Comprehensive investigation in oncogenic functions and immunological roles of NCBP2 and its validation in prostate cancer.

BACKGROUND: Nuclear cap-binding protein 2 (NCBP2), as the component of the cap-binding complex, participates in a number of biological processes, including pre-mRNA splicing, transcript export, translation regulation and other gene expression steps. However, the role of NCBP2 on the tumor cells and immune microenvironment remains unclear. To systematically analyze and validate functions of NCBP2, we performed a pan-cancer analysis using multiple approaches. METHODS: The data in this study were derived from sequencing, mutation, and methylation data in the TCGA cohort, normal sample sequencing data in the GTEx project, and cell line expression profile data in the CCLE database. RESULTS: Survival analyses including the Cox proportional-hazards model and log-rank test revealed the poor prognostic role of NCBP2 in multiple tumors. We further validated the oncogenic ability of NCBP2 in prostate cancer cell lines, organoids and tumor-bearing mice. A negative correlation was observed between NCBP2 expression and immune score by the ESTIMATE algorithm. Simultaneously, the NCBP2-induced immunosuppressive microenvironment might be related to the decline in CD8+T cells and the increase in regulatory T cells and neutrophils, examined by flow cytometry experiments for NCBP2 overexpressed tumor-bearing mice. CONCLUSION: This research offered strong proof supporting NCBP2 as the prognostic marker and the therapeutic target in the future.

Enhancing high-quality fat survival: A novel strategy using cell-free fat extract.

High-quality fat (HQF) improves the survival rate of fat and volumetric filling compared to traditional Coleman fat. However, this HQF strategy inevitably leads to a significant amount of unused fat being wasted. "CEFFE" (cell-free fat extract) is an acellular aqueous-phase liquid, rich in bioactive proteins. The remaining fat from preparing HQF can be further processed into CEFFE to promote the survival of HQF. HQF was obtained and the remaining fat was processed into CEFFE, then HQF was transplanted subcutaneously in nude mice. Animal studies showed that CEFFE significantly improved the survival rate of HQF. Histological analysis revealed that CEFFE improved the survival rate of HQF, by enhancing cell proliferation activity, reducing apoptosis, increasing angiogenesis, and improving the inflammatory state. Under simulated anaerobic conditions, CEFFE also improved the viability of HQF. In vitro, studies demonstrated that CEFFE enhanced the survival rate of HQF through multiple mechanisms. Transcriptomic analysis and qPCR showed that CEFFE increased the expression of angiogenesis-related genes in ADSCs while enhancing their proliferation-related gene expression and suppressing the expression of three differentiation-related genes. Moreover, functional experiments demonstrated that CEFFE-induced ADSCs exhibited stronger proliferation and adipogenic differentiation abilities. Tube formation and migration assays revealed that CEFFE promoted tube formation and migration of HUVECs, indicating its inherent pro-angiogenic properties. CEFFE facilitated the development of M0 to M2 macrophages, suggesting its role in improving the inflammatory state. This innovative clinical strategy optimizes HQF transplantation strategy, minimizing fat wastage and enhancing the efficiency of fat utilization.

Cell-free DNA in the management of prostate cancer: Current status and future prospective.

Objective: With the escalating prevalence of prostate cancer (PCa) in China, there is an urgent demand for novel diagnostic and therapeutic approaches. Extensive investigations have been conducted on the clinical implementation of circulating free DNA (cfDNA) in PCa. This review aims to provide a comprehensive overview of the present state of cfDNA as a biomarker for PCa and to examine its merits and obstacles for future clinical utilization. Methods: Relevant peer-reviewed manuscripts on cfDNA as a PCa marker were evaluated by PubMed search (2010-2022) to evaluate the roles of cfDNA in PCa diagnosis, prognosis, and prediction, respectively. Results: cfDNA is primarily released from cells undergoing necrosis and apoptosis, allowing for non-invasive insight into the genomic, transcriptomic, and epigenomic alterations within various PCa disease states. Next-generation sequencing, among other detection methods, enables the assessment of cfDNA abundance, mutation status, fragment characteristics, and epigenetic modifications. Multidimensional analysis based on cfDNA can facilitate early detection of PCa, risk stratification, and treatment monitoring. However, standardization of cfDNA detection methods is still required to expedite its clinical application. Conclusion: cfDNA provides a non-invasive, rapid, and repeatable means of acquiring multidimensional information from PCa patients, which can aid in guiding clinical decisions and enhancing patient management. Overcoming the application barriers of cfDNA necessitates increased data sharing and international collaboration.

Utilizing Ubiquitination Patterns to Predict Prostate Cancer Prognosis and Devise a Therapeutic Response.

BACKGROUND: Ubiquitination, a post-translational modification, is crucial for cancer regulation. However, the predictive significance of ubiquitination-related genes (URGs) for prostate adenocarcinoma (PRAD) remains unclear. OBJECTIVES: The objectives of the study were to investigate the role of URGs in PRAD and their potential impact on patient prognosis. METHODS: This study acquired data for more than 800 patients with PRAD from public databases. The unique ubiquitination-related patterns of PRAD were detected by unsupervised clustering approach. URGs relevant to the prognosis of patients with PRAD and a ubiquitination-related prognostic index (URPI) were identified and generated using the log-rank test, univariate and multivariate Cox proportional hazards regression, least absolute shrinkage and selection operator (LASSO) Cox regression, and bootstrap strategy. RESULTS: Four ubiquitination-related subpopulations were then defined, and 39 ubiquitination-related differentially expressed genes in prostate cancer and paracancerous samples were screened, with LASSO analysis distinguishing six of them. The URPI was built and verified using the identified URGs that played critical roles in survival stratification. Several potential URPI-targeting drugs were also analyzed. Subsequently, the URPI was combined with clinical characteristics, which provided a more accurate estimate of PRAD survival and was a superior choice for PRAD prognostic forecasts. CONCLUSIONS: This investigation has thus established and verified a URPI, which may provide unique insights to improve survival estimations for patients with PRAD.

Advances in landscape and related therapeutic targets of the prostate tumor microenvironment.

The distinct tumor microenvironment (TME) of prostate cancer (PCa), which promotes tumor proliferation and progression, consists of various stromal cells, immune cells, and a dense extracellular matrix (ECM). The understanding of the prostate TME extends to tertiary lymphoid structures (TLSs) and metastasis niches to provide a more concise comprehension of tumor metastasis. These constituents collectively structure the hallmarks of the pro-tumor TME, including immunosuppressive, acidic, and hypoxic niches, neuronal innervation, and metabolic rewiring. In combination with the knowledge of the tumor microenvironment and the advancement of emerging therapeutic technologies, several therapeutic strategies have been developed, and some of them have been tested in clinical trials. This review elaborates on PCa TME components, summarizes various TME-targeted therapies, and provides insights into PCa carcinogenesis, progression, and therapeutic strategies.

Utilizing Ubiquitination Patterns to Predict Prostate Cancer Prognosis and Devise a Therapeutic Response

Background: Ubiquitination, a post-translational modification, is crucial for cancer regulation. However, the predictive significance of ubiquitination-related genes (URGs) for prostate adenocarcinoma (PRAD) remains unclear. Objectives: The objectives of the study were to investigate the role of URGs in PRAD and their potential impact on patient prognosis. Methods: This study acquired data for more than 800 patients with PRAD from public databases. The unique ubiquitination-related patterns of PRAD were detected by unsupervised clustering approach. URGs relevant to the prognosis of patients with PRAD and a ubiquitination-related prognostic index (URPI) were identified and generated using the log-rank test, univariate and multivariate Cox proportional hazards regression, least absolute shrinkage and selection operator (LASSO) Cox regression, and bootstrap strategy. Results: Four ubiquitination-related subpopulations were then defined, and 39 ubiquitination-related differentially expressed genes in prostate cancer and paracancerous samples were screened, with LASSO analysis distinguishing six of them. The URPI was built and verified using the identified URGs that played critical roles in survival stratification. Several potential URPI-targeting drugs were also analyzed. Subsequently, the URPI was combined with clinical characteristics, which provided a more accurate estimate of PRAD survival and was a superior choice for PRAD prognostic forecasts. Conclusions: This investigation has thus established and verified a URPI, which may provide unique insights to improve survival estimations for patients with PRAD (AU)

Integrative analysis of transcriptomic landscape and urinary signature reveals prognostic biomarkers for clear cell renal cell carcinoma.

Background: Clear cell renal cell carcinoma (ccRCC) patients with venous tumor thrombus (VTT) have poor prognosis. We aimed to reveal features of ccRCC with VTT and develop a urine-based prognostic classifier to predict ccRCC prognosis through integrative analyses of transcriptomic landscape and urinary signature. Methods: RNA sequencing was performed in five patients with ccRCC thrombus-tumor-normal tissue triples, while mass spectrometry was performed for urine samples from 12 ccRCC and 11 healthy controls. A urine-based classifier consisting of three proteins was developed to predict patients' survival and validated in an independent cohort. Results: Transcriptomic analysis identified 856 invasion-associated differentially expressed genes (DEGs). Furthermore, proteomic analysis showed 133 differentially expressed proteins (DEPs). Integration of transcriptomic landscape and urinary signature reveals 6 urinary detectable proteins (VSIG4, C3, GAL3ST1, TGFBI, AKR1C3, P4HB) displaying abundance changes consistent with corresponding genes in transcriptomic profiling. According to TCGA database, VSIG4, TGFBI, and P4HB were significantly overexpressed in patients with shorter survival and might be independent prognostic factors for ccRCC (all p<0.05). A prognostic classifier consisting of the three DEPs highly associated with survival performed satisfactorily in predicting overall survival (HR=2.0, p<0.01) and disease-free survival (HR=1.6, p<0.001) of ccRCC patients. The ELISA analysis of urine samples from an independent cohort confirmed the satisfied predictive power of the classifier for pathological grade (AUC=0.795, p<0.001) and stage (AUC=0.894, p<0.001). Conclusion: Based on integrative analyses of transcriptomic landscape and urinary signature, the urine-based prognostic classifier consisting of VSIG4, TGFBI, and P4HB has satisfied predictive power of ccRCC prognosis and may facilitate ccRCC molecular subtyping and treatment.

Neoadjuvant radiohormonal therapy for oligo-metastatic prostate cancer: safety and efficacy outcomes from an open-label, dose-escalation, single-center, phase I/II clinical trial.

To evaluate the safety and efficacy of neoadjuvant radiohormonal therapy for oligometastatic prostate cancer (OMPC), we conducted a 3 + 3 dose escalation, prospective, phase I/II, single-arm clinical trial (CHiCTR1900025743), in which long-term neoadjuvant androgen deprivation was adopted 1 month before radiotherapy, comprising intensity modulated radiotherapy to the pelvis, and stereotactic body radiation therapy to all extra-pelvic bone metastases for 4-7 weeks, at 39.6, 45, 50.4, and 54 Gy. Robotic-assisted radical prostatectomy was performed after 5-14 weeks. The primary outcome was treatment-related toxicities and adverse events; secondary outcomes were radiological treatment response, positive surgical margin (pSM), postoperative prostate-specific antigen (PSA), pathological down-grading and tumor regression grade, and survival parameters. Twelve patients were recruited from March 2019 to February 2020, aging 66.2 years in average (range, 52-80). Median baseline PSA was 62.0 ng/mL. All underwent RARP successfully without open conversions. Ten patients recorded pathological tumor down-staging (83.3%), and 5 (41.7%) with cN1 recorded negative regional lymph nodes on final pathology. 66.7% (8/12) recorded tumor regression grading (TRG) -I and 25% (3/12) recorded TRG-II. Median follow-up was 16.5 months. Mean radiological progression-free survival (RPFS) was 21.3 months, with 2-year RPFS of 83.3%. In all, neoadjuvant radiohormonal therapy is well tolerated for oligometastatic prostate cancer.

Community characteristics of autotrophic CO2-fixing bacteria in karst wetland groundwaters with different nitrogen levels.

Karst wetlands are important in the global carbon and nitrogen cycles as well as in security of water resources. Huixian wetland (Guilin) is the largest natural karst wetland in China. In recent years, groundwater nitrogen pollution has increasingly affected the wetland ecosystem integrity due to anthropogenic activities. In this study, it was hypothesized that autotrophic microbial diversity is impacted with the advent of pollution, adversely affecting autotrophs in the carbon and nitrogen cycles. Autotrophic microbes have important roles in abating groundwater nitrogen pollution. Thus, it is of great significance to study the characteristics of autotrophic bacterial communities and their responses to environmental parameters in nitrogen-polluted karst groundwaters. The abundances of the Calvin-Benson cycle functional genes cbbL and cbbM as well as the autotrophic CO2-fixing bacterial communities were characterized in the karst groundwater samples with different levels of nitrogen pollution. The cbbM gene was generally more abundant than the cbbL gene in the groundwater samples. The cbbL gene abundance was significantly positively correlated with dissolved inorganic nitrogen (DIN) concentration (P < 0.01). In the autotrophic CO2-fixing bacterial communities, Alphaproteobacteria, Betaproteobacteria, and Gammaproteobacteria of the phylum Proteobacteria were predominant. At the genus level, Rubrivivax and Methylibium were the dominant cbbL gene containing genera, while Halothiobacillus and Endothiovibrio were the dominant genera for the cbbM gene. The abundance of autotrophic CO2-fixing bacterial communities increased but their diversity decreased with the inflow of nitrogen into the karst groundwater system. The community structure of autotrophic CO2-fixing bacteria in the groundwaters was also significantly affected by environmental factors such as the carbonic anhydrase (CA) activity, dissolved inorganic carbon (DIC) concentration, temperature, and oxidation-reduction potential (ORP). Nitrogen inflow significantly changed the characteristics of autotrophic CO2-fixing bacterial communities in the karst groundwaters. Some key genera such as Nitrosospira and Thiobacillus were clearly abundant in the karst groundwaters with high nitrogen levels. Their respective roles in nitrification and denitrification impact nitrogen removal in this ecosystem. The findings in this study provide an important reference for biological abatement of nitrogen pollution in the karst groundwater system.

Safety and Efficacy Study of Neoadjuvant Radiohormonal Therapy for Oligometastatic Prostate Cancer: Protocol of an Open-Label, Dose-Escalation, Single-Centre Phase I/II Clinical Trial.

BACKGROUND: The optimal treatment for oligometastatic prostate cancer (OMPC) is still on its way. Accumulating evidence has proven the safety and feasibility of radical prostatectomy and local or metastasis-directed radiotherapy for oligometastatic patients. The aim of this trial is to demonstrate the safety and feasibility outcomes of metastasis-directed neoadjuvant radiotherapy (naRT) and neoadjuvant androgen deprivation therapy (naADT) followed by robotic-assisted radical prostatectomy (RARP) for treating OMPC. METHODS: The present study will be conducted as a prospective, open-label, dose-escalation, phase I/II clinical trial. The patients with oligometastatic PCa will receive 1 month of naADT, followed by metastasis-directed radiation and abdominal or pelvic radiotherapy. Then, radical prostatectomy will be performed at intervals of 4-8 weeks after radiotherapy, and ADT will be continued for 2 years. The primary endpoints of the study are safety profiles, assessed by the Common Terminology Criteria for Adverse Events (CTCAE) 5.0 grading scale, and perioperativemorbidities, assessed by the Clavien-Dindo classification system. The secondary endpoints include positive surgical margin (pSM), biochemical recurrence-free survival (bPFS), radiological progression-free survival (RPFS), postoperative continence, and quality of life (QoL) parameters. DISCUSSION: The optimal treatment for OMPC is still on its way, prompting investigation for novel multimodality treatment protocol for this patient population. Traditionally, radical prostatectomy has been recommended as one of the standard therapies for localized prostate cancer, but indications have expanded over the years as recommended by NCCN and EAU guidelines. RP has been carried out in some centres for OMPC patients, but its value has been inconclusive, showing elevated complication risks and limited survival benefit. Neoadjuvant radiotherapy has been proven safe and effective in colorectal cancer, breast cancer and other various types of malignant tumors, showing potential advantages in terms of reducing metastatic stem-cell activity, providing clinical downstaging, and reducing potential intraoperative risks. Existing trials have shown that naRT is well tolerated for high-risk and locally-advanced prostate cancer. In this study, we hope to further determine the optimal irradiation dose and patient tolerance for genitourinary, gastrointestinal and systemic toxicities with the design of 3+3 dose escalation; also, final pathology can be obtained following RP to further determine treatment response and follow-up treatment plans. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900025743. http://www.chictr.org.cn/showprojen.aspx?proj=43065.

Circulating exosomal mRNA signatures for the early diagnosis of clear cell renal cell carcinoma.

BACKGROUND: There are no proven tumor biomarkers for the early diagnosis of clear cell renal cell carcinoma (ccRCC) thus far. This study aimed to identify novel biomarkers of ccRCC based on exosomal mRNA (emRNA) profiling and develop emRNA-based signatures for the early detection of ccRCC. METHODS: Four hundred eighty-eight participants, including 226 localized ccRCCs, 73 patients with benign renal masses, and 189 healthy controls, were recruited. Circulating emRNA sequencing was performed in 12 ccRCCs and 22 healthy controls in the discovery phase. The candidate emRNAs were evaluated with 108 ccRCCs and 70 healthy controls in the test and training phases. The emRNA-based signatures were developed by logistic regression analysis and validated with additional cohorts of 106 ccRCCs, 97 healthy controls, and 73 benign individuals. RESULTS: Five emRNAs, CUL9, KMT2D, PBRM1, PREX2, and SETD2, were identified as novel potential biomarkers of ccRCC. We further developed an early diagnostic signature that comprised KMT2D and PREX2 and a differential diagnostic signature that comprised CUL9, KMT2D, and PREX2 for RCC detection. The early diagnostic signature displayed high accuracy in distinguishing ccRCCs from healthy controls, with areas under the receiver operating characteristic curve (AUCs) of 0.836 and 0.830 in the training and validation cohorts, respectively. The differential diagnostic signature also showed great performance in distinguishing ccRCCs from benign renal masses (AUC = 0.816), including solid masses (AUC = 0.810) and cystic masses (AUC = 0.832). CONCLUSIONS: We established and validated novel emRNA-based signatures for the early detection of ccRCC and differential diagnosis of uncertain renal masses. These signatures could be promising and noninvasive biomarkers for ccRCC detection and thus improve the prognosis of ccRCC patients.

Targeting signaling pathways in prostate cancer: mechanisms and clinical trials.

Prostate cancer (PCa) affects millions of men globally. Due to advances in understanding genomic landscapes and biological functions, the treatment of PCa continues to improve. Recently, various new classes of agents, which include next-generation androgen receptor (AR) signaling inhibitors (abiraterone, enzalutamide, apalutamide, and darolutamide), bone-targeting agents (radium-223 chloride, zoledronic acid), and poly(ADP-ribose) polymerase (PARP) inhibitors (olaparib, rucaparib, and talazoparib) have been developed to treat PCa. Agents targeting other signaling pathways, including cyclin-dependent kinase (CDK)4/6, Ak strain transforming (AKT), wingless-type protein (WNT), and epigenetic marks, have successively entered clinical trials. Furthermore, prostate-specific membrane antigen (PSMA) targeting agents such as 177Lu-PSMA-617 are promising theranostics that could improve both diagnostic accuracy and therapeutic efficacy. Advanced clinical studies with immune checkpoint inhibitors (ICIs) have shown limited benefits in PCa, whereas subgroups of PCa with mismatch repair (MMR) or CDK12 inactivation may benefit from ICIs treatment. In this review, we summarized the targeted agents of PCa in clinical trials and their underlying mechanisms, and further discussed their limitations and future directions.

Super-veil nerve-sparing extraperitoneal pure single-port robotic-assisted radical prostatectomy on da Vinci Si robotic system.

OBJECTIVES: To investigate the safety profile and short-term outcome of super-veil nerve-sparing extraperitoneal single-port robotic-assisted radical prostatectomy (espRARP) on da Vinci Si platform. METHODS: From December 2018 to March 2021, 106 consecutive patients with treatment-naive prostate cancer were prospectively included. espRARP was performed on da Vinci Si surgical platform. Operative time, estimated blood loss, Clavien-Dindo complication classification, continence, potency recovery, quality-of-life scores, and postoperative prostate-specific antigen (PSA) were documented. RESULTS: Patients aged 52-79 years (mean ± SD, 64.8 ± 6.15 yrs), with a median PSA of 9.2 ng/ml (IQR: 6.70, 16.83) and median prostate volume of 31.9 ml (IQR: 30.01, 38.54). 95.28% (101/106) were clinically localized. All patients underwent espRARP successfully with no open conversions. Operative time was 94.2 ± 30.26 min with an estimated blood loss of 68.5 ml (range, 50-120 ml). No Grade III complications or above were documented. Positive surgical margin was 17.9% (19/106). Median pain score at discharge was 0 (IQR: 0, 1.75) without use of opioid narcotics. Postoperative length of stay was 3 days (IQR: 1, 3), in which 28 patients were discharged within 24 h. Instant, 1-, 3-, and 6 month continence recovery was 18.9, 45.3, 79.2, 93.4, and 96.4%, respectively. Of the 43 patients who received nerve-sparing procedures, 13 (30.23%) resumed potency 6 months postoperatively. 12 month biochemical recurrence-free survival was 92.77% (77/83). CONCLUSIONS: Extraperitoneal single-port robotic-assisted radical prostatectomy is a safe and feasible technique. Combined with super-veil nerve-sparing procedures, it may provide satisfactory outcome in short-term functional recovery.

Single-Cell Analysis Reveals EP4 as a Target for Restoring T-Cell Infiltration and Sensitizing Prostate Cancer to Immunotherapy.

PURPOSE: Immunotherapies targeting immune checkpoint molecules have shown promising treatment for a subset of cancers; however, many "cold" tumors, such as prostate cancer, remain unresponsive. We aimed to identify a potential targetable marker relevant to prostate cancer and develop novel immunotherapy. EXPERIMENTAL DESIGN: Analysis of transcriptomic profiles at single-cell resolution was performed in clinical patients' samples, along with integrated analysis of multiple RNA-sequencing datasets. The antitumor activity of YY001, a novel EP4 antagonist, combined with anti-programmed cell death protein 1 (PD-1) antibody was evaluated both in vitro and in vivo. RESULTS: We identified EP4 (PTGER4) as expressed in epithelial cells and various immune cells and involved in modulating the prostate cancer immune microenvironment. YY001, a novel EP4 antagonist, inhibited the differentiation, maturation, and immunosuppressive function of myeloid-derived suppressor cells (MDSC) while enhancing the proliferation and anticancer functions of T cells. Furthermore, it reversed the infiltration levels of MDSCs and T cells in the tumor microenvironment by overturning the chemokine profile of tumor cells in vitro and in vivo. The combined immunotherapy demonstrated a robust antitumor immune response as indicated by the robust accumulation and activation of CD8+ cytotoxic T cells, with a significantly decreased MDSC ratio and reduced MDSC immunosuppression function. CONCLUSIONS: Our study identified EP4 as a specific target for prostate cancer immunotherapy and demonstrated that YY001 inhibited the growth of prostate tumors by regulating the immune microenvironment and strongly synergized with anti-PD-1 antibodies to convert completely unresponsive prostate cancers into responsive cancers, resulting in marked tumor regression, long-term survival, and lasting immunologic memory.

Detection of wavelength in the range from ultraviolet to near infrared light using two parallel PtSe2/thin Si Schottky junctions.

A wavelength sensor as a representative optoelectronic device plays an important role in many fields including visible light communication, medical diagnosis, and image recognition. In this study, a wavelength-sensitive detector with a new operation mechanism was reported. The as-proposed wavelength sensor which is composed of two parallel PtSe2/thin Si Schottky junction photodetectors is capable of distinguishing wavelength in the range from ultraviolet to near infrared (UV-NIR) light (265 to 1050 nm), in that the relationship between the photocurrent ratio of both photodetectors and incident wavelength can be numerically described by a monotonic function. The unique operation mechanism of the thin Si based wavelength sensor was unveiled by theoretical simulation based on Synopsys Sentaurus Technology Computer Aided Design (TCAD). Remarkably, the wavelength sensor has an average absolute error of ±4.05 nm and an average relative error less than ±0.56%, which are much better than previously reported devices. What is more, extensive analysis was performed to reveal how and to what extent the working temperature and incident light intensity, and the thickness of the PtSe2 layer will influence the performance of the wavelength sensor.

Filterless Discrimination of Wavelengths in the Range from Ultraviolet to Near-Infrared Light Using Two PdSe2/Thin Si/PdSe2 Heterojunction Photodetectors.

In this study, we present a wavelength sensor that is capable of distinguishing the spectrum in the range from ultraviolet (UV) to near-infrared (NIR) light. The filterless device is composed of two horizontally stacking PdSe2/20 µm Si/PdSe2 heterojunction photodetectors with a photovoltaic (PV) behavior, which makes it possible for the device to work at 0 bias voltage. Due to the relatively small thickness of Si and the wavelength-dependent absorption coefficient, the two PdSe2/20 µm Si/PdSe2 photodetectors according to theoretical simulation display a sharp contrast in distribution of the photoabsorption rate. As a result, the photocurrents of both photodetectors evolve in completely different ways with increasing wavelengths, leading to a monotonic decrease in the photocurrent ratio from 6800 to 22 when the wavelength gradually increases from 265 to 1050 nm. The corresponding relationship between both the photocurrent ratio and wavelength can be easily described by the monotonic function, which can help to precisely determine the wavelength in the range from 265 to 1050 nm, with an average relative error less than ±1.6%. It is also revealed that by slightly revising the monotonic function, the wavelength in other different temperatures can also be estimated.

FOXA1 overexpression suppresses interferon signaling and immune response in cancer.

Androgen receptor-positive prostate cancer (PCa) and estrogen receptor-positive luminal breast cancer (BCa) are generally less responsive to immunotherapy compared with certain tumor types such as melanoma. However, the underlying mechanisms are not fully elucidated. In this study, we found that FOXA1 overexpression inversely correlated with interferon (IFN) signature and antigen presentation gene expression in PCa and BCa patients. FOXA1 bound the STAT2 DNA-binding domain and suppressed STAT2 DNA-binding activity, IFN signaling gene expression, and cancer immune response independently of the transactivation activity of FOXA1 and its mutations detected in PCa and BCa. Increased FOXA1 expression promoted cancer immuno- and chemotherapy resistance in mice and PCa and BCa patients. These findings were also validated in bladder cancer expressing high levels of FOXA1. FOXA1 overexpression could be a prognostic factor to predict therapy resistance and a viable target to sensitize luminal PCa, BCa, and bladder cancer to immuno- and chemotherapy.

D-ribose: Potential clinical applications in congestive heart failure and diabetes, and its complications (Review).

The quality of life of patients with certain diseases may be improved through the development of technologies and advancements in pharmacology, with the aim of prolonging their life. However, congestive heart failure (CHF), as well their complications, continue to be the leading cause of disease-associated death. The mechanisms underlying the development and progression of diabetes and CHF have been uncovered in a stepwise manner and the understanding of these mechanisms has improved the management of these diseases, resulting in reduced mortality and morbidity rates; however, CHF remains the leading cause of death worldwide, particularly in developed countries. In the past decades, research has indicated that several supplements and naturally occurring compounds may be used to treat muscle weakness, for cardiac failure management, rehabilitation following myocardial ischemia-reperfusion and various complications of diabetes. D-ribose is an essential component of the respiratory, skeletal and nervous systems and is a popular compound, as its supplementation may have beneficial effects. In the present review, the physiological roles, toxic reactions and the potential use of D-ribose in the management of clinical diseases are summarized.