Study on the acute and subchronic oral toxicity of Calculus Bovis Sativus in rats.

This study aims to assess the acute and subchronic toxicity of Calculus Bovis Sativus (CBS), which is an ideal substitute for natural Calculus Bovis. After conducting a test of acute toxicity with KM mice of both sexes, it was determined that oral CBS had a lethal dosage (LD50) of greater than 9.26 g/kg BW. For ninety days, Wistar rats were fed on CBS orally at dosages of 0, 167, 501, and 1503 mg/kg BW/day, respectively, as part of the subchronic investigation. A comparison of the controls with the 1503 mg/kg and 501 mg/kg dosage groups revealed significant differences in the hematological and serum biochemical parameters, such as RBC, HGB, MONO%, PLT, LYMPH% and GLU, TP, ALB, and Ca2+, were observed. However, values of the above parameters fell within our laboratory's normal range. In terms of body weight, food intake, urinalysis, clinical chemistry, and pathology, no other adverse effects were observed. After 90 days of exposure, the no observed adverse effect level (NOAEL) of CBS in rats was determined to be 1503 mg/kg BW/day.

UPCARE: Urinary Extracellular Vesicles-Derived Prostate Cancer Assessment for Risk Evaluation.

In the quest for efficient tumor diagnosis via liquid biopsy, extracellular vesicles (EVs) have shown promise as a source of potential biomarkers. This study addresses the gap in biomarker efficacy for predicting clinically significant prostate cancer (csPCa) between the Western and Chinese populations. We developed a urinary extracellular vesicles-based prostate score (EPS) model, utilizing the EXODUS technique for EV isolation from 598 patients and incorporating gene expressions of FOXA1, PCA3, and KLK3. Our findings reveal that the EPS model surpasses prostate-specific antigen (PSA) testing in diagnostic accuracy within a training cohort of 234 patients, achieving an area under the curve (AUC) of 0.730 compared to 0.659 for PSA (p = 0.018). Similarly, in a validation cohort of 101 men, the EPS model achieved an AUC of 0.749, which was significantly better than PSA's 0.577 (p < 0.001). Our model has demonstrated a potential reduction in unnecessary prostate biopsies by 26%, with only a 3% miss rate for csPCa cases, indicating its effectiveness in the Chinese population.

Spatial multiomics reveals a subpopulation of fibroblasts associated with cancer stemness in human hepatocellular carcinoma.

BACKGROUND: Cancer-associated fibroblasts (CAFs) are the prominent cell type in the tumor microenvironment (TME), and CAF subsets have been identified in various tumors. However, how CAFs spatially coordinate other cell populations within the liver TME to promote cancer progression remains unclear. METHODS: We combined multi-region proteomics (6 patients, 24 samples), 10X Genomics Visium spatial transcriptomics (11 patients, 25 samples), and multiplexed imaging (92 patients, 264 samples) technologies to decipher the expression heterogeneity, functional diversity, spatial distribution, colocalization, and interaction of fibroblasts. The newly identified CAF subpopulation was validated by cells isolated from 5 liver cancer patients and in vitro functional assays. RESULTS: We identified a liver CAF subpopulation, marked by the expression of COL1A2, COL4A1, COL4A2, CTGF, and FSTL1, and named F5-CAF. F5-CAF is preferentially located within and around tumor nests and colocalizes with cancer cells with higher stemness in hepatocellular carcinoma (HCC). Multiplexed staining of 92 patients and the bulk transcriptome of 371 patients demonstrated that the abundance of F5-CAFs in HCC was associated with a worse prognosis. Further in vitro experiments showed that F5-CAFs isolated from liver cancer patients can promote the proliferation and stemness of HCC cells. CONCLUSIONS: We identified a CAF subpopulation F5-CAF in liver cancer, which is associated with cancer stemness and unfavorable prognosis. Our results provide potential mechanisms by which the CAF subset in the TME promotes the development of liver cancer by supporting the survival of cancer stem cells.

Protocol for Evaluating the Efficacy and Safety of Radiotherapy for Prostate and Oligometastatic Lesions in Patients With Low-Burden Sensitive Oligometastatic Prostate Cancer: An Open, Exploratory Pilot Clinical Trial.

INTRODUCTION: The existing large prospective study demonstrates the benefits of primary radiotherapy in patients with low-volume oligometastatic prostate cancer (OMPC), and there is additional evidence of the benefits of local metastasis-directed therapy (MDT) for metastatic lesions. However, there are no results from a prospective study to demonstrate the efficacy of radiotherapy for prostate and oligometastases. Therefore, the aim of the protocol is to illustrate the efficacy of radiotherapy for prostate and oligometastatic lesions in patients with low-volume de novo hormone-sensitive OMPC. METHODS AND ANALYSIS: This study involves a prospective, single-center, limited-sample, single-arm exploration of radiotherapy for prostate and oligometastatic lesions in patients diagnosed with low-volume hormone-sensitive OMPC. Eligible participants undergo thorough assessments and treatment involving endocrine therapy alongside radiation targeting metastatic lesions and the pelvic region. The primary site is treated with volumetric modulated arc therapy (VMAT), while metastatic sites are treated with either VMAT or stereotactic body radiation therapy (SBRT) depending on their location. All patients received radiation therapy for both the primary and metastatic lesions combined with endocrine therapy. Endocrine therapy with an antiandrogen (bicalutamide, for 4 weeks) androgen deprivation therapy combined with novel hormonal agents (acetate abiraterone) will be continued for 2 years. The primary objective is to evaluate progression-free survival-2 (PFS-2), while secondary endpoints include androgen deprivation therapy (ADT)-free survival, quality of life (QoL), overall survival, time to castration-resistant prostate cancer (CRPC), radiation-related complications, and endocrine therapy-related adverse events. ETHICS AND DISSEMINATION: Approval was obtained from the ethics committee of the First Affiliated Hospital of Naval Medical University (CHEC2023-220). This is a single-arm exploration pilot trial evaluating radiotherapy for prostate and oligometastatic lesions in patients with OMPC. It aims to disseminate its findings through peer-reviewed journals and relevant medical conferences, with the intention of publication and presentation at these events. TRIAL REGISTRATION NUMBERS: Clinicaltrials.gov identifier NCT06198387.

Proteomic landscape profiling of primary prostate cancer reveals a 16-protein panel for prognosis prediction.

Prostate cancer (PCa) is the most common malignant tumor in men. Currently, there are few prognosis indicators for predicting PCa outcomes and guiding treatments. Here, we perform comprehensive proteomic profiling of 918 tissue specimens from 306 Chinese patients with PCa using data-independent acquisition mass spectrometry (DIA-MS). We identify over 10,000 proteins and define three molecular subtypes of PCa with significant clinical and proteomic differences. We develop a 16-protein panel that effectively predicts biochemical recurrence (BCR) for patients with PCa, which is validated in six published datasets and one additional 99-biopsy-sample cohort by targeted proteomics. Interestingly, this 16-protein panel effectively predicts BCR across different International Society of Urological Pathology (ISUP) grades and pathological stages and outperforms the D'Amico risk classification system in BCR prediction. Furthermore, double knockout of NUDT5 and SEPTIN8, two components from the 16-protein panel, significantly suppresses the PCa cells to proliferate, invade, and migrate, suggesting the combination of NUDT5 and SEPTIN8 may provide new approaches for PCa treatment.

Soy Protein Isolate Gel Subjected to Freezing Treatment: Influence of Methylcellulose and Sodium Hexametaphosphate on Gel Stability, Texture and Structure.

Freezing affects texture and induces the loss of gel quality. This study investigated the effects of methylcellulose (MC) (0.2%, 0.4%, 0.6%) and sodium hexametaphosphate (SHMP) (0.15%, 0.3%) on the gel textural and structural properties of SPI gels before and after freezing, and explores the synergistic enhancement of gel texture and the underlying mechanisms resulting from the simultaneous addition of SHMP and MC to SPI gels. It was revealed that MC improved the strength of SPI gels through its thickening properties, but it could not inhibit the reduction of SPI gels after freezing. The 0.4% MC-SPI gel exhibited the best gel strength (193.2 ± 2.4 g). SHMP inhibited gel reduction during freezing through hydrogen bonding and ionic interactions; it enhanced the freezing stability of SPI gels. The addition of 0.15% SHMP made the water-holding capacity in SPI gels reach the highest score after freezing (58.2 ± 0.32%). The synergistic effect of MC and SHMP could improve the strength and the freezing stability of SPI gels. MC facilitated the release of ionizable groups within SPI, causing negatively charged SHMP groups to aggregate on the SPI and inhibit the freezing aggregation of proteins. These results provide a strong basis for the improvement of cryogenic soy protein gel performance by SHMP and MC.

Integrated bioinformatics investigation of adenylyl cyclase family co-expression network in bladder cancer followed by preliminary validation of member 2 (ADCY2) in tumorigenesis and prognosis.

Background: The adenylyl cyclase (ADCY) gene family encodes enzymes responsible for the synthesis of cyclic adenosine monophosphate (cAMP) from adenosine triphosphate (ATP), which comprises nine transmembrane isoforms (ADCYs 1-9). Although ADCYs correlate with intracellular signalling and tumorigenesis in different malignancies, their roles in bladder cancer remain unclear. Methods: Utilizing the bladder urothelial carcinoma (BLCA) dataset from The Cancer Genome Atlas (TCGA), we employed the R package 'limma' to identify differential genes. Subsequent correlation analysis with corresponding clinical data was conducted. Prognostic significance of ADCY family genes was assessed through survival analysis. Univariate and multivariate Cox regression determined ADCY2 as a potential independent risk factor for BLCA. Validation was performed using immunohistochemistry results from independent cohorts. Additionally, we delved into the mechanism of genetic variations, methylation modifications, and signalling pathways of ADCY family genes. Evaluation of their role in the immune microenvironment was achieved through R packages single-sample gene set enrichment analysis (ssGSEA), CIBERPORT, and ESTIMATE. Results: Cases of bladder cancer were retrieved from TCGA, and the transcriptionally differentially expressed members of ADCY were identified (members 2, 4, and 5). Genomic alteration, epigenomic modification, clinicopathological characteristics and clinical survival were systematically investigated. A co-expression network was established based on the intersection of correlated genes, which was centred around ADCY2, ADCY4, and ADCY5. Enrichment analysis revealed that correlated genes were involved in epithelial-mesenchymal transition (EMT). The ADCY2 was selected as the most representative biomarker for prognosis in bladder cancer. Bladder tumour with higher ADCY2 expression had higher prognostic risk and worse survival outcomes. Moreover, ADCY2 was correlated with classic immune checkpoints, and a better responsiveness to immunotherapy was exhibited in high-expression subsets. To ameliorate universality of the conclusion, our study also included several real-world cohorts into the preliminary validation, using datasets from the Gene Expression Omnibus (GEO; GSE13507), tissue microarray (TMA) with 80 bladder cancer inclusion and clinical trial IMvigor210, which were associated with immunotherapy sensitivity, prognosis, and common biomarker presentation. Conclusions: Our study reveals that ADCY family has prognostic value in patients with bladder cancer; the ADCY2 is a prominent prognostic biomarker. The bioinformatics analyses and validation provide direction for further functional and mechanistic studies on the screened members of ADCY family.

Novel embedding model predicting the credit card's default using neural network optimized by harmony search algorithm and vortex search algorithm.

In today's banking and financial system, using a credit card has become indispensable. The credit card industry has existed due to a shift in consumer preferences and a rise in national economic growth. The number of issuing banks, card issuers, and transaction volumes has increased significantly. Nevertheless, owing to the growth in the number of transactions made with credit cards, both the total amount due and the rate of defaults on credit card loans have become issues that cannot be neglected. This issue must be resolved to ensure the continued and prosperous growth of the banking industry in the years to come. Currently, a few optimization algorithms-Whale optimization algorithm (WOA), Harmony Search (HS), Multi-verse optimization (MVO), and Vortex Search (VS)-have been used to achieve this purpose. However, because credit card default data is volatile and unequal, it is challenging for typical optimization algorithms to offer steady approaches with optimal performance. Studies have indicated that optimizing algorithms with suitable properties can significantly improve performance. To improve performance, some tuning was applied to the ANN. This study will assess twenty-three parameters, and the efficacy of all four approaches will be compared using ROC and AUC evaluations. The suggested model's performance is contrasted with a scenario where the classifiers were trained using original data. In contrast, the AUC values for VS-MLP were 0.7407 and 0.7271, while those for HS-MLP were 0.7074 and 0.6997. In the training and testing phases, AUC values of 0.7469 and 0.7329 from MVO-MLP and 0.72 and 0.7185 from WOA-MLP, respectively. The results show that the training accuracy of HS, VSA, MVO, and WOA are similar; MVO has the highest training accuracy. The credit card industry can benefit significantly from this methodology, which may help resolve default probabilities.

Comparison of Remimazolam and Propofol on Postoperative Delirium in Elderly Patients Undergoing Radical Resection of Colon Cancer: A Single-Center Prospective Randomized Controlled Study.

BACKGROUND We compared the effect of remimazolam and propofol intravenous anesthesia on postoperative delirium in elderly patients undergoing laparoscopic radical resection of colon cancer. MATERIAL AND METHODS One hundred patients undergoing elective radical operation of colon cancer under general anesthesia were divided into a remimazolam group (group R) and propofol group (group P) by a random number table method. During anesthesia induction and maintenance, group R was intravenously injected with remimazolam to exert sedation; however, in group P, propofol was injected instead of remimazolam. The occurrence of postoperative delirium was assessed with the Confusion Assessment Method for the Intensive Care Unit scale and postoperative pain was assessed with the visual analogue score (VAS). The primary outcome measures were the incidence and duration of delirium within 7 days following surgery. Secondary outcome measures included postoperative VAS scores, intraoperative anesthetic drug dosage, and adverse reactions, including nausea and vomiting, hypoxemia, and respiratory depression. RESULTS There was no significant difference in baseline data between the 2 groups (P>0.05). There was no statistically significant difference in the incidence and duration of postoperative delirium between the 2 groups (P>0.05). There were no significant differences in VAS scores, remifentanil consumption, and adverse reactions, including nausea and vomiting, hypoxemia, and respiratory depression between the 2 groups (P>0.05). CONCLUSIONS In elderly patients undergoing radical colon cancer surgery, remimazolam administration did not improve or aggravate the incidence and duration of delirium, compared with propofol.

Stability and integrity of self-assembled bovine parvovirus virus­like particles (BPV­VLPs) of VP2 and combination of VP1VP2 assisted by baculovirus-insect cell expression: a potential logistical platform for vaccine deployment.

BACKGROUND: Bovine parvovirus (BPV) is an autonomous DNA virus with a smaller molecular size and subtle differences in its structural proteins, unlike other animal parvoviruses. More importantly, this virus has the potential to produce visible to silent economic catastrophes in the livestock business, despite receiving very little attention. Parvoviral virus-like particles (VLPs) as vaccines and as logistical platforms for vaccine deployment are well studied. However, no single experimental report on the role of VP1 in the assembly and stability of BPV-VLPs is available. Furthermore, the self-assembly, integrity and stability of the VLPs of recombinant BPV VP2 in comparison to VP1 VP2 Cap proteins using any expression method has not been studied previously. In this study, we experimentally evaluated the self-assembling ability with which BPV virus-like particles (VLPs) could be synthesized from a single structural protein (VP2) and by integrating both VP2 and VP1 amino acid sequences. METHODS: In silico and experimental cloning methods were carried out. His-tagged and without-His-tag VP2 and V1VP2-encoding amino acid sequences were cloned and inserted into pFastbacdual, and insect cell-generated recombinant protein was evaluated by SDS‒PAGE and western blot. Period of infectivity and expression level were determined by IFA. The integrity and stability of the BPV VLPs were evaluated by transmission electron microscopy. The secondary structure of the BPV VLPs from both VP2 and V1VP2 was analyzed by circular dichroism. RESULTS: Our findings show that VP2 alone was equally expressed and purified into detectable proteins, and the stability at different temperatures and pH values was not appreciably different between the two kinds of VLPs. Furthermore, BPV-VP2 VLPs were praised for their greater purity and integrity than BPV-VP1VP2 VLPs, as indicated by SDS‒PAGE. Therefore, our research demonstrates that the function of VP1 has no bearing on the stability or integrity of BPV-VLPs. CONCLUSIONS: In summary, incredible physiochemically stable BPV VP2-derived VLPs have been found to be promising candidates for the development of multivalent vaccines and immunodiagnostic kits against enteric viruses and to carry heterogeneous epitopes for various economically important livestock diseases.

A positive feedback inhibition of isocitrate dehydrogenase 3ß on paired-box gene 6 promotes Alzheimer-like pathology.

Impaired brain glucose metabolism is an early indicator of Alzheimer's disease (AD); however, the fundamental mechanism is unknown. In this study, we found a substantial decline in isocitrate dehydrogenase 3ß (IDH3ß) levels, a critical tricarboxylic acid cycle enzyme, in AD patients and AD-transgenic mice's brains. Further investigations demonstrated that the knockdown of IDH3ß induced oxidation-phosphorylation uncoupling, leading to reduced energy metabolism and lactate accumulation. The resulting increased lactate, a source of lactyl, was found to promote histone lactylation, thereby enhancing the expression of paired-box gene 6 (PAX6). As an inhibitory transcription factor of IDH3ß, the elevated PAX6 in turn inhibited the expression of IDH3ß, leading to tau hyperphosphorylation, synapse impairment, and learning and memory deficits resembling those seen in AD. In AD-transgenic mice, upregulating IDH3ß and downregulating PAX6 were found to improve cognitive functioning and reverse AD-like pathologies. Collectively, our data suggest that impaired oxidative phosphorylation accelerates AD progression via a positive feedback inhibition loop of IDH3ß-lactate-PAX6-IDH3ß. Breaking this loop by upregulating IDH3ß or downregulating PAX6 attenuates AD neurodegeneration and cognitive impairments.

Lumpy skin disease virus ORF127 protein suppresses type I interferon responses by inhibiting K63-linked ubiquitination of tank binding kinase 1.

Lumpy skin disease (LSD) is a severe animal infectious disease caused by lumpy skin disease virus (LSDV), inducing extensive nodules on the cattle mucosa or the scarfskin. LSDV genome encodes multiple proteins to evade host innate immune response. However, the underlying molecular mechanisms are poorly understood. In this study, we found that LSDV could suppress the expression of IFN-ß and interferon-stimulated genes (ISGs) in MDBK cells during the early stage of infection. Subsequently, an unbiased screen was performed to screen the LSDV genes with inhibitory effects on the type I interferon (IFN-I) production. ORF127 protein was identified as one of the strongest inhibitory effectors on the expression of IFN-ß and ISGs, meanwhile, the 1-43 aa of N-terminal of ORF127 played a vital role in suppressing the expression of IFN-ß. Overexpression of ORF127 could significantly promote LSDV replication through inhibiting the production of IFN-ß and ISGs in MDBK cells. Mechanism study showed that ORF127 specifically interacted with TBK1 and decreased the K63-linked polyubiquitination of TBK1 which suppressed the phosphorylation of TBK1 and ultimately decreased the production of IFN-ß. In addition, truncation mutation analysis indicated that the 1-43 aa of N-terminal of ORF127 protein was the key structural domain for its interaction with TBK1. In short, these results validated that ORF127 played a negative role in regulating IFN-ß expression through cGAS-STING signaling pathway. Taken together, this study clarified the molecular mechanism of ORF127 gene antagonizing IFN-I-mediated antiviral, which will helpfully provide new strategies for the treatment and prevention of LSD.

Acute and subchronic oral toxicity study of Camelina sativa oil in Wistar rats.

Objective: The aim of these studies was to ascertain if Camelina sativa oil is harmful in both the acute and subchronic states. Methods: Wistar rats of both sexes were used in an acute toxicity test, and the fatal dosage (LD50) of oral Camelina sativa oil was greater than 27.6 g/kg bw. Rats were gavaged with Camelina sativa oil at dosages of 0.00, 0.92, 1.84, and 3.68 g/kg bw per day for 90 days. In addition, satellite groups were established in the control and high-dose groups for a 28-day recovery period. The following factors were assessed: mortality, clinical anomalies, body weight, food intake, hematological, serum biochemistry, urine, gross necropsy, and histology. Results: There were no observable toxicity-related changes in any of the three dosage groups. There is no toxicological relevance to the change in the high-dose hematological indicator PLT at the conclusion of the recovery period because it was within the usual range for this strain in our laboratory. The test material did not result in any pathological alterations, according to a pathological examination. Conclusion: Since the results of the current study, the no-observed-adverse-effect-level (NOAEL) for Camelina sativa oil in rats has been determined to be greater than 3.68 g/kg bw.

Histone deacetylase 6's function in viral infection, innate immunity, and disease: latest advances.

In the family of histone-deacetylases, histone deacetylase 6 (HDAC6) stands out. The cytoplasmic class IIb histone deacetylase (HDAC) family is essential for many cellular functions. It plays a crucial and debatable regulatory role in innate antiviral immunity. This review summarises the current state of our understanding of HDAC6's structure and function in light of the three mechanisms by which it controls DNA and RNA virus infection: cytoskeleton regulation, host innate immune response, and autophagy degradation of host or viral proteins. In addition, we summed up how HDAC6 inhibitors are used to treat a wide range of diseases, and how its upstream signaling plays a role in the antiviral mechanism. Together, the findings of this review highlight HDAC6's importance as a new therapeutic target in antiviral immunity, innate immune response, and some diseases, all of which offer promising new avenues for the development of drugs targeting the immune response.

How education level affects postoperative rehabilitation and follow-up: a single-center experience.

BACKGROUND: Radical prostatectomy remains the fundamental treatment for prostate cancer, and improving patients' compliance with postoperative follow-ups is essential for improving patients' quality of life. This study investigates the effect of education levels on patients' recovery and follow-up after radical prostatectomy. METHODS: Data from 1,112 patients undergoing radical prostatectomy between 2011 and 2020 were collected using medical records, and "pc-follow" systems were used to collect patients' baseline information, education level, pathological information, number of outpatient visits, the time interval between each visit, and PSA test data. RESULTS: Regarding postoperative outpatient data, there was no difference in the number of outpatient visits among the different education level groups in Shanghai (P = 0.063). A significant difference was found in the interval between outpatient visits among the groups (P < 0.001). Furthermore, significant differences were detected in the number and duration of outpatient clinic visits among the education level groups in all patients (P = 0.016, P = 0.0027). By contrast, no significant difference was found in the recovery time of urinary continence between all patients and those in Shanghai, grouped according to education level (P = 0.082, P = 0.68). For all patients and patients in the Shanghai area, the number of PSA follow-ups increased gradually with an increasing level of education (P < 0.001, P = 0.0029). CONCLUSIONS: Education level affected the number of postoperative clinic visits, compliance, and the number of PSA tests. However, no significant effect on the recovery of urinary continence was found. Further, clinicians must increase their focus on patients with low education levels to achieve equitable access to health services for all patients.

Foot-and-mouth disease virus structural protein VP3 interacts with HDAC8 and promotes its autophagic degradation to facilitate viral replication.

Macroautophagy/autophagy has been utilized by many viruses, including foot-and-mouth disease virus (FMDV), to facilitate replication, while the underlying mechanism of the interplay between autophagy and innate immune responses is still elusive. This study showed that HDAC8 (histone deacetylase 8) inhibits FMDV replication by regulating innate immune signal transduction and antiviral response. To counteract the HDAC8 effect, FMDV utilizes autophagy to promote HDAC8 degradation. Further data showed that FMDV structural protein VP3 promotes autophagy during virus infection and interacts with and degrades HDAC8 in an AKT-MTOR-ATG5-dependent autophagy pathway. Our data demonstrated that FMDV evolved a strategy to counteract host antiviral activity by autophagic degradation of a protein that regulates innate immune response during virus infection.Abbreviations: 3-MA: 3-methyladenine; ATG: autophagy related; Baf-A1: bafilomycin A1; CCL5: C-C motif chemokine ligand 5; Co-IP: co-immunoprecipitation; CQ: chloroquine phosphate; DAPI: 4",6-diamidino-2-phenylindole; FMDV: foot-and-mouth disease virus; HDAC8: histone deacetylase 8; ISG: IFN-stimulated gene; IRF3: interferon regulatory factor 3; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MOI: multiplicity of infection; MAVS: mitochondria antiviral signaling protein; OAS: 2"-5'-oligoadenylate synthetase; RB1: RB transcriptional corepressor 1; SAHA: suberoylanilide hydroxamic acid; TBK1: TANK binding kinase 1; TCID50: 50% tissue culture infectious doses; TNF/TNF-α: tumor necrosis factor; TSA: trichostatin A; UTR: untranslated region.

Identification of novel molecular subtypes and a signature to predict prognosis and therapeutic response based on cuproptosis-related genes in prostate cancer.

Background: Prostate cancer (PCa) is the most common malignant tumor of the male urinary system. Cuproptosis, as a novel regulated cell death, remains unclear in PCa. This study aimed to investigate the role of cuproptosis-related genes (CRGs) in molecular stratification, prognostic prediction, and clinical decision-making in PCa. Methods: Cuproptosis-related molecular subtypes were identified by consensus clustering analysis. A prognostic signature was constructed with LASSO cox regression analyses with 10-fold cross-validation. It was further validated in the internal validation cohort and eight external validation cohorts. The tumor microenvironment between the two risk groups was compared using the ssGSEA and ESTIMATE algorithms. Finally, qRT-PCR was used to explore the expression and regulation of these model genes at the cellular level. Furthermore, 4D Label-Free LC-MS/MS and RNAseq were used to investigate the changes in CRGs at protein and RNA levels after the knockdown of the key model gene B4GALNT4. Results: Two cuproptosis-related molecular subtypes with significant differences in prognoses, clinical features, and the immune microenvironment were identified. Immunosuppressive microenvironments were associated with poor prognosis. A prognostic signature comprised of five genes (B4GALNT4, FAM83D, COL1A, CHRM3, and MYBPC1) was constructed. The performance and generalizability of the signature were validated in eight completely independent datasets from multiple centers. Patients in the high-risk group had a poorer prognosis, more immune cell infiltration, more active immune-related functions, higher expression of human leukocyte antigen and immune checkpoint molecules, and higher immune scores. In addition, anti-PDL-1 immunotherapy prediction, somatic mutation, chemotherapy response prediction, and potential drug prediction were also analyzed based on the risk signature. The validation of five model genes' expression and regulation in qPCR was consistent with the results of bioinformatics analysis. Transcriptomics and proteomics analyses revealed that the key model gene B4GALNT4 might regulate CRGs through protein modification after transcription. Conclusion: The cuproptosis-related molecular subtypes and the prognostic signature identified in this study could be used to predict the prognosis and contribute to the clinical decision-making of PCa. Furthermore, we identified a potential cuproptosis-related oncogene B4GALNT4 in PCa, which could be used as a target to treat PCa in combination with cuproptosis.

Sub-Bowman keratomileusis versus femtosecond laser in situ keratomileusis on the long-term visual recovery: A comparative study.

Purpose: To explore the long-term visual quality of the same subjects after sub-Bowman keratomileusis (SBK) or femtosecond laser in situ keratomileusis (FS-LASIK). Methods: This prospective study included patients screened for corneal refractive surgery at the Refractive Surgery Center of our Hospital between November 2017 and March 2018. One eye underwent SBK, while the other eye underwent FS-LASIK. Total higher-order aberrations, coma aberrations, and clover aberrations were evaluated before and at 1 month and 3 years after the procedure. The visual satisfaction of both eyes was investigated, respectively. The participants completed a surgical satisfaction questionnaire. Results: Thirty-three patients were included. There were no significant differences in total higher-order aberrations, coma aberrations, and clover aberrations between the two procedures before and 1 month and 3 years after surgery (all P > 0.05), except for the total coma aberrations in FS-LASIK were significantly higher compared with the SBK group at 1 month after surgery [0.51 (0.18, 0.93) vs. 0.77 (0.40, 1.22), P = 0.019]. The surgical satisfaction questionnaire scores of the SBK group and the FS-LASIK group were 9.8 ± 0.8 and 9.8 ± 0.8, respectively, at 1 month, and 9.7 ± 0.9 and 9.7 ± 1.0, respectively, at 3 years (all P > 0.05). Conclusion: There were no differences in corneal aberrations and satisfaction between SBK and FS-LASIK procedures at 1 month and 3 years.

Impact of Insoluble Dietary Fiber and CaCl2 on Structural Properties of Soybean Protein Isolate-Wheat Gluten Composite Gel.

The effect and mechanism of soybean insoluble dietary fiber (SIDF) (0~4%) and CaCl2 (0~0.005 M) on the properties of soybean protein isolate (SPI)-wheat gluten (WG) composite gel were studied. It was revealed that the addition of insoluble dietary fiber (1~2%) increased the strength and water-holding capacity (WHC) of the composite gel (p < 0.05) and enhanced the gel network structure compared with the control. WHC and LF-NMR showed that the water-binding ability of the gel system with only 2% SIDF was the strongest. The addition of excessive SIDF increased the distance between protein molecules, impeded the cross-linking of protein, and formed a three-dimensional network with low gel strength. The infrared spectrum and intermolecular force indicated that the interaction between SIDF and SPI were mainly physical, and the hydrophobic interaction and disulfide bond were the main forces in the gel system. The addition of CaCl2 can increase the critical content of gel texture destruction caused by SIDF, and the gel strength attained its peak at 3% SIDF, indicating that appropriate CaCl2 improved gel structure weakening caused by excessive SIDF. This study provides insights in enhancing the production of multi-component composite gel systems.