A minimum functional form of the Escherichia coli BAM complex constituted by BamADE assembles outer membrane proteins in vitro.

The biogenesis of outer membrane proteins is mediated by the ß-barrel assembly machinery (BAM), which is a heteropentomeric complex composed of five proteins named BamA-E in Escherichia coli. Despite great progress in the BAM structural analysis, the molecular details of BAM-mediated processes as well as the exact function of each BAM component during OMP assembly are still not fully understood. To enable a distinguishment of the function of each BAM component, it is the aim of the present work to examine and identify the effective minimum form of the E. coli BAM complex by use of a well-defined reconstitution strategy based on a previously developed versatile assay. Our data demonstrate that BamADE is the core BAM component and constitutes a minimum functional form for OMP assembly in E. coli, which can be stimulated by BamB and BamC. While BamB and BamC have a redundant function based on the minimum form, both together seem to cooperate with each other to substitute for the function of the missing BamD or BamE. Moreover, the BamAE470K mutant also requires the function of BamD and BamE to assemble OMPs in vitro, which vice verse suggests that BamADE are the effective minimum functional form of the E. coli BAM complex.

Signal peptide replacement of Ag43 enables an efficient bacterial cell surface display of receptor-binding domain of coronavirus.

To enable an efficient bacterial cell surface display with effective protein expression and cell surface loading ability via autotransporter for potential vaccine development applications, the inner membrane protein translocation efficiency was investigated via a trial-and-error strategy by replacing the original unusual long signal peptide of E. coli Ag43 with 11 different signal peptides. The receptor-binding domain (RBD) of coronavirus was used as a neutral display substrate to optimize the expression conditions, and the results showed that signal peptides from PelB, OmpC, OmpF, and PhoA protein enhance the bacterial cell surface display efficiency of RBD. In addition, the temperature has also a significant effect on the autodisplay efficiency of RBD. Our data provide further technical basis for the biotechnological application of Ag43 as a bacterial surface display carrier system and further potential application in vaccine development.

Dynamically Encircling Exceptional Points in Different Riemann Sheets for Orbital Angular Momentum Topological Charge Conversion.

Orbital angular momentum (OAM) provides an additional degree of freedom for optical communication systems, and manipulating on-chip OAM is important in integrated photonics. However, there is no effective method to realize OAM topological charge conversion on chip. In this Letter, we propose a way to convert OAM by encircling two groups of exceptional points in different Riemann sheets. In our framework, any OAM conversion can be achieved on demand just by manipulating adiabatic and nonadiabatic evolution of modes in two on-chip waveguides. More importantly, the chiral OAM conversion is realized, which is of great significance since the path direction can determine the final topological charge order. Our Letter presents a special chiral behavior and provides a new method to manipulate OAM on the chip.

Pazopanib stimulates senescence of renal carcinoma cells through targeting nuclear factor E2-related factor 2 (Nrf2).

Renal cell carcinoma (RCC) is the most common kidney cancer with high mortality rate. Pazopanib has been approved for the treatment of RCC. However, the underlying mechanism is not clear. Here, we report a novel finding by showing that treatment with Pazopanib could promote cellular senescence of the human RCC cell line ACHN. Cells were stimulated with 5, 10, and 20 µM Pazopanib, respectively. Cellular senescence was measured using senescence-associated ß-galactosidase (SA-ß-Gal) staining. Western blot analysis and real-time polymerase chain reaction were used to measure the mRNA and protein expression of nuclear factor E2-related factor 2 (Nrf2), γH2AX, human telomerase reverse transcriptase (hTERT), telomeric repeat binding factor 2 (TERF2), p53 and plasminogen activator inhibitor (PAI). First, we found that exposure to Pazopanib reduced the cell viability of ACHN cells. Additionally, Pazopanib induced oxidative stress  by increasing the production of reactive oxygen species, reducing the levels of glutathione peroxidase, and promoting nuclear translocation of Nrf2. Interestingly, Pazopanib exposure resulted in DNA damage by increasing the expression of γH2AX. Importantly, Pazopanib increased cellular senescence and reduced telomerase activity. Pazopanib also reduced the gene expression of hTERT but increased the gene expression of TERF2. Correspondingly, we found that Pazopanib increased the expression of p53 and PAI at both the mRNA and protein levels. To elucidate the underlying mechanism, the expression of Nrf2 was knocked down by transduction with Ad- Nrf2 shRNA. Results indicate that silencing of Nrf2 in ACHN cells abolished the effects of Pazopanib in stimulating cellular senescence and reducing telomerase activity. Consistently, knockdown of Nrf2 restored the expression of p53 and PAI in ACHN cells. Based on these results, we explored a novel mechanism whereby which Pazopanib displays a cytotoxicity effect in RCC cells through promoting cellular senescence mediated by Nrf2.

Serum α-hydroxybutyrate dehydrogenase as a biomarker for predicting survival outcomes in patients with UTUC after radical nephroureterectomy.

PURPOSE: We aimed to determine the prognostic value of α-hydroxybutyrate dehydrogenase (α-HBDH) in upper tract urothelial carcinoma (UTUC) patients after radical nephroureterectomy (RNU). MATERIALS AND METHODS: We retrospectively enrolled the data of 544 UTUC patients at West China Hospital from May 2003 to June 2019. Cancer-specific survival (CSS) was the endpoint of interest. The optimal cutoff value of α-HBDH was identified by X-Tile program. After propensity score matching (PSM), we utilized Kaplan‒Meier curves to estimate survival and Cox proportional hazard model for risk assessment. A nomogram was built based on the results of multivariate analysis, and calibration curve, time-dependent receiver operating characteristic (ROC) curves and decision curve analysis were also performed to evaluate the predictive accuracy. RESULTS: Overall, 394 and 150 patients were divided into the α-HBDH-low group and α-HBDH -high group at the cutoff value of 158 U/L, respectively. After PSM, the two groups were well matched for all confounding factors. High α-HBDH was associated with inferior CSS (P = 0.006), and preoperative α-HBDH was an independent predictor for CSS (HR: 1.36; 95% CI:1.08, 1.80), especially in localized UTUC patients (HR: 2.04; 95% CI:1.11, 3.74). Furthermore, the nomogram based on α-HBDH achieved great predictive ability for CSS with areas under the curves of 0.800 and 0.778 for 3-year and 5-year CSS, respectively. CONCLUSION: Serum α-HBDH was a novel and reliable biomarker for predicting survival outcomes in UTUC patients after RNU but should be further explored.

Siamese Transformer-Based Building Change Detection in Remote Sensing Images.

To address the challenges of handling imprecise building boundary information and reducing false-positive outcomes during the process of detecting building changes in remote sensing images, this paper proposes a Siamese transformer architecture based on a difference module. This method introduces a layered transformer to provide global context modeling capability and multiscale features to better process building boundary information, and a difference module is used to better obtain the difference features of a building before and after a change. The difference features before and after the change are then fused, and the fused difference features are used to generate a change map, which reduces the false-positive problem to a certain extent. Experiments were conducted on two publicly available building change detection datasets, LEVIR-CD and WHU-CD. The F1 scores for LEVIR-CD and WHU-CD reached 89.58% and 84.51%, respectively. The experimental results demonstrate that when utilized for building change detection in remote sensing images, the proposed method exhibits improved robustness and detection performance. Additionally, this method serves as a valuable technical reference for the identification of building damage in remote sensing images.

Degradation of organic pollutants by the Cl-/PMS process.

The viewpoints on whether high concentrations of chloride ion (Cl-) promote or inhibit the oxidation activity of activated persulfates are still inconclusive. Furthermore, the degradation of organic pollutants by the persulfates in the presence of high Cl- concentrations without any activation medium has not yet been studied. In this work, the efficiency and mechanism of degradation of organic pollutants such as carbamazepine (CBZ), sulfadiazine (SDZ), and phenol (PN) by Cl--activated PMS (denoted as Cl-/PMS) were investigated. Results showed that Cl- could effectively activate PMS for the complete removal of CBZ, SDZ, and PN with reaction kinetic constants of 0.4516 min-1, 0.01753 min-1, and 0.06805 min-1, respectively. Parameters such as PMS dose, Cl- concentration, solution pH, and initial concentrations of organic pollutants that affect the degradation efficiencies of the Cl-/PMS process were optimized. Unlike conventional activated persulfates, it was confirmed that the free chlorine was the main active species in the Cl-/PMS process. Finally, the degradation by-products of CBZ and SDZ as well as their toxicity were detected, and a possible degradation pathway for CBZ and SDZ was proposed. Though higher toxic chlorinated by-products were generated, the Cl-/PMS process was still an efficient oxidation method for the removal of organic pollutants in aqueous solutions which contain high concentrations of Cl-.

Information-entropy enabled identifying topological photonic phase in real space.

The topological photonics plays an important role in the fields of fundamental physics and photonic devices. The traditional method of designing topological system is based on the momentum space, which is not a direct and convenient way to grasp the topological properties, especially for the perturbative structures or coupled systems. Here, we propose an interdisciplinary approach to study the topological systems in real space through combining the information entropy and topological photonics. As a proof of concept, the Kagome model has been analyzed with information entropy. We reveal that the bandgap closing does not correspond to the topological edge state disappearing. This method can be used to identify the topological phase conveniently and directly, even the systems with perturbations or couplings. As a promotional validation, Su-Schrieffer-Heeger model and the valley-Hall photonic crystal have also been studied based on the information entropy method. This work provides a method to study topological photonic phase based on information theory, and brings inspiration to analyze the physical properties by taking advantage of interdisciplinarity.

Survival impact of variant histology in patients with upper tract urothelial carcinoma after radical nephroureterectomy.

OBJECTIVE: To investigate the prognostic impact of variant histology (VH) on survival outcomes in upper tract urothelial carcinoma (UTUC) patients after radical nephroureterectomy (RNU). MATERIALS AND METHODS: Data from 635 UTUC patients who underwent RNU at our institution from May 2003 to June 2019 were retrospectively acquired and analyzed. After propensity score matching (PSM), we investigated the impact of VH on overall survival (OS) and cancer-specific survival (CSS) by using cumulative incidence plots with the log-rank test, Cox regression models, and competing risk regression models. RESULTS: Overall, 121 (19.1%) patients were diagnosed with VH, including 68 (10.7%) with squamous cell differentiation (SCD) and 28 (4.4%) with adenocarcinoma differentiation (AD). After PSM, the presence of VH was significantly associated with worse OS (HR 1.70, 95% CI 1.25-2.32) and CSS (HR 1.64, 95% CI 1.17-2.31) only in locally advanced UTUC patients (pT>2). In the subgroup analysis, SCD revealed inferior outcomes (OS: HR 1.81, 95% CI 1.28-2.57; CSS: HR 1.73, 95% CI 1.18-2.54) compared with pure urothelial carcinoma (pUC), whereas AD conferred comparable outcomes. In addition, compared with pUC patients, SCD patients with extensive squamous components had significantly decreased OS (HR 4.17, 95% CI 1.84-9.44) and CSS (HR 1.10, 95% CI 0.61-1.99), whereas those with regional squamous components had similar survival outcomes. CONCLUSION: For UTUC patients after RNU, the presence of VH is associated with aggressive clinicopathological features and inferior survival outcomes. However, the survival outcomes of localized UTUC patients (pT≤2) with VH, and patients with the AD or regional SCD subtype are comparable to those of patients with pUC.

Preoperative Systemic Inflammation Score Predicts the Prognosis of Patients with Upper Tract Urothelial Carcinoma Undergoing Radical Nephroureterectomy.

Background: To investigate the prognostic significance of systemic inflammation score (SIS) in upper tract urothelial carcinoma (UTUC) in patients undergoing radical nephroureterectomy (RNU). Methods: A total of 313 UTUC patients who underwent RNU at West China Hospital from May 2014 to June 2019 were retrospectively analyzed. The predictive value of SIS for relevant endpoints, including overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS), was assessed by Kaplan-Meier curves and the Cox proportional hazards model. Results: According to inclusion and exclusion criteria, 218 UTUC patients were ultimately included in this cohort study. Statistical analysis shows that increased SIS was significantly associated with higher TNM stage (p = 0.017), lower BMI (p = 0.037), absence of hemoglobin (p < 0.001), and pathologic necrosis (p = 0.007). Kaplan-Meier survival curves clearly visually stratified survival for the three outcomes. After adjusting for tumor grade, the multivariate Cox proportional hazards model results showed that SIS was an independent risk factor for poor OS and CSS (HR = 1.89, 95% CI: 1.11-3.21, p = 0.0183, HR = 1.89, 95% CI: 1.07-3.33, p = 0.0285) in the advanced group. Conclusions: SIS was an independent risk factor for OS and CSS after RNU in patients with high-grade UTUC. It may be a novel and conducive tool for preoperative risk stratification and guiding individualized therapy for high-risk UTUC patients.

Ultracompact and multifunctional integrated photonic platform.

Realizing a multifunctional integrated photonic platform is one of the goals for future optical information processing, which usually requires large size to realize due to multiple integration challenges. Here, we realize a multifunctional integrated photonic platform with ultracompact footprint based on inverse design. The photonic platform is compact with 86 inverse designed-fixed couplers and 91 phase shifters. The footprint of each coupler is 4 µm by 2 µm, while the whole photonic platform is 3 mm by 0.2 mm-one order of magnitude smaller than previous designs. One-dimensional Floquet Su-Schrieffer-Heeger model and Aubry-André-Harper model are performed with measured fidelities of 97.90 (±0.52) % and 99.34 (±0.44) %, respectively. We also demonstrate a handwritten digits classification task with the test accuracy of 87% using on-chip training. Moreover, the scalability of this platform has been proved by demonstrating more complex computing tasks. This work provides an effective method to realize an ultrasmall integrated photonic platform.

Current treatment for male infertility: an umbrella review of systematic reviews and meta-analyses.

This umbrella review aimed to summarize and provide a general evaluation of the effectiveness of current treatments for male infertility and assess the quality of evidence and possible biases. An umbrella review of systematic reviews and meta-analyses available in PubMed, Web of Science, and Scopus, covering studies published up to October 2023, was conducted. Sperm concentration, morphology, and motility were used as endpoints to evaluate the effectiveness of the treatments. Of 2998 studies, 18 published meta-analyses were extracted, yielding 90 summary effects on sperm concentration (n = 36), sperm morphology (n = 26), and sperm motility (n = 28) on 28 interventions. None of the meta-analyses were classified as having low methodological quality, whereas 12 (66.7%) and 6 (33.3%) had high and moderate quality, respectively. Of the 90 summary effects, none were rated high-evidence quality, whereas 53.3% (n = 48), 25.6% (n = 23), and 21.1% (n = 19) were rated moderate, low, and very low, respectively. Significant improvements in sperm concentration, morphology, and motility were observed with pharmacological interventions (N-acetyl-cysteine, antioxidant therapy, aromatase inhibitors, selective estrogen receptor modulators, hormones, supplements, and alpha-lipoic acid) and nonpharmacological interventions (varicocele repair and redo varicocelectomy). In addition, vitamin supplementation had no significant positive effects on sperm concentration, motility, or morphology. Treatments for male infertility are increasingly diverse; however, the current evidence is poor because of the limited number of patients. Further well-designed studies on single treatment and high-quality meta-analysis of intertreatment comparisons are recommended.

Mast cell degranulation-triggered by SARS-CoV-2 induces tracheal-bronchial epithelial inflammation and injury.

SARS-CoV-2 infection-induced hyper-inflammation is a key pathogenic factor of COVID-19. Our research, along with others', has demonstrated that mast cells (MCs) play a vital role in the initiation of hyper-inflammation caused by SARS-CoV-2. In previous study, we observed that SARS-CoV-2 infection induced the accumulation of MCs in the peri-bronchus and bronchioalveolar-duct junction in humanized mice. Additionally, we found that MC degranulation triggered by the spike protein resulted in inflammation in alveolar epithelial cells and capillary endothelial cells, leading to subsequent lung injury. The trachea and bronchus are the routes for SARS-CoV-2 transmission after virus inhalation, and inflammation in these regions could promote viral spread. MCs are widely distributed throughout the respiratory tract. Thus, in this study, we investigated the role of MCs and their degranulation in the development of inflammation in tracheal-bronchial epithelium. Histological analyses showed the accumulation and degranulation of MCs in the peri-trachea of humanized mice infected with SARS-CoV-2. MC degranulation caused lesions in trachea, and the formation of papillary hyperplasia was observed. Through transcriptome analysis in bronchial epithelial cells, we found that MC degranulation significantly altered multiple cellular signaling, particularly, leading to upregulated immune responses and inflammation. The administration of ebastine or loratadine effectively suppressed the induction of inflammatory factors in bronchial epithelial cells and alleviated tracheal injury in mice. Taken together, our findings confirm the essential role of MC degranulation in SARS-CoV-2-induced hyper-inflammation and the subsequent tissue lesions. Furthermore, our results support the use of ebastine or loratadine to inhibit SARS-CoV-2-triggered degranulation, thereby preventing tissue damage caused by hyper-inflammation.