Searching for Two-Neutrino and Neutrinoless Double Beta Decay of

^{134}Xe is a candidate isotope for neutrinoless double beta decay (0νßß) search. In addition, the two-neutrino case (2νßß) allowed by the standard model of particle physics has not yet been observed. With the 656-kg natural xenon in the fiducial volume of the PandaX-4T detector, which contains 10.4% of ^{134}Xe, and its initial 94.9-day exposure, we have established the most stringent constraints on 2νßß and 0νßß of ^{134}Xe half-lives, with limits of 2.8×10^{22} yr and 3.0×10^{23} yr at 90% confidence level, respectively. The 2νßß (0νßß) limit surpasses the previously reported best result by a factor of 32 (2.7), highlighting the potential of large monolithic natural xenon detectors for double beta decay searches.

Basement membrane-related MMP14 predicts poor prognosis and response to immunotherapy in bladder cancer.

BACKGROUND: Basement membrane (BM) is an important component of the extracellular matrix, which plays an important role in the growth and metastasis of tumor cells. However, few biomarkers based on BM have been developed for prognostic assessment and prediction of immunotherapy in bladder cancer (BLCA). METHODS: In this study, we used the BLCA public database to explore the relationship between BM-related genes (BMRGs) and prognosis. A novel molecular typing of BLCA was performed using consensus clustering. LASSO regression was used to construct a signature based on BMRGs, and its relationship with prognosis was explored using survival analysis. The pivotal BMRGs were further analyzed to assess its clinical characteristics and immune landscape. Finally, immunohistochemistry was used to detect the expression of the hub gene in BLCA patients who underwent surgery or received immune checkpoint inhibitor (ICI) immunotherapy in our hospital. RESULTS: We comprehensively analyzed the relationship between BMRGs and BLCA, and established a prognostic-related signature which was an independent influence on the prognostic prediction of BLCA. We further screened and validated the pivotal gene-MMP14 in public database. In addition, we found that MMP14 expression in muscle invasive bladder cancer (MIBC) was significantly higher and high MMP14 expression had a poorer response to ICI treatment in our cohort. CONCLUSIONS: Our findings highlighted the satisfactory value of BMRGs and suggested that MMP14 may be a potential biomarker in predicting prognosis and response to immunotherapy in BLCA.

Propensity score-matched analysis examining the role of obesity on outcomes in retroperitoneal laparoscopic adrenalectomy: a cohort study.

Background: There is inconsistent evidence regarding obesity's effect on surgical outcomes following retroperitoneal laparoscopic adrenalectomy (RLA). This study aimed to investigate the influence of obesity on surgical outcomes in patients undergoing RLA, with an emphasis on operative time, drainage tube removal time, postoperative hospital stays and perioperative complications. Methods: In this retrospective, single-center, observational study, all consecutive cases of unilateral RLA for adrenal disease from January 2012 to December 2021 were incorporated. The patients were divided into two groups based on their body mass index (BMI) of 28 kg/m2. To mitigate selection bias, propensity score matching (PSM) was conducted, using logistic regression to calculate propensity scores for balancing baseline characteristics. A multivariate logistic regression analysis was performed to assess how obesity affects operative time and intraoperative blood loss as well. The linear correlation between BMI and surgical outcomes, including prolonged operative time and increased intraoperative blood loss, was also examined using restricted cubic spline (RCS) analysis. Results: A total of 569 patients who underwent RLA were included. After PSM, 122 patients were apportioned to each group. Statistically significant differences were observed between the obese and non-obese group in operative time (97.5 vs. 115 min, P<0.001). There were no statistically significant differences between the two groups regarding hospital stay (6.7 vs. 6.8 days, P=0.58), drainage tube removal time (3.0 vs. 3.0 days, P=0.19), nor postoperative complications (9.0% vs. 12.3%, P=0.41). Furthermore, univariate logistic regression analysis revealed that, obese patients undergoing RLA were linked to prolonged operative time and increased intraoperative blood loss. After adjusting for potential confounders, the obese group showed a 67% increased risk of prolonged operative time and a 69% increased intraoperative blood loss. The RCS analysis revealed that BMI had a linear relationship with operative time (P for nonlinearity =0.47) and blood loss during surgery (P for linearity =0.89). Conclusions: In patients undergoing RLA, obesity exerts a significant influence on surgical outcomes, particularly with regard to operative time and intraoperative blood loss, as shown in multivariable logistic regression analysis and PSM to balance baseline characteristics.

Development and validation of a circulating tumor cells-related signature focusing on biochemical recurrence and immunotherapy response in prostate cancer.

Background: Studies have shown that the circulating tumor cells (CTCs) play a key role for invasion and formation of distant metastases in prostate cancer (PCa). However, few CTCs-related genes (CRGs) have been developed for biochemical recurrence (BCR) prediction and clinical applications of PCa patients. Materials and methods: Bioinformatics analysis with public PCa datasets were used to investigate the relationship between the differentially expressed CRGs and BCR. Lasso-COX regression analysis was used to constructed and validated a CRGs-based BCR prediction signature for PCa. Single-cell data were used to validate the expression levels of signature genes in different cell types and then explored the cell-cell communication relationships. Finally, the expression levels of signature genes were verified and the CRGs involved in immunotherapy response were further identified. Results: Thirteen CRGs were differentially expressed and closely associated with BCR in PCa. Then we constructed and validated a BCR prediction signature for PCa patients based on 3 differentially expressed CRGs (EMID1, SPP1 and UBE2C), and the signature was an independent factor to predict BCR for PCa. Single-cell data showed the specific expression patterns of the signature genes, while the SPP1 pathway plays an important role in cell-cell communication. Further analyses suggested UBE2C was highly expressed in BCR group and high expression of UBE2C had a better response for patients who received immunotherapy. Moreover, the expression levels of UBE2C in CTCs were higher than other cells and tissues, indicated that UBE2C may affect the BCR event of PCa patients through CTCs. Conclusion: Our findings demonstrated that CRGs were significantly associated with BCR and immunotherapy efficacy in PCa and CRGs may influence the BCR event through CTCs.

Determination of Double Beta Decay Half-Life of 136Xe with the PandaX-4T Natural Xenon Detector.

Precise measurement of two-neutrino double beta decay (DBD) half-life is an important step for the searches of Majorana neutrinos with neutrinoless double beta decay. We report the measurement of DBD half-life of 136Xe using the PandaX-4T dual-phase Time Projection Chamber (TPC) with 3.7-tonne natural xenon and the first 94.9-day physics data release. The background model in the fiducial volume is well constrained in situ by events in the outer active region. With a 136Xe exposure of 15.5 kg-year, we establish the half-life as 2.27 ± 0.03(stat.) ± 0.10(syst.) × 1021 years. This is the first DBD half-life measurement with natural xenon and demonstrates the physics capability of a large-scale liquid xenon TPC in the field of rare event searches.