Anillin contributes to prostate cancer progression through the regulation of IGF2BP1 to promote c-Myc and MAPK signaling.

Prostate cancer (PCa), especially castration-resistant PCa, is a common and fatal disease. Anillin (ANLN) is an actin-binding protein that is involved in various malignancies, including PCa. However, the regulatory mechanism of ANLN in PCa remains unclear. Exploring the role of ANLN in PCa development and discovering novel therapeutic targets are crucial for PCa therapy. In the current work, we discovered that ANLN expression was considerably elevated in PCa tissues and cell lines when compared to nearby noncancerous prostate tissues and normal prostate epithelial cells. ANLN was associated with more advanced T stage, N stage, higher Gleason score, and prostate-specific antigen (PSA) level. In addition, we discovered that overexpression of ANLN promoted PCa cell proliferation, migration, and invasion in vitro and in vivo. Mechanistically, we performed RNA-seq to identify the regulatory influence of ANLN on the MAPK signal pathway. Furthermore, a favorable association between ANLN expression and IGF2BP1 expression was identified. The tumor-suppressive impact of ANLN downregulation on PCa cell growth was partially reversed by overexpressing IGF2BP1. Meanwhile, we discovered that ANLN can stabilize the proto-oncogene c-Myc and activate the MAPK signaling pathway through IGF2BP1. These findings indicate that ANLN could be a potential therapeutic target in PCa.

Repetition Suppression Reveals Cue-Specific Spatial Representations for Landmarks and Self-Motion Cues in the Human Retrosplenial Cortex.

The efficient use of various spatial cues within a setting is crucial for successful navigation. Two fundamental forms of spatial navigation, landmark-based and self-motion-based, engage distinct cognitive mechanisms. The question of whether these modes invoke shared or separate spatial representations in the brain remains unresolved. While nonhuman animal studies have yielded inconsistent results, human investigation is limited. In our previous work (Chen et al., 2019), we introduced a novel spatial navigation paradigm utilizing ultra-high field fMRI to explore neural coding of positional information. We found that different entorhinal subregions in the right hemisphere encode positional information for landmarks and self-motion cues. The present study tested the generalizability of our previous finding with a modified navigation paradigm. Although we did not replicate our previous finding in the entorhinal cortex, we identified adaptation-based allocentric positional codes for both cue types in the retrosplenial cortex (RSC), which were not confounded by the path to the spatial location. Crucially, the multi-voxel patterns of these spatial codes differed between the cue types, suggesting cue-specific positional coding. The parahippocampal cortex exhibited positional coding for self-motion cues, which was not dissociable from path length. Finally, the brain regions involved in successful navigation differed from our previous study, indicating overall distinct neural mechanisms recruited in our two studies. Taken together, the current findings demonstrate cue-specific allocentric positional coding in the human RSC in the same navigation task for the first time and that spatial representations in the brain are contingent on specific experimental conditions.

CircUBE3A(2,3,4,5) promotes adenylate-uridylate-rich binding factor 1 nuclear translocation to suppress prostate cancer metastasis.

Metastatic progression is the primary cause of mortality in prostate cancer (PCa) patients. Although circular RNAs (circRNAs) have been implicated in cancer progression and metastasis, our current understanding of their role in PCa metastasis remains limited. In this study, we identified that circUBE3A(2,3,4,5), which originated from exons 2, 3, 4 and 5 of the human ubiquitin-protein ligase E3A (UBE3A) gene, was specifically downregulated in PCa tissues and correlated with the Gleason score, bone metastasis, and D'Amico risk classification. Through the in vitro and in vivo experiments, we demonstrated that overexpression of circUBE3A(2,3,4,5) inhibited PCa cell migration, invasion, metastasis, and proliferation. Mechanistically, circUBE3A(2,3,4,5) was found to bind to adenylate-uridylate-rich binding factor 1 (AUF1), promoting the translocation of AUF1 into the nucleus. This led to decreased AUF1 in the cytoplasm, resulting in methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) mRNA instability and a subsequent reduction at the protein level. The downregulation of MTHFD2 further inhibited vimentin expression, thereby suppressing PCa cell epithelial-mesenchymal transition. Additionally, two pairs of the short-inverted repeats (TSIRs) in flanking introns were identified to synergistically facilitate the generation of circUBE3A(2,3,4,5) and other circRNAs. In summary, TSIRs-induced circUBE3A(2,3,4,5) acts as a suppressor of PCa metastasis by enhancing AUF1 nuclear translocation, reducing MTHFD2, and subsequently inhibiting vimentin expression. This study characterizes circUBE3A(2,3,4,5) as a functional circRNA and proposes it as a highly promising target for preventing PCa metastasis.

Effect of a High-Starch or a High-Fat Diet on the Milk Performance, Apparent Nutrient Digestibility, Hindgut Fermentation Parameters and Microbiota of Lactating Cows.

In this study, changes in milk performance, nutrient digestibility, hindgut fermentation parameters and microflora were observed by inducing milk fat depression (MFD) in dairy cows fed with a high-starch or a high-fat diet. Eight Holstein cows were paired in a completely randomized cross-over design within two 35 d periods (18 d control period and 17d induction period). During the control period, all cows were fed the low-starch and low-fat diet (CON), and at the induction period, four of the cows were fed a high-starch diet with crushed wheat (IS), and the other cows were fed a high-fat diet with sunflower fat (IO). The results showed that, compared to when the cows were fed the CON diet, when cows were fed the IS or IO diet, they had lower milk fat concentrations, energy corrected milk, 3.5% fat-corrected milk yield, feed efficiency and apparent digestibility of NDF and ADF. However, cows fed the IO diet had a lower apparent digestibility of ether extracts. In addition, we observed that when cows were fed the high-starch (IS) or high-fat (IO) diet, they had a higher fecal concentration of propionate and acetate, and a lower NH3-N. Compared to when the cows were fed the CON diet, cows fed the IS diet had a lower pH, and cows fed the IO diet had a lower concentration of valerate in feces. In the hindgut microbiota, the relative abundance of Oscillospiraceae_UCG-005 was increased, while the Verrucomicrobiota and Lachnospiraceae_AC2044_group were decreased when cows were fed the IO diet. The relative abundance of Prevotellaceae_UCG-003 was increased, while the Alistipes and Verrucomicrobiota decreased, and the Treponema, Spirochaetota and Lachnospiraceae_AC2044_group showed a decreasing trend when cows were fed the IS diet. In summary, this study suggested that high-starch or high-fat feeding could induce MFD in dairy cows, and the high-fat diet had the greatest effect on milk fat; the high-starch or high-fat diet affected hindgut fermentation and apparent fiber digestibility. The changes in hindgut flora suggested that hindgut microbiota may be associated with MFD in cows.

A Gradient Doping Strategy toward Superior Electrochemical Performance for Li-Rich Mn-Based Cathode Materials.

Lithium-rich layered oxides (LLOs) are concerned as promising cathode materials for next-generation lithium-ion batteries due to their high reversible capacities (larger than 250 mA h g-1 ). However, LLOs suffer from critical drawbacks, such as irreversible oxygen release, structural degradation, and poor reaction kinetics, which hinder their commercialization. Herein, the local electronic structure is tuned to improve the capacity energy density retention and rate performance of LLOs via gradient Ta5+ doping. As a result, the capacity retention elevates from 73% to above 93%, and the energy density rises from 65% to above 87% for LLO with modification at 1 C after 200 cycles. Besides, the discharge capacity for the Ta5+ doped LLO at 5 C is 155 mA h g-1 , while it is only 122 mA h g-1 for bare LLO. Theoretical calculations reveal that Ta5+ doping can effectively increase oxygen vacancy formation energy, thus guaranteeing the structure stability during the electrochemical process, and the density of states results indicate that the electronic conductivity of the LLOs can be boosted significantly at the same time. This strategy of gradient doping provides a new avenue to improve the electrochemical performance of the LLOs by modulating the local structure at the surface.

Nostalgia and consumer behavior.

The present review examines how and when nostalgia, a social emotion with a rich history in marketing, affects consumption-relevant outcomes. It comments that in recent years, nostalgia's role within consumer behavior, including advertising, consumption, and product choice operates through feelings of social connectedness, and thus research must consider boundary conditions based on social parameters. Moreover, it discusses the role of nostalgia in buffering the self from threats, how these threats may elicit nostalgia, and the impact on downstream consumption. It finally examines whether nostalgia always does or does not have a positive impact on consumption-relevant outcomes. Across these areas, the review suggests potential future research directions on potential discrepancies that operate through social boundary conditions.

Better timing for HoLEP: a retrospective analysis of patients treated with HoLEP over a 10-year period with a 1-year follow-up.

The aim of this study was to explore the optimal timing of holmium laser enucleation of the prostate (HoLEP) in patients presenting benign prostatic hyperplasia (BPH) with lower urinary tract symptoms (LUTS). A retrospective analysis was conducted based on the perioperative and postoperative outcome data of 1212 patients who underwent HoLEP in Shanghai Ninth People's Hospital (Shanghai, China) between January 2009 and December 2018. According to the preoperative International Prostate Symptom Score (IPSS), all patients whom we analyzed were divided into Group A (IPSS of 8-18) and Group B (IPSS of 19-35). Peri- and postoperative outcome data were obtained during the 1-year follow-up. IPSS changes were the main postoperative outcomes. The postoperative IPSS, quality of life, peak urinary flow rate, postvoid residual, and overactive bladder symptom score (OABSS) improved significantly. The IPSS improved further in the group with severe LUTS symptoms, but the postoperative IPSS was still higher than that in the moderate LUTS group. OABSSs showing moderate and severe cases after follow-up were more frequent in Group B (9.1%) than in Group A (5.2%) (P < 0.05). There were no significant intergroup differences in the intraoperative American Society of Anesthesiologists or hospitalization expense scores, and the medication costs, as well as the total costs, were significantly higher in Group B. In this retrospective study, HoLEP was an effective treatment for symptomatic BPH. For patients with LUTS, earlier surgery in patients with moderate severity may result in a marginally better 12-month IPSS than that in men with severe symptoms.

The short inverted repeats-induced circEXOC6B inhibits prostate cancer metastasis by enhancing the binding of RBMS1 and HuR.

Circular RNAs (circRNAs) are a novel class of endogenous RNAs with a covalently closed loop structure. Many circRNAs have been found to participate in cancer progression. However, the detailed generation process, functions, and related mechanisms of circRNAs in prostate cancer (PCa) remain largely unknown. In the present study, we identified circEXOC6B, a novel suppressor in the metastasis of PCa. Functionally, circEXOC6B, originating from the exocyst complex component 6B (EXOC6B) gene, inhibited migration and invasion of PCa in vitro and in vivo. Mechanistically, by acting as a protein scaffold, circEXOC6B enhanced the binding of human RNA binding motif single strand interacting protein 1 (RBMS1) and human antigen R (HuR) and further increased A-kinase anchoring protein 12 (AKAP12) expression to inhibit PCa metastasis. Unlike previous studies, we found that one pair of short inverted repeats in flanking introns at least partly promoted the circularization of circEXOC6B. Our study presents a novel mechanism for the inhibitory role of circEXOC6B in PCa metastasis and provides new insight into the molecular process of circRNA generation.

Erratum: Long non-coding RNA SNHG5 affects the invasion and apoptosis of renal cell carcinoma by regulating the miR-363-3p-Twist1 interaction.

[This corrects the article on p. 697 in vol. 12, PMID: 32194916.].

In Situ Growth of CoP Nanosheet Arrays on Carbon Cloth as Binder-Free Electrode for High-Performance Flexible Lithium-Ion Batteries.

Cobalt phosphide (CoP) is considered as one of the most promising candidates for anode in lithium-ion batteries (LIBs) owing to its low-cost, abundant availability, and high theoretical capacity. However, problems of low conductivity, heavy aggregation, and volume change of CoP, hinder its practical applicability. In this study, a binder-free electrode is successfully prepared by growing CoP nanosheets arrays directly on a carbon cloth (CC) via a facile one-step electrodeposition followed by an in situ phosphorization strategy. The CoP@CC anode exhibits good interfacial bonding between the CoP and CC, which can improve the conductivity of the integrated electrode. More importantly, the 3D network structure composed of CoP nanosheets and CC provides sufficient space to alleviate the volume expansion of CoP and shorten the electron/ion transport paths. Moreover, the support of CC effectively prevents the agglomeration of CoP. Based on these advantages, when CoP@CC is paired with the NCM523 cathode, the full cell delivers a high discharge capacity 919.6 mAh g-1 (2.1 mAh cm-2 ) after 200 cycles at 0.5 A g-1 . The feasibility and safety of producing pouch cells are also explored, which show good flexibility and safety despite rigorous strikes (mechanical damage and severe deformations), implying a great potential for practical applications.

Systemic regulation of soybean nodulation and nitrogen fixation by nitrogen via isoflavones.

Nitrogen (N) inhibits soybean (Glycine max L.) nodulation and N2 fixation. Isoflavones secreted by soybean roots can stimulate signal transduction for symbiotic nodules, thus playing a key role in root nodule development and N2 fixation. The relationship between the inhibition of soybean nodulation, N2 fixation and isoflavones by N is still unclear. In this study, dual-root soybean plants were prepared by grafting, and N or isoflavones were supplied to unilateral roots. The number and dry weight of the soybean nodules, nitrogenase activity, isoflavone concentrations and relative changes in the level of expression of nodulation-related genes were measured to study the response relationship between the N systemic regulation the soybean nodule N2 fixation and changes in the concentrations of isoflavones in its roots. The results showed that N supply to one side of the dual-root soybeans systematically affected the N2 fixation of root nodules on both sides, and this effect began in the early stage of nodulation. Moreover, a unilateral supply of N systematically affected the concentrations of daidzein and genistein on both sides of the roots. The concentrations of isoflavones were consistent with the change trend of soybean root nodule and nodulation-related gene expression level. Treatment with unilateral N or isoflavones affected the soybean nodule N2 fixation and its nodulation-related genes, which had the same response to the changes in concentrations of root isoflavones. N regulates soybean nodulation and N2 fixation by systematically affecting the concentrations of isoflavones in the roots.

Three new experimental models of anterior urethral stricture in rabbits.

Background: This study describes and compares three surgical procedures for the construction of urethral stricture (US) models in rabbits. Methods: Forty adult male rabbits were allocated to four groups: 36 rabbits were randomly assigned to three experimental groups, while the remaining 4 were assigned to a sham group. The penis was separated from the rectum. Then along the ventral midline, a longitudinal penile skin incision was made while ensuring that the urethral mucosa was intact and the muscular layer was not completely incised. In group 1 (n=12), ventral semi-circumferential mucosa electrocoagulation of a 1-cm length of the anterior urethra was performed until ulceration occurred. In group 2 (n=12), the ventral urethral mucosa was incised, and electrocoagulation of the dorsal semi-circumferential mucosa was performed. In group 3 (n=12), whole-circumferential mucosa electrocoagulation was performed. In group 4 (n=4), no special treatment was performed. Four weeks later, urethrography, urethroscopy, and histological evaluation were carried out. Results: The weights of the rabbits in the four groups were comparable. There was no significant difference between groups 2 and 3 with regard to operative time, but the operative time in these groups was significantly longer than that in group 1 (group 2 vs. group 1: P<0.05, group 3 vs. group 1: P<0.001). After the surgery, urinary fistula with infection occurred in one rabbit in group 1, and one rabbit died due to urethral atresia in group 3. According to the urethrography and urethroscopy findings, 9 out of 12 rabbits in group 1, 5 out of 12 rabbits in group 2, and 11 out of 11 rabbits in group 3 developed US, while no rabbits in the sham group developed US. Histopathological examination revealed injury to the urothelium, inflammatory infiltration, a decrease in the amount of blood vessels and smooth muscle fibers, and a decrease in the amount of collagen fibers. Conclusions: Compared with the semi-circumferential procedures, the whole-circumferential procedure had a higher success rate. Therefore, this procedure seems to have potential for the construction of long-segment rabbit US models.

Deep Learning-Based Multi-Omics Integration Robustly Predicts Relapse in Prostate Cancer.

Objective: Post-operative biochemical relapse (BCR) continues to occur in a significant percentage of patients with localized prostate cancer (PCa). Current stratification methods are not adequate to identify high-risk patients. The present study exploits the ability of deep learning (DL) algorithms using the H2O package to combine multi-omics data to resolve this problem. Methods: Five-omics data from 417 PCa patients from The Cancer Genome Atlas (TCGA) were used to construct the DL-based, relapse-sensitive model. Among them, 265 (63.5%) individuals experienced BCR. Five additional independent validation sets were applied to assess its predictive robustness. Bioinformatics analyses of two relapse-associated subgroups were then performed for identification of differentially expressed genes (DEGs), enriched pathway analysis, copy number analysis and immune cell infiltration analysis. Results: The DL-based model, with a significant difference (P = 6e-9) between two subgroups and good concordance index (C-index = 0.767), were proven to be robust by external validation. 1530 DEGs including 678 up- and 852 down-regulated genes were identified in the high-risk subgroup S2 compared with the low-risk subgroup S1. Enrichment analyses found five hallmark gene sets were up-regulated while 13 were down-regulated. Then, we found that DNA damage repair pathways were significantly enriched in the S2 subgroup. CNV analysis showed that 30.18% of genes were significantly up-regulated and gene amplification on chromosomes 7 and 8 was significantly elevated in the S2 subgroup. Moreover, enrichment analysis revealed that some DEGs and pathways were associated with immunity. Three tumor-infiltrating immune cell (TIIC) groups with a higher proportion in the S2 subgroup (p = 1e-05, p = 8.7e-06, p = 0.00014) and one TIIC group with a higher proportion in the S1 subgroup (P = 1.3e-06) were identified. Conclusion: We developed a novel, robust classification for understanding PCa relapse. This study validated the effectiveness of deep learning technique in prognosis prediction, and the method may benefit patients and prevent relapse by improving early detection and advancing early intervention.

"Fenestration and Tunnel Method" a Modification for the Holmium Laser Transurethral Prostatectomy of Large-Volume Prostates >80 ml: A Retrospective Study Based on 1-Year Follow-Up.

The purpose of this study was to promote the holmium laser enucleation of the prostate (HoLEP) technology for large-volume prostates (>80 ml) and compare it with the traditional method, we modified the technique and applied this technology to clinical practice. A retrospective study comprising 118 patients who underwent HoLEP surgery from February 2018 to December 2019 was conducted in our center. Group A consisted of 57 patients with large-volume prostate (>80 ml) who received modified "fenestration and tunnel method" from February 2019 till December 2019, while group B consisted of 61 patients who received the traditional trivalvular operation method from February 2018 to December 2018 for comparison. Control subjects are selected such that they match the cases concerning certain characteristics, and perioperative data, voiding outcomes, and complications were evaluated at 1- and 12-month follow-up. The international prostatic symptomatic score (IPSS), quality of life (QoL), and maximum flow rate (Qmax) at 1 month and 12 months were both significantly improved compared with the preoperative baseline, and no significant differences were found between Groups A and B. The mean enucleation time, operation time, catheter indwelling duration, and hemoglobin decrease during the operation of Group A showed superiority compared with Group B (p<.05). The modified "fenestration and tunnel method" of HoLEP was statistically superior to the traditional trivalvular method in terms of the operation time, enucleation time, catheter indwelling duration, and hemoglobin decrease. For large-volume prostates (>80 ml), modified HoLEP was suggested to be a better treatment option.

Transcriptome sequencing reveals a lncRNA-mRNA interaction network in extramammary Paget's disease.

BACKGROUND: Extramammary Paget's disease (EMPD) is a rare malignant intraepidermal adenocarcinoma that is poorly understood. Regulatory long noncoding RNAs (lncRNAs) are characterized in many species and shown to be involved in processes such as development and pathologies, revealing a new layer of regulation in different diseases, especially in cancer studies. In the present study, we used high-throughput sequencing to reveal the lncRNA-mRNA interaction network in extramammary Paget's disease. METHODS: High-throughput sequencing was used to identify differentially expressed lncRNA and mRNA profiles between EMPD patients and healthy controls. Then, a series of bioinformatics analyses were conducted to construct the lncRNA-mRNA interaction network, which was finally confirmed in vitro. RESULTS: Six pairs of EMPD tumor and normal skin samples were collected and sequenced to identify the differentially expressed lncRNA and mRNA profiles between EMPD and healthy controls. A total of 997 differentially expressed mRNAs and 785 differentially expressed lncRNAs were identified. The GO and KEGG analyses show that epidermal development and cell adhesion play important roles in EMPD. The results of the lncRNA-mRNA interaction network analysis suggested that NEAT1, PGAP1, FKBP5 and CDON were the pivotal nodes of the network and that lncRNA NEAT1 might regulate mRNA PGAP1, FKBP5 and CDON. The results of the quantitative real-time RT-PCR performed in ten other patients for NEAT1, PGAP1, FKBP5 and CDON were consistent with those of the sequencing analysis. Moreover, an in vitro experiment confirmed the interactions between NEAT1 and PGAP1, FKBP5 and CDON in human immortalized keratinocytes. CONCLUSION: These findings suggest that the lncRNA-mRNA interaction network based on four pivotal nodes, NEAT1, PGAP1 FKBP5 and CDON, may play an important role in EMPD, which will contribute to a deeper understanding of the pathogenesis of EMPD.

[Clinical efficiency of holmium laser enucleation of the prostate for small-volume benign prostatic hyperplasia with severe LUTS].

OBJECTIVE: To evaluate the safety and clinical efficiency of holmium laser enucleation of the prostate (HoLEP) in the treatment of small-volume BPH (SBPH) complicated by severe lower urinary tract symptoms (LUTS). METHODS: We retrospectively analyzed the clinical data on 82 cases of SBPH with severe LUTS treated by HoLEP from January 2017 to December 2018. The patients were aged (65.5 ± 7.6) years, with a mean prostate volume of <40 ml, a total IPSS of 24.8 ± 4.6, a QOL score of 5.2 ± 0.8, the maximum urinary flow rate (Qmax) of (7.6 ± 3.7) ml/s, and a mean PSA level of (1.8 ± 1.4) µg/L. RESULTS: All the operations were successfully completed, the mean operation time averaging (30.2 ± 5.0) min, enucleation time (26.7 ± 5.6) min and comminution time (3.5 ± 1.1) min, and the enucleated tissue weighing (20.3 ± 4.9) g. After surgery, the bladders were irrigated for (3.5 ± 1.9) h, with (3.0 ± 1.7) L of rinse solution, and catheterization lasted (24.8 ± 9.7) h. Histopathology revealed moderate or severe lymphocytic infiltration in 69 cases (84.1%). At 6 months after operation, significant improvement was observed in the IPSS, QOL, Qmax and PSA level compared with the baseline (P < 0.05). To date, no urethral stricture-related reoperation was ever necessitated. CONCLUSIONS: HoLEP is safe and effective for the treatment of SBPH complicated by severe LUTS and can be employed after adequate preoperative evaluation of the patient.《.

Voltage-dependent potassium channel Kv4.2 alleviates the ischemic stroke impairments through activating neurogenesis.

As well as their ion transportation function, the voltage-dependent potassium channels could act as the cell signal inducer in a variety of pathogenic processes. However, their roles in neurogenesis after stroke insults have not been clearly illustrated. In our preliminary study, the expressions of voltage-dependent potassium channels Kv4.2 was significantly decreased after stroke in cortex, striatum and hippocampus by real-time quantitative PCR assay. To underlie the neuroprotection of Kv4.2 in stroke rehabilitation, recombinant plasmids encoding the cDNAs of mouse Kv4.2 was constructed. Behavioral tests showed that the increased Kv4.2 could be beneficial to the recovery of the sensory, the motor functions and the cognitive deficits after stroke. Temozolomide (TMZ), an inhibitor of neurogenesis, could partially abolish the mentioned protections of Kv4.2. The immunocytochemical staining showed that Kv4.2 could promote the proliferations of neural stem cells and induce the neural stem cells to differentiate into neurons in vitro and in vivo. And Kv4.2 could up-regulate the expressions of ERK1/2, p-ERK1/2, p-STAT3, NGF, p-TrkA, and BDNF, CAMKII and the concentration of intracellular Ca2+. Namely, we concluded that Kv4.2 promoted neurogenesis through ERK1/2/STAT3, NGF/TrkA, Ca2+/CAMKII signal pathways and rescued the ischemic impairments. Kv4.2 might be a potential drug target for ischemic stroke intervention.

Characterization of a Hyaluronic Acid Utilization Locus and Identification of Two Hyaluronate Lyases in a Marine Bacterium Vibrio alginolyticus LWW-9.

Hyaluronic acid (HA) is a negatively charged and linear polysaccharide existing in the tissues and body fluids of all vertebrates. Some pathogenic bacteria target hyaluronic acid for adhesion and/or infection to host cells. Vibrio alginolyticus is an opportunistic pathogen related to infections of humans and marine animals, and the hyaluronic acid-degrading potential of Vibrio spp. has been well-demonstrated. However, little is known about how Vibrio spp. utilize hyaluronic acid. In this study, a marine bacterium V. alginolyticus LWW-9 capable of degrading hyaluronic acid has been isolated. Genetic and bioinformatic analysis showed that V. alginolyticus LWW-9 harbors a gene cluster involved in the degradation, transport, and metabolism of hyaluronic acid. Two novel PL8 family hyaluronate lyases, VaHly8A and VaHly8B, are the key enzymes for the degradation of hyaluronic acid. VaHly8A and VaHly8B have distinct biochemical properties, reflecting the adaptation of the strain to the changing parameters of the aquatic habitats and hosts. Based on genomic and functional analysis, we propose a model for the complete degradation of hyaluronic acid by V. alginolyticus LWW-9. Overall, our study expands our knowledge of the HA utilization paradigm within the Proteobacteria, and the two novel hyaluronate lyases are excellent candidates for industrial applications.

Plasma Kinetic Enucleation vs Holmium Laser Enucleation for Treating Benign Prostatic Hyperplasia: A Randomized Controlled Trial with a 3-Year Follow-Up.

Purpose: To compare the efficacy and safety of plasma kinetic enucleation of the prostate (PKEP) with holmium laser enucleation of the prostate (HoLEP) for treatment of benign prostatic hyperplasia (BPH). Methods: A total of 160 patients with indications for the surgical treatment of BPH were randomly assigned to receive either PKEP or HoLEP prospectively. Baseline characteristics, perioperative data, and postoperative outcomes of the patients were recorded. One hundred twenty-six (78.75%) patients (PKEP 64 vs HoLEP 62) completed the 3-year follow-up assessment. Results: Patients in both groups had similar baseline characteristics. Compared with PKEP, HoLEP was associated with shorter operative time as well as take-out time, lower perioperative hemoglobin decrease, and shorter bladder irrigation time, catheterization time, and hospital stay time. PKEP was superior to HoLEP in terms of the noise of the machine and hospitalization expenses. There were no significant differences in enucleating time, resected weight, and serum sodium levels. Both groups achieved satisfactory results and maintained improvement from baseline in terms of maximum urinary flow rate (Qmax), International Prostatic Symptomatic Score, quality of life, and postvoid residual at 3-year follow-up, with no significant differences between the two procedures. Except for re-catheterization rate, postoperative data such as transrectal ultrasound volume, International Index of Erectile Function-5, and follow-up scores of the flexible cystourethroscopy results, as well as the acute and mid-to long-term complications after surgery, were statistically similar. Conclusion: The 3-year follow-up data of this randomized trial confirmed that both PKEP and HoLEP were effective and safe surgical procedures for the transurethral management of BPH. HoLEP presented certain advantages compared to PKEP, such as reduced operative duration, decreased risk of blood loss, and less bladder irrigation, hospital stay time, and re-catheterization rate, whereas PKEP had lower noise and no additional laser cost. Chinese Clinical Trial Registry (ChiCTR-TRC-13004468).

Hypoxia-preconditioned adipose-derived stem cells combined with scaffold promote urethral reconstruction by upregulation of angiogenesis and glycolysis.

RATIONALE: Tissue engineering is a promising alternative for urethral reconstruction, and adipose-derived stem cells (ADSCs) are widely used as seeding cells. Hypoxia preconditioning can significantly enhance the therapeutic effects of ADSCs. The low oxygen tension of postoperative wound healing is inevitable and may facilitate the nutritional function of ADSCs. This study aimed to investigate if hypoxia-preconditioned ADSCs, compared to normoxia-preconditioned ADSCs, combined with scaffold could better promote urethral reconstruction and exploring the underlying mechanism. METHODS: In vitro, paracrine cytokines and secretomes that were secreted by hypoxia- or normoxia-preconditioned ADSCs were added to cultures of human umbilical vein endothelial cells (HUVECs) to measure their functions. In vivo, hypoxia- or normoxia-preconditioned ADSCs were seeded on a porous nanofibrous scaffold for urethral repair on a defect model in rabbits. RESULTS: The in vitro results showed that hypoxia could enhance the secretion of VEGFA by ADSCs, and hypoxia-preconditioned ADSCs could enhance the viability, proliferation, migration, angiogenesis, and glycolysis of HUVECs (p < 0.05). After silencing VEGFA, angiogenesis and glycolysis were significantly inhibited (p < 0.05). The in vivo results showed that compared to normoxia-preconditioned ADSCs, hypoxia-preconditioned ADSCs combined with scaffolds led to a larger urethral lumen diameter, preserved urethral morphology, and enhanced angiogenesis (p < 0.05). CONCLUSIONS: Hypoxia preconditioning of ADSCs combined with scaffold could better promote urethral reconstruction by upregulating angiogenesis and glycolysis. Hypoxia-preconditioned ADSCs combined with novel scaffold may provide a promising alternative treatment for urethral reconstruction.