A genomic and epigenomic atlas of prostate cancer in Asian populations.

Prostate cancer is the second most common cancer in men worldwide1. Over the past decade, large-scale integrative genomics efforts have enhanced our understanding of this disease by characterizing its genetic and epigenetic landscape in thousands of patients2,3. However, most tumours profiled in these studies were obtained from patients from Western populations. Here we produced and analysed whole-genome, whole-transcriptome and DNA methylation data for 208 pairs of tumour tissue samples and matched healthy control tissue from Chinese patients with primary prostate cancer. Systematic comparison with published data from 2,554 prostate tumours revealed that the genomic alteration signatures in Chinese patients were markedly distinct from those of Western cohorts: specifically, 41% of tumours contained mutations in FOXA1 and 18% each had deletions in ZNF292 and CHD1. Alterations of the genome and epigenome were correlated and were predictive of disease phenotype and progression. Coding and noncoding mutations, as well as epimutations, converged on pathways that are important for prostate cancer, providing insights into this devastating disease. These discoveries underscore the importance of including population context in constructing comprehensive genomic maps for disease.

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.

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.

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.

Sustainable functional urethral reconstruction improves early urinary continence after robot-assisted radical prostatectomy: a randomised controlled trial.

OBJECTIVE: To evaluate the impact of sustainable functional urethral reconstruction (SFUR) on early recovery of urinary continence (UC) after robot-assisted radical prostatectomy. PATIENTS AND METHODS: Overall, 96 patients with primary prostate cancer were randomised into the SFUR or standard group (n = 48 each). The primary outcome was the 1-month UC recovery. Secondary outcomes included short-term (≤3 months) UC recovery, urinary function, micturition-related bother, perioperative complications, and oncological outcomes. Kaplan-Meier curves and Cox proportional hazard models were used to assess the 3-month UC recovery. Generalised estimating equations were used to compare postoperative urinary function and micturition-related bother. RESULTS: The 1-month UC recovery rates, median 24-h pad weights, and median operative time in the SFUR and standard groups were 73% and 49% (P = 0.017), 0 and 47 g (P = 0.001), and 125 and 103 min (P = 0.025), respectively. The UC recovery rates in the SFUR vs standard groups were 53% vs 23% at 1 week (P = 0.003), 53% vs 32% at 2 weeks (P = 0.038), and 93% vs 77% at 3 months (P = 0.025). The median time to UC recovery in the SFUR and standard groups was 5 and 34 days, respectively (log-rank P = 0.006); multivariable Cox regression supported this result (hazard ratio 1.73, 95% confidence interval 1.08-2.79, P = 0.024). Similar results were observed when UC was defined as 0 pads/day. Urinary function (P = 0.2) and micturition-related bother (P = 0.8) were similar at all follow-up intervals. The perioperative complication rates, positive surgical margin rates, and 1-year biochemical recurrence-free survival were comparable between both groups (all P > 0.05). CONCLUSION: SFUR resulted in earlier UC recovery without compromising postoperative urinary function. Long-term validation and multicentre studies are required to confirm the results of this novel technique.

Comorbid anxiety and depressive symptoms and the related factors among international medical students in China during COVID-19 pandemic: a cross-sectional study.

BACKGROUND: The two most prevalent mental health conditions are anxiety and depression and they often coexist (comorbidity) in an individual aggravating the person's psychological or medical conditions. College students suffered from anxiety and depressive symptoms during the COVID-19 pandemic, according to numerous studies. The lack of information on the comorbidity of anxiety and depression (CAD) among international medical students, however, makes it difficult to develop effective policies or strategies to support these students. OBJECTIVE: The present research seeks to investigate the incidence of CAD among international medical students in China and to identify the variables that may be useful in predicting CAD. METHOD: A cross-sectional study was conducted at China Medical University in Shenyang, China, for international medical students during November 2020. A total of 519 international students provided information on their demographics, stress related to the COVID-19 pandemic, generalized anxiety disorder assessment (GAD-7), patient health questionnaire-9 (PHQ-9), simplified coping style questionnaire (SCSQ), perceived stress scale (PSS-10), the multidimensional scale of perceived social support (MSPSS), revised life orientation test (LOT-R), and resilience scale-14 (RS-14). To investigate the potential predictors of CAD, a chi-square test, a nonparametric test, and multinomial logistic regression analyses were carried out as appropriate. RESULTS: The incidence of anxiety, depression, and CAD in the current study was 5.8%, 8.9%, and 22.7%, respectively. The predictors for students having symptoms of anxiety were observed to be the negative coping style (ß = 0.662, OR = 1.938, CI:1.07-3.694) and perceived stress (ß = 0.167, OR = 1.181, CI:1.076-1.297); the predictors for students having symptoms of depression were observed to be the COVID-19 pandemic-related stress (ß = 0.323,OR = 1.382,CI:1.211-1.577), negative coping style (ß = 0.693,OR = 2.000, CI:1.21-3.568), and perceived stress (ß = 0.135,OR = 1.145,CI:1.050-1.248); whereas the predictors for students with CAD were observed to be staying up late (Yes VS No) (ß = 1.028,OR = 2.794,CI:1.227-6.364), current place of residence (Other continents VS China) (ß = -1.413, OR = 0.243,CI:0.065-0.910), COVID-19 pandemic-related stress (ß = 0.371,OR = 1.450,CI:1.284-1.636), negative coping style (ß = 1.092,OR = 2.979,CI:1.706-5.203), and perceived stress (ß = 0.339,OR = 1.403,CI:1.289-1.527). CONCLUSION: Single anxiety and depressive symptoms were moderately prevalent among international medical students in China. However, CAD turned out to be the most prevalent mental health issue due to its relatively higher incidence. Negative coping style and perceived stress were the communal predictors of the three categories, whereas stress related to the COVID-19 pandemic was linked to both depression and CAD, and staying up late and in residential places were specific predictors for CAD. Study results suggest that COVID-19 pandemic-related stress was related to students' CAD and depressive symptoms, and specific intervention measures with stress reduction, proper coping strategy, and a good lifestyle might be useful in improving the international students' mental health status.

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.

Use of soybean oil to modulate the gel properties of soybean protein isolation-wheat gluten composite with or without CaCl2.

BACKGROUND: Plant protein is widely used in the study of animal protein substitutes and healthy sustainable products. The gel properties are crucial for the production of plant protein foods. Therefore, the present study investigated the use of soybean oil to modulate the gel properties of soybean protein isolation-wheat gluten composite with or without CaCl2 . RESULTS: Oil droplets filled protein network pores under the addition of soybean oil (1-2%). This resulted in an enhanced gel hardness and water holding capacity. Further addition of soybean oil (3-4%), oil droplets and some protein-oil compounds increased the distance between the protein molecule chain. The results of Fourier transform infrared spectroscopy and intermolecular interaction also showed that the disulfide bond and ß-sheet ratio decreased in the gel system, which damaged the overall structure of the gel network. Compared with the addition of 0 m CaCl2 , salt ion reduced the electrostatic repulsion between proteins, and local protein cross-linking was more intense at 0.005 m CaCl2 concentration. In the present study, structural properties and rheological analysis showed that the overall strength of the gel was weakened after the addition of CaCl2 . CONCLUSION: The presence of appropriate amount of soybean oil can fill the gel pores and improve the texture properties and network structure of soy protein isolate-wheat gluten (SPI-WG) composite gel. Excessive soybean oil may hinder protein-protein interaction and adversely affect protein gel. In addition, the presence or absence of CaCl2 significantly affected the gelling properties of SPI-WG composite protein gels. © 2023 Society of Chemical Industry.

Analysis of the diagnostic accuracy of Belin/Ambrósio Enhanced Ectasia and Corvis ST parameters for subclinical keratoconus.

OBJECTIVE: To investigate the diagnostic accuracy of the parameters in the Belin/Ambrósio Enhanced Ectasia Display built in Pentacam, which is designed for the screening of subclinical keratoconus (SKC) built in Pentacam, and the parameters in Corneal visualization Scheimpflug technology (Corvis ST). METHODS: A retrospective study: The fellow eyes of unilateral keratoconus cases were diagnosed with SKC. Patients presented to Shanxi Eye Hospital with SKC from October 2020 to November 2021 were included as the SKC group, and myopic patients undergoing corneal refractive surgery at the Refractive Surgery Department in our hospital within the same period were included as the control group. The Belin/Ambrósio and Corvis ST parameters were extracted from the system and analyzed using independent samples t test. Receiver operating curves (ROCs) were also created to test the diagnostic accuracy of each parameter. RESULTS: There were 70 patients (70 eyes) in the SKC group and 137 patients (137 eyes) in the control group. For Corvis ST parameters, Radius (P = 0.021), PachySlope (P = 0.040), SP-A1 (P = 0.002), A2 Deformation Amp. (P = 0.028), A2 Deflection Length (P < 0.001), Max ICR (P = 0.005), DA Ratio Max (1 mm) (P = 0.023), IR (P = 0.016), CBI (P = 0.003) and TBI (P < 0.001) were statistically different between the two groups. For Belin/Ambrósio parameters, PPI min. Axis, ART min, ART max, ART avg, Pachy min, Front K2, Astig, BAD-Df, BAD-Db, BAD-Dp, BAD-Dt, BAD-Da, BAD-D, PPI min, PPI max, PPI max. Axis, PPI avg and Dist.Apex-Thin.Loc. were significantly different between the two groups (all p < 0.001). TBI and BAD-D showed the best diagnostic accuracy, with AUCs of 0.944 and 0.965, respectively. CONCLUSIONS: Some Belin/Ambrósio and Corvis ST parameters differed between SKC eyes and eyes with normal cornea. TBI and BAD-D showed the ideal diagnostic performance for SKC. In clinical practice, conventional corneal topography could not be replaced by Corvis ST.

Effects of Abdominal Wall Blocks on Postoperative Delirium in Elderly Patients Undergoing Laparoscopic Surgery: A Randomized Controlled Study.

BACKGROUND Postoperative delirium (POD) seriously affects the rapid postoperative recovery of elderly patients. We investigated the effect of abdominal wall blocks on POD in elderly patients undergoing laparoscopic radical resection of colon cancer and underlying mechanisms. MATERIAL AND METHODS A total of 100 patients undergoing laparoscopic radical resection of colon cancer were randomly assigned to group C (control) and group R (regional nerve blocks). In group R, 20 mL of local anesthesia-mixed solution was injected into the bilateral transverse abdominis muscle plane and 10 mL was injected into the bilateral posterior sheath of the rectus abdominis muscle. In group C, the same amount of saline was used for nerve block. The consumption of propofol and remifentanil during surgery was recorded. Levels of serum interleukin (IL)-6 and highly sensitive C-reactive protein (hs-CRP) during surgery were evaluated. The Confusion Assessment Method for the Intensive Care Unit Scale and the Richmond Agitation-Sedation Scale were adopted to evaluate POD. RESULTS The incidence of POD was lower in group R than in group C (P=0.048). The consumption of propofol and remifentanil was significantly reduced in group R, compared with group C (P<0.05). Compared with T0, serum IL-6 and hs-CRP levels in both groups were significantly increased at T1 and T2 (P<0.05). Moreover, serum IL-6 and hs-CRP were lower at T1 and T2 in group R compared with group C (P<0.05). CONCLUSIONS Abdominal wall blocks may alleviate POD in elderly patients undergoing laparoscopic surgery, which may be related to the reduction of anesthetic consumption and inflammatory response.

The modification of biomass waste by cerium-based MOFs for efficient phosphate removal: excellent performance and reaction mechanism.

Due to the possibility of causing eutrophication, excessive phosphate discharged into water bodies always threatens the stabilization of aquatic ecosystem. A promising strategy is to remove phosphate from water by the utilization of biomass waste as adsorbents. In this paper, the corn straw (CS) and pine sawdust (PS) are chosen for adsorption; however, the phosphate removal capacities of them are very limited. Considering the high phosphate uptake of trivalent cerium, Ce (III)-based nanoparticles (CD and CT) are selected to be loaded on the biomass by hydrothermal synthesis to obtain four modified materials. CD is metal organic frameworks (MOFs) with Ce5(BDC)7.5(DMF)4 as its molecular structure, while CT is MOFs derivatives with [Ce (HCOO)]n as its crystal structure. The adsorption capacities of CS-CD, PS-CD, CS-CT and PS-CT reach 181.38, 183.27, 225.55 and 186.23 mg/g. But on account of the different molecular structures, CS-CD and PS-CD achieve great phosphate uptake under wide applicable scope of pH from 2 to 11, whereas CS-CT and PS-CT only under acidic conditions. The analysis of the adsorption mechanism indicates that due to the unsaturated coordination bond of CD, it could remove phosphate through coprecipitation and ion exchange even under alkaline conditions.

Lipoxin A4 ameliorates renal ischaemia-reperfusion-induced acute lung injury in rats.

Lipoxin A4 (LA4), a bioactive product of arachidonic acid, has been shown to exert strong anti-inflammatory activity. By contrast, the anti-inflammatory action of LA4 in a renal ischaemia-reperfusion (RIR)-mediated acute lung inflammation (ALI) model and the potential pathogenesis of the condition is still unclear. The aim of the current research was to investigate the effect of LA4 on RIR-induced ALI. The rat ALI model was induced by RIR. LA4 was injected via the tail vein immediately after RIR. The results indicate that LA4 markedly inhibits inflammatory cells infiltration, attenuates myeloperoxidase activity, and reduces the concentration of inflammatory mediators and Toll-like receptor 4 (TLR4) in RIR-induced ALI. Furthermore, LA4 suppressed nuclear factor kappa B (NF-κB) p65 and mitogen-activated protein kinase (MAPK) activation. The protective effect of LA4 in RIR-stimulated ALI was reversed by BOC-2 (an antagonist of the LA4 receptor). These results indicate that LA4 exerts powerful anti-inflammatory functions in RIR-induced ALI by attenuating TLR4 expression via MAPK and NF-κB signalling. Accordingly, LA4 might be an underlying treatment drug for RIR-induced ALI.

Quantification of lower extremity physical exposures in various combinations of sit/stand time duration associated with sit-stand workstation.

BACKGROUND: Sit-stand workstations are available for office work purposes but there is a dearth of quantitative evidence to state benefits for lower limb outcomes while using them. And there are no guidelines on what constitutes appropriate sit/stand time duration. The primary aim of this study has been to compare muscle activity and perceived discomfort in the lower extremity during various combinations of sit/stand time duration associated with a sit-stand workstation separately and to evaluate the effects of the sit-stand workstation on the lower extremity during the text entry task. MATERIAL AND METHODS: During the 5 days, all participants completed a 2-h text entry task each day for various sit/stand time duration combinations as follows: 5/25 min, 10/20 min, 15/15 min, 20/10 min, 25/5 min. Lower extremity muscular exposure of 12 male and 13 female participants was collected at 8 sites by surface electromyography and body discomfort was calculated by a questionnaire under those 5 conditions. RESULTS: Results have demonstrated that lower extremity muscle activity has been significantly varied among the 5 sit/stand time duration groups. Perceived level of discomfort (PLD) has not differed significantly for 9 out of 10 body parts. CONCLUSIONS: The muscle activity of the thigh region was influenced by sit/stand time duration significantly. Ergonomic exposures of lower extremity when using a sit-stand workstation were increased, particularly during the long time standing posture. Results indicate that body mass index (BMI) and gender were not significant factors in this study. Combination of sit/stand time duration 25/5 min appears to show positive effects on relief of muscle exposure of back of thigh in the shifts of sitting and standing work position. Med Pr 2017;68(3):315-327.

Arabidopsis AtbHLH112 regulates the expression of genes involved in abiotic stress tolerance by binding to their E-box and GCG-box motifs.

Plant basic helix-loop-helix (bHLH) transcription factors play essential roles in abiotic stress tolerance. However, most bHLHs have not been functionally characterized. Here, we characterized the functional role of a bHLH transcription factor from Arabidopsis, AtbHLH112, in response to abiotic stress. AtbHLH112 is a nuclear-localized protein, and its nuclear localization is induced by salt, drought and abscisic acid (ABA). In addition, AtbHLH112 serves as a transcriptional activator, with the activation domain located at its N-terminus. In addition to binding to the E-box motifs of stress-responsive genes, AtbHLH112 binds to a novel motif with the sequence 'GG[GT]CC[GT][GA][TA]C' (GCG-box). Gain- and loss-of-function analyses showed that the transcript level of AtbHLH112 is positively correlated with salt and drought tolerance. AtbHLH112 mediates stress tolerance by increasing the expression of P5CS genes and reducing the expression of P5CDH and ProDH genes to increase proline levels. AtbHLH112 also increases the expression of POD and SOD genes to improve reactive oxygen species (ROS) scavenging ability. We present a model suggesting that AtbHLH112 is a transcriptional activator that regulates the expression of genes via binding to their GCG- or E-boxes to mediate physiological responses, including proline biosynthesis and ROS scavenging pathways, to enhance stress tolerance.

[New progress in prostate cancer biomarker research].

Prostate cancer is one of the major problems of men's health. It has more obvious cancer heterogeneity, affecting the diagnosis, treatment and prognosis monitoring when comparing with other cancer. Thus, cancer related biomarkers are urgently needed to guide biopsy, treatment selection and follow-up. In the aspect of diagnosis, though the emerging of prostate specific antigen can raise the rate of diagnosis to some extent, it brings more unnecessary biopsies because of its low specificity. Cancer related long non-coding RNAs, single nucleotide polymorphism and fusion genes are proved to increase the diagnostic efficiency through high-throughput sequencing techniques. In the aspect of molecular classification, traditional Gleason score can discriminate different risk level of the cancer, but it is limited by the technicians. It is reported that copy number variations from DNA level and small RNAs, long non-coding RNAs from RNA level are related with the progress of cancer, indicating the potential role in cancer molecular classification. Although we are still on the way of the initial stage in exploring prostate cancer biomarkers, more useful and promising biomarkers will be found by high-throughput sequencing and molecular biotechniques.

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.

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.

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.

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.

Influence of HbCO structure of the bar-headed goose on photolysis thermodynamics as studied by the nanosecond laser-ultrasonic technique.

The bar-headed goose, a specialized high-altitude species, has a capacity for high oxygen uptake from a hypoxic environment. It thus has a higher oxygen affinity than other bird species of lower-altitude environments. Oxygen affinity is determined by molecular structures and genetic mutations of hemoglobin (Hb), which can also influence the coordinating structures and dynamics of oxygen-Hb. To explore the structural differences in Hbs as between high and low altitude species, photolysis dynamic parameters, including quantum yield, enthalpy, and conformational volume changes in carboxy-Hbs (HbCO) for the bar-headed goose and low altitude counterparts (the Chinese goose and chicken) were investigated by the laser pumping-probing technique and photoacoustic calorimetry. Comparing the photolysis results for HbCO of the three species, the enthalpy and conformational volume changes of the bar-headed goose were much smaller than those of the others, although the quantum yields of all three species are similar. To explain the possible mechanisms of these differences, modifications of salt bridges and key residue mutations at the α ß subunit interfaces of the proteins are described and discussed briefly.