPs. Moreover, the potential leaching of dissolved organics from M-NPs and the production of disinfection byproducts during the disinfection process are discussed in detail. Moreover, due to the diversity and complexity of M-NPs, their adverse effects may exceed those of conventional organics (e.g., antibiotics, pharmaceuticals, and algae) after the disinfection process. Finally, we propose enhanced conventional drinking water treatment processes (e.g., enhanced coagulation, air flotation, advanced adsorbents, and membrane technologies), detection of residual M-NPs, and biotoxicological assessment as promising and ecofriendly candidates to efficiently remove M-NPs and avoid the release of secondary hazards.

Micafungin: A promising inhibitor of UBE2M in cancer cell growth suppression.

Neddylation is a protein modification process similar to ubiquitination, carried out through a series of activating (E1), conjugating (E2), and ligating (E3) enzymes. This process has been found to be overactive in various cancers, leading to increased oncogenic activities. Ubiquitin-conjugating enzyme 2 M (UBE2M) is one of two neddylation enzymes that play a vital role in this pathway. Studies have shown that targeting UBE2M in cancer treatment is crucial, as it regulates many molecular mechanisms like DNA damage, apoptosis, and cell proliferation. However, developing small molecule inhibitors against UBE2M remains challenging due to the lack of suitable druggable pockets. We have discovered that Micafungin, an antifungal agent that inhibits the production of 1,3-ß-D-glucan in fungal cell walls, acts as a neddylation inhibitor that targets UBE2M. Biochemical studies reveal that Micafungin obstructs neddylation and stabilizes UBE2M. In cellular experiments, the drug was found to interact with UBE2M, prevent neddylation, accumulate cullin ring ligases (CRLs) substrates, reduce cell survival and migration, and induce DNA damage in gastric cancer cells. This research uncovers a new anti-cancer mechanism for Micafungin, paving the way for the development of a novel class of neddylation inhibitors that target UBE2M.

Electrochemical reduction of wastewater by non-noble metal cathodes: From terminal purification to upcycling recovery.

A shift beyond conventional environmental remediation to a sustainable pollutant upgrading conversion is extremely desirable due to the rising demand for resources and widespread chemical contamination. Electrochemical reduction processes (ERPs) have drawn considerable attention in recent years in the fields of oxyanion reduction, metal recovery, detoxification and high-value conversion of halogenated organics and benzenes. ERPs also have the potential to address the inherent limitations of conventional chemical reduction technologies in terms of hydrogen and noble metal requirements. Fundamentally, mechanisms of ERPs can be categorized into three main pathways: direct electron transfer, atomic hydrogen mediation, and electrode redox pairs. Furthermore, this review consolidates state-of-the-art non-noble metal cathodes and their performance comparable to noble metals (e.g., Pd, Pt) in electrochemical reduction of inorganic/organic pollutants. To overview the research trends of ERPs, we innovatively sort out the relationship between the electrochemical reduction rate, the charge of the pollutant, and the number of electron transfers based on the statistical analysis. And we propose potential countermeasures of pulsed electrocatalysis and flow mode enhancement for the bottlenecks in electron injection and mass transfer for electronegative pollutant reduction. We conclude by discussing the gaps in the scientific and engineering level of ERPs, and envisage that ERPs can be a low-carbon pathway for industrial wastewater detoxification and valorization.