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Abstract Background The novel nanomaterials PNA-TN (PN) and PNA-TN-Dox (PND) have been shown to have strong inhibitory effects on breast cancer; however, it is unclear whether PN and PND have anti-head and neck squamous cell carcinoma (HNSCC) activity, and their potential mechanisms of activity are unknown. So, our study aims to explore the therapeutic effects of PN and PND on HNSCC and their possible mechanisms. Methods We used a series of phenotypic research to evaluate the effects of PN + Laser (L) and PND + L on the biological function of HNSCC cells in vitro and in vivo. We subsequently used mechanism research to examine changes in mRNA and protein expression related to apoptosis, epithelial‒mesenchymal transition (EMT), and the JNK signalling pathway. Results Our study revealed that PN and PND have strong inhibitory effects on HNSCC cells both in vitro and in vivo. In vitro, PN and PND significantly inhibited the proliferation, migration, invasion and EMT ability of HNSCC cells and promoted apoptosis; the inhibitory effect in the PND + L group was significantly greater than that in the PN + L group. In vivo, both treatments led to significant reductions in tumour volume and weight. Notably, the tumour volume and weight in the PND + L group were significantly lower than those in the PN + L group. Mechanism research confirmed that PN + L activated the expression of apoptosis-related proteins and inhibited the expression of EMT-related proteins via the JNK pathway. Furthermore, the anti-HNSCC effect of PN + L was blocked after the use of a JNK pathway inhibitor. Conclusion Treatment with PN + L or PND + L significantly inhibited the malignant progress of HNSCC cells, and the therapeutic effect of PND + L was significantly stronger than that of PN + L. The JNK signalling pathway is a key mechanism by which PN exerts its anti-HNSCC activity.

Programmed cell death (PCD) is a fundamental biological process for maintaining cellular equilibrium and regulating development, health, and disease across all living organisms. Among the various types of PCD, apoptosis plays a pivotal role in numerous diseases, notably cancer. Cancer cells frequently develop mechanisms to evade apoptosis, increasing resistance to standard chemotherapy treatments. This resistance has prompted extensive research into alternative mechanisms of programmed cell death. One such pathway is oncosis, characterized by significant energy consumption, cell swelling, dilation of the endoplasmic reticulum, mitochondrial swelling, and nuclear chromatin aggregation. Recent research suggests that oncosis can impact conditions such as chemotherapeutic cardiotoxicity, myocardial ischemic injury, stroke, and cancer, mediated by specific oncosis-related proteins. In this review, we provide a detailed examination of the morphological and molecular features of oncosis and discuss various natural or small molecule compounds that can induce this type of cell death. Additionally, we summarize the current understanding of the molecular mechanisms underlying oncosis and its role in both normal physiology and pathological conditions. These insights aim to illuminate future research directions and propose innovative strategies for leveraging oncosis as a therapeutic tool against human diseases and cancer resistance.

Abstract Background and Aims There are currently no clear conclusions about whether major depression (MD) and bipolar disorder (BD) increase the risk of erectile dysfunction (ED). In our study, we used a Mendelian randomization (MR) analysis to discover the causal associations between MD, BD and ED. Methods We got single-nucleotide polymorphisms (SNPs) related to MD, BD and ED from the MRC IEU Open genome-wide association study (GWAS) datasets. After a series of selection, SNPs left were selected as instrumental variables (IVs) of MD and BD for the following MR test to evaluate the relationship of genetically predicted MD or BD with the incidence of ED. Among them, we used the random-effects inverse-variance weighted (IVW) method as the main analysis. Finally, sensitivity analyses were further performed using Cochran’s Q test, funnel plots, MR-Egger regression, Leave-one-out method and MR- pleiotropy residual sum and outlier (PRESSO). Results Genetically-predicted MD was causally related to the incidence of ED in the IVW methods (odds ratio (OR), 1.53; 95% confidence interval (CI), 1.19–1.96; p = 0.001), while no causal impact of BD on the risk of ED (OR = 0.95, 95% CI 0.87–1.04; p = 0.306). The results of sensitivity analyses supported our conclusion, and no directional pleiotropy were found. Conclusion The findings of this research found evidence of a causal relationship between MD and ED. However, we did not find a causal relationship between BD and ED in European populations.

IntroductionTo compare the perioperative outcomes of robotic partial nephrectomy (RPN) vs. laparoscopic partial nephrectomy (LPN) for complex renal tumors with a RENAL nephrometry score ≥7.MethodsWe searched PubMed, EMBASE and the Cochrane Central Register for studies from 2000 to 2020 to evaluate the perioperative outcomes of RPN and LPN in patients with a RENAL nephrometry score ≥7. We used RevMan 5.2 to pool the data.ResultsSeven studies were acquired in our study. No significant differences were found in the estimated blood loss (WMD: 34.49; 95% CI: −75.16–144.14; p = 0.54), hospital stay (WMD: −0.59; 95% CI: −1.24–0.06; p = 0.07), positive surgical margin (OR: 0.85; 95% CI: 0.65–1.11; p = 0.23), major postoperative complications (OR: 0.90; 95% CI: 0.52–1.54; p = 0.69) and transfusion (OR: 0.72; 95% CI: 0.48–1.08; p = 0.11) between the groups. RPN showed better outcomes in the operating time (WMD: −22.45; 95% CI: −35.06 to −9.85; p = 0.0005), postoperative renal function (WMD: 3.32; 95% CI: 0.73–5.91; p = 0.01), warm ischemia time (WMD: −6.96; 95% CI: −7.30–−6.62; p

BackgroundVery few studies have been published on the causes of death of upper tract urothelial carcinoma (UTUC). We sought to explore the mortality patterns of contemporary UTUC survivors.MethodsWe performed a retrospective cohort study involving patients with upper urinary tract carcinoma from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database (2000 and 2015). We used standardized mortality ratios (SMRs) to compare death rates among patients with UTUC in the general population and excess absolute risks (EARs) to quantify the disease-specific death burden.ResultsA total of 10,179 patients with UTUC, including 7,133 who died, were included in our study. In total, 302 (17.17%) patients with the localized disease died of UTUC; however, patients who died from other causes were 4.8 times more likely to die from UTUC (n = 1,457 [82.83%]). Cardiovascular disease was the most common non-cancer cause of death (n = 393 [22.34% of all deaths]); SMR, 1.22; 95% confidence intervals [CI], 1.1–1.35; EAR, 35.96). A total of 4,046 (69.99%) patients with regional stage died within their follow-up, 1,413 (34.92%) of whom died from UTUC and 1,082 (26.74%) of whom died from non-cancer causes. UTUC was the main cause of death (SMR, 242.48; 95% CI, 230–255.47; EAR, 542.47), followed by non-tumor causes (SMR, 1.18; 95% CI, 1.11–1.25; EAR, 63.74). Most patients (94.94%) with distant stage died within 3 years of initial diagnosis. Although UTUC was the leading cause of death (n = 721 [54.29%]), these patients also had a higher risk of death from non-cancer than the general population (SMR, 2.08; 95% CI, 1.67–2.56; EAR, 288.26).ConclusionsNon-UTUC deaths accounted for 82.48% of UTUC survivors among those with localized disease. Patients with regional/distant stages were most likely to die of UTUC; however, there is an increased risk of dying from non-cancer causes that cannot be ignored. These data provide the latest and most comprehensive assessment of the causes of death in patients with UTUC.

Abstract Purpose to describe the methodology of transurethral seminal vesiculoscopy and the anatomy of the area of the verumontanum, and to determine the safety of this procedure, especially in terms of postoperative complications. Methods This retrospective observational study enrolled 144 patients with intractable hematospermia from May 2011 and August 2019. A 4.5/6.5-Fr vesiculoscope was inserted into the seminal vesicle to deal with the positive findings. The solution of quinolones was used to rinse each seminal vesicle. Results In this study, Transurethral seminal vesiculoscopy was successfully performed in 139 patients (96.53%). Hematospermia was alleviated or disappeared in 116 (80.56%) patients by less than half a year after surgery. Common intraoperative manifestations were hemorrhage, stones, utricle polyps and cysts. The surgical approach in our study were categorized into four types, including 24 (16.7%), 73 (50.7%), 42 (29.2%), and 5 (3.5%) cases in Type A (natural opening of the ejaculatory duct), B (trans-duct fenestration), C (trans-utricle fenestration), and D (not founded), respectively. Sexual function change was recorded in 12 patients of 111 patients, all by the method of trans-utricle fenestration, including 8 (7.21%), 3 (2.70%), and 1 (0.90%) patients in shorter intravaginal ejaculatory latency time, worse erection hardness and loss of orgasm, respectively. Conclusion Transurethral seminal vesiculoscopy is an effective and safe procedure for the management of hematospermia. The anatomy of the distal seminal tract should be understood more deeply and Wu’method (uncover-curtain method) needs to be promoted to verify its universality and safety. Besides, the complications of the function dysfunction should be discussed in the future in multi-center clinical trials.

BackgroundAs the survival rates of patients with renal cell carcinoma (RCC) continue to increase, noncancer causes of death cannot be ignored. The cause-specific mortality in patients with RCC is not well understood.ObjectiveOur study aimed to explore the mortality patterns of contemporary RCC survivors.MethodsWe performed a retrospective cohort study involving patients with RCC from the Surveillance, Epidemiology, and End Results (SEER) database. We used standardized mortality ratios (SMRs) to compare the death rates in patients with RCC with those in the general population.ResultsA total of 106,118 patients with RCC, including 39,630 who died (27%), were included in our study. Overall, compared with the general US population, noncancer SMRs were increased 1.25-fold (95% confidence intervals [CI], 1.22 to 1.27; observed, 11,235), 1.19-fold (95% CI, 1.14 to 1.24; observed, 2,014), and 2.24-fold (95% CI, 2.11 to 2.38; observed, 1,110) for stage I/II, III, and IV RCC, respectively. The proportion of noncancer causes of death increased with the extension of survival time. A total of 4,273 men with stage I/II disease (23.13%) died of RCC; however, patients who died from other causes were 3.2 times more likely to die from RCC (n = 14,203 [76.87%]). Heart disease was the most common noncancer cause of death (n = 3,718 [20.12%]; SMR, 1.23; 95% CI, 1.19–1.27). In patients with stage III disease, 3,912 (25.98%) died from RCC, and 2,014 (13.37%) died from noncancer causes. Most patients (94.99%) with stage IV RCC died within 5 years of initial diagnosis. Although RCC was the leading cause of death (n = 12,310 [84.65%]), patients with stage IV RCC also had a higher risk of noncancer death than the general population (2.24; 95% CI, 2.11–2.38).ConclusionsNon-RCC death causes account for more than 3/4 of RCC survivors among patients with stage I/II disease. Patients with stage IV are most likely to die of RCC; however, there is an increased risk of dying from septicemia, and suicide cannot be ignored. These data provide the latest and most comprehensive assessment of the causes of death in patients with RCC.

Autophagy has been shown to have a protective effect against brain damage. Ligustilide (LIG) is a bioactive substance isolated from Ligusticum chuanxiong, a traditional Chinese medicine. LIG has a neuroprotective effect; however, it is unclear whether this neuroprotective effect involves autophagy. In this study, PC12 cells were treated with 1 × 10–5–1 × 10–9 M LIG for 0, 3, 12 or 24 hours, and cell proliferation was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. Treatment with 1 × 10–6 M LIG for 3 hours had the greatest effect on cell proliferation, and was therefore used for subsequent experiments. PC12 cells were pre-treated with 1 × 10–6 M LIG for 3 hours, cultured in 95% N2/5% CO2 in Dulbecco’s modified Eagle’s medium without glucose or serum for 4 hours, and then cultured normally for 16 hours, to simulate oxygen-glucose deprivation/reoxygenation (OGD/R). Cell proliferation was assessed with the MTS assay. Apoptosis was detected by flow cytometry. The expression levels of apoptosis-related proteins, Bcl-2 and Bax, autophagy-related proteins, Beclin 1 and microtubule-associated protein l light chain 3B (LC3-II), and liver kinase B1 (LKB1)-5′-adenosine monophosphate-activated protein kinase (AMPK)-mammalian target of rapamycin (mTOR) signaling pathway-related proteins were assessed by western blot assay. Immunofluorescence staining was used to detect LC3-II expression. Autophagosome formation was observed by electron microscopy. LIG significantly decreased apoptosis, increased Bcl-2, Beclin 1 and LC3-II expression, decreased Bax expression, increased LC3-II immunoreactivity and the number of autophagosomes, and activated the LKB1-AMPK-mTOR signaling pathway in PC12 cells exposed to OGD/R. The addition of the autophagy inhibitor 3-methyladenine or dorsomorphin before OGD/R attenuated the activation of the LKB1-AMPK-mTOR signaling pathway in cells treated with LIG. Taken together, our findings show that LIG promotes autophagy and protects PC12 cells from apoptosis induced by OGD/R via the LKB1-AMPK-mTOR signaling pathway.

Background and Aims: There is a lack of research on metastatic renal pelvis cell carcinoma in the current literature. In this study, we aimed to detect distant metastatic patterns in renal pelvis cell carcinoma, and illustrated the affection of different metastatic sites, surgery to primary site and chemotherapy on prognosis outcomes in patients with diverse conditions. Methods: We collected data between 2010 and 2015 from the Surveillance, Epidemiology and End Results database. Kaplan–Meier analysis with log-rank test was used for survival comparisons. Multivariate Cox regression model was employed to analyze the effect of distant metastatic sites on overall survival (OS) and cancer-specific survival (CSS). Results: A total of 424 patients were included in the analysis, the median follow-up time was 5 months (interquartile range (IQR): 2-12) and 391 deaths (92.2%) in all patients were recorded. Among them, 192 (45.3%), 153 (36.1%), 137 (32.3%) and 127 (30.0%) patients were diagnosed with lung, bone, liver and brain metastases, respectively, while only 12 (2.8%) patients had brain metastases. The bi-organ, tri-organ and tetra-organ metastatic pattern was found in 135 (31.8%), 32 (7.5%) and 11 (2.6%) patients, respectively. The multivariate Cox analyses showed that distant lymph nodes (DL) metastases was not an independent prognostic factor for both OS and CSS (OS: Hazard ratios (HR) = 1.1, 95% CI = 0.8-1.4, P = 0.622; CSS: HR = 1.0, 95% CI = 0.8-1.3, P = 0.906). Besides, there was no significant difference of survival in patients with T3-T4 stage (OS: HR = 0.8, 95% CI = 0.5–1.2, P = 0.296; CSS: HR = 0.8, 95% CI = 0.5–1.2, P = 0.224), N2-3 stage (OS: HR = 0.8, 95% CI = 0.5–1.3, P = 0.351; CSS: HR = 0.7, 95% CI = 0.4–1.2, P = 0.259) and multi-organ metastases (OS: HR = 0.8, 95% CI = 0.5–1.3, P = 0.359; CSS: HR = 0.7, 95% CI = 0.4–1.2, P = 0.179) between surgery to primary site group and no-surgery to primary site group. Conclusion: we described the metastatic patterns of mRPCC and the prognosis outcomes of DL metastases, surgery to primary site and chemotherapy. Our findings provide more information for clinical therapeutic intervention and translational study designs.

Long non-coding RNAs (lncRNAs) have been shown to be involved in the regulation of skeletal muscle development through multiple mechanisms. The present study revealed that the lncRNA SOX6 AU (SRY-box transcription factor 6 antisense upstream) is reverse transcribed from upstream of the bovine sex-determining region Y (SRY)-related high-mobility-group box 6 (SOX6) gene. SOX6 AU was significantly differentially expressed in muscle tissue among different developmental stages in Xianan cattle. Subsequently, knockdown and overexpression experiments discovered that SOX6 AU promoted primary skeletal muscle cells proliferation, apoptosis, and differentiation in bovine. The overexpression of SOX6 AU in bovine primary skeletal muscle cells resulted in 483 differentially expressed genes (DEGs), including 224 upregulated DEGs and 259 downregulated DEGs. GO functional annotation analysis showed that muscle development-related biological processes such as muscle structure development and muscle cell proliferation were significantly enriched. KEGG pathway analysis revealed that the PI3K/AKT and MAPK signaling pathways were important pathways for DEG enrichment. Notably, we found that SOX6 AU inhibited the mRNA and protein expression levels of the SOX6 gene. Moreover, knockdown of the SOX6 gene promoted the proliferation and apoptosis of bovine primary skeletal muscle cells. Finally, we showed that SOX6 AU promoted the proliferation and apoptosis of bovine primary skeletal muscle cells by cis-modulation of SOX6 in cattle. This work illustrates our discovery of the molecular mechanisms underlying the regulation of SOX6 AU in the development of beef.

We aimed to develop a pharmacokinetic (PK) and pharmacodynamic (PD) model from healthy Chinese subjects and real-world non-valvular atrial fibrillation (NVAF) patients. We also investigated meaningful intrinsic and extrinsic factors and related biomarkers for bleeding events. We characterized the integrated PK/PD models based on rich PK/PD data [dabigatran concentration, activated partial thromboplastin time (APTT), prothrombin time (PT), and anti-factor IIa (anti-FIIa) activity] from 118 healthy volunteers and sparse PD data [APTT, PT, and anti-FIIa] from 167 patients with NVAF after verifying the model extrapolation performance. We also documented the correlations between PD biomarkers and clinically relevant bleeding events over one year. Next, we used the final integrated PK/PD model (a two-compartment, linear model with first-order absorption) to evaluate the influence of dosage and individual covariates on PD parameters. The age, high-density liptein cholesterol (HDL-C), and creatinine clearance (CrCL) improved the PK model fit. The linear direct-effects PD model described the correlation between APTT, PT, and anti-FIIa and plasma concentration. CrCL improved the PD model fit. Anti-FIIa was more sensitive to the increase in dabigatran exposure than APTT and PT in the PD model. Therefore, fixed dabigatran doses could be prescribed for patients with NVAF without adjusting for age and HDL-C. We observed an elevated bleeding tendency with higher peak and trough values of APTT, PT, and anti-FIIa. Randomized studies should be performed to evaluate the efficacy and safety of low-dose dabigatran in Chinese patients with NVAF.

To address the problems of grid connection and power dispatching caused by non-stationary wind power output, an improved Jellyfish Search algorithm optimization support vector regression (IJS-SVR) model was proposed in this study to achieve high-precision wind power prediction. The random selection of internal parameters of SVR model will affect its performance. In this study, the Jellyfish Search (JS) algorithm was selected and improved to propose an Improved Jellyfish Search (IJS) algorithm. Compared with the comparative algorithms, the optimized values of IJS algorithm are closer to 0. It exhibits good convergence ability, search stability, and optimization-seeking ability, as well as being more suitable for solving optimization problems. Therefore, IJS was used to optimize SVR, and the prediction model of IJS-SVR was established. Different weather and seasons affect wind power and model prediction accuracy. The wind power in spring and winter was selected for model prediction verification in this study. Compared with other methods, the IJS-SVR model proposed in this study could achieve better prediction results than other models in both seasons, and its prediction performance was better, which could improve the prediction accuracy of wind power. This study provides a more economical and effective method of wind power to solve its uncertainties and can be used as a reference for grid power generation planning and power system economic dispatch.

Cotton Verticillium wilt is a serious soil-borne disease that leads to significant losses in fiber yield and quality worldwide. Currently, the most effective way to increase Verticillium wilt resistance is to develop new resistant cotton varieties. Lines 5026 and 60182 are two Verticillium wilt-resistant upland cotton accessions. We previously identified a total of 25 quantitative trait loci (QTLs) related to Verticillium wilt resistance from 5026 and 60182 by assembling segregating populations from hybridization with susceptible parents. In the current study, using 13 microsatellite markers flanking QTLs related to Verticillium wilt resistance, we developed 155 cotton inbred lines by pyramiding different QTLs related to Verticillium wilt resistance from a filial generation produced by crossing 5026 and 60182. By examining each allele's effect and performing multiple comparison analysis, we detected four elite QTLs/alleles (q-5/NAU905-2, q-6/NAU2754-2, q-8/NAU3053-1 and q-13/NAU6598-1) significant for Verticillium wilt resistance, pyramiding these elite alleles increased the disease resistance of inbred lines. Furthermore, we selected 34 elite inbred lines, including five lines simultaneously performing elite fiber quality, high yield and resistance to V. dahliae, 14 lines with elite fiber quality and disease resistance, three lines with high yield and disease resistance, and 12 lines with resistance to V. dahliae. No correlation between Verticillium wilt resistance and fiber quality traits/yield and its components was detected in the 155 developed inbred lines. Our results provide candidate markers for disease resistance for use in marker-assisted breeding (MAS), as well as elite germplasms for improving important agronomic traits via modern cotton breeding.

The influence of nitrogen (N) limitation on the cell growth, chlorophyll content, intracellular lipid production and expression levels of two pathway genes in Chlorella sorokiniana was investigated in mixotrophic culture in this study. The maximum biomass concentration of C. sorokinianacultured in modified BG11 medium containing 3, 6, 9, 12 and 15 mM N were 1.60, 2.21, 2.74, 3.18 and 3.21 g/L of dry cell weight, respectively with maximum specific growth rate of 0.180, 0.198, 0.201, 0.203, 0.206 day−1 during culture with an initial N feed of 3, 6, 9, 12 and 15 mM in the first eight days, respectively. The maximum lipid content was 51 % with 3 mM N. However, the maximum lipid productivity of 0.00884 g L−1 day−1 was achieved with 6 mM N. Expression levels of accD (heteromeric acetyl-CoA carboxylase beta subunit) and accI (homomeric acetyl-CoA carboxylase) genes in C. sorokiniana were studied by real-time PCR. Increased expression levels of accD reflected the increased lipid content in stationary phase. In contrast, expression of the acc1 gene always remained low, showing that the gene might not be critical for lipid accumulation.

Aim: To investigate the effect of the ''minimizing tacrolimus'' strategy on long-term survival of patients after liver transplantation (LT)., Methods: We conducted a retrospective study of 319 patients who received LT between January 2009 and December 2011 at the First Affiliated Hospital of Zhejiang University School of Medicine. Following elimination of ineligible patients, 235 patients were included in the study. The relationship between early tacrolimus (TAC) exposure and survival period was analyzed by Kaplan Meier curves. Adverse effects related to TAC were evaluated by the χ(2) test. Routine monitoring of blood TAC concentration (TC) was performed using the PRO-Trac(TM) II Tacrolimus Elisa Kit (Diasorin, United States)., Results: Of 235 subjects enrolled in the study, 124 (52.8%) experienced adverse effects due to TAC. When evaluating mean TC, the survival time of patients with a mean TC < 5 ng/mL was significantly shorter than that in the other groups (911.3 ± 131.6 d vs 1381.1 ± 66.1 d, 911.3 ± 131.6 d vs 1327.3 ± 47.8 d, 911.3 ± 131.6 d vs 1343.2 ± 83.1 d, P < 0.05), while the survival times of patients with a mean TC of 5-7, 7-10 and 10-15 ng/mL were comparable. Adverse effects due to TAC in all four groups were not significantly different. When comparing the standard deviation (SD) of TC among the groups, the survival time of patients with a SD of 2-4 was significantly longer than that in the other groups (1388.8 ± 45.4 d vs 1029.6 ± 131.3 d, 1388.8 ± 45.4 d vs 1274.9 ± 57.0 d, P < 0.05), while in patients with a SD < 2 and SD > 4, the survival time was not statistically different. Adverse effects experienced in all three groups were not statistically different. In Cox regression analysis, male patients and those with a primary diagnosis of benign disease, mean TC > 5 ng/mL and TC SD 2-4 had better outcomes., Conclusion: The early ''minimizing tacrolimus'' strategy with a mean TC of 5-10 ng/mL and SD of 2-4 was beneficial in terms of long-term survival after LT.