Peripheral platelet count is a diagnostic marker for predicting the risk of rapid ejaculation: findings from a pilot study in rats.

Parameters of peripheral blood cell have been shown as the potential predictors of erectile dysfunction (ED). To investigate the clinical significance of hematological parameters for predicting the risk of rapid ejaculation, we established a rat copulatory model on the basis of ejaculation distribution theory. Blood samples from different ejaculatory groups were collected for peripheral blood cell counts and serum serotonin (5-HT) tests. Meanwhile, the relationship between hematological parameters and ejaculatory behaviors was assessed. Final analysis included 11 rapid ejaculators, 10 normal ejaculators, and 10 sluggish ejaculators whose complete data were available. The platelet (PLT) count in rapid ejaculators was significantly lower than that in normal and sluggish ejaculators, whereas the platelet distribution width (PDW) and mean platelet volume (MPV) were significantly greater in rapid ejaculators. Multivariate logistic regression analysis and receiver operating characteristic (ROC) curve analysis showed that the PLT was an independent protective factor for rapid ejaculation. Meanwhile, rapid ejaculators were found to have the lowest serum 5-HT compared to normal and sluggish ejaculators (P < 0.001). Furthermore, there was a positive correlation between the PLT and serum 5-HT (r = 0.662, P < 0.001), indicating that the PLT could indirectly reflect the serum 5-HT concentration. In addition, we assessed the association between the PLT and ejaculatory parameters. There was a negative correlation between ejaculation frequency (EF) and the PLT (r = -0.595, P < 0.001), whereas there was a positive correlation between ejaculation latency (EL) and the PLT (r = 0.740, P < 0.001). This study indicated that the PLT might be a useful and convenient diagnostic marker for predicting the risk of rapid ejaculation.

Ventricular dysfunction consequences of mechanical dyssynchrony in isolated complete right bundle branch block versus left bundle branch block.

Background: Complete bundle branch block in individuals without structural heart disease is known as isolated complete bundle branch block. Isolated complete left bundle branch block (CLBBB) is correlated with ventricular dysfunction secondary to dyssynchrony; however, few studies have investigated isolated complete right bundle branch block (CRBBB), which was previously considered benign but was recently found to be associated with adverse cardiovascular outcomes. This study aimed to evaluate cardiac mechanical synchrony, and systolic and diastolic function in patients with isolated CRBBB and compare cardiac synchrony and function to patients with isolated CLBBB. Methods: This cross-sectional study was conducted at The First Hospital of China Medical University in Shenyang, China, from 2020 to 2021. A total of 44 isolated CRBBB patients, 44 isolated CLBBB patients, and 42 healthy subjects were enrolled in the study. Transthoracic echocardiography was performed in all subjects. Synchrony parameters, including the mechanical dispersion of the right ventricle [the standard deviation of time to the peak longitudinal strain of six right ventricular (RV) segments] and atrioventricular dyssynchrony parameter [the ratio of left ventricular (LV) diastolic filling time to the time interval between two adjacent R waves (RR interval) measured by tissue Doppler imaging]. RV and LV function were assessed by the global longitudinal strain (GLS) of six RV segments and 18 LV segments, and the ratio of the peak early diastolic flow velocity to annular velocity (E/e') of the tricuspid valve and mitral valve. Statistical analyses were performed, including an analysis of variance, Pearson correlation analysis, and linear regression analysis. Results: Compared with the healthy subjects, the mechanical dispersion of the right ventricle was significantly increased, and ventricular function was impaired as evidenced by the decreased RV GLS and LV GLS, and the increased E/e' of the tricuspid valve and mitral valve in the isolated CRBBB patients (all P<0.001). Moreover, compared with the isolated CLBBB patients, the mechanical dispersion of the right ventricle and E/e' of the tricuspid valve were increased, and RV GLS was significantly reduced in the isolated CRBBB patients (all P<0.001). Mechanical dispersion of the right ventricle was independently associated with RV GLS [coefficient, 0.13; 95% confidence interval (CI): 0.004-0.26; P=0.04] in the isolated CRBBB patients. RV GLS (coefficient, 0.10; 95% CI: 0.01-0.20; P=0.03) and the ratio of the LV diastolic filling time to the RR interval measured (coefficient, -0.30; 95% CI: -0.53 to -0.07; P=0.01) were independent factors of LV GLS. Conclusions: The isolated CRBBB patients had impaired cardiac mechanical synchrony and ventricular function, and more decreased RV synchrony and function than the isolated CLBBB patients. Right intraventricular synchrony was independently associated with RV systolic dysfunction in patients with isolated CRBBB. Atrioventricular synchrony and RV systolic function were independently associated with the LV systolic function. Therefore, comprehensive evaluations of echocardiography results and close monitoring is required for isolated CRBBB patients.

Single-Shot Direct Transmission Terahertz Imaging Based on Intense Broadband Terahertz Radiation.

There are numerous applications of terahertz (THz) imaging in many fields. However, current THz imaging is generally based on scanning technique due to the limited intensity of the THz sources. Thus, it takes a long time to obtain a frame image of the target and cannot meet the requirement of fast THz imaging. Here, we demonstrate a single-shot direct THz imaging strategy based on a broadband intense THz source with a frequency range of 0.1~23 THz and a THz camera with a frequency response range of 1~7 THz. This THz source was generated from the laser-plasma interaction, with its central frequency at ~12 THz. The frame rate of this imaging system was 8.5 frames per second. The imaging resolution reached 146.2 µm. With this imaging system, a single-shot THz image for a target object with a size of more than 7 cm was routinely obtained, showing a potential application for fast THz imaging. Furthermore, we proposed and tested an image enhancement algorithm based on an improved dark channel prior (DCP) theory and multi-scale retinex (MSR) theory to optimize the image brightness, contrast, entropy and peak signal-to-noise ratio (PSNR).

Does the presence of blind-ended vas deferens and spermatic vessels in laparoscopic exploration of non-palpable testes conclusively indicate testicular absence?

Objective: The purpose of this study was to determine whether the presence of blind-ended vas deferens and spermatic vessels (VDSV) during laparoscopic exploration of non-palpable testes (NPT) indicates testicular absence or atrophy. Materials and methods: A retrospective analysis was conducted on clinical data of patients diagnosed with NPT and treated with surgical intervention at our center from April 2013-April 2023. The dataset encompassed information such as the children's age, affected side, size of the contralateral testis, surgical procedures employed, outcomes, and histopathological examination results. All patients underwent physical examination and ultrasonography preoperatively, followed by a combination of laparoscopic exploration and exploration through inguinal or scrotal incisions during surgery. Long-term follow-up was conducted postoperatively. Results: A total of 476 cases comprising 504 NPT were included in this study: 302 cases on the left side, 146 cases on the right side, and 28 cases bilaterally. All patients underwent surgical treatment within 6-126 months (median 13 months). During laparoscopic exploration, blind-ended VDSV were found in 90 testes (72 on the left side, 18 on the right side), while exploration through inguinal or scrotal incisions revealed 52 (57.8%) testicular nodules with atrophy, which were excised, leaving 38 (42.2%) without any findings. Histopathological examination of atrophic nodules revealed fibrosis as the most common finding in 41 cases (78.8%), followed by involvement of the vas deferens in 33 cases (63.5%), calcification in 24 cases (46.2%), epididymis in 23 cases (44.2%), and hemosiderin deposition in 7 cases (13.6%). Fibrosis, calcification, hemosiderin deposition, involvement of the vas deferens, and epididymis were found in combination in 47 specimens (90.4%). Seminiferous tubules (SNT) were found in 3 specimens (5.7%), and germ cells (GC) were found in 1 specimen (1.9%). Conclusion: The presence of blind-ended VDSV during laparoscopic exploration of NPT does not necessarily indicate testicular absence or disappearance. It is possible that atrophic testicular nodules are located within the inguinal canal or scrotum. This understanding contributes to the management of non-palpable testes. Considering their unpredictable malignant potential, we recommend excision.

SFN promotes renal fibrosis via binding with MYH9 in chronic kidney disease.

Chronic kidney disease (CKD) is a clinical syndrome characterized by persistent renal function decline. Renal fibrosis is the main pathological process in CKD, but an effective treatment does not exist. Stratifin (SFN) is a highly-conserved, multi-function soluble acidic protein. Therefore, this study explored the effects of SFN on renal fibrosis. First, we found that SFN was highly expressed in patients with CKD, as well as in renal fibrosis animal and cell models. Next, transforming growth factor-beta 1 (TGF-ß1) induced injury and fibrosis in human renal tubule epithelial cells, and SFN knockdown reversed these effects. Furthermore, SFN knockdown mitigated unilateral ureteral obstruction (UUO)-induced renal tubular dilatation and renal interstitial fibrosis in mice. Liquid chromatography-tandem mass spectrometry/mass spectrometry (LC-MS/MS), co-immunoprecipitation (Co-IP), and immunofluorescence co-localization assays demonstrated that SFN bound the non-muscle myosin-encoding gene, myosin heavy chain 9 (MYH9), in the cytoplasm of renal tubular epithelial cells. MYH9 knockdown also reduced Col-1 and α-SMA expression, which are fibrosis markers. Finally, silencing SFN decreased MYH9 expression, alleviating renal fibrosis. These results suggest that SFN promotes renal fibrosis in CKD by interacting with MYH9. This study may provide potential strategies for the treatment of CKD.

A miR-361-5p/ ORC6/ PLK1 axis regulates prostate cancer progression.

Prostate cancer (PCa) is the most prevalent malignant tumor of the genitourinary system, and metastatic disease has a significant impact on the prognosis of PCa patients. As a result, knowing the processes of PCa development can help patients achieve better outcomes. Here, we investigated the expression and function of ORC6 in PCa. Our findings indicated that ORC6 was elevated in advanced PCa tissues. Patients with PCa who exhibited high levels of ORC6 had a poor prognosis. Following that, we investigated the function of ORC6 in PCa progression using a variety of functional experiments both in vivo and in vitro, and discovered that ORC6 knockdown inhibited PCa cell proliferation, growth, and migration. Furthermore, RNA-seq was employed to examine the molecular mechanism of PCa progression. The results revealed that ORC6 might promote the expression of PLK1, a serine/threonine kinase in PCa cells. We also discovered that ORC6 as a novel miR-361-5p substrate using database analysis, and miR-361-5p was found to lower ORC6 expression. Additionally, RNA immunoprecipitation (RIP) and luciferase reporter tests revealed that the transcription factor E2F1 could regulate ORC6 expression in PCa cells. PLK1 overexpression or miR-361-5p inhibitor treatment effectively removed the inhibitory effects caused by ORC6 silencing. Notably, our data showed that therapeutically targeting the miR-361-5p/ORC6/PLK1 axis may be a viable therapy option for PCa.

A zebrafish tufm mutant model for the COXPD4 syndrome of aberrant mitochondrial function.

Mitochondrial dysfunction is a critical factor leading to a wide range of clinically heterogeneous and often severe disorders due to its central role in generating cellular energy. Mutations in the TUFM gene are known to cause combined oxidative phosphorylation deficiency 4 (COXPD4), a rare mitochondrial disorder characterized by a comprehensive quantitative deficiency in mitochondrial respiratory chain (MRC) complexes. The development of a reliable animal model for COXPD4 is crucial for elucidating the roles and mechanisms of TUFM in disease pathogenesis and benefiting its medical management. In this study, we construct a zebrafish tufm-/- mutant that closely resembles the COXPD4 syndrome, exhibiting compromised mitochondrial protein translation, dysfunctional mitochondria with oxidative phosphorylation (OXPHOS) defects, and significant metabolic suppression of the tricarboxylic acid (TCA) cycle. Leveraging this COXPD4 zebrafish model, we comprehensively validate the clinical relevance of TUFM mutations and identify probucol as a promising therapeutic approach for managing COXPD4. Our data offer valuable insights for understanding mitochondrial diseases and developing effective treatments.

RNA Isoforms as Broad Targets for Cancer Immunotherapy.

While immunotherapy is typically reserved for cancer patients with a high mutational burden, neoantigens produced from post-transcriptional regulation provide a possible untapped reservoir of common immunogenic targets for new targeted cancer therapies. In this review, we describe new and emerging technologies, unconventional molecular targets and challenges for the precision immune targeting of diverse malignancies. In particular, we focus on the unique potential of targeting alternative mRNA isoforms as a source for broadly presented neoantigens and cell surface proteins. Finally, we discuss emerging challenges for alternative isoform immune targeting, with an emphasis in silico prioritization and high-throughput target validation.

Single-Pixel Imaging Based on Deep Learning Enhanced Singular Value Decomposition.

We propose and demonstrate a single-pixel imaging method based on deep learning network enhanced singular value decomposition. The theoretical framework and the experimental implementation are elaborated and compared with the conventional methods based on Hadamard patterns or deep convolutional autoencoder network. Simulation and experimental results show that the proposed approach is capable of reconstructing images with better quality especially under a low sampling ratio down to 3.12%, or with fewer measurements or shorter acquisition time if the image quality is given. We further demonstrate that it has better anti-noise performance by introducing noises in the SPI systems, and we show that it has better generalizability by applying the systems to targets outside the training dataset. We expect that the developed method will find potential applications based on single-pixel imaging beyond the visible regime.

Strong Covalent Coupling in Vertically Layered SnSe2/PTAA Heterojunctions Enabled High Performance Inorganic-Organic Hybrid Photodetectors.

Controllable large-scale integration of two-dimensional (2D) materials with organic semiconductors and the realization of strong coupling between them still remain challenging. Herein, we demonstrate a wafer-scale, vertically layered SnSe2/PTAA heterojunction array with high light-trapping ability via a low-temperature molecular beam epitaxy method and a facile spin-coating process. Conductive probe atomic force microscopy (CP-AFM) measurements reveal strong rectification and photoresponse behavior in the individual SnSe2 nanosheet/PTAA heterojunction. Theoretical analysis demonstrates that vertically layered SnSe2/PTAA heterojunctions exhibit stronger C-Se covalent coupling than that of the conventional tiled type, which could facilitate more efficient charge transfer. Benefiting from these advantages, the SnSe2/PTAA heterojunction photodetectors with an optimized PTAA concentration show high performance, including a responsivity of 41.02 A/W, an external quantum efficiency of 1.31 × 104%, and high uniformity. The proposed approach for constructing large-scale 2D inorganic-organic heterostructures represents an effective route to fabricate high-performance broadband photodetectors for integrated optoelectronic systems.

Association of serum soluble α­klotho with risk of kidney stone disease: a population-based cross-sectional study.

BACKGROUND: The aim of the study was to explore the association of serum soluble klotho with kidney stone disease (KSD) in the general population over the age of 40 years in the United States. METHODS: We integrated the data in National Health and Nutrition Examination Survey from 2007 to 2016 years. The relationship between serum soluble α­klotho and prevalence of KSD was analyzed by constructing weighted multivariable logistic regression model, restricted cubic spline (RCS) curve, and subgroup analyses. RESULTS: In the study, a total of 13,722 individuals were included in our study. A U-shaped association between serum soluble klotho and the risk of KSD was shown by the RCS curve (P value for nonlinear < 0.05). In the full adjusted model, compared with the lowest quartile of serum soluble α­klotho, the adjusted odd ratios (95% confidence intervals) for KSD across the quartiles were (0.999 (0.859, 1.164), 1.005 (0.858, 1.176), and 1.061 (0.911, 1.235)). Subgroup analyses also showed that the U-shaped association of serum soluble α­klotho with KSD was found among subjects who were age < 60 years, female or male, with or without hypertension, and BMI ≥ 30 kg/m2. CONCLUSIONS: Our findings suggested that serum klotho levels had a U-shaped correlation with risk of KSD. When the Klotho level is at 818.66 pg/mL, prevalence of KSD is lowest. Therefore, maintaining a certain level of serum soluble α­klotho could prevent the occurrence of KSD.

Widespread variation in molecular interactions and regulatory properties among transcription factor isoforms.

Most human Transcription factors (TFs) genes encode multiple protein isoforms differing in DNA binding domains, effector domains, or other protein regions. The global extent to which this results in functional differences between isoforms remains unknown. Here, we systematically compared 693 isoforms of 246 TF genes, assessing DNA binding, protein binding, transcriptional activation, subcellular localization, and condensate formation. Relative to reference isoforms, two-thirds of alternative TF isoforms exhibit differences in one or more molecular activities, which often could not be predicted from sequence. We observed two primary categories of alternative TF isoforms: "rewirers" and "negative regulators", both of which were associated with differentiation and cancer. Our results support a model wherein the relative expression levels of, and interactions involving, TF isoforms add an understudied layer of complexity to gene regulatory networks, demonstrating the importance of isoform-aware characterization of TF functions and providing a rich resource for further studies.

Performance Enhancement of Tin-Based Perovskite Photodetectors through Bifunctional Cesium Fluoride Engineering.

Tin halide perovskites are rising as promising candidates for next-generation optoelectronic materials due to their good optoelectronic properties and relatively low toxicity. However, the high defect density and the easy oxidation of Sn2+ have limited their optoelectronic performance. Herein, we report the treatment of the FASnI3 (formamidinium tin, FA) perovskite film by a bifunctional cesium fluoride (CsF) additive, which improves the film quality and significantly enhances the photoelectric performance. The responsivity of the perovskite-based photodetector (PD) with an optimal CsF concentration of 15% is over 60 times larger than that of the PD without CsF. It indicates that both the Cs substitution and the fluoride anion additive from CsF inhibit the oxidation of Sn2+, optimize the crystal growth, and passivate the defects, demonstrating the dual roles of the CsF additive in improving the photoelectric performance. This work offers valuable insights into the additive selection for developing high-quality tin-based perovskite films and devices.

Association of novel anthropometric indices with prevalence of kidney stone disease: a population-based cross-sectional study.

BACKGROUND: The purpose of this study was to investigate the correlation between novel anthropometric indices, specifically the body shape index (ABSI) and body roundness index (BRI), and the prevalence of kidney stone disease (KSD) within the general population of the United States (U.S.). METHODS: This study employed a cross-sectional analysis of participants in the National Health and Nutrition Examination Survey from 2007 to 2020. Various statistical methods, including multivariable logistic regression analysis, restricted cubic spline (RCS) plot curve, receiver operating characteristic (ROC) curves, and subgroup analysis, were utilized to examine the association between ABSI and BRI and the risk of KSD. RESULTS: A total of 39,251 individuals were included in the study. First, the RCS plot presented that a linear positive association was found between ABSI and BRI and KSD risk. Second, the results of the multivariable logistic regression analysis revealed that, compared to the lowest quartile, the adjusted odds ratios (with 95% confidence intervals) for the prevalence of KSD across the quartiles of ASBI and BRI were 0.94 (0.67, 1.30), 1.55 (1.15, 2.10), and 1.74 (1.28, 2.35), respectively, in the fully adjusted model. Third, the ROC curve demonstrated that the area under the curve of ABSI, and BRI was significantly higher than traditional anthropometry or body composition measures, including BMI and waist circumference. CONCLUSIONS: The findings of our study indicate that the discriminant ability of ABSI and BRI for KSD is significantly superior to that of BMI and waist circumference. Consequently, ABSI and BRI have the potential to more accurately identify an individual's risk of developing KSD in a clinical setting.

An immunophenotype-coupled transcriptomic atlas of human hematopoietic progenitors.

Analysis of the human hematopoietic progenitor compartment is being transformed by single-cell multimodal approaches. Cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) enables coupled surface protein and transcriptome profiling, thereby revealing genomic programs underlying progenitor states. To perform CITE-seq systematically on primary human bone marrow cells, we used titrations with 266 CITE-seq antibodies (antibody-derived tags) and machine learning to optimize a panel of 132 antibodies. Multimodal analysis resolved >80 stem, progenitor, immune, stromal and transitional cells defined by distinctive surface markers and transcriptomes. This dataset enables flow cytometry solutions for in silico-predicted cell states and identifies dozens of cell surface markers consistently detected across donors spanning race and sex. Finally, aligning annotations from this atlas, we nominate normal marrow equivalents for acute myeloid leukemia stem cell populations that differ in clinical response. This atlas serves as an advanced digital resource for hematopoietic progenitor analyses in human health and disease.

Identification of cell differentiation trajectory-related gene signature to reveal the prognostic significance and immune landscape in prostate cancer based on multiomics analysis.

Background: In the context of prostate cancer (PCa), the occurrence of biochemical recurrence (BCR) stands out as a pivotal factor significantly impacting prognosis, potentially leading to metastasis and mortality. However, the early detection of BCR poses a substantial challenge for PCa patients. There is an urgent need to pinpoint hub genes that can serve as predictive indicators for BCR in PCa patients. Methods: Our primary goal was to identify cell differentiation trajectory-related gene signature in PCa patients by pseudo-time trajectory analysis. We further explored the functional enrichment of overlapped marker genes and probed clinically relevant modules and BCR-related genes using Weighted Gene Co-expression Network Analysis (WGCNA) in PCa patients. Key genes predicting recurrence-free survival were meticulously identified through univariate and multivariate Cox regression analyses. Subsequently, these genes were utilized to construct a prognostic gene signature, the expression, predictive efficacy, putative functions, and immunological landscape of which were thoroughly validated. Additionally, we employed immunohistochemistry (IHC) and a western blotting assay to quantify the expression of PYCR1 in clinical samples. Results: Our single-cell RNA (scRNA) sequencing analysis unveiled three subgroups characterized by distinct differentiation trajectories, and the marker genes associated with these groups were extracted from PCa patients. These marker genes successfully classified the PCa sample into two molecular subtypes, demonstrating a robust correlation with clinical characteristics and recurrence-free survival. Through WGCNA and Lasso analysis, we identified four hub genes (KLK3, CD38, FASN, and PYCR1) to construct a risk profile of prognostic genes linked to BCR. Notably, the high-risk patient group exhibited elevated levels of B cell naive, Macrophage M0, and Macrophage M2 infiltration, while the low-risk group displayed higher levels of T cells CD4 memory activated and monocyte infiltration. Furthermore, IHC and western blotting assays confirmed the heightened expression of PYCR1 in PCa tissues. Conclusion: This study leveraged the differentiation trajectory and genetic variability of the microenvironment to uncover crucial prognostic genes associated with BCR in PCa patients. These findings present novel perspectives for tailoring treatment strategies for PCa patients on an individualized basis.

Splicing neoantigen discovery with SNAF reveals shared targets for cancer immunotherapy.

Immunotherapy has emerged as a crucial strategy to combat cancer by "reprogramming" a patient's own immune system. Although immunotherapy is typically reserved for patients with a high mutational burden, neoantigens produced from posttranscriptional regulation may provide an untapped reservoir of common immunogenic targets for new targeted therapies. To comprehensively define tumor-specific and likely immunogenic neoantigens from patient RNA-Seq, we developed Splicing Neo Antigen Finder (SNAF), an easy-to-use and open-source computational workflow to predict splicing-derived immunogenic MHC-bound peptides (T cell antigen) and unannotated transmembrane proteins with altered extracellular epitopes (B cell antigen). This workflow uses a highly accurate deep learning strategy for immunogenicity prediction (DeepImmuno) in conjunction with new algorithms to rank the tumor specificity of neoantigens (BayesTS) and to predict regulators of mis-splicing (RNA-SPRINT). T cell antigens from SNAF were frequently evidenced as HLA-presented peptides from mass spectrometry (MS) and predict response to immunotherapy in melanoma. Splicing neoantigen burden was attributed to coordinated splicing factor dysregulation. Shared splicing neoantigens were found in up to 90% of patients with melanoma, correlated to overall survival in multiple cancer cohorts, induced T cell reactivity, and were characterized by distinct cells of origin and amino acid preferences. In addition to T cell neoantigens, our B cell focused pipeline (SNAF-B) identified a new class of tumor-specific extracellular neoepitopes, which we termed ExNeoEpitopes. ExNeoEpitope full-length mRNA predictions were tumor specific and were validated using long-read isoform sequencing and in vitro transmembrane localization assays. Therefore, our systematic identification of splicing neoantigens revealed potential shared targets for therapy in heterogeneous cancers.

Ultrahigh-Q Metasurface Transparency Band Induced by Collective-Collective Coupling.

The metasurface analogue of electromagnetically induced transparency (EIT) provides a chip-scale platform for achieving light delay and storage, high Q factors, and greatly enhanced optical fields. However, the literature relies on the coupling between localized and localized or localized and collective resonances, limiting the Q factor and related performance. Here, we report a novel approach for realizing collective EIT-like bands with a measured Q factor reaching 2750 in silicon metasurfaces in the near-infrared regime, exceeding the state of the art by more than 5 times. It employs the coupling between two collective resonances, the Mie electric dipole surface lattice resonance (SLR) and the out-of-plane/in-plane electric quadrupole SLR (EQ-SLR). Remarkably, the collective EIT-like resonance can have diverging Q factor and group delay due to the bound state in the continuum characteristics of the in-plane EQ-SLR. With these findings, our study opens a new route for tailoring light flow in metasurfaces.

Real-world effectiveness and safety of RC48-ADC alone or in combination with PD-1 inhibitors for patients with locally advanced or metastatic urothelial carcinoma: A multicenter, retrospective clinical study.

INTRODUCTION: Previous RC48 (Disitamab Vedotin) studies established that the safety and efficacy of RC48-antibody-drug conjugate (ADC), either alone or combined with toripalimab, for metastatic urothelial carcinoma (mUC) patients exhibiting human epidermal growth factor receptor 2 (HER2)-positive or even HER2-negative status after standard chemotherapy failure. METHODS: With locally advanced or metastatic urothelial carcinoma (la/mUC), patients who received RC48-ADC monotherapy or a combination with programmed cell death protein 1 (PD-1) inhibitors between August 2021 and October 2022 were enrolled in this retrospective observational study to evaluate the real-world antitumor effectiveness and safety. RESULTS: Among the 38 enrolled patients (29 males; median age 67.5 years [38-93]), 8 received RC48-ADC monotherapy, while 30 received combination therapy. Initially, 63.2% (24/38) of the patients had received ≥1 line of prior treatment, and 63.2% (24/38) had visceral metastasis. UC of the bladder represented the majority type in 68.4% (26/38) of cases. By the data cutoff in March 2023, the overall objective response rate (ORR) was 63.2% (95% CI, 47.1%-79.2%), with a disease control rate (DCR) of 89.5% (95% CI, 79.3%-99.7%). Median follow-up time was 10.6 months. The median progression-free survival (PFS) was 8.2 months (95% CI, 5.9-10.5), with a 6-month PFS rate of 63.2% and a 12-month PFS rate of 34.1%. Median overall survival (OS) was not reached, with a 12-month OS rate of 76.7%. The median duration of response was 7.3 months (95% CI, 4.6-10.0) among 24 patients evaluated as partial response (PR). The most common treatment-related adverse events (TRAEs) included anemia (71.1%), anorexia (57.9%), asthenia (52.6%), hypoesthesia (52.6%), bone marrow suppression (47.4%), alopecia (47.4%), nausea (44.7%), proteinuria (36.8%), vomiting (34.2%), and hypoalbuminemia (31.6%). No patient experienced TRAEs of Grade ≥3. One patient had an immune-related adverse event (irAE) of rash related to toripalimab. CONCLUSIONS: Both as monotherapy and in combination with PD-1 inhibitors, RC48-ADC exhibits promising effectiveness and manageable safety profile for mUC patients in real-world settings.

The value of urinary exosomal lncRNA SNHG16 as a diagnostic biomarker for bladder cancer.

OBJECTIVE: To detect the expression level of urinary exosomal lncRNA SNHG16 in patients with bladder cancer and healthy individuals and explore its clinical application value in the diagnosis of bladder cancer. METHODS: Urine samples were collected from 42 patients with bladder cancer and 42 healthy volunteers who visited Lu'an Hospital of Anhui Medical University and the Second Hospital of Tianjin Medical University from January 2020 to December 2022. The expression levels of lncRNA SNHG16 in urinary exosomes of the two groups were detected by RT‒qPCR, and their correlation with clinical pathological parameters of bladder cancer patients was analysed. An Receiver Operating Characteristic(ROC) curve was drawn to analyse the diagnostic value of urinary exosomal lncRNA SNHG16 for bladder cancer and compared with urinary cytology. RESULTS: The expression of urinary exosomal lncRNA SNHG16 in patients with bladder cancer was significantly higher (P < 0.05), and the expression level had no correlation with the age, sex, pathological T stage, pathological grade, or tumour size of bladder cancer patients (P > 0.05). The Area Under Curve(AUC) of urinary exosomal lncRNA SNHG16 in diagnosing bladder cancer was 0.791, which was superior to that of urinary cytology (AUC = 0.597). CONCLUSION: Urinary exosomal lncRNA SNHG16 with high expression can serve as a potential diagnostic biological marker for bladder cancer.