Intercalated and Surface-Adsorbed Phosphate Anions in NiFe Layered Double-Hydroxide Catalysts Synergistically Enhancing Oxygen Evolution Reaction Activity.

The oxygen evolution reaction (OER), a crucial semireaction in water electrolysis and rechargeable metal-air batteries, is vital for carbon neutrality. Hindered by a slow proton-coupled electron transfer, an efficient catalyst activating the formation of an O-H bond is essential. Here, we proposed a straightforward one-step hydrothermal procedure for fabricating PO43--modified NiFe layered double-hydroxide (NiFe LDH) catalysts and investigated the role of PO43- anions in enhancing OER. Phosphate amounts can efficiently regulate LDH morphology, crystallinity, composition, and electronic configuration. The optimized sample showed a low overpotential of 267 mV at 10 mA cm-2. Density functional theory calculations revealed that intercalated and surface-adsorbed PO43- anions in NiFe LDH reduced the Gibbs free energy in the rate-determining step of *OOH formation, balancing oxygen-containing intermediate adsorption/dissociation and promoting the OER. Intercalated phosphate ions accelerated precatalyst dehydrogenation kinetics, leading to a rapid reconstruction into active NiFe oxyhydroxide species. Surface-adsorbed PO43- interacted favorably with adsorbed *OOH on the active Ni sites, stabilizing *OOH. Overall, the synergistic effects of intercalated and surface-adsorbed PO43- anions significantly contributed to enhanced OER activity. Achieving optimal catalytic activity requires a delicate equilibrium between thermodynamic and kinetic factors by meticulously regulating the quantity of introduced PO43- ions. This endeavor will facilitate a deeper comprehension of the influence of anions in electrocatalysis for OER.

Micropeptide MIAC inhibits the tumor progression by interacting with AQP2 and inhibiting EREG/EGFR signaling in renal cell carcinoma.

BACKGROUND: Although, micropeptides encoded by non-coding RNA have been shown to have an important role in a variety of tumors processes, there have been no reports on micropeptide in renal cell carcinoma (RCC). Based on the micropeptide MIAC (micropeptide inhibiting actin cytoskeleton) discovered and named in the previous work, this study screened its tumor spectrum, and explored its mechanism of action and potential diagnosis and treatment value in the occurrence and development of renal carcinoma. METHODS: The clinical significance of MIAC in RCC was explored by bioinformatics analysis through high-throughput RNA-seq data from 530 patients with kidney renal clear cell carcinoma (KIRC) in the TCGA database, and the detection of clinical samples of 70 cases of kidney cancer. In vitro and in vivo experiments to determine the role of MIAC in renal carcinoma cell growth and metastasis; High-throughput transcriptomics, western blotting, immunoprecipitation, molecular docking, affinity experiments, and Streptavidin pulldown experiments identify MIAC direct binding protein and key regulatory pathways. RESULTS: The analysis of 600 renal carcinoma samples from different sources revealed that the expression level of MIAC is significantly decreased, and corelated with the prognosis and clinical stage of tumors in patients with renal carcinoma. Overexpression of MIAC in renal carcinoma cells can significantly inhibit the proliferation and migration ability, promote apoptosis of renal carcinoma cells, and affect the distribution of cells at various stages. After knocking down MIAC, the trend is reversed. In vivo experiments have found that MIAC overexpression inhibit the growth and metastasis of RCC, while the synthetized MIAC peptides can significantly inhibit the occurrence and development of RCC in vitro and in vivo. Further mechanistic studies have demonstrated that MIAC directly bind to AQP2 protein, inhibit EREG/EGFR expression and activate downstream pathways PI3K/AKT and MAPK to achieve anti-tumor effects. CONCLUSIONS: This study revealed for the first time the tumor suppressor potential of the lncRNA-encoded micropeptide MIAC in RCC, which inhibits the activation of the EREG/EGFR signaling pathway by direct binding to AQP2 protein, thereby inhibiting renal carcinoma progression and metastasis. This result emphasizes that the micropeptide MIAC can provide a new strategy for the diagnosis and treatment of RCC.

Cation/Anion Dual-Vacancy Pair Modulated Atomically-Thin Sex -Co3 S4 Nanosheets with Extremely High Water Oxidation Performance in Ultralow-Concentration Alkaline Solutions.

The density functional theory calculation results reveal that the adjacent defect concentration and electronic spin state can effectively activate the CoIII sites in the atomically thin nanosheets, facilitating the thermodynamic transformation of *O to *OOH, thus offering ultrahigh charge transfer properties and efficiently stabilizing the phase. This undoubtedly evidences that, for metal sulfides, the atom-scale cation/anion vacancy pair and surface electronic spin state can play a great role in enhancing the oxygen evolution reaction. Inspired by the theoretical prediction, interconnected selenium (Se) wired ultrathin Co3 S4 (Sex -Co3 S4 ) nanosheets with Co/S (Se) dual-vacancies (Se1.0 -Co3 S4 -VS/Se -VCo ) pairs are constructed by a simple approach. As an efficient sulfur host material, in an ultralow-concentration KOH solution (0.1 m), Se1.0 -Co3 S4 -VS/Se -VCo presents outstanding durability up to 165 h and a low overpotential of 289.5 mV at 10 mA cm-2 , which outperform the commercial Co3 S4 nanosheets (NSs) and RuO2 . Moreover, the turnover frequency of Se1.0 -Co3 S4 -VS/Se -VCo is 0.00965 s-1 at an overpotential of 0.39 V, which is 5.7 times that of Co3 S4 NSs, and 5.8 times that of commercial RuO2 . The finding offers a rational design strategy to create the multi-defect structure in catalysts toward high-efficiency water electrolysis.

Functional and oncologic outcomes of robot-assisted simple enucleation with and without renal arterial cold perfusion in complex renal tumors: a propensity score-matched analysis.

BACKGROUND: To compare robot-assisted simple enucleation with renal arterial cold perfusion (RACP-RASE) and RASE alone in complex renal tumors with regard to perioperative, functional and oncologic outcomes by propensity score-matched analysis. METHODS: Data from 351 patients who underwent RACP-RASE or RASE for complex renal tumors were recorded between September 2014 and December 2017. Propensity score-matched analysis was performed on age, sex, BMI, ECOG score, tumor side and size, preoperative estimated glomerular filtration rate (eGFR), RENAL score and PADUA score. RESULTS: The study included 31 RACP-RASE and 320 RASE procedures. RENAL score and PADUA score were higher and tumor diameter was greater under RACP-RASE than RASE. After matching, the two groups were similar in estimated blood loss (208.3 vs 230.7 ml; p = 0.696) and ischemic time (34.8 vs 32.8 min; p = 0.342). The RACP-RASE group had significantly longer operative time than the RASE group (264.1 ± 55.7 vs 206.9 ± 64.0 min, p = 0.001). There was no difference in the incidence of postoperative complications between the two groups (13.8% vs 24.1%; p = 0.315), as was the overall incidence of positive surgical margins (3.4 vs 0%; p = 1.000). The changes in eGFR significantly differed between the two groups at 3 months (p = 0.018) and 12 months (p = 0.038). More patients in the RASE group were CKD upstaged (p = 0.043). At multivariable analysis, preoperative eGFR and the type of procedure were significant predictive factors for a change of more than 10% in eGFR at 3 months postoperatively. There was no local recurrence or distant metastasis during follow-up. CONCLUSIONS: RACP-RASE is an effective and safe technique for complex renal tumors that can provide appropriate temporary arterial occlusion and renal hypothermic perfusion. Renal arterial cold perfusion may be helpful in protecting renal function in RASE as compared with warm ischemia.

Expression and Histopathological Significance of Disabled-2 in Aldosterone-Producing Adenoma.

The current pathological diagnosis of aldosterone-producing adenoma (APA) is challenging because no histological markers of aldosterone production are available in routine practice. A previous study demonstrated that Disabled-2 (DAB2) is a specific marker of the zona glomerulosa (ZG) in rodents. The aim of the present study was to investigate the significance of immunohistochemical staining to detect DAB2 in the adrenal tissue of patients with APA. We investigated the expression of DAB2 in 36 adrenal glands with APA, 23 adrenal glands with cortisol-producing adenoma (CPA), and 33 adrenal glands with non-functioning adenoma (NFA). Immunohistochemical staining was performed using anti-DAB2 antibodies on paraffin-embedded sections. We analysed the expression of DAB2 semi-quantitatively by scoring staining intensity, and assessed the correlation of this information with the clinical findings. DAB2 mRNA expression in adenoma tissues was evaluated by RT-PCR. DAB2 was highly expressed in the ZG in normal human adrenal glands. DAB2 expression was heterogeneous in APA, with spotted, strong staining noted in most samples (25 of 36 APA). CPA and NFA also exhibited extensive low or moderate DAB2 expression. DAB2 mRNA was significantly increased and positively correlated with CYP11B2 in APA (p<0.05). In APA, the DAB2 score adjusted for tumour volume was positively correlated with plasma aldosterone (p<0.05). Patients with low or moderate DAB2 staining more frequently exhibited high blood pressure and were diagnosed at a younger age compared with patients with high DAB2 staining. The present study clearly demonstrates that DAB2 is a specific marker of the ZG in normal human adrenal glands but that DAB2 immunostaining is not sufficiently powerful for histopathological diagnosis of APA. DAB2 might be involved in excessive aldosterone biosynthesis and correlate with specific clinical characteristics of APA patients.

Laparoscopic Partial Nephrectomy for Peripelvic Cystic Renal Cell Carcinoma: A Single-Center Experience.

OBJECTIVE: The study aimed to report our experiences of laparoscopic and open partial nephrectomies on patients with peripelvic cystic renal cell carcinoma (cRCC). METHODS: From July 2003 and October 2014, 18 patients with suspected peripelvic cRCCs underwent partial nephrectomies via an open or laparoscopic approach at Nanjing Drum Tower Hospital. Patients' perioperative and oncological outcomes were analyzed and compared between the open partial nephrectomy (OPN) and the laparoscopic partial nephrectomy (LPN) groups. RESULTS: Seven patients underwent OPNs, and 11 patients underwent LPNs for their peripelvic lesions. All procedures were performed successfully; no conversion to open surgery was encountered in the LPN group. There was no significant difference between the groups in mean operation time, blood loss, warm ischemia time or complication rates. The mean hospital stay in the LPN group was significantly shorter than in the OPN group (p = 0.004). The mean follow-up of the OPN and LPN group was 95.0 and 65.1 months, respectively. No local recurrence or metastasis has been noted during the follow-up period. CONCLUSIONS: Peripelvic cRCC represents an uncommon variant of RCCs; few cases have been reported addressing peripelvic cRCC treatment. Although technically challenging, LPN is an effective minimally invasive modality for treating peripelvic cRCC in experienced hands.

Laparoscopic Radiofrequency Ablation versus Partial Nephrectomy for cT1a Renal Tumors: Long-Term Outcome of 179 Patients.

OBJECTIVES: To compare the long-term functional and oncological results between laparoscopic radiofrequency ablation (LRFA) and laparoscopic partial nephrectomy (LPN) in selected clinical T1a (cT1a) renal tumor patients. METHODS: We retrospectively analyzed the medical records of patients with cT1a renal tumors who had LRFA or LPN at our institution between February 2006 and February 2015. Student's t test was used to compare the perioperative data between the two groups. Survival analyses were calculated using the Kaplan-Meier method. RESULTS: A total of 179 patients were included in the study. Patients in the LRFA cohort were significantly older and had higher American Society of Anesthesiologists sore than in the LPN cohort. The LRFA group had a significantly lower mean blood loss than the LPN group (p = 0.03). The percent decrease of GFR in the LRFA group was significantly lower than in the LPN group (p = 0.021). The 5-year overall, cancer-specific and disease-free survival were 93.3 vs. 94.6%, 98.0 vs. 98.5% and 97.1 vs. 97.3%, for LRFA and LPN, respectively (all p value >0.05). CONCLUSIONS: The excellent perioperative results, long-term functional and oncological outcomes of LRFA confirm that this technique is safe, nephron sparing and oncologically effective for the treatment of cT1a renal tumors.

[A clinical observation of cool-tip radiofrequency ablation assisted enucleation for giant renal angiomyolipoma].

OBJECTIVE: To initially explore the clinical effect of cool-tip radiofrequency ablation combined with enucleation for the giant hamartoma of kidney with narrow base and export-oriented way of growth. METHODS: The clinical date of 15 patients including 6 male and 9 female with special hamartoma of kidney underwent cool-tip radiofrequency ablation assisted enucleation from July 2011 to October 2014 were reviewed.The median age was 49 years (ranging from 35 to 71 years). There were 6 cases with left renal tumor, 8 cases with right renal tumor and 1 case with solitary kidney tumor.All patients were confirmed by B ultrasound or CT scan, the mean diameter of hamartoma of kidney was 9.7 cm(8.5-12.7)cm, all tumors were located distant from the collecting system and presents with a special way of growth.The preoperative hemoglobin was (129±18)g/L, SCr was (92±41)µmol/L, glomerular filtration rate (GFR) was (32±12)ml·min(-1)·1.73 m(-2). RESULTS: Cool-tip radiofrequency ablation assisted enucleation was technically successful in all patients.The mean operative duration was (115±31)minutes, and the average intraoperative bleeding was (72±21)ml with no blooding transfusion.The postoperative hospital stay was(7±2)days, and the postoperative hemoglobin was(129±18)g/L, SCr (92±41)µmol/L, GFR(30±15)ml·min(-1)·1.73 m(-2). No statistic change of hemoglobin and SCr or glomerular filtration rate after operations(all P>0.05). Postoperative pathology showed that all cases were hamartoma of kidney.During a mean follow-up period of 19.5 months, none of them had local tumor recurrence or chronic renal insufficiency. CONCLUSIONS: Cool-tip radiofrequency ablation assisted enucleation is both safe and effective in the treatment of huge hamartoma of kidney with a narrow base and export-oriented way of growth. The short-term follow-up shows a satisfactory therapeutic effect.

The Comparison of R.E.N.A.L., PADUA and Centrality Index Score in Predicting Perioperative Outcomes and Complications after Laparoscopic Radio Frequency Ablation of Renal Tumors.

PURPOSE: We assessed the association between the R.E.N.A.L., PADUA and centrality index scores and perioperative outcomes, and determined the efficacy of each scoring system over the simple parameter of tumor size. MATERIALS AND METHODS: We conducted a retrospective review of the records of patients who underwent laparoscopic radio frequency ablation of renal tumors from February 2006 to April 2014 at our institution. Tumors were categorized using the R.E.N.A.L., PADUA and centrality index score, which were determined by analyzing preoperative imaging. The relationships between each variable and change in glomerular filtration rate, estimated blood loss, operative time and postoperative complications were examined. RESULTS: Laparoscopic radio frequency ablation was performed in 215 selected patients with preoperative imaging available. The interclass correlations coefficient of the 3 observers was 0.87, 0.84 and 0.82 for the C-Index, the R.E.N.A.L. and the PADUA scoring system, respectively. R.E.N.A.L. score, PADUA score and PADUA complexity were significantly associated with postoperative complications (p=0.040, 0.015 and 0.006, respectively). However, major complications were only associated with high PADUA complexity (chi-square 23.851, p <0.05). Each scoring system had a significant association with operative time and estimated blood loss (p <0.05), except that the C-index score had no relationship with estimated blood loss (p=0.083). The accuracy of each scoring system in predicting perioperative outcomes and postoperative complications was superior to that of tumor size. CONCLUSIONS: Each scoring system has an advantage over tumor size in describing tumor complexity and may help with surgical decision making. Further studies are required to validate their efficacy in evaluating the intraoperative and postoperative results after renal laparoscopic radio frequency ablation.

Improved split renal function after percutaneous nephrostomy in young adults with severe hydronephrosis due to ureteropelvic junction obstruction.

PURPOSE: We evaluated percutaneous nephrostomy for adult kidneys with severe hydronephrosis due to ureteropelvic junction obstruction and less than 10% split renal function. MATERIALS AND METHODS: In this retrospective analysis we included patients who underwent percutaneous nephrostomy for unilateral ureteropelvic junction obstruction of the kidneys with hydronephrosis and less than 10% split renal function at our hospital between May 2009 and January 2012. Adults (age 18 years or greater) were divided into those 35 years or younger (young adults) and older than 35 years (older adults). The percutaneous nephrostomy remained in situ a mean ± SD of 6.62 ± 2.55 weeks and patients underwent repeat renography before pyeloplasty. When there was no significant improvement in split renal function (10% or greater) and drainage (greater than 400 ml per day), nephrectomy was performed. Otherwise pyeloplasty was performed. Patients were followed by renography, ultrasound and contrast computerized tomography at 3 and 6 months, at 1 year and annually thereafter. RESULTS: Of 53 patients 30 (56.6%) showed improvement after percutaneous nephrostomy drainage and urine output greater than 400 ml per day with percutaneous nephrostomy. Pyeloplasty was then performed. Of 29 young adults 24 (82.8%) showed improved split renal function vs 6 of 24 older adults (25%). Nephrectomy of the other 23 kidneys was performed. At a mean followup of 19.27 ± 7.82 months (range 12 to 36), no patient showed hypertension or urinary tract infection. CONCLUSIONS: Split renal function detected by renography may not accurately predict recovered, poorly functioning kidneys, especially in young adults. First observing the recoverability of hydronephrotic kidneys by percutaneous nephrostomy drainage and then preserving select kidneys may be an effective method to manage poorly functioning kidneys due to ureteropelvic junction obstruction.

Robot-assisted Simple Enucleation Versus Standard Robot-assisted Partial Nephrectomy for Low- or Intermediate-complexity, Clinical T1 Renal Tumors: A Randomized Controlled Noninferiority Trial.

BACKGROUND: Although partial nephrectomy has become the gold standard for T1 renal tumors whenever technically feasible, simple enucleation has shown superior results. To the best of our knowledge, no randomized controlled trials comparing these two surgical approaches have been published. OBJECTIVE: To compare the surgical margin status for robot-assisted simple enucleation (RASE) and standard robot-assisted partial nephrectomy (sRAPN) for clinical T1 renal tumors. DESIGN, SETTING, AND PARTICIPANTS: This is a prospective, randomized, controlled, noninferiority trial. A total of 380 patients aged 18-80 yr with newly diagnosed, sporadic, unilateral clinical T1 renal tumors (RENAL score <10) were enrolled and randomized to RASE or sRAPN. The primary endpoint was the positive surgical margin (PSM) rate, with a noninferiority margin of 7.5% set. The study was registered on ClinicalTrials.gov (NCT03624673). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We defined noninferiority for RASE versus standard RAPN as an upper 95% confidence interval (CI) bound of <7.5% for the difference in the proportion of patients with a PSM. RESULTS AND LIMITATIONS: A cohort of 380 patients was enrolled and randomly assigned to RASE (n = 190) or sRAPN (n = 190). On intention-to-treat analysis for patients with malignant tumors, 2.3% of patients in the RASE group and 3.0% in the sRAPN group had a PSM. The RASE group showed noninferiority to the sRAPN group within a 7.5% margin (difference -0.7%, 95% CI -4.0% to 2.7%). Per-protocol analysis also demonstrated noninferiority of RASE. The RASE group had a shorter median operative time (145 vs 155 min; p = 0.018) and a lower rate of tumor bed suturing (8.9% vs 43%; p < 0.001) in comparison to the sRAPN group. Estimated blood loss was considerably lower in the sRAPN group than in the RASE group (p = 0.046). The rate of recurrence did not differ between the groups (p > 0.9). CONCLUSIONS: RASE for the management of low- to intermediate-complexity tumors is noninferior to sRAPN in terms of the PSM rate. Long-term follow-up is needed to draw conclusions regarding oncological outcomes. PATIENT SUMMARY: We carried out a trial to compare simple tumor enucleation versus partial nephrectomy for renal tumors. The outcome we assessed was the proportion of patients with a positive surgical margin. Our results show that simple tumor enucleation is not inferior to partial nephrectomy for this outcome. Longer follow-up is needed to assess other cancer control outcomes.

Gender disparity of living donor renal transplantation in East China.

Gender disparity among living kidney donors is common world wide, which demonstrates different social and economic problems in different countries. However, few data are available for China. Therefore, we retrospectively analyzed all 139 living donor renal transplants performed in our center between 2003 and 2010. The annual number of living donor renal transplants increased from six to 26 cases per year during the observation period. Among them, 69.2% of all kidney donors were females, whereas 79.5% of the recipients were male. The average age of recipients was 34.1 ± 7.6 yr and 94% (110/117) were younger than 44 yr. In contrast, 53% (62/117) of all donors were "middle-aged" (45-59 yr) with an average donor age of 47.8 ± 9.2 yr. The first-degree relatives accounted for the majority of the donor pool, as the most common donor-recipient combination consisted of mother to son. In conclusion, there was a male and young preponderance among recipients, and a female and middle-aged one among donors of living kidney transplants in our transplant center, which might be related to socio-cultural as well as economic factors.

Impact of immunosenescence on transplant outcome.

Aging affects all compartments of the immune response and has a major impact on transplant outcome and organ quality. Although clinical trials in the aging transplant population remain rare, our current understanding of immunosenescence provides a basis for an age-adapted immunosuppression and organ allocation with the goal to optimize utilization and to improve outcomes in older recipients. From a more general perspective, understanding the mechanisms and consequences of immunosenescence will have a broad impact on immune therapies in and beyond transplantation.

[Mid-term follow-up results of laparoscopic radiofrequency ablation for renal cell carcinoma of T1aN0M0 stage].

OBJECTIVE: To determine the effect of laparoscopic radiofrequency ablation of T1aN0M0 renal cell carcinoma (RCC) with regular follow-up. METHODS: All patients underwent surgery from March 2006 to March 2009. Eight cases were solitary kidney. Twenty-two cases of left RCC and 18 cases of right RCC were diagnozed by ultrasonography and CT scanning.All of the cases were T1aN0M0 stage. No metastasis was found by iconography test. By ultrasound positioning, laparoscopic radiofrequency were performed on the renal tumor. All patients were followed up with eGFR and enhanced-CT. RESULTS: All patients underwent laparoscopic radiofrequency ablation surgery successfully. The mean operation time was (101 ± 19) minutes and the mean blood loss was (90 ± 14) ml (no blood transfusion pre- and post-operation). During postoperative follow-up, enhanced CT revealed complete ablation in 39 cases (the success rate was 97.5%), and 1 residue tumor was confirmed by enhanced CT 7 days post operation. This patient was under close surveillance because of solitary kidney. No progression of the residue tumor was found during the follow-up. One case of recurrence was confirmed by enhanced CT in 6 month after operation. The 3-year recurrence rate was 2.5%. No further intervation was performed on this patient and no change was found in the recurrence area during the follow-up. Both 3-year total survival rate and 3-year cancer specific survival rate were 100%. The mean eGFR was (72 ± 9) ml/(min·1.73 m(2)) in 3 years after surgery. There was no significant difference between pre-and post-operation (P > 0.05). CONCLUSION: Mid-term follow-up results show the effectiveness and safety of laparoscopic radiofrequency ablation in the treatment for T1aN0M0 RCC and have no negative influence on the renal function.

Effect of extensive artery isolation during robotic-assisted partial nephrectomy on blood pressure of patients with poorly controlled hypertension: a preliminary study.

PURPOSE: To investigate whether extensive renal artery isolation during robotic-assisted partial nephrectomy (RAPN) for renal cell carcinoma (RCC) affects blood pressure (BP) of patients with poorly controlled hypertension. METHODS: We included 60 patients diagnosed with poorly controlled hypertension who underwent RAPN by an experienced surgeon. The renal artery of the treated kidney was sufficiently isolated. Systolic BP (SBP), diastolic BP (DBP) and antihypertensive medication information were obtained at baseline and 3- and 6-month follow-up after surgery. Primary endpoints were changes in BP, and medications. Predictors of SBP reduction at 3 months were assessed by multivariable logistic regression. RESULTS: All 60 RAPN procedures were successful, with no major intra- or postoperative complications. Mean SBP and DBP decreased significantly at 3 months after surgery (SBP, -7.8 ± 6.3 mmHg, P < 0.001; DBP, -4.2 ± 6.4 mmHg, P = 0.01). SBP and DBP did not differ between 3- and 6-month follow-up. The mean number of BP medications prescribed was lower at 3 months than baseline (1.7 ± 1.0 vs 2.1 ± 1.0, P = 0.016). The only significant predictor of SBP reduction at 3 months was baseline SBP. CONCLUSIONS: Renal denervation with extensive renal artery isolation during RAPN may improve BP control among patients with poorly controlled hypertension in short term.

Stabilized cyclic peptides as modulators of protein-protein interactions: promising strategies and biological evaluation.

Protein-protein interactions (PPIs) control many essential biological pathways which are often misregulated in disease. As such, selective PPI modulators are desirable to unravel complex functions of PPIs and thus expand the repertoire of therapeutic targets. However, the large size and relative flatness of PPI interfaces make them challenging molecular targets for conventional drug modalities, rendering most PPIs "undruggable". Therefore, there is a growing need to discover innovative molecules that are able to modulate crucial PPIs. Peptides are ideal candidates to deliver such therapeutics attributed to their ability to closely mimic structural features of protein interfaces. However, their inherently poor proteolysis resistance and cell permeability inevitably hamper their biomedical applications. The introduction of a constraint (i.e., peptide cyclization) to stabilize peptides' secondary structure is a promising strategy to address this problem as witnessed by the rapid development of cyclic peptide drugs in the past two decades. Here, we comprehensively review the recent progress on stabilized cyclic peptides in targeting challenging PPIs. Technological advancements and emerging chemical approaches for stabilizing active peptide conformations are categorized in terms of α-helix stapling, ß-hairpin mimetics and macrocyclization. To discover potent and selective ligands, cyclic peptide library technologies were updated based on genetic, biochemical or synthetic methodologies. Moreover, several advances to improve the permeability and oral bioavailability of biologically active cyclic peptides enable the de novo development of cyclic peptide ligands with pharmacological properties. In summary, the development of cyclic peptide-based PPI modulators carries tremendous promise for the next generation of therapeutic agents to target historically "intractable" PPI systems.

Corrigendum: Gut microbes reveal Pseudomonas medicates ingestion preference via protein utilization and cellular homeostasis under feed domestication in freshwater drum, Aplodinotus grunniens.

[This corrects the article DOI: 10.3389/fmicb.2022.861705.].

The proton conduction behavior of two 1D open-framework metal phosphates with similar crystal structures and different hydrogen bond networks.

Two open-framework zinc phosphates [C3N2H12][Zn(HPO4)2] (1) and [C6N4H22]0.5[Zn(HPO4)2] (2) were synthesized via hydrothermal reaction and characterized by powder X-ray diffraction, thermogravimetric analysis and scanning electron microscopy. Both compounds have a similar crystal structure and macroscopic morphology. However, the difference in equilibrium cations, in which the propylene diamine is for 1 and the triethylenetetramine is for 2, results in a significant distinction in the dense hydrogen grid. The diprotonated propylene diamine molecule in 1 is more favorable for forming a hydrogen-bond network in three dimensions than in 2, in which the twisted triethylenetetramine forms a hydrogen bond grid with the inorganic framework only in two dimensions owing to its large steric effect. This distinction further leads to a disparity in the proton conductivity of both compounds. The proton conductivity of 1 can reach 1.00 × 10-3 S cm-1 under ambient conditions (303 K and 75% RH) and then increase to 1.11 × 10-2 S cm-1 at 333 K and 99% RH, which is the highest value among the open-framework metal phosphate proton conductors operated in the same conduction. In contrast, the proton conductivity of 2 is four orders of magnitude smaller than 1 at 303 K and 75% RH and two orders smaller than 1 at 333 K and 99% RH.

Zero ischemia laparoscopic radio frequency ablation assisted enucleation of renal cell carcinoma: experience with 42 patients.

PURPOSE: We evaluated the safety and efficacy of zero ischemia, radio frequency ablation assisted tumor enucleation for renal cell carcinoma. We report the incidence of complications, positive surgical margins, local recurrence, and progression-free and disease specific survival rates. MATERIALS AND METHODS: We retrospectively reviewed data on 42 patients with renal cell carcinoma treated with zero ischemia laparoscopic radio frequency ablation assisted tumor enucleation between March 2006 and November 2009. Median age was 60 years (range 37 to 82) and 31 patients (73.8%) were male. The median greatest tumor dimension was 3.4 cm (range 1.8 to 6.1). The Mann-Whitney U, chi-square and Fisher exact tests were used to compare bleeding and complications. The paired t and Mann-Whitney U tests were used to compare glomerular filtration rates. The Kaplan-Meier method was used to calculate survival. RESULTS: We found 32 tumors with a greatest dimension of 4 cm or less and 10 with a greatest dimension of 4 to 7 cm. Median blood loss was 82.5 ml (range 15 to 210). Overall 7 complications (16.6%) occurred, including postoperative fever in 4 cases (Clavien grade II) and prolonged urinary leakage in 3 (Clavien grade III). The PADUA (preoperative aspects and dimensions used for an anatomical) score was associated with prolonged urinary leakage (p = 0.03) but not with overall complications. No patient had positive surgical margins. The glomerular filtration rate did not differ before vs 12 months after surgery. Three-year cancer specific, cumulative and progression-free survival was 100%, 97.3% and 96.4%, respectively. CONCLUSIONS: Zero ischemia, laparoscopic radio frequency ablation assisted tumor enucleation of renal cell carcinoma is a safe, effective nephron sparing treatment that provides excellent oncological and functional outcomes.

Radiofrequency ablation of synchronous bilateral renal cell carcinoma.

OBJECTIVES: The treatment of synchronous bilateral renal cell carcinoma is challenging. Radiofrequency ablation has been increasingly applied in the management of renal tumors. Herein, we report our experience of radiofrequency ablation on 12 patients with synchronous bilateral renal cell carcinoma. METHODS: From March 2006 to September 2010, 12 patients with bilateral synchronous sporadic renal cell carcinoma (29 lesions overall) were identified from our kidney database. The mean age was 62.3 years (range 35-81). The mean tumor diameter was 4.5 cm (range 0.9-9.0). Three patients received unilateral radiofrequency ablation and contralateral radical nephrectomy, whereas nine patients received bilateral radiofrequency ablation. The oncological and functional outcomes were analyzed. Contrast-enhanced computed tomography examinations were carried out at day 7, and at 3 and 6 months after the procedure, and every 6 months thereafter. RESULTS: The mean follow-up period was 33 months (range 10-64). The local tumor control rate was 93.1% (27/29). Cancer-specific survival and the overall survival rates were 100%. No death or renal failure after the procedure was found. In patients who underwent bilateral radiofrequency ablation, the latest mean glomerular filtration rate had not significantly declined compared with preoperative levels (93.7 ± 13.0 mL/min/1.73 m(2) vs 96.9 ± 13.3 mL/min/1.73 m(2), respectively; P > 0.05). CONCLUSION: Radiofrequency ablation shows encouraging outcomes in the treatment of bilateral renal cell carcinoma. It can provide adequate local tumor control and cancer-specific survival compared with nephron-sparing surgery while not affecting the renal function.