Patients with ASPSCR1-TFE3 fusion achieve better response to ICI based combination therapy among TFE3-rearranged renal cell carcinoma.

BACKGROUND: TFE3-rearranged renal cell carcinoma (TFE3-rRCC) is a rare but highly heterogeneous renal cell carcinoma (RCC) entity, of which the clinical treatment landscape is largely undefined. This study aims to evaluate and compare the efficacy of different systemic treatments and further explore the molecular correlates. METHODS: Thirty-eight patients with metastatic TFE3-rRCC were enrolled. Main outcomes included progression-free survival (PFS), overall survival, objective response rate (ORR) and disease control rate. RNA sequencing was performed on 32 tumors. RESULTS: Patients receiving first-line immune checkpoint inhibitor (ICI) based combination therapy achieved longer PFS than those treated without ICI (median PFS: 11.5 vs. 5.1 months, P = 0.098). After stratification of fusion partners, the superior efficacy of first-line ICI based combination therapy was predominantly observed in ASPSCR1-TFE3 rRCC (median PFS: not reached vs. 6.5 months, P = 0.01; ORR: 67.5% vs. 10.0%, P = 0.019), but almost not in non-ASPSCR1-TFE3 rRCC. Transcriptomic data revealed enrichment of ECM and collagen-related signaling in ASPSCR1-TFE3 rRCC, which might interfere with the potential efficacy of anti-angiogenic monotherapy. Whereas angiogenesis and immune activities were exclusively enriched in ASPSCR1-TFE3 rRCC and promised the better clinical outcomes with ICI plus tyrosine kinase inhibitor combination therapy. CONCLUSIONS: The current study represents the largest cohort comparing treatment outcomes and investigating molecular correlates of metastatic TFE3-rRCC based on fusion partner stratification. ICI based combination therapy could serve as an effective first-line treatment option for metastatic ASPSCR1-TFE3 rRCC patients. Regarding with other fusion subtypes, further investigations should be performed to explore the molecular mechanisms to propose pointed therapeutic strategy accordingly.

Predicting abiraterone efficacy in advanced prostate cancer: Insights from marker of proliferation Ki67.

BACKGROUND: KI67 is a well-known biomarker reflecting cell proliferation. We aim to elucidate the predictive role of KI67 in the efficacy of abiraterone for patients with advanced prostate cancer (PCa). METHODS: Clinicopathological data of 152 men with metastatic PCa, who received abiraterone therapy were retrospectively collected. The KI67 positivity was examined by immunohistochemistry using the prostate biopsy specimen. The predictive value of KI67 on the therapeutic efficacy of abiraterone was explored using Kaplan-Meier curve and Cox regression analysis. The endpoints included prostate-specific antigen (PSA) progression-free survival (PSA-PFS), radiographic PFS (rPFS), and overall survival (OS). RESULTS: In total, 85/152 (55.9%) and 67/152 (44.1%) cases, respectively, received abiraterone at metastatic hormone-sensitive (mHSPC) and castration-resistant PCa (mCRPC) stage. The median KI67 positivity was 20% (interquartile range: 10%-30%). Overall, KI67 rate was not correlated with PSA response. Notably, an elevated KI67-positive rate strongly correlated with unfavorable abiraterone efficacy, with KI67 ≥ 30% and KI67 ≥ 20% identified as the optimal cutoffs for prognosis differentiation in mHSPC (median PSA-PFS: 11.43 Mo vs. 26.43 Mo, p < 0.001; median rPFS: 16.63 Mo vs. 31.90 Mo, p = 0.003; median OS: 21.77 Mo vs. not reach, p = 0.005) and mCRPC (median PSA-PFS: 7.17 Mo vs. 12.20 Mo, p = 0.029; median rPFS: 11.67 Mo vs. 16.47 Mo, p = 0.012; median OS: 21.67 Mo vs. not reach, p = 0.073) patients, respectively. Multivariate analysis supported the independent predictive value of KI67 on abiraterone efficacy. In subgroup analysis, an elevated KI67 expression was consistently associated with unfavorable outcomes in the majority of subgroups. Furthermore, data from another cohort of 79 PCa patients with RNA information showed that those with KI67 RNA levels above the median had a significantly shorter OS than those below the median (17.71 vs. 30.72 Mo, p = 0.035). CONCLUSIONS: This study highlights KI67 positivity in prostate biopsy as a strong predictor of abiraterone efficacy in advanced PCa. These insights will assist clinicians in anticipating clinical outcomes and refining treatment decisions for PCa patients.

The survival benefit of metastasectomy for metastatic non-clear cell renal cell carcinoma: a retrospective cohort study.

PURPOSE: The aim of this study was to explore the benefit the metastasectomy for patients with metastatic non-clear cell carcinoma (non-ccRCC). METHODS: This study enrolled 120 patients with confirmed metastatic non-ccRCC from the RCC database of our center from 2008 to 2021. Patients without metastasectomy were grouped as radical nephrectomy without metastasectomy patients. The clinical outcomes included overall survival (OS) and progression-free survival (PFS). Cox regression and Kaplan-Meier analyses were used to assess potential factors that predict clinical benefits from metastasectomy. RESULTS: A total of 100 patients received radical nephrectomy alone, while the remaining 20 patients underwent both radical nephrectomy and metastasectomy. There was no significant difference in age between the two groups. Out of 100 patients who underwent radical nephrectomy, 60 were male, and out of 20 patients who had both radical nephrectomy and metastasectomy, 12 were male. Patients who underwent systemic therapy plus radical nephrectomy and metastasectomy had significantly better PFS (27.1 vs. 14.0, p = 0.032) and OS (67.3 vs. 24.0, p = 0.043) than those who underwent systemic therapy plus radical nephrectomy alone. Furthermore, for patients without liver metastasis (n = 54), systemic therapy plus radical nephrectomy and metastasectomy improved both PFS (p = 0.028) and OS (p = 0.043). Similarly, for patients with metachronous metastasis, systemic therapy plus radical nephrectomy and metastasectomy improved both PFS (p = 0.043) and OS (p = 0.032). None of the patients experienced serious perioperative complications (Clavien-Dindo Classification ≥ III grade). CONCLUSION: Metastasectomy in patients with metastatic non-ccRCC may provide clinical benefits in terms of improved PFS and OS, especially in patients without liver metastasis and those with metachronous metastasis.

A Multiple Attention Convolutional Neural Networks for Diesel Engine Fault Diagnosis.

Fault diagnosis can improve the safety and reliability of diesel engines. An end-to-end method based on a multi-attention convolutional neural network (MACNN) is proposed for accurate and efficient diesel engine fault diagnosis. By optimizing the arrangement and kernel size of the channel and spatial attention modules, the feature extraction capability is improved, and an improved convolutional block attention module (ICBAM) is obtained. Vibration signal features are acquired using a feature extraction model alternating between the convolutional neural network (CNN) and ICBAM. The feature map is recombined to reconstruct the sequence order information. Next, the self-attention mechanism (SAM) is applied to learn the recombined sequence features directly. A Swish activation function is introduced to solve "Dead ReLU" and improve the accuracy. A dynamic learning rate curve is designed to improve the convergence ability of the model. The diesel engine fault simulation experiment is carried out to simulate three kinds of fault types (abnormal valve clearance, abnormal rail pressure, and insufficient fuel supply), and each kind of fault varies in different degrees. The comparison results show that the accuracy of MACNN on the eight-class fault dataset at different speeds is more than 97%. The testing time of the MACNN is much less than the machine running time (for one work cycle). Therefore, the proposed end-to-end fault diagnosis method has a good application prospect.

Crop diversification promotes soil aggregation and carbon accumulation in global agroecosystems: A meta-analysis.

Soil aggregation contributes to the stability of soil structure and the sequestration of soil organic carbon (SOC), making it an important indicator of soil health in agroecosystems. Crop diversification is considered a rational management practice for promoting sustainable agriculture. However, the complexity of cropping systems and crop species across different regions limits our comprehensive understanding of soil aggregation and associated carbon (C) content under crop diversification. Therefore, we conducted a meta-analysis by integrating 1924 observations from three diversification strategies (cover crops, crop rotation, and intercropping) in global agroecosystems to explore the effects of crop diversification on soil aggregates and associated C content. The results showed that compared to monoculture, crop diversification significantly increased the mean weight diameter and bulk soil C by 7.5% and 3.3%, respectively. Furthermore, there was a significant increase in the proportion of macroaggregates and their associated C content by 5.0% and 12.5%, while there was a significant decrease in the proportion of microaggregates as well as silt-clay fractions along with their associated C under crop diversification. Through further analysis, we identified several important factors that influence changes in soil aggregation and C content induced by crop diversification including climatic conditions, soil properties, crop species, and agronomic practices at the experimental sites. Interestingly, no significant differences were found among the three cropping systems (cover crops, crop rotation, and intercropping), while the effects induced by crop diversifications showed relatively consistent results for monoculture crops as well as additive crops and crop diversity. Moreover, the impact of crop diversification on soil aggregates and associated C content is influenced by soil properties such as pH and SOC. In general, our findings demonstrate that crop diversification promotes soil aggregation and enhances SOC levels in agroecosystems worldwide.

Pressure-Induced Free Exciton Emission in a Quasi-Zero-Dimensional Hybrid Lead Halide.

Structural dimensionality and electronic dimensionality play a crucial role in determining the type of excitonic emission in hybrid metal halides (HMHs). It is important but challenging to achieve free exciton (FE) emission in zero-dimensional (0D) HMHs based on the control over the electronic dimensionality. In this work, a quasi-0D HMH (C7 H15 N2 Br)2 PbBr4 with localized electronic dimensionality is prepared as a prototype model. With increasing pressure onto (C7 H15 N2 Br)2 PbBr4 , the broad and weak self-trapped exciton (STE) emission at ambient conditions is considerably enhanced before 3.6 GPa, which originates from more distorted [PbBr4 ]2- seesaw units upon compression. Notably, a narrow FE emission in (C7 H15 N2 Br)2 PbBr4 appears at 3.6 GPa, and then this FE emission is gradually strengthened up to 8.4 GPa. High pressure structural characterizations reveal that anisotropic contraction of (C7 H15 N2 Br)2 PbBr4 results in a noticeable reduction in the distance between adjacent [PbBr4 ]2- seesaw units, as well as an obvious enhancement of crystal stiffness. Consequently, the electronic connectivity in (C7 H15 N2 Br)2 PbBr4 is sufficiently promoted above 3.6 GPa, which is also supported with theoretical calculations. The elevation of electronic connectivity and enhanced stiffness together lead to pressure-induced FE emission and subsequent emission enhancement in quasi-0D (C7 H15 N2 Br)2 PbBr4 .

Safety and efficacy associated with single-fraction high-dose-rate brachytherapy in localized prostate cancer: a systematic review and meta-analysis.

OBJECTIVE: Although single-fraction high-dose-rate brachytherapy (SFHDR) for localized prostate cancer has been tried in clinical trials, relevant medical evidence is currently lacking. It is necessary to systematically analyze the safety and efficacy of SFHDR. METHODS: Comprehensive and systematic searches for eligible studies were performed in PubMed, Embase, and the Cochrane Library databases. The primary endpoints included safety and efficacy, represented by toxic effects and biochemical recurrence-free survival (bRFS), respectively. The proportion rates were used as the effect measure for each study and were presented with corresponding 95% confidence intervals (CI) and related 95% prediction interval (PI). Restricted maximum-likelihood estimator (REML) and the Hartung-Knapp method were used in the meta-analysis. RESULTS: Twenty-five studies met the inclusion criteria for quantitative analysis, including 1440 patients. The median age of patients was 66.9 years old (62-73 years old) and the median follow-up was 47.5 months (12-75 months). The estimates of cumulative occurrence for severe gastrointestinal (GI) and genitourinary (GU) toxic effects were 0.1% (95% CI 0-0.2%) and 0.4% (95% CI 0-1.2%), and for grade 2 toxic effects were 1.6% (95% CI 0.1-4.7%) and 17.1% (95% CI 5.4-33.5%), respectively. The estimate of 3­year bRFS was 87.5% (95% CI 84.4-90.3%) and 71.0% (95% CI 63.0-78.3%) for 5­year bRFS. The pooled bRFS rates for low-risk patients were 99.0% (95% CI 85.2-100.0%) at 3 years and 80.9% (95% CI 75.4-85.9%) at 5 years, and the risk group was found to be statistically correlated with bRFS (3-year bRFS, P < 0.01; 5­year bRFS, P = 0.04). CONCLUSION: SFHDR is associated with favorable tolerability and suboptimal clinical benefit in patients with localized prostate cancer. Ongoing and planned high-quality prospective studies are necessary to verify its safety and efficacy.

The tumor-repressing effect of CYP27A1 on renal cell carcinoma by 27-HC arising from cholesterol metabolism.

As a key approach to mediate cholesterol metabolism, the role of the CYP27A1/27-HC axis in renal cell carcinoma (RCC) remains unclear. Analysis of CYP27A1 expression from public databases and metastatic cases in our center suggested that CYP27A1 was obviously downregulated in RCC tissues, and survival analysis further showed its correlation with favorable clinicopathological features and prognosis. In vitro, up and downregulation of CYP27A1 expression in RCC cell lines could definitely illustrate its anticipation involving apoptosis, proliferation, invasion, migration, and clonality. This could be achieved through upregulation of 27-HC concentration, which mediates the activation of signaling pathways of apoptosis and cell cycle arrest. Further, recovery of CYP27A1 expression could definitely inhibit the proliferation of RCC tumors in vivo. This is the first study to explore the role of the CYP27A1/27-HC axis in RCC. Attempts to maintain the normal function of the axis may be a potential strategy in the treatment of RCC, and the predictive value of CYP27A1 detection on the efficacy of targeted therapy in metastatic RCC is also worthy of attention.

Analysis of adverse event of interstitial lung disease in men with prostate cancer receiving hormone therapy using the Food and Drug Administration Adverse Event Reporting System.

AIMS: To investigate interstitial lung disease (ILD) in men with prostate cancer receiving hormone therapy. METHODS: We gathered cases diagnosed with prostate cancer based on the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database from 2004 to 2020. We divided the included cases into 3 groups based on the primary suspected drugs: a hormone therapy group, a positive control group (taxanes), and a negative control group. We employed reporting odds ratio, a disproportionality method, to detect the association between ILD events and target drugs. RESULTS: We finally included a total of 85 403 cases, 69 894 cases (628 ILD event cases) in the hormone therapy group, 2302 cases (158 ILD event cases) in the positive control group and 13 207 cases (72 ILD event cases) in the negative control group. There were 394 ILD event cases (62.74%) in the hormone therapy group in Japan; 78.68% of the ILD events occurred within the first year after hormone treatment. Disproportionality analysis indicated that ILD events were significantly associated with nilutamide, flutamide, bicalutamide, goserelin, degarelix and apalutamide; the reporting odds ratios (95% confidence interval) were 32.14 (11.03-93.63), 9.93 (3.62-27.21), 8.19 (6.01-11.16), 3.74 (2.61-5.37), 2.41 (1.55-3.75) and 1.94 (1.01-3.75), respectively. CONCLUSION: Based on this FAERS pharmacovigilance analysis, the association between ILD events and hormone therapy drugs, including bicalutamide, flutamide, nilutamide, goserelin, degarelix and apalutamide, should not be ignored, especially in the Japanese population. Lung function of prostate cancer patients should be monitored when receiving the hormone therapy drugs mentioned above, especially for the first year post medication.

Single-Sensor Engine Multi-Type Fault Detection.

Engine fault detection is conducive to improving equipment reliability and reducing maintenance costs. In practical scenarios, high-quality data is difficult to obtain. Usually, only single-sensor data is available. This paper proposes a fault detection method combining Variational Mode Decomposition (VMD) and Random Forest (RF). At first, the spectral energy distribution is obtained by decomposing and statistic the engine data of multiple working conditions. Based on the spectral energy distribution, the overall optimal mode number was identified, and the quadratic penalty term was optimized using SNR. The improved VMD (IVMD) improves mode aliasing and iterative efficiency and unifies feature dimensions. Decomposition of real signals demonstrates the effectiveness. The paper designs a feature vector composed of seven types of attributes, including unit bandwidth energy, center frequency, maximum singular value and so on. The feature vector is then fed to RF for classification. Features are selected in order of importance to classification to improve the training efficiency. By comparing with various algorithms, the proposed method has higher accuracy and faster training efficiency in single-speed, multi-speed and cross-speed single-sensor data diagnosis. The results show that the method has application prospects with little training data and low hardware requirements.

Plasma Exosomal AKR1C3 mRNA Expression Is a Predictive and Prognostic Biomarker in Patients with Metastatic Castration-Resistant Prostate Cancer.

PURPOSE: Aldo-keto reductase family 1 member C3 (AKR1C3) is important in prostate cancer progression, being a potential biomarker in metastatic castration-resistant prostate cancer (mCRPC). Previous explorations of AKR1C3 are mainly based on tissue samples. This study investigates using plasma-based liquid biopsy to validate the prognostic and predictive value of AKR1C3 in patients with mCRPC . MATERIALS AND METHODS: We prospectively recruited 62 patients with mCRPC. All patients received repeated prostate biopsies at the time of mCRPC diagnosis, and immunohistochemistry (IHC) staining was used to detect protein expression of AKR1C3 in the tissues. We took their blood simultaneously and performed digital droplet polymerase chain reaction (ddPCR) to measure expression levels of AKR1C3 in the exosomes. The detected plasma and tissue AKR1C3 expression levels were analyzed for patients' overall survival (OS) and progression-free survival under first-line abiraterone use (ABI-PFS). RESULTS: All other baseline characteristics were balanced between the 2 groups. 15/62 (24.2%) and 25/62 (40.3%) patients showed AKR1C3-EXO positive (≥20 copies/20 µL) and AKR1C3-IHC positive, respectively. Positive AKR1C3-EXO expression was associated with decreased patients' survival [ABI-PFS: 3.9 vs 10.1 months, P < .001; OS: 16.2 vs 32.5 months, P < .001]. AKR1C3-IHC positivity was also correlated with ABI-PFS and OS (P = .010, P = .016). In patients with worse baseline blood tests (including higher alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) level and lower hemoglobin (HB) level), and lower ISUP/WHO group (<4), their OS was significantly worse when showing AKR1C3-EXO positive. CONCLUSION: AKR1C3-EXO is associated with patient prognosis regarding OS and ABI-PFS and can be used as a biomarker in mCRPC.

Homologous recombination deficiency (HRD) score in aggressive prostatic adenocarcinoma with or without intraductal carcinoma of the prostate (IDC-P).

BACKGROUND: Intraductal carcinoma of the prostate (IDC-P) is a subtype of prostate cancer featured by poor prognosis. Previous studies suggested IDC-P could have a potentially unstable genome. Homologous recombination deficiency (HRD) score is a result-oriented method to describe the genomic instability status. This study investigates the association of HRD scores with IDC-P and other clinicopathological factors and the prognostic implication of HRD scores in an aggressive prostate cancer cohort. METHODS: This study involved 123 PCa patients, including high-risk localized (M0) and de novo metastatic (M1) diseases. HRD score is calculated based on over 10,000 single-nucleotide polymorphisms distributed across the human genome. We explored the association between HRD scores and clinicopathological characteristics, genomic alterations, and patients' prognoses using rank-sum tests, chi-square tests, Kaplan-Meier curves, and Cox proportional hazards method. RESULTS: The median HRD score of this cohort is 21.0, with 65 (52.8%) patients showing HRD score≥21. Tumors with IDC-P displayed higher HRD scores than adenocarcinoma (P=0.002); other high HRD score-related factors included M1 (P =0.008) and high ISUP grades (4-5) (P=0.001). MYC mutations were associated with high HRD scores (P<0.001) in the total cohort. TP53 mutations (P=0.010) and HRR pathway mutations (P=0.028) corresponded to high HRD scores in IDC-P positive and non-IDC-P patients, respectively, but not vice versa. HRD scores higher than 21 indicated significantly worse survival in the total cohort. CONCLUSIONS: M1, high Gleason score, and IDC-P pathology represent higher HRD scores in PCa. Tumors with IDC-P might have different driven mechanisms for high HRD scores than non-IDC-P. HRD score displayed prognostic value in this aggressive prostate cancer cohort.

Circulating tumour DNA reveals genetic traits of patients with intraductal carcinoma of the prostate.

OBJECTIVES: To investigate the genetic alterations of patients with prostate cancer (PCa) with and without intraductal carcinoma of the prostate (IDC-P). PATIENTS AND METHODS: We performed targeted sequencing of plasma cell-free DNA on 161 patients with prostate adenocarcinoma (PAC) with IDC-P and 84 without IDC-P. Genomic alterations were compared between these two groups. The association between genetic alterations and patients' survival outcomes was also explored. RESULTS: We identified that 29.8% (48/161) and 21.4% (18/84) of patients with and without IDC-P harboured genomic alterations in DNA repair pathways, respectively (P = 0.210). Pathogenic germline DNA repair alterations were frequently detected in IDC-P carriers compared to IDC-P non-carriers (11.8% [19/161] vs 2.4% [two of 84], P = 0.024). Germline BReast CAncer type 2 susceptibility protein (BRCA2) and somatic cyclin-dependent kinase 12 (CDK12) defects were specifically identified in IDC-P carriers relative to PAC (BRCA2: 8.7% [14/161] vs 0% and CDK12: 6.8% [11/161] vs 1.2% [one of 84]). Patients with IDC-P had a distinct androgen receptor (AR) pathway alteration, characterised by an enrichment of nuclear receptor corepressor 2 (NCOR2) mutations compared with patients with pure PAC (21.1% [34/161] vs 6.0% [five of 84], P = 0.004). Increased AR alterations were detected in patients harbouring tumours with an IDC-P proportion of ≥10% vs those with an IDC-P proportion of <10% (6.4% [five of 78] vs 18.1% [15/83], P = 0.045). For IDC-P carriers, tumour protein p53 (TP53) mutation was associated with shorter castration-resistant-free survival (median 10.9 vs 28.9 months, P = 0.026), and BRCA2 alteration was related to rapid prostate-specific antigen progression for those receiving abiraterone treatment (median 9.1 vs 11.9 months, P = 0.036). CONCLUSION: Our findings provide genomic evidence explaining the aggressive phenotype of tumours with IDC-P, highlighting the potential therapeutic strategies for this patient population.

Primary melanoma of the bladder: case report and review of the literature.

BACKGROUND: Primary melanoma of the bladder is extremely rare and has been sporadically reported in case reports. Its incidence, diagnosis, treatment, and outcomes are still unclear. CASE PRESENTATION: We report a 67-year-old female patient who presented with hematuria and was diagnosed with primary melanoma of the bladder by transurethral resection. No distant metastasis was detected by fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT). After a multidisciplinary discussion, the patient received laparoscopic radical resection of the bladder tumor. There was no tumor recurrence or distant metastasis after 15 months of follow-up. CONCLUSION: Primary melanoma of the bladder is easily confused with urothelium carcinoma in morphology. The immunohistochemical is crucial in diagnosis. Because of a lack of in-depth understanding of primary melanoma of the bladder, the "gold standard" treatment has not been set. We would like to provide some rare information about it and discuss the proper treatment strategy for this rare disease.

The heterogeneity of intraductal carcinoma of the prostate is associated with different efficacy of standard first-line therapy for patients with metastatic castration-resistant prostate cancer.

BACKGROUND: To explore whether metastatic castration-resistant prostate cancer (mCRPC) patients with distinct intraductal carcinoma of the prostate (IDC-P) subtypes respond differently to abiraterone and docetaxel treatment. METHODS: We retrospectively analyzed data of 170 mCRPC patients receiving abiraterone or docetaxel as first-line therapy. PSA response, PSA progression-free survival (PSA-PFS), radiographic progression-free survival (rPFS), and overall survival (OS) were analyzed based on the presence of IDC-P and its subpatterns. RESULTS: IDC-P was confirmed in 91/170 (53.5%) patients. Among them 36/91 (39.6%) and 55/91 (60.4%) harbored IDC-P patterns 1 and 2, respectively. Patients with IDC-P pattern 1 shared similar clinical outcomes to those without IDC-P in both abiraterone and docetaxel treatment. However, against cases without IDC-P or with IDC-P pattern 1, patients with IDC-P pattern 2 had markedly poorer prognosis in either abiraterone (mPSA-PFS: 11.9 vs. 11.1 vs. 6.1 months, p < 0.001; mrPFS: 18.9 vs. 19.4 vs. 9.6 months, p < 0.001) or docetaxel (mPSA-PFS: 6.2 vs. 6.6 vs. 3.0 months, p < 0.001; mrPFS: 15.1 vs. 12.6 vs. 5.5 months, p < 0.001) treatment. For patients without IDC-P, docetaxel had comparable therapeutic efficacy with abiraterone. However, the efficacy of docetaxel was significantly inferior to abiraterone in patients with either IDC-P pattern 1 (mPSA-PFS: 6.6 vs. 11.1 months, p = 0.021; mrPFS: 12.6 vs. 19.4 months, p = 0.027) or pattern 2 (mPSA-PFS: 3.0 vs. 6.1 months, p = 0.003; mrPFS: 5.5 vs. 9.6 months, p = 0.007). CONCLUSION: Compared to docetaxel, abiraterone exhibited better efficacy in patients with IDC-P of either pattern. However, IDC-P pattern 2 responded unsatisfactorily to either abiraterone or docetaxel therapy. Novel therapeutic strategies for IDC-P pattern 2 need further investigations.

Dynamic multidisciplinary team discussions can improve the prognosis of metastatic castration-resistant prostate cancer patients.

BACKGROUND: Multidisciplinary team (MDT) management is a popular treatment paradigm in managing cancer patients, which provides fully-discussed, interdisciplinary treatment recommendations for patients. However, there has been a lack of data on its actual impact on the overall survival (OS) of metastatic castration-resistant prostate cancer (mCRPC) patients. mCRPC is the end stage of prostate cancer, facing a treatment dilemma of overwhelming options; therefore, we hypothesize dynamic MDT discussions can be helpful in comprehensively managing these patients. METHODS: We retrospectively collected 422 mCRPC patients' clinical information from 2013 to 2020 from our institute. Patients can voluntarily choose whether to enroll in the dynamic MDT group, which includes discussions at CRPC diagnosis and subsequent disease progression. All patients were followed up regularly, and OS from CRPC diagnosis to death was set as the endpoint of this study. RESULTS: Participating in MDT discussions is a favorable independent indicator of longer overall survival (median OS: MDT (+): 39.7 months; MDT (-): 27.0 months, hazard ratio: 0.549, p = .001). Moreover, this survival benefit of MDT remained in subgroups with first-line therapy [median OS: MDT (+): not reached; MDT (-): 27.0 months, p = .001) and with multi-line therapy until the end of follow-up (median OS: MDT (+): 36.7 months; MDT (-): 25.6 months, p = .044). CONCLUSION: Therefore, regular MDT discussions are valuable in the management of mCRPC patients. Clinicians are encouraged to tailor MDT discussions dynamically to provide mCRPC patients with a better and more individualized treatment plan and more prolonged survival. Take-home messages ● The MDT model is defined as dynamic MDT discussions at the time of mCRPC diagnosis and each time they progressed later on throughout the disease management. ● Prostate cancer MDT usually includes specialists in urologic oncology, pathology, chemotherapy, radiotherapy, ultrasound, imaging and nuclear medicine. ● MDT model can benefit mCRPC patients in terms of overall survival.

Structure and Photoluminescence Transformation in Hybrid Manganese(II) Chlorides.

Hybrid metal halides with tunable photoluminescence (PL) properties have emerged as a novel light-emitting material. Hybrid manganese halides are especially attractive due to the eco-friendly and highly emissive advantages. However, the PL tunability induced by structural modulation in manganese halides has rarely been investigated. Herein, a new one-dimensional (1D) hybrid manganese chloride, (4AMP)4ClMn3Cl13·HCl (4AMP = 4-(aminomethyl)pyridinium), where the corner-sharing octahedral manganese chloride chains of [Mn3Cl137-]∞ are surrounded by organic cations, has been prepared. The addition of Zn2+ ions into precursor solution results in the formation of zero-dimensional (0D) single crystals of (4AMP)Zn1-xMnxCl4·H2O (x = 0-1) with isolated [Zn1-xMnxCl42-] tetrahedral geometry. This structural transformation leads to the PL conversion from red to green emission with an increase of photoluminescence quantum yield (PLQY) from 4.9% to 12.7%. Moreover, the incorporation of other transition metal ions (e.g., Zn2+, Co2+, and Cu2+) reveals the concentration-dependent structure modulation, where the 1D to 0D structure transformations are achieved upon the introduction of these transition metal ions at high concentrations. This work provides a new strategy to modulate the structure and luminescence in manganese halides with tunable PL properties, which could be expanded to other hybrid metal halides.

Roles of ompA of Citrobacter werkmanii in bacterial growth, biocide resistance, biofilm formation and swimming motility.

The genus Citrobacter is commonly found in environmental and industrial settings, some members of which have been used for bioremediation of heavy metals owing to the absorption ability of their biofilms. Although our previous studies have found that the outer membrane protein A (OmpA) contributes to the process of Citrobacter werkmanii biofilm formation, the underlying mechanisms remain elusive. Therefore, we deleted ompA from the genome of C. werkmanii and investigated its phenotypes in comparison to the wild type strain (WT) and the complementary strain using biochemical and molecular techniques including RNA-Seq. Our results demonstrated that the deletion of ompA led to an increase in biofilm formation on both polystyrene and glass surfaces due to upregulation of some biofilm formation related genes. Meanwhile, swimming ability, which is mediated by activation of flagellar assembly genes, was increased on semi-solid plates in the ∆ompA strain when compared with WT. Additionally, inactivation of ompA also caused increased 1,2-benzisothiazolin-3-one (BIT) resistance, differential responses to Ca2+ stress, curli protein expression and cellulose production. Finally, ∆ompA caused differential expression of a total of 1470 genes when compared with WT, of which 146 were upregulated and 1324 were downregulated. These genes were classified into different Gene Ontology (GO) and KEGG pathways. In summary, ompA in C. werkmanii contributes to a variety of biological functions and may act as a target site to modulate biofilm formation. KEY POINTS: • ompA is a negative regulator for biofilm formation by C. werkmanii. • ompA inhibits swimming motility of C. werkmanii. • ompA deletion causes different expression profiles in C. werkmanii.

Development of Recombinase Polymerase Amplification Combined with Lateral Flow Detection Assay for Rapid and Visual Detection of Ralstonia solanacearum in Tobacco.

Bacterial wilt caused by Ralstonia solanacearum is a serious soilborne disease that results in severe losses to tobacco (Nicotiana tabacum) production in China. In this study, a novel RPA-LFD assay for the rapid visual detection of R. solanacearum was established using recombinase polymerase amplification (RPA) and lateral-flow dipstick (LFD). The RPA-LFD assay was performed at 37°C in 30 min without complex equipment. Targeting the sequence of the RipTALI-9 gene, we designed RPA primers (Rs-rpa-F/R) and an LF probe (Rs-LF-probe) that showed high specificity to R. solanacearum. The sensitivity of RPA-LFD assay to R. solanacearum was the same as that in conventional PCR at 1 pg genomic DNA, 103 CFU/g artificially inoculated tobacco stems, and 104 CFU/g artificially inoculated soil. The RPA-LFD assay could also detect R. solanacearum from plant and soil samples collected from naturally infested tobacco fields. These results suggest that the RPA-LFD assay developed in this study is a rapid, accurate molecular diagnostic tool with high sensitivity for the detection of R. solanacearum.

The Impact of Renal Impairment on Survival Outcomes in Patients With Metastatic Renal Cell Carcinoma Treated With Tyrosine Kinase Inhibitors.

PURPOSE: It remained unclear whether tyrosine kinase inhibitors (TKIs) related renal impairment had impact on the survival of patients with metastatic renal cell carcinoma (mRCC). METHODS: Clinicopathological parameters of patients with mRCC treated with TKIs were retrospectively reviewed. Blood urea nitrogen (BUN), proteinuria and estimated glomerular filtration rate (eGFR) at baseline and during TKIs treatment were recorded. BUN > 7.1mol/L, eGFR <60 ml/min/1.73m2 and/or proteinuria level > 0.3 g/L were defined as renal impairment. eGFR and proteinuria were furtherly classified into different levels. Treatment outcomes were defined as progression-free survival (PFS) and overall survival (OS). RESULTS: At baseline, the presence of abnormal BUN, eGFR and proteinuria level were observed in 25 (22.7%), 27 (25.5%) and 30 (27.3%) patients, which increased to 46 (41.8%), 55 (50.0%) and 64 (58.2%) respectively after TKIs treatment. In the whole cohort (N = 110), survival analysis suggested that only post-treatment renal impairment was related to survival outcomes. Interestingly, sub-analysis showed that post-treatment eGFR level (p = 0.004), proteinuria (p = 0.014) and eGFR decrease >10% (p = 0.012) and elevated proteinuria compared with baseline (p = 0.006) were statistically correlated with OS among patients without RI at baseline (N = 51). On the contrary, deterioration of renal impairment after TKIs treatment in patients with renal impairment at baseline (N = 59) had no relationship with either PFS or OS. Furthermore, eGFR (p = 0.020) and eGFR decrease >10% (p = 0.016) within 1 year after TKIs therapy were potential biomarkers for OS. CONCLUSION: Dynamic changes of TKI-induced RI during TKIs treatment, especially eGFR and proteinuria level, could be considered as potential biomarkers predicting survival outcomes of mRCC patients.