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To study the genetic variation leading to the arrest phenotype of pronuclear (PN) zygotes. We recruited a family characterized by recurrent PN arrest during in vitro fertilization (IVF) and intracytoplasmic sperm injection cycles (ICSI) and performed whole-exome sequencing for 2 individuals. The transcriptome profiles of PN-arrest zygotes were assessed by single-cell RNA sequencing analysis. The variants were then validated by PCR amplification and Sanger sequencing in the affected individuals and other family members. A family characterized by recurrent PN arrest during IVF and ICSI cycles were enrolled after giving written informed consent. Peripheral blood samples were taken for DNA extraction. Three PN-arrest zygotes from patient III-3 were used for singlecell RNA-seq as described. This phenotype was reproduced after multiple cycles of egg retrieval and after trying different fertilization methods and multiple ovulation regimens. The mutant genes of whole exon sequencing were screened and verified. The missense variant c. C1630T (p.R544W) in RGS12 was responsible for a phenotype characterized by paternal transmission. RGS12 controls Ca2+ oscillation, which is required for oocyte activation after fertilization. Single-cell transcriptome profiling of PN-arrest zygotes revealed defective established translation, RNA processing and cell cycle, which explained the failure of complete oocyte activation. Furthermore, we identified proximal genes involved in Ca2+ oscillation-cytostatic factor-anaphase-promoting complex (Ca2+ oscillation-CSF-APC) signaling, including upregulated CaMKII, ORAI1, CDC20, and CDH1 and downregulated EMI1 and BUB3. The findings indicate abnormal spontaneous Ca2+ oscillations leading to oocytes with prolonged low CSF level and high APC level, which resulted in defective nuclear envelope breakdown and DNA replication. We have identified an RGS12 variant as the potential cause of female infertility characterized by arrest at the PN stage during multiple IVF and ICSI. [ABSTRACT FROM AUTHOR]

4-Hydroxy-2,5-dimethyl-3 (2H)-furanone (HDMF) is widely used in the food industry as a spice and flavoring agent with high market demand. In this study, fructose-1,6-bisphosphate aldolase (FBA) and triose phosphate isomerase (TPI) were overexpressed in Zygosaccharomyces rouxii in the form of single and double genes, respectively, via electroporation. High-yield HDMF-engineered yeast strains were constructed by combining the analysis of gene expression levels obtained by real-time fluorescence quantitative PCR technology and HDMF production measured by HPLC. The results showed that there was a significant positive correlation between the production of HDMF and the expression levels of the FBA and TPI genes in yeast; the expression levels of the FBA and TPI genes were also positively correlated (p < 0.05). Compared with the wild type (WT), the engineered strains F10-D, T17-D, and TF15-A showed marked increases in HDMF production and FBA and TPI gene expression (p < 0.05) and exhibited great genetic stability with no obvious differences in biomass or colony morphology. In addition, the exogenous addition of d-fructose promoted the growth of Z. rouxii. Among the engineered strains, when fermented in YPD media supplemented with d-fructose for 5 days, TF15-A (overexpressing the FBA and TPI genes) generated the highest HDMF production of 13.39 mg/L, which is 1.91 times greater than that of the wild-type strain. The results above indicated that FBA and TPI, which are key enzymes involved in the process of HDMF biosynthesis by Z. rouxii, positively regulate the synthesis of HDMF at the transcriptional level. d-fructose can be used as a precursor for the biosynthesis of HDMF by engineered yeast in industrial production. [ABSTRACT FROM AUTHOR]

Anti-IgLON5 disease is a recently discovered autoimmune encephalopathy with sleep disorder as a hallmark in the majority of reported cases. Additional neurological manifestations include bulbar dysfunction, gait problems, movement disorders, oculomotor abnormalities, and hyperexcitability of the nervous system. At present, an increasing number of publications have dealt with the course and possible treatment options for anti-IgLON5 disease, and its clinical spectrum has expanded wider and more heterogeneous. Here, we report a case of a 66-year-old female with cognitive impairment accompanied by slow reaction, impaired memory, and decreased orientation. A positive cerebral MRI change and serum and cerebrospinal fluid (CSF) antibodies against IgLON5 were found during the diagnostic course. Subsequently the patient received immunotherapy and was generally in good health with no new symptoms during follow-up. Early testing for IgLON5 antibodies should be considered in patients with atypical neurological symptoms such as cognitive impairment, slow reaction, or decreased orientation. In clinical practice, immunotherapy should be considered in all cases of anti-IgLON5 encephalopathies. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant immunochemotherapy may benefit patients with non-small cell lung cancer (NSCLC), but its impact requires further investigation. Methods: A meta-analysis was conducted. PubMed, Embase, Web of Science, and the Cochrane Library were searched. The study was registered in PROSPERO (registration no. CRD42022360893). Results: 60 studies of 3,632 patients were included. Comparing with neoadjuvant chemotherapy, neoadjuvant immunochemotherapy showed higher pCR (RR: 4.71, 95% CI: 3.69, 6.02), MPR (RR, 3.20, 95% CI: 2.75, 3.74), and ORR (RR, 1.46, 95% CI: 1.21, 1.77), fewer surgical complications (RR: 0.67, 95%CI: 0.48, 0.94), higher R0 resection rate (RR: 1.06, 95%CI: 1.03, 1.10, I² = 52%), and longer 1-year and 2-year OS, without affecting TRAEs. For neoadjuvant immunochemotherapy in NSCLC, the pooled pCR rate was 0.35 (95% CI: 0.31, 0.39), MPR was 0.59 (95% CI: 0.54, 0.63), and ORR was 0.71 (95% CI: 0.66, 0.76). The pooled incidence of all grade TRAEswas 0.70 (95% CI: 0.60, 0.81), and that of >= grade 3 TRAEs was 0.24 (95% CI: 0.16, 0.32). The surgical complications rate was 0.13 (95% CI: 0.07, 0.18) and R0 resection rate was 0.98 (95% CI: 0.96, 0.99). The pooled 1-year OS was 0.97 (95%CI: 0.96, 0.99), and 2-year OS was 0.89 (95%CI: 0.83, 0.94). Patients with squamous cell carcinoma, stage III or higher PD-L1 performed better. Notably, no significant differences were observed in pCR, MPR, and ORR between 2 or more treatment cycles. Pembrolizumab-, or toripalimab-based neoadjuvant immunochemotherapy demonstrated superior efficacy and tolerable toxicity. Conclusion: According to our analysis, reliable efficacy, safety, and survival of neoadjuvant immunochemotherapy for operable NSCLC were demonstrated. [ABSTRACT FROM AUTHOR]

Image sentiment analysis technology can predict, measure and understand the emotional experience of human beings through images. Aiming at the problem of extracting emotional characteristics in art appreciation, this article puts forward an innovative method. Firstly, the PageRank algorithm is enhanced using tweet content similarity and time factors; secondly, the SE-ResNet network design is used to integrate Efficient Channel Attention (ECA) with the residual network structure, and ResNeXt50 is optimized to enhance the extraction of image sentiment features. Finally, the weight coefficients of overall emotions are dynamically adjusted to select a specific emotion incorporation strategy, resulting in effective bimodal fusion. The proposed model demonstrates exceptional performance in predicting sentiment labels, with maximum classification accuracy reaching 88.20%. The accuracy improvement of 21.34% compared to the traditional deep convolutional neural networks (DCNN) model attests to the effectiveness of this study. This research enriches images and texts' emotion feature extraction capabilities and improves the accuracy of emotion fusion classification. [ABSTRACT FROM AUTHOR]

Sarcopenia and osteoporosis, two degenerative diseases in older patients, have become severe health problems in aging societies. Muscles and bones, the most important components of the motor system, are derived from mesodermal and ectodermal mesenchymal stem cells. The adjacent anatomical relationship between them provides the basic conditions for mechanical and chemical signals, which may contribute to the co-occurrence of sarcopenia and osteoporosis. Identifying the potential common crosstalk genes between them may provide new insights for preventing and treating their development. In this study, DEG analysis, WGCNA, and machine learning algorithms were used to identify the key crosstalk genes of sarcopenia and osteoporosis; this was then validated using independent datasets and clinical samples. Finally, four crosstalk genes (ARHGEF10, PCDH7, CST6, and ROBO3) were identified, and mRNA expression and protein levels of PCDH7 in clinical samples from patients with sarcopenia, with osteoporosis, and with both sarcopenia and osteoporosis were found to be significantly higher than those from patients without sarcopenia or osteoporosis. PCDH7 seems to be a key gene related to the development of both sarcopenia and osteoporosis. [ABSTRACT FROM AUTHOR]

Background: Evaluating caregiver burden and its health impact is an essential component of long‐term care plan for children with disabilities; the Caregiver Difficulties Scale (CDS) has high conceptual sensitivity. The aim of this study was to adapt the CDS to Chinese and investigates the psychometric properties of this tool. Methods: The study was carried out among caregivers of children with cerebral palsy (n = 194). The CDS, Caregivers Burden Inventory (CBI) and World Health Organization Quality of Life‐BREF (WHOQOL‐BREF) were used for data collection. Twenty experts were consulted to evaluate the content validity of the scale. The confirmatory factor analysis was conducted to measure the construct validity of CDS. The Spearman correlation coefficients were calculated among CDS, CBI and WHOQOL‐BREF to examine the convergent validity and discriminant validity. The reliability was evaluated by examining internal consistency and test–retest reliability. Results: The result of expert consultation showed that the S‐CVI was 0.894 and the I‐CVI ranged from 0.70 to 1.00. The fit indices showed that the original correlated four‐factor model of CDS was adequate: χ2 = 268.397; df = 243; χ2/df = 1.105; RMSEA = 0.023; CFI = 0.985; NNFI = 0.869; TLI = 0.982; IFI = 0.986. The score of CDS was positively strong associated with the scores of CBI (r = +0.764); negatively correlating with the scores of WHOQOL‐BREF (r = −0.627). The Cronbach's alpha was 0.840; intraclass correlation coefficient (ICC) value was 0.843. Conclusions: The Chinese version of the CDS is a valid and reliable tool to evaluate burden for caregivers of children with CP in China. [ABSTRACT FROM AUTHOR]

Background: Previous studies have shown that systemic inflammation indicators could predict the survival outcomes of patients with malignant tumors receiving various treatments. Radiotherapy, as a crucial treatment modality, effectively alleviates discomfort in patients with bone metastasis (BM) and greatly improves the quality of life for them. This study aimed to investigate the prognostic value of systemic inflammation index in hepatocellular carcinoma (HCC) patients with BM treated with radiotherapy. Methods: We retrospectively analyzed clinical data collected from HCC patients with BM who received radiotherapy in our institution between January 2017 and December 2021. The pre-treatment neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) were derived to determine their relationship with overall survival (OS) and progression-free survival (PFS), using the Kaplan-Meier survival curves. The optimal cut-off value of the systemic inflammation indicators for predicting prognosis was assessed by receiver operating characteristic (ROC) curves. Univariate and multivariate analyses were performed to ultimately evaluate the factors associated with survival. Results: The study included 239 patients with a median 14-month follow-up. The median OS was 18 months (95% confidence interval [CI] = 12.0-24.0) and the median PFS was 8.5 months (95% CI = 6.5-9.5). The optimal cut-off values for the patients were determined by ROC curve analysis as follows: SII =395.05, NLR=5.43 and PLR = 108.23. The area under the receiver operating characteristic curve values for SII, NLR and PLR in disease control prediction were 0.750, 0.665 and 0.676, respectively. Elevated systemic immune-inflammation index (SII>395.05) and higher NLR (NLR>5.43) were independently associated with poor OS and PFS. In multivariate analysis, Child-Pugh class (P = 0.038), intrahepatic tumor controlled (P = 0.019), SII (P = 0.001) and NLR (P = 0.007) were independent prognostic factors of OS and Child-Pugh class (P = 0.042), SII (P < 0.001) and NLR (P = 0.002) were independently correlated with PFS. Conclusion: NLR and SII were associated with poor prognosis in HCC patients with BM receiving radiotherapy and might be considered reliable and independent prognostic biomarkers for HCC patients with BM. [ABSTRACT FROM AUTHOR]

In this paper, we develop a Malliavin calculus approach for hedging a fixed strike lookback option in fuzzy space. Due to the uncertainty in financial markets, it is not accurate to describe the problems of option pricing and hedging in terms of randomness alone. We consider a fuzzy pricing model by introducing a fuzzy stochastic differential equation with Skorohod sense. In this way, our model simultaneously involves randomness and fuzziness. A well-known hedging strategy for vanilla options is so-called A-hedging, which is usually derived from the Ito formula and some properties of partial differentiable equations. However, when dealing with some complex path-dependent options (such as lookback options), the major challenge is that the payoff function of these options may not be smooth, resulting in the estimates are computationally expensive. With the help of the Malliavin derivative and the Clark-Ocone formula, the difficulty will be readily solved, and it is also possible to apply this hedging strategy to fuzzy space. To obtain the explicit expression of the fuzzy hedging portfolio for lookback options, we adopt the Esscher transform and reflection principle techniques, which are beneficial to the calculation of the conditional expectation of fuzzy random variables and the payoff function with extremum, respectively. Some numerical examples are performed to analyze the sensitivity of the fuzzy hedging portfolio concerning model parameters and give the permissible range of the expected hedging portfolio of lookback options with uncertainty by a financial investor's subjective judgment. [ABSTRACT FROM AUTHOR]

Introduction: In recent years, numerous studies have confirmed that chronic stress is closely related to the development of cancer. Our previous research showed that high levels of stress hormones secreted in the body during chronic stress could inhibit the cancer-killing activity of granulocytes, which could further promote the development of cancer. Therefore, reversing the immunosuppressive effect of stress hormones on granulocytes is an urgent problem in clinical cancer treatment. Here, we selected noradrenaline (NA) as a representative stress hormone. Methods and results: After screening many traditional Chinese herbal medicine active ingredients, a promising compound, ginsenoside Rg1, attracted our attention. We verified the immunoprotective effect of ginsenoside Rg1 on granulocytes in vitro and ex vivo, and attempted to understand its potential immunoprotective mechanism. We confirmed the immunoprotective effect of ginsenoside Rg1 on granulocytes using cell and animal experiments. Cell counting kit-8 (CCK-8) and ex vivo experiments were performed to investigate the immunoprotective effects of ginsenoside Rg1 on the anti-cancer function of granulocytes inhibited by NA. Transcriptome sequencing analysis and qRT-PCR showed that NA elevated themRNA expression of ARG2, MMP1, S100A4, and RAPSN in granulocytes, thereby reducing the anti-cancer function of granulocytes. In contrast, ginsenoside Rg1 downregulated the mRNA expression of ARG2, MMP1, S100A4, and RAPSN, and upregulated the mRNA expression of LAMC2, DSC2, KRT6A, and FOSB, thereby enhancing the anti-cancer function of granulocytes inhibited by NA. Transwell cell migration experiments were performed to verify that ginsenoside Rg1 significantly enhanced the migration capability of granulocytes inhibited by NA. Tumor-bearing model mice were used to verify the significant immunoprotective effects in vivo. Finally, CCK-8 and hematoxylin and eosin staining experiments indicated that ginsenoside Rg1 exhibited high biosafety in vitro and in vivo. Discussion: In future clinical treatments, ginsenoside Rg1 may be used as an adjuvant agent for cancer treatment to alleviate chronic stress-induced adverse events in cancer patients. [ABSTRACT FROM AUTHOR]

Objectives: Familial aggregation of primary Sjögren's syndrome (pSS), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and co-aggregation of these autoimmune diseases (ADs) (also called familial autoimmunity) is well recognised. However, the genetic predisposition variants that explain this clustering remains poorly defined.Methods: We used whole-exome sequencing on 31 families (9 pSS, 11 SLE, 6 RA and 5 mixed autoimmunity), followed by heterozygous filtering and cosegregation analysis of a family-focused approach to document rare variants predicted to be pathogenic by in silico analysis. Potential importance in immune-related processes, gene ontology, pathway enrichment and overlap analyses were performed to prioritise gene sets.Results: A range from 1 to 50 rare possible pathogenic variants, including 39 variants in immune-related genes across SLE, RA and pSS families, were identified. Among this gene set, regulation of T cell activation (p=4.06×10-7) and T cell receptor (TCR) signalling pathway (p=1.73×10-6) were particularly concentrated, including PTPRC (CD45), LCK, LAT-SLP76 complex genes (THEMIS, LAT, ITK, TEC, TESPA1, PLCL1), DGKD, PRKD1, PAK2 and NFAT5, shared across 14 SLE, RA and pSS families. TCR-interactive genes P2RX7, LAG3, PTPN3 and LAX1 were also detected. Overlap analysis demonstrated that the antiviral immunity gene DUS2 variant cosegregated with SLE, RA and pSS phenotypes in an extended family, that variants in the TCR-pathway genes CD45, LCK and PRKD1 occurred independently in three mixed autoimmunity families, and that variants in CD36 and VWA8 occurred in both RA-pSS and SLE-pSS families.Conclusions: Our preliminary results define common genetic characteristics linked to familial pSS, SLE and RA and highlight rare genetic variations in TCR signalling pathway genes which might provide innovative molecular targets for therapeutic interventions for those three ADs. [ABSTRACT FROM AUTHOR]

Fusion transcripts are used as biomarkers in companion diagnoses. Although more than 15,000 fusion RNAs have been identified from diverse cancer types, few common features have been reported. Here, we compared 16,410 fusion transcripts detected in cancer (from a published cohort of 9,966 tumor samples of 33 cancer types) with genome-wide RNA-DNA interactions mapped in two normal, noncancerous cell types [using iMARGI, an enhanced version of the mapping of RNA-genome interactions (MARGI) assay]. Among the top 10 most significant RNA-DNA interactions in normal cells, 5 colocalized with the gene pairs that formed fusion RNAs in cancer. Furthermore, throughout the genome, the frequency of a gene pair to exhibit RNA-DNA interactions is positively correlated with the probability of this gene pair to present documented fusion transcripts in cancer. To test whether RNA-DNA interactions in normal cells are predictive of fusion RNAs, we analyzed these in a validation cohort of 96 lung cancer samples using RNA sequencing (RNA-seq). Thirty-seven of 42 fusion transcripts in the validation cohort were found to exhibit RNA-DNA interactions in normal cells. Finally, by combining RNA-seq, single-molecule RNA FISH, and DNA FISH, we detected a cancer sample with EML4-ALK fusion RNA without forming the EML4-ALK fusion gene. Collectively, these data suggest an RNA-poise model, where spatial proximity of RNA and DNA could poise for the creation of fusion transcripts. [ABSTRACT FROM AUTHOR]

The article discusses a study which examined the distribution and expression of nerve growth factor and inducible nitric oxide synthase in the mesencephalon and diencephalon. The study performed immunohistochemistry to detect the distribution and expression of the growth factor. Results showed a decrease in nerve growth factor expression and an increase in inducible nitric oxide synthase.