Characterizing cell interactions at scale with made-to-order droplet ensembles (MODEs).

Cell-cell interactions are important to numerous biological systems, including tissue microenvironments, the immune system, and cancer. However, current methods for studying cell combinations and interactions are limited in scalability, allowing just hundreds to thousands of multicell assays per experiment; this limited throughput makes it difficult to characterize interactions at biologically relevant scales. Here, we describe a paradigm in cell interaction profiling that allows accurate grouping of cells and characterization of their interactions for tens to hundreds of thousands of combinations. Our approach leverages high-throughput droplet microfluidics to construct multicellular combinations in a deterministic process that allows inclusion of programmed reagent mixtures and beads. The combination droplets are compatible with common manipulation and measurement techniques, including imaging, barcode-based genomics, and sorting. We demonstrate the approach by using it to enrich for chimeric antigen receptor (CAR)-T cells that activate upon incubation with target cells, a bottleneck in the therapeutic T cell engineering pipeline. The speed and control of our approach should enable valuable cell interaction studies.

Evolutionary analysis of conserved non-coding elements subsequent to whole-genome duplication in opium poppy.

Whole-genome duplication (WGD) leads to the duplication of both coding and non-coding sequences within an organism's genome, providing an abundant supply of genetic material that can drive evolution, ultimately contributing to plant adaptation and speciation. Although non-coding sequences contain numerous regulatory elements, they have been understudied compared to coding sequences. In order to address this gap, we explored the evolutionary patterns of regulatory sequences, coding sequences and transcriptomes using conserved non-coding elements (CNEs) as regulatory element proxies following the recent WGD event in opium poppy (Papaver somniferum). Our results showed similar evolutionary patterns in subgenomes of regulatory and coding sequences. Specifically, the biased or unbiased retention of coding sequences reflected the same pattern as retention levels in regulatory sequences. Further, the divergence of gene expression patterns mediated by regulatory element variations occurred at a more rapid pace than that of gene coding sequences. However, gene losses were purportedly dependent on relaxed selection pressure in coding sequences. Specifically, the rapid evolution of tissue-specific benzylisoquinoline alkaloid production in P. somniferum was associated with regulatory element changes. The origin of a novel stem-specific ACR, which utilized ancestral cis-elements as templates, is likely to be linked to the evolutionary trajectory behind the transition of the PSMT1-CYP719A21 cluster from high levels of expression solely in P. rhoeas root tissue to its elevated expression in P. somniferum stem tissue. Our findings demonstrate that rapid regulatory element evolution can contribute to the emergence of new phenotypes and provide valuable insights into the high evolvability of regulatory elements.

Modified Retzius-sparing robot-assisted radical prostatectomy for cases with anterior tumor: a propensity score-matched analysis.

OBJECTIVE: To compare the outcomes between a modified Retzius-sparing robot-assisted radical prostatectomy (mRS-RARP) technique and conventional robot-assisted radical prostatectomy (Con-RARP) technique for cases with anterior prostate cancer (PCa), especially positive surgical margin (PSM) rates and urinary continence (UC). PATIENTS AND METHODS: We retrospectively included 193 mRS-RARP and 473 Con-RARP consecutively performed by a single surgeon for anterior PCa. Perioperative complications, pathology, and continence were compared after propensity score matching using 9 variables. RESULTS: After matching (n = 193 per group), PSM were not significantly different in the two groups (16.1% in mRS-RARP group vs. 15.0% in Con-RARP group, p = 0.779). The UC at catheter removal and at 1-month was significantly higher in the mRS-RARP (24.9% vs. 9.8%, p < 0.001; 29.0% vs. 13.5%, p < 0.001, respectively), but not at 3-, 6-, and 12-month follow-ups (p = 0.261, 0.832, and 0.683, respectively). CONCLUSION: mRS-RARP seems to be an oncologically safe approach for patients with anterior PCa. Compared with the conventional approach, mRS-RARP approach shows benefits in the short-term postoperative UC recovery.

Cascaded stimulated Brillouin laser and Brillouin-Kerr optical frequency comb in high-Q MgF2 disk resonators.

Backward stimulated Brillouin scattering (SBS) in optical microcavities has been widely used in nonlinear optics and microwave photonics. Compared with glass material microcavity, magnesium fluoride crystal microcavity has the advantages of small absorption coefficient, fewer defects and larger nonlinear coefficient, moreover, it usually has a narrow gain bandwidth of tens of megahertz. Here, we design a high precision machining system to produce ultra-smooth surface magnesium fluoride crystal disk cavities with a diameter of about 5 mm, Q value exceeding 108, FSR matching material Brillouin gain. By simply modulating the pump wavelength and coupling power, we observe SBS phenomena with a 13.47 GHz Brillouin frequency shift near 1.55µm and cascaded stimulated Brillouin lasers (SBL) of up to 12 orders. In addition, the Brillouin-Kerr optical frequency comb in this device is demonstrated, observing nearly 300 comb lines spanning across a spectral window of 250 nm. Our research provides a way to fabricate high-Q crystal microcavities and demonstrates the potential of these devices in applications such as microwave sources and nonlinear optics.

Microbial and metabolic features in renal transplant recipients with post-transplantation diabetes mellitus.

OBJECTIVE: Post-transplantation diabetes mellitus (PTDM) is a common complication in renal transplant recipients (RTRs). Gut microbiome plays important roles in a variety of chronic metabolic diseases, but its association with the occurrence and development of PTDM is still unknown. The present study integrates the analysis of gut microbiome and metabolites to further identify the characteristics of PTDM. METHODS: A total of 100 RTRs fecal samples were collected in our study. Among them, 55 samples were submitted to Hiseq sequencing, and 100 samples were used for non-targeted metabolomics analysis. The gut microbiome and metabolomics of RTRs were comprehensively characterized. RESULTS: The species Dialister invisus was significantly associated with fasting plasma glucose (FPG). The functions of tryptophan and phenylalanine biosynthesis were enhanced in RTRs with PTDM, while the functions of fructose and butyric acid metabolism were reduced. Fecal metabolome analysis indicated that RTRs with PTDM had unique metabolite distribution characteristics, and two differentially expressed specific metabolites were significantly correlated with FPG. The correlation analysis of gut microbiome and metabolites showed that gut microbiome had an obvious effect on the metabolic characteristics of RTRs with PTDM. Moreover, the relative abundance of microbial function is associated with the expression of several specific gut microbiome and metabolites. CONCLUSIONS: Our study identified the characteristics of gut microbiome and fecal metabolites in RTRs with PTDM, and we also found two important metabolites and a bacterium were significantly associated with PTDM, which might be used as novel targets in the research field of PTDM.

Epi-illumination SPIM for volumetric imaging with high spatial-temporal resolution.

We designed an epi-illumination SPIM system that uses a single objective and has a sample interface identical to that of an inverted fluorescence microscope with no additional reflection elements. It achieves subcellular resolution and single-molecule sensitivity, and is compatible with common biological sample holders, including multi-well plates. We demonstrated multicolor fast volumetric imaging, single-molecule localization microscopy, parallel imaging of 16 cell lines and parallel recording of cellular responses to perturbations.

Engineered Bacillus subtilis for the de novo production of 2'-fucosyllactose.

BACKGROUND: The most abundant human milk oligosaccharide in breast milk, 2'-fucosyllactose (2'-FL), has been approved as an additive to infant formula due to its multifarious nutraceutical and pharmaceutical functions in promoting neonate health. However, the low efficiency of de novo synthesis limits the cost-efficient bioproduction of 2'-FL. RESULTS: This study achieved 2'-FL de novo synthesis in a generally recognized as safe (GRAS) strain Bacillus subtilis. First, a de novo biosynthetic pathway for 2'-FL was introduced by expressing the manB, manC, gmd, wcaG, and futC genes from Escherichia coli and Helicobacter pylori in B. subtilis, resulting in 2'-FL production of 1.12 g/L. Subsequently, a 2'-FL titer of 2.57 g/L was obtained by reducing the competitive lactose consumption, increasing the regeneration of the cofactor guanosine-5'-triphosphate (GTP), and enhancing the supply of the precursor mannose-6-phosphate (M6P). By replacing the native promoter of endogenous manA gene (encoding M6P isomerase) with a constitutive promoter P7, the 2'-FL titer in shake flask reached 18.27 g/L. The finally engineered strain BS21 could produce 88.3 g/L 2'-FL with a yield of 0.61 g/g lactose in a 3-L bioreactor, without the addition of antibiotics and chemical inducers. CONCLUSIONS: The efficient de novo synthesis of 2'-FL can be achieved by the engineered B. subtilis, paving the way for the large-scale bioproduction of 2'-FL titer in the future.

Transcriptional Analysis of Mice Melanoma B16-F10 Cells in Response to Directed Current Electric Fields.

The endogenous electric field (EF) is widely observed among tissues. It is supposed to be an important environmental factor in tumor metastasis. To explore the role of endogenous EFs in tumor metastasis, the migration of mouse melanoma B16-F10 cells in directed current EFs (dcEFs) was investigated. The transcriptome of melanoma B16-F10 cells in response to EF stimulation was analyzed using RNA sequencing. The results demonstrated that the mouse melanoma B16-F10 cells migrated toward the cathode in applied dcEFs. Directional migration occurred in a voltage-dependent manner. Approximately 3000 upregulated and 2613 downregulated genes were identified under dcEF. Some genes correlated with cell migration, such as Serpine1, Ctgf, Fosb, and Fos, were upregulated. The signaling pathways involved in cell motility were significantly altered. Some genes, highly related to tumorigenesis, invasion, and metastasis, are upregulated in response to EF stimulation. Endogenous EFs may play a role in tumorigenesis and metastasis in vivo. © 2022 Bioelectromagnetics Society.

Functions of non-coding RNAs in regulating cancer drug targets.

With the development of precision medicine, the efficiency of tumor treatment has been significantly improved. More attention has been paid to targeted therapy and immunotherapy as the key to precision treatment of cancer. Targeting epidermal growth factor receptor (EGFR) has become one of the most important targeted treatments for various cancers. Comparing with traditional chemotherapy drugs, targeting EGFR is highly selective in killing tumor cells with better safety, tolerability and less side effect. In addition, tumor immunotherapy has become the fourth largest tumor therapy after surgery, radiotherapy and chemotherapy, especially immune checkpoint inhibitors. However, these treatments still produce a certain degree of drug resistance. Non-coding RNAs (ncRNAs) were found to play a key role in carcinogenesis, treatment and regulation of the efficacy of anticancer drugs in the past few years. Therefore, in this review, we aim to summarize the targeted treatment of cancers and the functions of ncRNAs in cancer treatment.

Nephron-Sparing Surgery for Adult Xp11.2 Translocation Renal Cell Carcinoma at Clinical T1 Stage: A Multicenter Study in China.

PURPOSE: To evaluate the oncologic efficacy and feasibility of nephron-sparing surgery (NSS) in adult Xp11.2 translocation renal cell carcinoma (RCC). PATIENTS AND METHODS: Seventy patients with Xp11.2 translocation RCC and 273 with conventional RCC from five institutions in Nanjing were retrospectively studied. All patients were older than 18 years and were categorized into clinical T1 (cT1) stage using preoperative imaging. Using the preoperative imaging and electronic medical records, anatomical and pathological features were collected and analyzed. RESULTS: Among patients with Xp11.2 translocation RCC, 18/36 (50.0%) with cT1a and 12/34 (35.3%) with cT1b tumors underwent NSS. The respective proportions in the conventional RCC group were 121/145 (83.4%) and 93/128 (72.7%). Among cT1a tumors, the Xp11.2 translocation RCCs tended to be adjacent to the collecting system, sinus, and axial renal midline compared with conventional RCCs. Patients with Xp11.2 translocation RCCs who underwent NSS had comparable progression-free survival (PFS) and overall survival to radical nephrectomy (RN) patients (P > 0.05). Among cT1b tumors, surgical margin positivity and pelvicalyceal, vascular, and region lymphatic involvement were more likely to occur in the Xp11.2 translocation RCCs (P < 0.05). Patients with Xp11.2 translocation RCC who underwent RN had a more favorable PFS than those who underwent NSS (P = 0.048). However, multivariate analysis of PFS did not identify surgical method as a risk factor (P = 0.089). CONCLUSIONS: Among adults with Xp11.2 translocation RCC, NSS can be an alternative for patients with cT1a tumor but should be performed with more deliberation in patients with cT1b tumors.

Electrostatic Self-Assembly Synthesis of Three-Dimensional Mesoporous Lepidocrocite-Type Layered Sodium Titanate as a Superior Adsorbent for Selective Removal of Cationic Dyes via an Ion-Exchange Mechanism.

Three-dimensional mesoporous lepidocrocite-type layered sodium titanate (LST) was constructed at room temperature by the electrostatic interaction between Ti1-δO24δ- nanosheets and Na+ ions. The results of a systematic X-ray diffraction investigation manifested the transition from the Ti1-δO24δ- nanosheets phase to the titanate/titania phase, which determined a phase diagram as a function of the temperature and NaCl concentration. In addition, scanning electron microscopy, inductively coupled plasma-mass spectrometry, thermogravimetric and differential thermal, N2 adsorption-desorption, Raman spectroscopy, Fourier transform infrared spectroscopy, as well as ζ-potential analyses were utilized for adequate characterization of the LST physical and chemical properties. Furthermore, batch adsorption experiments demonstrated that LST had superior adsorption property and adsorption selectivity toward cationic dyes compared to those of anionic dyes. A multifarious influencing effect on the cationic dye adsorption behavior during the adsorption process was systematically investigated. Moreover, the pseudo-second-order kinetic model felicitously depicted the cationic dye adsorption behavior through an elaborate kinetic study, namely, chemisorption was the main adsorption action. Meanwhile, different adsorption isotherm models were utilized to process the experimental data, uncovering that the adsorption isotherms of cationic dyes on LST were suitable for a Langmuir isothermal model. More importantly, an ion-exchange mechanism was proposed for the cationic dye adsorption on LST, and the ion-exchange reaction occurred with a stoichiometric exchange between 1 mol of Na+ ions in the LST interlayer and 1 mol of MB molecules in the solution. In parallel, the electrochemical impedance spectroscopy and cyclic voltammogram measurements verified that the high ionic conductivity of Na+ ions in the LST interlayer resulted in a superior adsorption property. A two-step acid-base procedure was ultimately adopted to effectively regenerate LST adsorbent. This work provides not only an alternative adsorbent with superior adsorption capacity and adsorption selectivity but also some guiding significance for research on the adsorption mechanism of layered titanates.

[Modified Vattikuti Institute prostatectomy for the treatment of localized prostate cancer].

OBJECTIVE: To investigate the effect of modified Vattikuti Institute prostatectomy (mVIP) in the treatment of localized PCa. METHODS: This retrospective study included 50 cases of localized PCa treated by mVIP and another 50 by robot-assisted radical prostatectomy (RARP) from March 2018 to April 2019. We analyzed the baseline data, the surgical techniques used and the results of short-term follow-up. RESULTS: All the operations were completed successfully without conversion to open surgery. The mVIP group, compared with the RARP, showed longer operation time (ï¼»90.35 ± 24.22ï¼½ vs ï¼»84.46 ± 19.18ï¼½ min, P > 0.05), more intraoperative blood loss (ï¼»220.00 ± 15.10ï¼½ vs ï¼»215.00 ± 15.10ï¼½ ml, P > 0.05), shorter postoperative hospital stay (ï¼»5.75 ± 1.45ï¼½ vs ï¼»6.20 ± 1.50ï¼½ d, P > 0.05), and higher rates of positive surgical margins (22.00% vs 14.00%, P > 0.05) and urinary continence at 1 month (76%vs 22%,P < 0.05), 6 months (84% vs 79%, P > 0.05) and 12 months after surgery (96% vs 94%, P > 0.05). CONCLUSIONS: Modified VIP can better preserve the lateral and posterolateral prostatic fascial tissue in the treatment of localized PCa and therefore significantly promote the recovery of urinary continence after surgery.

Are tumor-associated micro-angiogenesis and lymphangiogenesis considered as the novel prognostic factors for patients with Xp11.2 translocation renal cell carcinoma?

BACKGROUND: Tumor micro-angiogenesis and lymphangiogenesis are effective prognostic predictors in many solid malignancies. However, its role on Xp11.2 translocation RCC has not been fully elucidated. Herein, we purposed to explore the correlation between quantitative parameters of tumor-related micro-angiogenesis or lymphangiogenesis and the prognosis of Xp11.2 translocation renal cell carcinoma (Xp11.2 translocation RCC). METHODS: Tissue samples were obtained from 34 Xp11.2 translocation RCC and 77 clear cell renal cell carcinoma (ccRCC) between January 2007 and December 2018. Micro-angiogenesis was detected using CD34 antibody and quantified with microvessel density (MVD) and microvessel area (MVA), while the lymphangiogenesis in RCC was immunostained with D2-40 antibody and assessed using lymphatic vessel density (LVD) and lymphatic vessel area (LVA). The Kaplan-Meier method of survival analysis was used to estimate prognosis, and both univariate and multivariate analysis was performing using the Cox proportional hazards. RESULTS: The MVD and MVA of Xp11.2 translocation RCC in two detected areas (intratumoral and peritumoral area) were not significantly different from that of ccRCC (all P > 0.05). Notably, D2-40-positive lymphatic vessels of Xp11.2 translocation RCC were highly detected in the peritumoral area compared to the intratumoral area. Interestingly, the peritumoral LVD and LVA of Xp11.2 translocation RCC were higher than that of ccRCC (all P < 0.05). Furthermore, both intratumoral MVD or MVA and peritumoral LVD or LVA were significantly associated with pT stage, pN stage, cM stage, AJCC stage, and WHO/ISUP grade (all P < 0.05). Univariate analysis of Cancer-specific survival (CSS) revealed that CSS was substantially longer in patients with low intratumoral MVD or MVA than in patients with high intratumoral MVD or MVA (P = 0.005 and P = 0.001, respectively). Lastly, the Cox proportional hazards model in CSS demonstrated that both intratumoral MVD or MVA and peritumoral LVD or LVA were not independent prognostic parameters (all P > 0.05). CONCLUSIONS: This study outlines that Xp11.2 translocation RCC is a highly vascularized solid RCC, characterized by rich lymph vessels in the peritumoral area. Quantitative parameters of micro-angiogenesis and lymphangiogenesis could not be considered as novel prognostic factors for patients with xp11.2 translocation RCC.

Tailored Hydrothermal Synthesis of Specific Facet-Dominated TiO2 Nanocrystals from Lepidocrocite-Type Layered Titanate Nanosheets: Systematical Investigation and Enhanced Photocatalytic Performance.

A series of samples including leaf-like and rod-like rutile TiO2 nanoparticles with various facets exposed on the surface, parallelepiped-shaped anatase nanoparticles with [111] vertical facet exposed on the surface, irregular anatase nanoparticles, microsized six-point star-like anatase aggregates, and almond-like brookite aggregates had been hydrothermally synthesized from lepidocrocite-type layered titanate nanosheets. A systematical investigation was established to uncover the phase transition and morphological evolution from nanosheets to TiO2 polymorphs, and a phase diagram was determined by adjusting the synthesis parameters of the pH value and temperature. Two kinds of mechanisms composed of the dissolution-deposition process following Ostwald's ripening mechanism and the in situ topochemical conversion process following Ostwald's step rule had been proposed based on the time-dependent hydrothermal experiments. Briefly, the formation of the single-crystalline rutile phase appeared only at high temperatures with very low pH values, and similarly, the brookite phase strictly formed at high temperatures with a very high pH value. Nevertheless, the anatase phase could moderately appear in a wide range of temperatures and pH values. In addition, the single-crystalline rutile adopted a leaf-like morphology at low temperatures with high pH values and a rod-like morphology at high temperatures with low pH values, while the morphological evolution of anatase particles proceeded from irregular to parallelepiped-shaped and finally to six-point star-like morphology, and the crystal size was reduced from 1000 to 5 nm with decreasing pH values. Meanwhile, with the prolongation of the hydrothermal time, the layered titanate nanosheets first dissolved into the amorphous state and further converted into small anatase nanoparticles and finally to rutile or anatase nanoparticles based on the dissolution-deposition process, or the {010}-faceted layered titanate structure first converted into the [111]-vertical faceted anatase nanosheets by the topochemical transformation reaction and then split into the [111]-vertical faceted anatase nanoparticles. More importantly, the mesoporous [111]-vertical faceted anatase nanoparticles exhibited enhanced photocatalytic performance compared to that of Degussa P25, which was ascribed to its superior electronic band structure and effective charge separation. The systematical investigation in this work would be significant for consummating the preparation of the TiO2 polymorphs from layered titanate nanosheets and provided some reference values and guide schemes for the preparation of TiO2 nanoparticles with outstanding photocatalytic performance.

Retzius-sparing robot-assisted radical prostatectomy improves early recovery of urinary continence: a randomized, controlled, single-blind trial with a 1-year follow-up.

OBJECTIVE: To evaluate the impact of Retzius-sparing robot-assisted radical prostatectomy (posterior approach) on early recovery of urinary continence (UC) compared to the conventional approach (anterior approach) for the treatment of clinically localized prostate cancer (PCa). METHODS: A total of 110 consecutive patients with clinically localized PCa were prospectively randomized in a 1:1 ratio to an anterior group (n = 55) or a posterior group (n = 55). The primary outcome was immediate UC, defined as freedom from any pad use within 1 week after removal of the urinary catheter. The UC rate following surgery was also calculated with Kaplan-Meier curves, and the log-rank test was used for statistical comparison. Intra-operative outcomes, pathological data and oncological outcomes, including positive surgical margin (PSM) status and biochemical recurrence-free survival (BCRFS), were also compared between the two groups. The comparison of the two approaches was also analysed in subgroups after risk stratification. RESULTS: Of the patients who underwent the posterior approach, 69.1% achieved immediate UC compared with 30.9% in the anterior group (relative risk 2.24, 95% confidence interval [CI] 1.48-3.51; P = 0.000). The relative Kaplan-Meier curves for UC during the 12-month follow-up revealed statistically better recovery in the posterior group when compared with the anterior group (hazard ratio [HR] 1.51, 95% CI 1.01-2.24; log-rank P = 0.007). No statistically significant differences were observed between the groups regarding complications (P = 0.399), PSM status (P = 0.225) or BCRFS (HR 4.80, 95% CI 0.97-23.78; log-rank P = 0.111). In sub-analyses, no significant difference between the two approaches with regard to UC recovery in patients with high-risk PCa was observed (HR 1.26, 95% CI 0.63-2.51; log-rank P = 0.415). CONCLUSIONS: The Retzius-sparing approach significantly improved early recovery of UC compared to the conventional approach. Further prospective studies are needed to confirm the benefits of the Retzius-sparing approach for clinically localized PCa, especially for high-risk cases.

Tumour location determined by preoperative MRI is an independent predictor for positive surgical margin status after Retzius-sparing robot-assisted radical prostatectomy.

OBJECTIVE: To investigate the influence of tumour location zone on positive surgical margin (PSM) status after Retzius-sparing robot-assisted radical prostatectomy (RS-RARP). MATERIALS AND METHODS: A total of 203 consecutive patients with prostate cancer (PCa) who underwent RS-RARP at our centre were divided into three cohorts according to the tumour zonal origin described on preoperative magnetic resonance imaging (MRI). Clinical and pathological characteristics were compared among the three groups. The associations of clinicopathological variables with PSM status after RS-RARP were also evaluated. RESULTS: The rates of PSM in patients with transition zone (TZ) and mixed origin tumours were significantly higher than in patients with peripheral zone tumours (P < 0.01). Of the PSMs in patients with TZ and mixed origin cancers, 42.0% and 40.9%, respectively, were located at the anterior part of the gland. On multivariate analysis, presence of a TZ tumour was significantly associated with a higher PSM rate after RS-RARP (P < 0.01). Sub-analysis showed that high-risk patients with TZ tumours had a higher risk of PSM after RS-RARP (P < 0.01). CONCLUSION: Presence of a TZ tumour is an independent risk factor for PSMs after RS-RARP. Preoperative identification of TZ tumours might aid surgical planning for the Retzius-sparing technique, especially in high-risk patients.

A nomogram to predict survival of patients with intermediate-stage hepatocellular carcinoma after transarterial chemoembolization combined with microwave ablation.

OBJECTIVES: To develop a prognostic nomogram based on the albumin-bilirubin (ALBI) grade for prediction of the long-term survival of patients with intermediate-stage hepatocellular carcinoma (HCC) after transarterial chemoembolization combined with microwave ablation (TACE-MWA). METHODS: We retrospectively studied 546 consecutive patients with intermediate-stage HCC according to the Barcelona Clinic Liver Cancer guidelines who underwent TACE-MWA between January 2000 and December 2016. Overall survival (OS) and progression-free survival (PFS) were analyzed. The predictive value of the ALBI grade was investigated. The prognostic nomogram was constructed using the independent predictors assessed by the multivariate Cox proportional hazards model. RESULTS: After a median follow-up of 35.0 months (range, 4.0-221.0 months), 380 patients had died. The median OS was 35.0 months (95% confidence interval (CI), 30.84-39.16 months), and the median PFS was 6.5 months (95% CI, 6.13-6.87 months). The ALBI grade was validated as an independent predictor of OS (p < 0.001). Multivariate analyses showed that Eastern Cooperative Oncology Group performance status score more than 0, presence of liver cirrhosis, a-fetoprotein level above 400 ng/mL, tumor size greater than 5 cm, tumor number more than 3, advanced ALBI grade, and treatment sessions of TACE or MWA fewer than 3 were independently associated with overall mortality. The prognostic nomogram incorporating these eight predictors achieved good calibration and discriminatory abilities with a concordance index of 0.770 (95% CI, 0.746-0.795). CONCLUSIONS: The prognostic nomogram based on the ALBI grade resulted in reliable efficacy for prediction of individualized OS in patients with intermediate-stage HCC after TACE-MWA. KEY POINTS: • TACE-MWA was associated with a median overall survival of 35.0 months for patients with intermediate-stage HCC. • A prognostic nomogram was built to predict individualized survival of patients with intermediate-stage HCC after TACE-MWA. • The prognostic nomogram incorporating eight predictors achieved good calibration and discriminatory abilities with a concordance index of 0.770.

Internal cross-linked polymeric nanoparticles with dual sensitivity for combination therapy of muscle-invasive bladder cancer.

BACKGROUND: Chemotherapy is a standard cancer treatment which uses anti-cancer drugs to destroy or slow the growth of cancer cells. However, chemotherapy has limited therapeutic effects in bladder cancer. One of the reasons of this resistance to chemotherapy is that higher levels of glutathione in invasive bladder cancer cells. We have fabricated nanoparticles that respond to high concentrations of glutathione and near-infrared laser irradiation in order to increase the drug accumulation at the tumor sites and combine chemotherapy with photothermal therapy to overcome the challenges of bladder cancer treatment. METHODS: The DOX&IR780@PEG-PCL-SS NPs were prepared by co-precipitation method. We investigated the tumor targeting capability of NPs in vitro and in vivo. The orthotopic bladder cancer model in C57BL/6 mice was established for in vivo study and the photothermal effects and therapeutic efficacy of NPs were evaluated. RESULTS: The DOX&IR780@PEG-PCL-SS NPs were synthesized using internal cross-linking strategy to increase the stability of nanoparticles. Nanoparticles can be ingested by tumor cells in a short time. The DOX&IR780@PEG-PCL-SS NPs have dual sensitivity to high levels of glutathione in bladder cancer cells and near-infrared laser irradiation. Glutathione triggers chemical structural changes of nanoparticles and preliminarily releases drugs, Near-infrared laser irradiation can promote the complete release of the drugs from the nanoparticles and induce a photothermal effect, leading to destroying the tumor cells. Given the excellent tumor-targeting ability and negligible toxicity to normal tissue, DOX&IR780@PEG-PCL-SS NPs can greatly increase the concentration of the anti-cancer drugs in tumor cells. The mice treated with DOX&IR780@PEG-PCL-SS NPs have a significant reduction in tumor volume. The DOX&IR780@PEG-PCL-SS NPs can be tracked by in vivo imaging system and have good tumor targeting ability, to facilitate our assessment during the experiment. CONCLUSION: A nanoparticle delivery system with dual sensitivity to glutathione and near-infrared laser irradiation was developed for delivering IR780 and DOX. Chemo-photothermal synergistic therapy of both primary bladder cancer and their metastases was achieved using this advanced delivery system.

Multi-Scale Shape Adaptive Network for Raindrop Detection and Removal from a Single Image.

Removing raindrops from a single image is a challenging problem due to the complex changes in shape, scale, and transparency among raindrops. Previous explorations have mainly been limited in two ways. First, publicly available raindrop image datasets have limited capacity in terms of modeling raindrop characteristics (e.g., raindrop collision and fusion) in real-world scenes. Second, recent deraining methods tend to apply shape-invariant filters to cope with diverse rainy images and fail to remove raindrops that are especially varied in shape and scale. In this paper, we address these raindrop removal problems from two perspectives. First, we establish a large-scale dataset named RaindropCityscapes, which includes 11,583 pairs of raindrop and raindrop-free images, covering a wide variety of raindrops and background scenarios. Second, a two-branch Multi-scale Shape Adaptive Network (MSANet) is proposed to detect and remove diverse raindrops, effectively filtering the occluded raindrop regions and keeping the clean background well-preserved. Extensive experiments on synthetic and real-world datasets demonstrate that the proposed method achieves significant improvements over the recent state-of-the-art raindrop removal methods. Moreover, the extension of our method towards the rainy image segmentation and detection tasks validates the practicality of the proposed method in outdoor applications.

Does the Fuhrman or World Health Organization/International Society of Urological Pathology Grading System Apply to the Xp11.2 Translocation Renal Cell Carcinoma?: A 10-Year Single-Center Study.

The Fuhrman and World Health Organization/International Society of Urological Pathology (WHO/ISUP) grading systems are widely used to predict survival for patients with conventional renal cell carcinoma. To determine the validity of nuclear grading systems (both the Fuhrman and the WHO/ISUP) and the individual components of the Fuhrman grading system in predicting the prognosis of Xp11.2 translocation renal cell carcinoma (Xp11.2 tRCC), we identified and followed up 47 patients with Xp11.2 tRCC in our center from January 2007 to June 2017. The Fuhrman and WHO/ISUP grading was reassigned by two pathologists. Nuclear size and shape were determined for each case based on the greatest degree of nuclear pleomorphism using image analysis software. Univariate and multivariate analyses were performed to evaluate the capacity of the grading systems and nuclear parameters to predict overall survival and progression-free survival. On univariate Cox regression analysis, the parameters of nuclear size were associated significantly with overall survival and progression-free survival, whereas the grading systems and the parameters of nuclear shape failed to reach a significant correlation. On multivariate analysis, however, none of the parameters was associated independently with survival. Our findings indicate that neither the Fuhrman nor the WHO/ISUP grading system is applicable to Xp11.2 tRCC. The assessment of nuclear size instead may be novel outcome predictors for patients with Xp11.2 tRCC.