Gibberellin Positively Regulates Tomato Resistance to Tomato Yellow Leaf Curl Virus (TYLCV).

Tomato yellow leaf curl virus (TYLCV) is a prominent viral pathogen that adversely affects tomato plants. Effective strategies for mitigating the impact of TYLCV include isolating tomato plants from the whitefly, which is the vector of the virus, and utilizing transgenic lines that are resistant to the virus. In our preliminary investigations, we observed that the use of growth retardants increased the rate of TYLCV infection and intensified the damage to the tomato plants, suggesting a potential involvement of gibberellic acid (GA) in the conferring of resistance to TYLCV. In this study, we employed an infectious clone of TYLCV to inoculate tomato plants, which resulted in leaf curling and growth inhibition. Remarkably, this inoculation also led to the accumulation of GA3 and several other phytohormones. Subsequent treatment with GA3 effectively alleviated the TYLCV-induced leaf curling and growth inhibition, reduced TYLCV abundance in the leaves, enhanced the activity of antioxidant enzymes, and lowered the reactive oxygen species (ROS) levels in the leaves. Conversely, the treatment with PP333 exacerbated TYLCV-induced leaf curling and growth suppression, increased TYLCV abundance, decreased antioxidant enzyme activity, and elevated ROS levels in the leaves. The analysis of the gene expression profiles revealed that GA3 up-regulated the genes associated with disease resistance, such as WRKYs, NACs, MYBs, Cyt P450s, and ERFs, while it down-regulated the DELLA protein, a key agent in GA signaling. In contrast, PP333 induced gene expression changes that were the opposite of those caused by the GA3 treatment. These findings suggest that GA plays an essential role in the tomato's defense response against TYLCV and acts as a positive regulator of ROS scavenging and the expression of resistance-related genes.

Phase-Dependent Magnetic Proximity Modulations on Valley Polarization and Splitting.

Proximate-induced magnetic interactions present a promising strategy for precise manipulation of valley degrees of freedom. Taking advantage of the splendid valleytronic platform of transition metal dichalcogenides, magnetic two-dimensional VSe2 with different phases are introduced to intervene in the spin of electrons and modulate their valleytronic properties. When constructing the heterostructures, 1T-VSe2/WX2 (X = S and Se) showcases significant improvement in the valley polarizations at room temperature, while 2H-VSe2/WX2 exhibits superior performance at low temperatures and demonstrates heightened sensitivity to the external magnetic field. Simultaneously, considerable valley splitting with a large geff factor up to -29.0 is observed in 2H-VSe2/WS2, while it is negligible in 1T-VSe2/WX2. First-principles calculations reveal a phase-dependent magnetic proximity mechanism on the valleytronic modulations, which is dominated by interfacial charge transfer in 1T-VSe2/WX2 and the proximity exchange field in 2H-VSe2/WX2 heterostructures. The effective control over valley degrees of freedom will bridge the valleytronic physics and devices, rendering enormous potential in the field of valley quantum applications.

MAL, a potential immunotherapy target, is associated with poor prognosis in cancer patients.

The MAL gene encodes Myelin and Lymphocyte Protein, mainly expressed in T cells with immunomodulatory effects, showing the potential as a target for immunotherapy. However, the mechanism of MAL in the regulation of immune infiltration and its association with the prognosis in pan-cancer patients remain elusive. We used the TCGA, TIMER2.0, GTEx, UCSC, and TISCH databases and the R programming tool to explore the role of MAL in cancers. MAL was differently expressed in the majority of malignancies relative to the matched healthy controls. Patients with low MAL levels had adverse survival outcomes in the BRCA and LUAD cohorts. In all cancer types, MAL showed a significant correlation to specific immune-subpopulation abundance in particular T cells as well as B cells. MAL was also implicated in immunological pathways in BRCA and LUAD, suggesting the important role of MAL in cancer immune regulation. In conclusion, the pan-cancer study indicates that MAL with excellent prognostic value is a potential immunotherapy target in multiple cancers.

Serum secreted phosphoprotein 1 level is associated with plaque vulnerability in patients with coronary artery disease.

Background: Vulnerable plaque was associated with recurrent cardiovascular events. This study was designed to explore predictive biomarkers of vulnerable plaque in patients with coronary artery disease. Methods: To reveal the phenotype-associated cell type in the development of vulnerable plaque and to identify hub gene for pathological process, we combined single-cell RNA and bulk RNA sequencing datasets of human atherosclerotic plaques using Single-Cell Identification of Subpopulations with Bulk Sample Phenotype Correlation (Scissor) and Weighted gene co-expression network analysis (WGCNA). We also validated our results in an independent cohort of patients by using intravascular ultrasound during coronary angiography. Results: Macrophages were found to be strongly correlated with plaque vulnerability while vascular smooth muscle cell (VSMC), fibrochondrocyte (FC) and intermediate cell state (ICS) clusters were negatively associated with unstable plaque. Weighted gene co-expression network analysis showed that Secreted Phosphoprotein 1 (SPP1) in the turquoise module was highly correlated with both the gene module and the clinical traits. In a total of 593 patients, serum levels of SPP1 were significantly higher in patients with vulnerable plaques than those with stable plaque (113.21 [73.65 - 147.70] ng/ml versus 71.08 [20.64 - 135.68] ng/ml; P < 0.001). Adjusted multivariate regression analysis revealed that serum SPP1 was an independent determinant of the presence of vulnerable plaque. Receiver operating characteristic curve analysis indicated that the area under the curve was 0.737 (95% CI 0.697 - 0.773; P < 0.001) for adding serum SPP1 in predicting of vulnerable plaques. Conclusion: Elevated serum SPP1 levels confer an increased risk for plaque vulnerability in patients with coronary artery disease.

The burden of low back pain in adolescents and young adults.

BACKGROUND: Low back pain is highly prevalent and the main cause of years lived with disability, but data on the burden and trends of low back pain (LBP) in adolescents and young adults (AYAs) are sparse. OBJECTIVE: To assess trends in the burden of LBP among AYAs aged 15-39 years at the global, regional and national levels from 1990 to 2019. METHODS: Data from the Global Burden of Disease (GBD) 2019 were used to analyze incidence, prevalence and Disability-adjusted life year (DALY) due to LBP at global, regional, and national levels. Joinpoint regression analysis calculated the average annual percentage changes (AAPC). Then analyse the association between incidence, prevalence and DALYs and socioeconomic development using the GBD Socio-demographic Index (SDI). Finally, projections were made until 2030 and calculated in Nordpred. RESULTS: The incidence, prevalence and DALYs rates (95%UI) were 2252.78 (1809.47-2784.79), 5473.43 (4488.62-6528.15) and 627.66 (419.71-866.97) in 2019, respectively. From 1990 to 2019, the incidence, prevalence, and DALYs rates AAPC (95%CI) were -0.49 (-0.56 to -0.42), -0.58 (-0.65 to -0.51) and -0.57 (-0.64 to -0.5), respectively. Incidence, prevalence, and DALYs rates in South Asia, East Asia, High-income North America, Western Europe, and Australasia decreased with SDI. Incidence, prevalence, and DALYs rates in Central Asia, Central Europe, and Eastern Europe decreased and then increased with SDI. At the national level, the incidence, prevalence, and DALYs rates are high in the United States and low in India and China. From the 2020 to 2030, most regions is predicted to decline. CONCLUSION: LBP in AYAs is a major global public problem with a high burden. There are large differences in incidence, prevalence and DALYs across SDIs, regions and countries. there is still a need to focus on LBP in AYAs and tailor interventions to reduce the future burden of this condition.

Remarkable response to third-generation EGFR-TKI plus crizotinib in a patient with pulmonary adenocarcinoma harboring EGFR and ROS1 co-mutation: a case report.

Background: Driver oncogene mutations, such as c-ros oncogene 1 (ROS1) and epidermal growth factor receptor (EGFR) were previously believed to be mutually exclusive in non-small cell lung cancer (NSCLC). Only sporadic cases of ROS1 and EGFR co-mutations have been reported. Hence, appropriate treatment options for these patients are still controversial. Case presentation: A 48-year-old female patient presented at our hospital complaining of a persistent cough that had been ongoing for a month. A chest computed tomography showed a mass in the left lung along with hilar and mediastinal lymphadenopathy. Pathological analysis of bronchoscopic biopsy and lung mass puncture confirmed the presence of lung adenocarcinoma. The patient was diagnosed with stage IIIC left lung adenocarcinoma with a clinical stage of cT2N3M0. Next-generation sequencing analysis conducted at both puncture sites revealed an EFGR 19 deletion mutation combined with ROS1 rearrangement. The lung mass exhibited a higher mutation abundance. Treatment with a combination of third-generation EGFR tyrosine kinase inhibitors (TKIs) and crizotinib yielded satisfactory results. During the follow-up period, the mass significantly reduced and almost disappeared. Conclusion: The co-mutation of EGFR and ROS1 is a rare phenomenon. Nevertheless, the combination of EGFR-TKI and crizotinib treatment appears to hold promise in providing positive results for patients, with manageable side effects. This therapeutic approach has the potential to enhance patients' overall prognosis.

Anillin contributes to prostate cancer progression through the regulation of IGF2BP1 to promote c-Myc and MAPK signaling.

Prostate cancer (PCa), especially castration-resistant PCa, is a common and fatal disease. Anillin (ANLN) is an actin-binding protein that is involved in various malignancies, including PCa. However, the regulatory mechanism of ANLN in PCa remains unclear. Exploring the role of ANLN in PCa development and discovering novel therapeutic targets are crucial for PCa therapy. In the current work, we discovered that ANLN expression was considerably elevated in PCa tissues and cell lines when compared to nearby noncancerous prostate tissues and normal prostate epithelial cells. ANLN was associated with more advanced T stage, N stage, higher Gleason score, and prostate-specific antigen (PSA) level. In addition, we discovered that overexpression of ANLN promoted PCa cell proliferation, migration, and invasion in vitro and in vivo. Mechanistically, we performed RNA-seq to identify the regulatory influence of ANLN on the MAPK signal pathway. Furthermore, a favorable association between ANLN expression and IGF2BP1 expression was identified. The tumor-suppressive impact of ANLN downregulation on PCa cell growth was partially reversed by overexpressing IGF2BP1. Meanwhile, we discovered that ANLN can stabilize the proto-oncogene c-Myc and activate the MAPK signaling pathway through IGF2BP1. These findings indicate that ANLN could be a potential therapeutic target in PCa.

Regional lymph node mapping in patients with penile cancer undergoing radical inguinal lymph node dissection - a retrospective cohort study.

BACKGROUND: Radical inguinal lymph node dissection (rILND) is the most available treatment to cure penile cancer (PC) with limited inguinal-confined disease. However, guidelines regarding acceptable boundaries of rILND are controversial, and consensus is lacking. The authors aimed to standardize the surgical boundaries of rILND with definite pathological evidence and explore the distribution pattern of inguinal lymph nodes (ILNs) in PC. METHODS: A total of 414 PC patients from two centers who underwent rILND were enrolled. The ILN distribution was divided into seven zones anatomically for pathological examination. Student's t test and Kaplan-Meier survival analysis were used. RESULTS: ILNs displayed a funnel-shaped distribution with high density in superior regions. ILNs and metastatic nodes are present anywhere within the radical boundaries. Positive ILNs were mainly concentrated in zone I (51.7%) and zone II (41.3%), but there were 8.7% and 12.3% in inferior zones V and VI, respectively, and 7.1% in the deep ILNs. More importantly, a single positive ILN and first-station positive zone was detected in all seven regions. Single positive ILNs were located in zones I through VI in 40.4%, 23.6%, 6.7%, 18.0%, 4.5%, and 1.1%, respectively, and 5.6% presented deep ILN metastasis directly. CONCLUSIONS: The authors established a detailed ILN distribution map and displayed lymphatic drainage patterns with definite pathological evidence using a large cohort of PC patients. Single positive ILNs and first-station metastatic zones were observed in any region, even directly with deep ILN metastasis. Only rILND can ensure tumor-free resection without the omission of positive nodes.

Diffuse infantile hepatic hemangioma successfully treated with propranolol orally: a case report and literature review.

Background: Infantile hepatic hemangioma (IHH) is a common vascular, fast-growing hepatic tumor that is usually accompanied by multiple cutaneous hemangiomas. Diffuse IHH (DIHH) is a rare type of IHH that exhibits many tumors with nearly complete hepatic parenchymal replacement. At present, there is no specific standardized treatment plan for DIHH. Herein, we present the case of a 2-month-old girl with DIHH and without cutaneous hemangioma who achieved complete remission after undergoing propranolol monotherapy. Case presentation: The infant with low birth weight was presented to the pediatric department with a 2-month history of persistent vomiting and feeding difficulty. Ultrasonography and abdominal magnetic resonance imaging revealed hepatomegaly and diffused intrahepatic lesions. A computed tomography-guided percutaneous liver biopsy was performed, and the pathological examination suggested the diagnosis was DIHH. The patient exhibited remarkably response to an increasing dose of oral propranolol, from 0.5 mg/kg to 2 mg/kg every day. The intrahepatic lesions were almost completely regressed after one year of treatment and no distinct adverse reaction was observed. Conclusion: DIHH can induce life-threatening complications that require prompt interventions. Propranolol monotherapy can be an effective and safe first-line treatment strategy for DIHH.

Simultaneously Regulated Highly Polarized and Long-Lived Valley Excitons in WSe2/GaN Heterostructures.

Interlayer excitons, with prolonged lifetimes and tunability, hold potential for advanced optoelectronics. Previous research on the interlayer excitons has been dominated by two-dimensional heterostructures. Here, we construct WSe2/GaN composite heterostructures, in which the doping concentration of GaN and the twist angle of bilayer WSe2 are employed as two ingredients for the manipulation of exciton behaviors and polarizations. The exciton energies in monolayer WSe2/GaN can be regulated continuously by the doping levels of the GaN substrate, and a remarkable increase in the valley polarizations is achieved. Especially in a heterostructure with 4°-twisted bilayer WSe2, a maximum polarization of 38.9% with a long lifetime is achieved for the interlayer exciton. Theoretical calculations reveal that the large polarization and long lifetime are attributed to the high exciton binding energy and large spin flipping energy during depolarization in bilayer WSe2/GaN. This work introduces a distinctive member of the interlayer exciton with a high degree of polarization and a long lifetime.

Manipulations of Electronic and Spin States in Co-Quantum Dot/WS2 Heterostructure on a Metal-Dielectric Composite Substrate by Controlling Interfacial Carriers.

Charge and spin are two intrinsic attributes of carriers governing almost all of the physical processes and operation principles in materials. Here, we demonstrate the manipulation of electronic and spin states in designed Co-quantum dot/WS2 (Co-QDs/WS2) heterostructures by employing a metal-dielectric composite substrate and via scanning tunneling microscope. By repeatedly scanning under a unipolar bias, switching the bias polarity, or applying a pulse through nonmagnetic or magnetic tips, the Co-QDs morphologies exhibit a regular and reproducible transformation between bright and dark dots. First-principles calculations reveal that these tunable characters are attributed to the variation of density of states and the transition of magnetic anisotropy energy induced by carrier accumulation. It also suggests that the metal-dielectric composite substrate is successful in creating the interfacial potential for carrier accumulation and realizes the electrically controllable modulations. These results will promote the exploration of electron-matter interactions in quantum systems and provide an innovative way to facilitate the development of spintronics.

Coexisting Phases in Transition Metal Dichalcogenides: Overview, Synthesis, Applications, and Prospects.

Over the past decade, significant advancements have been made in phase engineering of two-dimensional transition metal dichalcogenides (TMDCs), thereby allowing controlled synthesis of various phases of TMDCs and facile conversion between them. Recently, there has been emerging interest in TMDC coexisting phases, which contain multiple phases within one nanostructured TMDC. By taking advantage of the merits from the component phases, the coexisting phases offer enhanced performance in many aspects compared with single-phase TMDCs. Herein, this review article thoroughly expounds the latest progress and ongoing efforts on the syntheses, properties, and applications of TMDC coexisting phases. The introduction section overviews the main phases of TMDCs (2H, 3R, 1T, 1T', 1Td), along with the advantages of phase coexistence. The subsequent section focuses on the synthesis methods for coexisting phases of TMDCs, with particular attention to local patterning and random formations. Furthermore, on the basis of the versatile properties of TMDC coexisting phases, their applications in magnetism, valleytronics, field-effect transistors, memristors, and catalysis are discussed. Lastly, a perspective is presented on the future development, challenges, and potential opportunities of TMDC coexisting phases. This review aims to provide insights into the phase engineering of 2D materials for both scientific and engineering communities and contribute to further advancements in this emerging field.

Icariin decreases cell proliferation and inflammation of rheumatoid arthritis-fibroblast like synoviocytes via GAREM1/MAPK signaling pathway.

OBJECTIVE: Rheumatoid arthritis (RA) is an autoimmune disorder characterized by chronic inflammation and joint damage, leading to pain and reduced joint function. Icariin, a flavonoid compound, has been studied for its potential therapeutic role in RA due to its anti-inflammatory and anti-proliferative effects. Here, we aimed to investigate the action mechanism of icariin in regulating RA. MATERIALS AND METHODS: Fibroblast-like synoviocytes (FLS) were obtained from RA and trauma patients, generating RA-FLS and normal FLS. The cells were treated with varying concentrations of icariin (0, 10, 20, 40, 80 µM). We assessed the effects of icariin on cell proliferation, apoptosis, and levels of inflammatory factors using the CCK-8 assay, flow cytometry, and enzyme-linked immunosorbent assay, qRT-PCR, and western blotting. RESULTS: Icariin treatment had no significant impact on the cell proliferation of normal FLS. However, it dose-dependently repressed cell proliferation, reduced TNF-α, IL-6, and IL-1ß levels, and increased apoptosis in RA-FLS. The expression of GAREM1, p-p38, and p-ERK1/2 was upregulated in RA-FLS, which was reversed by icariin treatment. Overexpression of GAREM1 reversed the inhibitory effects of icariin on cell proliferation and inflammatory factor levels in RA-FLS. CONCLUSION: Our findings suggest that icariin treatment can alleviate the development of RA by reducing cell proliferation and inflammation in RA-FLS through the regulation of the GAREM1/MAPK signaling pathway. These results support the potential of icariin as a therapeutic agent for RA treatment. As icariin is safe and well-tolerated in previous studies, further research is warranted to explore its efficacy in clinical settings.

Extraperitonealization of the ileal conduit decreases the risk of parastomal hernia: A single-center, randomized clinical trial.

Parastomal hernia (PSH) is a common complication in patients receiving ileal conduit urinary diversion after radical cystectomy. In this randomized controlled clinical trial, we validate our previous finding that extraperitonealization of ileal conduit decreases incidence of PSH. In total, 104 consecutive patients undergoing radical cystectomy at Sun Yat-sen University Cancer Center are randomized 1:1 to receive either modified (extraperitonealized) ileal conduit (n = 52) or conventional ileal conduit (n = 52). Primary endpoint is incidence of radiological PSH during follow-up. Incidence of radiological PSH is lower in the modified group than in the conventional group (11.5% vs. 28.8%; p = 0.028) after a median follow-up of 32 months, corresponding to a hazard ratio of 0.374 (95% confidence interval: 0.145-0.965, p = 0.034) in the modified conduit group. The results support our previous finding that extraperitonealization of the ileal conduit is effective for reducing risk of PSH in patients receiving ileal conduit diversion.

Genome-Centric Metatranscriptomic Characterization of a Humin-Facilitated Anaerobic Tetrabromobisphenol A-Dehalogenating Consortium.

Tetrabromobisphenol A (TBBPA), a widely used brominated flame retardant in electronics manufacturing, has caused global contamination due to improper e-waste disposal. Its persistence, bioaccumulation, and potential carcinogenicity drive studies of its transformation and underlying (a)biotic interactions. This study achieved an anaerobic enrichment culture capable of reductively dehalogenating TBBPA to the more bioavailable bisphenol A. 16S rRNA gene amplicon sequencing and quantitative PCR confirmed that successive dehalogenation of four bromide ions from TBBPA was coupled with the growth of both Dehalobacter sp. and Dehalococcoides sp. with growth yields of 5.0 ± 0.4 × 108 and 8.6 ± 4.6 × 108 cells per µmol Br- released (N = 3), respectively. TBBPA dehalogenation was facilitated by solid humin and reduced humin, which possessed the highest organic radical signal intensity and reducing groups -NH2, and maintained the highest dehalogenation rate and dehalogenator copies. Genome-centric metatranscriptomic analyses revealed upregulated putative TBBPA-dehalogenating rdhA (reductive dehalogenase) genes with humin amendment, cprA-like Dhb_rdhA1 gene in Dehalobacter species, and Dhc_rdhA1/Dhc_rdhA2 genes in Dehalococcoides species. The upregulated genes of lactate fermentation, de novo corrinoid biosynthesis, and extracellular electron transport in the humin amended treatment also stimulated TBBPA dehalogenation. This study provided a comprehensive understanding of humin-facilitated organohalide respiration.

Genetic analysis of the causal relationship between gut microbiota and intervertebral disc degeneration: a two-sample Mendelian randomized study.

PURPOSE: Several recent studies have reported a possible association between gut microbiota and intervertebral disc degeneration; however, no studies have shown a causal relationship between gut microbiota and disc degeneration. This study was dedicated to investigate the causal relationship between the gut microbiota and intervertebral disc degeneration and the presence of potentially bacterial traits using two-sample Mendelian randomization. METHODS: A two-sample Mendelian randomization study was performed using the summary statistics of the gut microbiota from the largest available genome-wide association study meta-analysis conducted by the MiBioGen consortium. Summary statistics of intervertebral disc degeneration were obtained from the FinnGen consortium R8 release data. Five basic methods and MR-PRESSO were used to examine causal associations. The results of the study were used to examine the causal association between gut microbiota and intervertebral disc degeneration. Cochran's Q statistics were used to quantify the heterogeneity of instrumental variables. RESULTS: By using Mendelian randomization analysis, 10 bacterial traits potentially associated with intervertebral disc degeneration were identified: genus Eubacterium coprostanoligenes group, genus Lachnoclostridium, unknown genus id.2755, genus Marvinbryantia, genus Ruminococcaceae UCG003, family Rhodospirillaceae, unknown genus id.959, order Rhodospirillales, genus Lachnospiraceae NK4A136 grou, genus Eubacterium brachy group. CONCLUSION: This Mendelian Randomization study found a causal effect between 10 gut microbiota and intervertebral disc degeneration, and we summarize the possible mechanisms of action in the context of existing studies. However, additional research is essential to fully understand the contribution of genetic factors to the dynamics of gut microbiota and its impact on disc degeneration.

SPP1 is associated with adverse prognosis and predicts immunotherapy efficacy in penile cancer.

BACKGROUND: The effect of SPP1 in squamous cell carcinoma of the penis (PSCC) remained unknown. We attempted to clarify the function of the SPP1 gene in PSCC. METHOD: Eight paired penile cancer specimens (including penile cancer tissue, paracancerous tissue, and positive lymph node tissue) subjected to whole transcriptome sequencing were analysed to identify differentially expressed genes. We used immunohistochemistry to detect the expression of SPP1 protein and immune cell related proteins in penile cancer tissue. Then, we performed weighted gene coexpression network analysis (WGCNA) to identify the genes related to SPP1 in penile cancer tissue and positive lymph node tissue. Based on the GSE57955 dataset, the CIBERSORT and ssGSEA algorithms were carried out to investigate the immune environment of PSCC. GSVA analysis was conducted to identify the signaling pathways related to SPP1 subgroups. Enzyme-linked immunosorbent assay (ELISA) method was adopted to detect SPP1 level in the serum of 60 patients with penile cancer. RESULTS: Differential analysis indicated that SPP1 was the most differentially upregulated gene in both penile cancer tissues and positive lymph node tissues. Survival analysis suggested that the prognosis of the low-SPP1 group was significantly poorer than that of the high-SPP1 group. Subsequently, immune-related bioinformatics showed that SPP1 was significantly associated with B cells, CD8 + T cells, CD4 + T cells, macrophages, helper T cells, neutrophils and dendritic cells. The immunohistochemical results showed that the high-SPP1 group was characterized by relatively high expression of CD16 and relatively low expression of CD4. GSVA analysis indicated that high-SPP1 group was significantly associated with immune-related pathways such as PD-L1 expression and the PD-1 checkpoint pathway in cancer and the TNF signaling pathway. ELISA demonstrated that the serum level of SPP1 in patients with positive lymph node metastasis of penile cancer was significantly higher than that in patients with negative lymph node metastasis of penile cancer. CONCLUSION: Our study shows that the SPP1 gene might be an effective biomarker for predicting the prognosis and the efficacy of immunotherapy in PSCC patients.

Effect of chemotherapy alone or combined with immunotherapy for locally advanced or metastatic genitourinary small cell carcinoma: a real-world retrospective study.

BACKGROUND: Genitourinary small cell carcinoma is rare, and has a poor prognosis. However, effective treatment options for this disease are limited. We present a study to assess the efficacy of chemotherapy alone or combined with immunotherapy for locally advanced or metastatic genitourinary small cell carcinoma (GSCC). METHODS: We performed a retrospective analysis of patients with locally advanced or metastatic GSCC from Jan 2013 to September 2022 at Sun Yat-sen University Cancer Center. The survival and safety profiles were analyzed. RESULTS: Forty-two GSCC patients were enrolled, which included 20 with chemotherapy plus immunotherapy and 22 with chemotherapy alone. The median follow-up time was 15.13 months (95% CI, 8.84-21.42). The addition of immunotherapy to chemotherapy demonstrated no significant difference in median progression-free survival (p = 0.37). However, the median overall survival (OS) was 22.97 and 14.03 months with immunotherapy plus chemotherapy and chemotherapy alone, respectively (HR = 0.69, 95%CI 0.08-0.55, p = 0.017). Two patients with immunotherapy plus chemotherapy achieved clinical complete remission. The overall response rate for patients receiving chemotherapy combined with immunotherapy was 65%, which was higher in comparison to those treated with chemotherapy alone (50%). Univariate and multivariate analyses demonstrated that chemotherapy combined with immunotherapy independently achieved favorable OS. Four patients experienced immunotherapy-related adverse events, with one developing grade 3 hypothyroidism. CONCLUSIONS: Among patients with locally advanced or metastatic GSCC, immunotherapy combined with chemotherapy might be thought of as a potentially effective treatment option for patients with GSCC.

Prognostic Significance of HER2 Expression in Patients with Bacillus Calmette-Guérin-exposed Non-muscle-invasive Bladder Cancer.

BACKGROUND: Guidelines recommend intravesical instillation of bacillus Calmette-Guérin (BCG) as the first-choice treatment for intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC). However, there is no therapeutic biomarker for predicting BCG efficacy, especially in high-risk cases with high failure rates. HER2 expression is considered a prognostic factor for bladder cancer. OBJECTIVE: To elucidate the predictive value and significance of HER2 expression in patients with BCG-exposed NMIBC. DESIGN, SETTING, AND PARTICIPANTS: A total of 454 patients with NMIBC were included. All patients started BCG intravesical instillation (1.2 × 108 CFU, strain D2PB302) 2-6 wk after transurethral resection of bladder tumor and received 19 treatments over a period of 1 yr. HER2 immunohistochemistry (IHC) results available for 314 patients. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The outcomes investigated were recurrence-free survival (RFS) and progression-free survival (PFS). Outcome relationships were explored using multivariable Cox regression and log-rank analysis. RESULTS AND LIMITATIONS: In the IHC population, 35.7% of patients had HER2 overexpression (IHC score 2/3+). This group had a poor 5-yr RFS rate of 16.5%, in comparison to 68.0% in the group with low HER2 expression (p < 0.001). Patients with high-risk NMIBC and HER2 overexpression had the highest risk of BCG treatment failure, with 5-yr RFS and PFS rates of 19.0% and 58.2%, respectively. Conversely, HER2-negative (IHC score 0) patients with high-risk NMIBC experienced a long-term BCG benefit, with 5-yr RFS and PFS rates of 80.8% and 92.1%, respectively. Limitations include the retrospective study design and the limited details regarding BCG use. CONCLUSIONS: HER2 was an independent predictor of poor BCG efficacy in NMIBC. Patients with high-risk NMIBC and HER2 overexpression had the highest risk of disease recurrence and progression after exposure to BCG. Anti-HER2 targeted therapies could be considered for these patients. PATIENT SUMMARY: Measurement of blood levels of the protein HER2 can be used to predict outcomes after BCG (bacillus Calmette-Guérin) bladder therapy for patients with intermediate- or high-risk non-muscle-invasive bladder cancer. Measurement results for HER2 may help in guiding personalized treatment for these patients.

Genome-Wide Identification and Expression Analysis of Lipoxygenase Genes in Rose (Rosa chinensis).

Lipoxygenases (LOX) play pivotal roles in plant resistance to stresses. However, no study has been conducted on LOX gene identification at the whole genome scale in rose (Rosa chinensis). In this study, a total of 17 RcLOX members were identified in the rose genome. The members could be classified into three groups: 9-LOX, Type I 13-LOX, and Type II 13-LOX. Similar gene structures and protein domains can be found in RcLOX members. The RcLOX genes were spread among all seven chromosomes, with unbalanced distributions, and several tandem and proximal duplication events were found among RcLOX members. Expressions of the RcLOX genes were tissue-specific, while every RcLOX gene could be detected in at least one tissue. The expression levels of most RcLOX genes could be up-regulated by aphid infestation, suggesting potential roles in aphid resistance. Our study offers a systematic analysis of the RcLOX genes in rose, providing useful information not only for further gene cloning and functional exploration but also for the study of aphid resistance.