Hierarchical Assembly of Flexible Biopolymer Polyphosphate-Manganese into Nanosheets.

Polyphosphate (polyP) is one of the most compact inorganic polyanionic biopolymers that participates in various physiological processes. However, the development of polyP-based nanomaterials is still in its infancy. Here, biocompatible polyphosphate-manganese nanosheets are designed and synthesized by a hierarchical assembly strategy. The thickness and the lateral size of the resulting polyP-Mn nanosheets (PMNSs) are 5 nm and 120-130 nm, respectively. Molecular dynamics simulations suggested that the polyP-hexadecyl trimethyl ammonium bromide flat structure possesses a strong aggregating capacity and serves as the template for the 2D assembly of polyP-Mn. The PMNSs can activate the inflammatory response of macrophages resulting in the recovery of innate immunological functions to inhibit tumor proliferation. This work has initiated a new direction in constructing layered polyP-based nanomaterials and provides guidance for biocompatible and biodegradable biopolymer-based materials in the regulation of innate responses.

[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.《.

Biocompatible aggregation-induced emission active polyphosphate-manganese nanosheets with glutamine synthetase-like activity in excitotoxic nerve cells.

Glutamine synthetase (GS) is vital in maintaining ammonia and glutamate (Glu) homeostasis in living organisms. However, the natural enzyme relies on adenosine triphosphate (ATP) to activate Glu, resulting in impaired GS function during ATP-deficient neurotoxic events. To date, no reports demonstrate using artificial nanostructures to mimic GS function. In this study, we synthesize aggregation-induced emission active polyP-Mn nanosheets (STPE-PMNSs) based on end-labeled polyphosphate (polyP), exhibiting remarkable GS-like activity independent of ATP presence. Further investigation reveals polyP in STPE-PMNSs serves as phosphate source to activate Glu at low ATP levels. This self-feeding mechanism offers a significant advantage in regulating Glu homeostasis at reduced ATP levels in nerve cells during excitotoxic conditions. STPE-PMNSs can effectively promote the conversion of Glu to glutamine (Gln) in excitatory neurotoxic human neuroblastoma cells (SH-SY5Y) and alleviate Glu-induced neurotoxicity. Additionally, the fluorescence signal of nanosheets enables precise monitoring of the subcellular distribution of STPE-PMNSs. More importantly, the intracellular fluorescence signal is enhanced in a conversion-responsive manner, allowing real-time tracking of reaction progression. This study presents a self-sustaining strategy to address GS functional impairment caused by ATP deficiency in nerve cells during neurotoxic events. Furthermore, it offers a fresh perspective on the potential biological applications of polyP-based nanostructures.

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.

"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.

Improved l-phenylglycine synthesis by introducing an engineered cofactor self-sufficient system.

l-phenylglycine (L-phg) is a valuable non-proteinogenic amino acid used as a precursor to ß-lactam antibiotics, antitumor agent taxol and many other pharmaceuticals. L-phg synthesis through microbial bioconversion allows for high enantioselectivity and sustainable production, which will be of great commercial and environmental value compared with organic synthesis methods. In this work, an L-phg synthesis pathway was built in Escherichia coli resulting in 0.23 mM L-phg production from 10 mM l-phenylalanine. Then, new hydroxymandelate synthases and hydroxymandelate oxidases were applied in the L-phg synthesis leading to a 5-fold increase in L-phg production. To address 2-oxoglutarate, NH4 +, and NADH shortage, a cofactor self-sufficient system was introduced, which converted by-product l-glutamate and NAD+ to these three cofactors simultaneously. In this way, L-phg increased 2.5-fold to 2.82 mM. Additionally, in order to reduce the loss of these three cofactors, a protein scaffold between synthesis pathway and cofactor regeneration modular was built, which further improved the L-phg production to 3.72 mM with a yield of 0.34 g/g L-phe. This work illustrated a strategy applying for whole-cell biocatalyst converting amino acid to its value-added chiral amine in a cofactor self-sufficient manner.

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.

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).