The complex effects of miR-146a in the pathogenesis of Alzheimer's disease.

Alzheimer's disease is a neurodegenerative disorder characterized by cognitive dysfunction and behavioral abnormalities. Neuroinflammatory plaques formed through the extracellular deposition of amyloid-ß proteins, as well as neurofibrillary tangles formed by the intracellular deposition of hyperphosphorylated tau proteins, comprise two typical pathological features of Alzheimer's disease. Besides symptomatic treatment, there are no effective therapies for delaying Alzheimer's disease progression. MicroRNAs (miR) are small, non-coding RNAs that negatively regulate gene expression at the transcriptional and translational levels and play important roles in multiple physiological and pathological processes. Indeed, miR-146a, a NF-κB-regulated gene, has been extensively implicated in the development of Alzheimer's disease through several pathways. Research has demonstrated substantial dysregulation of miR-146a both during the initial phases and throughout the progression of this disorder. MiR-146a is believed to reduce amyloid-ß deposition and tau protein hyperphosphorylation through the TLR/IRAK1/TRAF6 pathway; however, there is also evidence supporting that it can promote these processes through many other pathways, thus exacerbating the pathological manifestations of Alzheimer's disease. It has been widely reported that miR-146a mediates synaptic dysfunction, mitochondrial dysfunction, and neuronal death by targeting mRNAs encoding synaptic-related proteins, mitochondrial-related proteins, and membrane proteins, as well as other mRNAs. Regarding the impact on glial cells, miR-146a also exhibits differential effects. On one hand, it causes widespread and sustained inflammation through certain pathways, while on the other hand, it can reverse the polarization of astrocytes and microglia, alleviate neuroinflammation, and promote oligodendrocyte progenitor cell differentiation, thus maintaining the normal function of the myelin sheath and exerting a protective effect on neurons. In this review, we provide a comprehensive analysis of the involvement of miR-146a in the pathogenesis of Alzheimer's disease. We aim to elucidate the relationship between miR-146a and the key pathological manifestations of Alzheimer's disease, such as amyloid-ß deposition, tau protein hyperphosphorylation, neuronal death, mitochondrial dysfunction, synaptic dysfunction, and glial cell dysfunction, as well as summarize recent relevant studies that have highlighted the potential of miR-146a as a clinical diagnostic marker and therapeutic target for Alzheimer's disease.

The predictive value of intraoperative bulbocavernosus re?ex monitoring for postoperative voiding function in patients with conus medullaris and cauda equina tumors: a retrospective single center study.

BACKGROUND CONTEXT: Surgical resection is the preferred treatment in most conus medullaris and cauda equina tumor (CMCET) cases. However, total resection is usually challenging to obtain and has a strong possibility of causing various complications if forcibly attempted. Intraoperative neurophysiological monitoring (IONM) has become a necessary adjunctive tool for CMCET resection. PURPOSE: The current study aimed to evaluate the application value of bulbocavernosus reflex (BCR) monitoring in CMCET surgery. STUDY DESIGN: A retrospective clinical study. PATIENT SAMPLE: The medical records of patients who underwent CMCET resection by the same neurosurgical team at our hospital from September 2020 to June 2022 were retrospectively reviewed. IONM was conducted in all surgeries. According to inclusion criteria and exclusion criteria, ultimately, 105 patients were enrolled in the study. OUTCOME MEASURES: The voiding function was assessed before surgery, one month after, and six months after surgery using the Neurogenic Bladder Symptom Score (NBSS). If the NBSS obtained one month after surgery exceeds 9 points than that before surgery, it can be considered that the patient suffered new-onset postoperative voiding dysfunctions (PVDs). Moreover, if the NBSS could restored (less than 9 points higher than before the surgery) at six months after surgery, it was defined as a short-term PVD. Otherwise, it was defined as a long-term PVD. METHODS: The amplitude reduction ratios (ARRs) of bilateral BCR waveforms were calculated and compared between patients with PVDs and those without. The receiver operating characteristic curve analysis was subsequently applied to determine the cut-off value of the maximal and minimal ARRs for predicting PVDs. RESULTS: The maximal and minimal ARRs were significantly correlated with short-term and long-term PVDs (p<0.001 for all comparisons, Mann-Whitney U test). The threshold values of maximal ARR for predicting short-term and long-term PVD were 68.80% (AUC=0.996, p<0.001) and 72.10% (AUC=0.996, p<0.001), respectively. While those of minimal ARR were 50.20% (AUC=0.976, p<0.001) and 53.70% AUC=0.999, p<0.001). CONCLUSIONS: The amplitude reduction of intraoperative bilateral BCR waveforms showed high predictive value for PVDs.

Regioselective analysis of heat-induced conformational changes of ß-lactoglobulin by quantitative liquid chromatography-mass spectrometry analysis of chemical labeling kinetics.

ß-Lactoglobulin is a main allergen in cow's milk; its allergenicity is strongly impacted by processing. To understand heat-induced epitope-specific effects, the present study analyzed regiospecific conformational changes of heated native ß-lactoglobulin variant A (BLG-A). Complementary fluorescence spectroscopy methods indicated two denaturation phases comprising minor sequential conformational changes (25-75 °C) and complete transitions (80-90 °C). Regioselective conformational changes of BLG-A in the native state (25 °C), sequential (70 °C) and complete transition (90 °C) were determined by quantitative liquid chromatography-mass spectrometry analysis of chemical labeling kinetics covering 14 lysine residues and the N-terminus. Conformational changes in two phases were observed for N-terminus, K8 (both N-terminal chain), K60 (ß-sheet C), K75 (ß-sheet D), K77 (DE loop), K83 (ß-sheet E), K100 and K101 (FG loop). The residues K14 (ß-sheet A1), K47 (ß-sheet B), K69, K70 (both ß-sheet D), and K91 (ß-sheet F) were not involved in conformational changes.

Cisplatin resistance-related transcriptome and methylome integration identifies PCDHB4 as a novel prognostic biomarker in small cell lung cancer.

Platinum-based chemo-resistance is the major issue for the treatment of small cell lung cancer (SCLC). The integrative analysis of multi-omics data is a reliable approach for discovering novel biomarkers associated with chemo-resistance. Here, multi-omics integrative analysis and Cox regression found that higher expression of PCDHB4 was associated with poorer survival of SCLC patients who received chemotherapy. PCDHB4 gene was hypomethylated and upregulated in SCLC, which was validated in the levels of promoter methylation, mRNA, and protein expression. Mechanistically, using bulk RNA-seq data, functional enrichment analysis indicated that higher PCDHB4 expression was associated with lower immune infiltration. The analysis of single-cell RNA-seq (scRNA-seq) found that SCLC cells with PCDHB4 expression exhibited the characteristics of stemness and EMT. In addition, the high expression and hypomethylation of PCDHB4 were also significantly associated with poor survival in lung squamous cell carcinoma. In summary, PCDHB4 is a potential prognostic biomarker of platinum-based chemotherapy in SCLC.

High-Throughput and Integrated CRISPR/Cas12a-Based Molecular Diagnosis Using a Deep Learning Enabled Microfluidic System.

CRISPR/Cas-based molecular diagnosis demonstrates potent potential for sensitive and rapid pathogen detection, notably in SARS-CoV-2 diagnosis and mutation tracking. Yet, a major hurdle hindering widespread practical use is its restricted throughput, limited integration, and complex reagent preparation. Here, a system, microfluidic multiplate-based ultrahigh throughput analysis of SARS-CoV-2 variants of concern using CRISPR/Cas12a and nonextraction RT-LAMP (mutaSCAN), is proposed for rapid detection of SARS-CoV-2 and its variants with limited resource requirements. With the aid of the self-developed reagents and deep-learning enabled prototype device, our mutaSCAN system can detect SARS-CoV-2 in mock swab samples below 30 min as low as 250 copies/mL with the throughput up to 96 per round. Clinical specimens were tested with this system, the accuracy for routine and mutation testing (22 wildtype samples, 26 mutational samples) was 98% and 100%, respectively. No false-positive results were found for negative (n = 24) samples.

SexAnnoDB, a knowledgebase of sex-specific regulations from multi-omics data of human cancers.

BACKGROUND: Sexual differences across molecular levels profoundly impact cancer biology and outcomes. Patient gender significantly influences drug responses, with divergent reactions between men and women to the same drugs. Despite databases on sex differences in human tissues, understanding regulations of sex disparities in cancer is limited. These resources lack detailed mechanistic studies on sex-biased molecules. METHODS: In this study, we conducted a comprehensive examination of molecular distinctions and regulatory networks across 27 cancer types, delving into sex-biased effects. Our analyses encompassed sex-biased competitive endogenous RNA networks, regulatory networks involving sex-biased RNA binding protein-exon skipping events, sex-biased transcription factor-gene regulatory networks, as well as sex-biased expression quantitative trait loci, sex-biased expression quantitative trait methylation, sex-biased splicing quantitative trait loci, and the identification of sex-biased cancer therapeutic drug target genes. All findings from these analyses are accessible on SexAnnoDB ( https://ccsm.uth.edu/SexAnnoDB/ ). RESULTS: From these analyses, we defined 126 cancer therapeutic target sex-associated genes. Among them, 9 genes showed sex-biased at both the mRNA and protein levels. Specifically, S100A9 was the target of five drugs, of which calcium has been approved by the FDA for the treatment of colon and rectal cancers. Transcription factor (TF)-gene regulatory network analysis suggested that four TFs in the SARC male group targeted S100A9 and upregulated the expression of S100A9 in these patients. Promoter region methylation status was only associated with S100A9 expression in KIRP female patients. Hypermethylation inhibited S100A9 expression and was responsible for the downregulation of S100A9 in these female patients. CONCLUSIONS: Comprehensive network and association analyses indicated that the sex differences at the transcriptome level were partially the result of corresponding sex-biased epigenetic and genetic molecules. Overall, SexAnnoDB offers a discipline-specific search platform that could potentially assist basic experimental researchers or physicians in developing personalized treatment plans.

Sexual variations at the molecular level have a profound impact on cancer biology and outcomes, influencing drug responses that diverge between men and women exposed to the same drugs. Despite existing databases on sex differences in human tissues, our understanding of the regulations governing sex disparities in cancer is limited, lacking detailed mechanistic studies on sex-biased molecules. This study addresses this gap by conducting a comprehensive examination of molecular distinctions and regulatory networks across 27 cancer types, specifically focusing on sex-biased effects. The analyses led to the identification of 126 cancer therapeutic target sex-associated genes and shed light on the intricate relationship between sexual differences and cancer. Furthermore, the findings from these analyses are made accessible through SexAnnoDB, providing a specialized search platform. This platform has the potential to assist basic experimental researchers or physicians in developing personalized treatment plans based on a deeper understanding of sex-specific factors in cancer.

Willingness to receive mpox vaccine among men who have sex with men: a systematic review and meta-analysis.

BACKGROUND: Since May 2022, mpox outbreaks have been occurring in non-mpox endemic areas, with the main population affected being men who have sex with men (MSM). Outbreak prevention and control depend not only on the effectiveness of vaccines but also on people's willingness to receive these vaccines. Currently, there is lack of synthesis on the overall rates and influence factors of MSMs' willingness to vaccinate against mpox. Therefore, we systematically reviewed studies that assessed the willingness of MSM to receive mpox vaccine. METHODS: Studies reporting mpox vaccination intentions among MSM were included by searching five databases (PubMed, Web of Science, EMBASE, CINAHL, and SCOPUS) from inception to May 12, 2024. The quality of the included literature was assessed using Joanna Briggs Institute's critical appraisal tool. The data analysis software is Stata17. The systematic review has been registered with Prospero (registration ID: CRD42023452357). RESULTS: Twenty cross-sectional studies were included in the review. Meta-analysis results showed that the pooled willingness rate of vaccinate against mpox was 77.0% (95% CI: 73-81%, I2 = 99.4%). According to subgroup analysis, study countries (P = 0.002), research sample size (P = 0.001), and whether participants were infected with HIV (P = 0.002) may be sources of heterogeneity. The results of the meta-analysis of influencing factors showed that more number of sexual partners (OR: 2.24, 95%CI: 1.86-2.69), pre-exposure prophylaxis use (OR: 6.04, 95%CI: 4.80-7.61), history of sexually transmitted infections (OR: 2.96, 95%CI: 2.33-3.76), confidence in the vaccine's effectiveness (OR: 2.79, 95%CI: 2.04-3.80) and safety (OR: 10.89, 95%CI: 5.22-22.72), fear of mpox infection (OR: 2.47, 95%CI: 2.11-2.89) and epidemics (OR: 2.87, 95%CI: 2.22-3.70), high mpox knowledge (OR: 2.35, 95%CI: 1.51-3.66), and the belief that people at high risk should be prioritized for vaccination (OR: 3.09, 95%CI: 1.40-6.84) were the facilitators of vaccine willingness. In addition, as a secondary outcome, meta-analysis results showed a pooled unwillingness rate of 16% (95% CI: 13-20%, I2 = 98.1%, 9 studies). CONCLUSION: Willingness to vaccinate mpox was high among MSM, but some participants still had negative attitudes towards vaccination. Therefore, the Ministry of Public Health should develop targeted and effective strategies against those influencing factors to prevent and manage mpox outbreaks.

A Comparison Analysis of Quality and Metabolic Compounds in Lilies with Different Drying Treatments.

The present study aimed to investigate the variations in the nutritional composition, antioxidant capacity, and metabolite profile of lilies subjected to different drying treatments, including vacuum freeze drying (VFD), hot air drying (HAD), vacuum drying (VD), and infrared drying (ID). The results show that VFD provided better preservation of the original coloration and displayed the highest levels of total amino acid content, total phenolic content, total flavonoid content, and polysaccharide and alkaloid content. Our results reveal that VFD treatment can be employed to obtain high-quality lilies with desirable appearance characteristics and nutrient compositions. Metabolomics analysis identified a total of 464 metabolites from various dried lilies. Differential metabolite screening found 150 differential metabolites across all pairwise comparisons. Hierarchical clustering analysis (HCA) indicated that lilies subjected to VFD treatment exhibited a higher abundance of steroids, saponin, flavonoids, and phenolic glycoside, whereas those subjected to HAD, VD, or ID treatments showed relatively elevated levels of specific amino acids or derivatives. This study elucidates the significant impact of various drying treatments on the quality and metabolic profile of lilies, thereby providing valuable insights for enhancing the nutritional quality of processed lilies.

Effects of nitrile compounds on the structure and function of soil microbial communities as revealed by metagenomes.

The proliferation of nitrile mixtures has significantly exacerbated environmental pollution. This study employed metagenomic analysis to investigate the short-term effects of nitrile mixtures on soil microbial communities and their metabolic functions. It also examined the responses of indigenous microorganisms and their functional metabolic genes across various land use types to different nitrile stressors. The nitrile compound treatments in this study resulted in an increase in the abundance of Proteobacteria, Actinobacteria, and Firmicutes, while simultaneously reducing overall microbial diversity. The key genes involved in the denitrification process, namely, nirK, nosZ, and hao, were down-regulated, and NO3--N, NO2--N, and NH4+-N concentrations decreased by 7.7%-12.3%, 11.1%-21.3%, and 11.3%-30.9%, respectively. Notably, pond sludge samples exhibited a significant increase in the abundance of nitrogen fixation-related genes nifH, vnfK, vnfH, and vnfG following exposure to nitrile compounds. Furthermore, the fumarase gene fumD, which is responsible for catalyzing fumaric acid into malic acid in the tricarboxylic acid cycle, showed a substantial increase of 7.2-10.6-fold upon nitrile addition. Enzyme genes associated with the catechol pathway, including benB-xylY, dmpB, dmpC, dmpH, and mhpD, displayed increased abundance, whereas genes related to the benzoyl-coenzyme A pathway, such as bcrA, dch, had, oah, and gcdA, were notably reduced. In summary, complex nitrile compounds were found to significantly reduce the species diversity of soil microorganisms. Nitrile-tolerant microorganisms demonstrated the ability to degrade and adapt to nitrile pollutants by enhancing functional enzymes involved in the catechol pathway and fenugreek conversion pathway. This study offers insights into the specific responses of microorganisms to compound nitrile contamination, as well as valuable information for screening nitrile-degrading microorganisms and identifying nitrile metabolic enzymes.

Discovery of the Natural Bibenzyl Compound Erianin in Dendrobium Inhibiting the Growth and EMT of Gastric Cancer through Downregulating the LKB1-SIK2/3-PARD3 Pathway.

Erianin, a bibenzyl compound found in dendrobium extract, has demonstrated broad anticancer activity. However, its mechanism of action in gastric cancer (GC) remains poorly understood. LKB1 is a tumor-suppressor gene, and its mutation is an important driver of various cancers. Yet some studies have reported contradictory findings. In this study, we combined bioinformatics and in vitro and in vivo experiments to investigate the effect and potential mechanism of Erianin in the treatment of GC. The results show that LKB1 was highly expressed in patients' tumor tissues and GC cells, and it was associated with poor patient prognosis. Erianin could promote GC cell apoptosis and inhibit the scratch repair, migration, invasion, and epithelial-mesenchymal transition (EMT) characteristics. Erianin dose-dependently inhibited the expression of LKB1, SIK2, SIK3, and PARD3 but had no significant effect on SIK1. Erianin also inhibited tumor growth in CDX mice model. Unexpectedly, 5-FU also exhibited a certain inhibitory effect on LKB1. The combination of Erianin and 5-FU significantly improved the anti-tumor efficacy of 5-FU in the growth of GC cells and xenograft mouse models. In summary, Erianin is a potential anti-GC compound that can inhibit GC growth and EMT properties by targeting the LKB1-SIK2/3-PARD3-signaling axis. The synergistic effect of Erianin and 5-FU suggests a promising therapeutic strategy for GC treatment.

Effect of α7 nAChR-autophagy axis of deciduous tooth pulp stem cells in regulating IL-1ß in the process of physiological root resorption of deciduous teeth.

Physiological root resorption of deciduous teeth is a normal phenomenon occurring during the developmental stages of children. Previous research has indicated the pivotal role of the inflammatory microenvironment in this process, although the specific mechanisms remain unclear. This study is aimed at elucidating the involvement of the alpha7 nicotinic acetylcholine receptors (α7 nAChR)-autophagy axis in the regulation of the inflammatory microenvironment during physiological root resorption in deciduous teeth. Samples were collected from deciduous teeth at various stages of physiological root resorption, and deciduous dental pulp stem cells (DDPSCs) were isolated and cultured during the mid-phase of root resorption. The findings revealed a substantial infiltration of the pulp of deciduous teeth at the mid-phase of root resorption, characterized by elevated expression levels of α7 nAChR and IL-1ß. Significantly increased IL-1ß and α7 nAChR expressions were observed in DDPSCs during the mid-phase of root resorption, with α7 nAChR demonstrating a regulatory effect on IL-1ß. Moreover, evidence suggested that mechanical stress may act as a trigger, regulating autophagy and IL-1 expression via α7 nAChR. In conclusion, mechanical stress was identified as a regulator of autophagy in DDPSCs through α7 nAChR, influencing the expression of IL-1ß and contributing to the formation of the inflammatory microenvironment. This mechanism plays a crucial role in the physiological root resorption of deciduous teeth. KEY MESSAGES: The pulp of deciduous teeth at mid-phase of root resorption was heavily infiltrated with high expression of α7nAChR and IL-1ß. α7 nAChR acts as an initiating factor to regulate IL-1ß through autophagy in DDPSCs. Mechanical stress can regulate autophagy of DDPSCs through α7 nAChR and thus affect IL-1ß expression and inflammatory microenvironment formation in physiological root resorption in deciduous teeth.

Effects of weight-bearing dance aerobics on lower limb muscle morphology, strength and functional fitness in older women.

Objective: To investigate the effects of 12-week weight-bearing dance aerobics (WBDA) on muscle morphology, strength and functional fitness in older women. Methods: This controlled study recruited 37 female participants (66.31y ± 3.83) and divided them into intervention and control groups according to willingness. The intervention group received 90-min WBDA thrice a week for 12 weeks, while the control group maintained normal activities. The groups were then compared by measuring muscle thickness, fiber length and pennation angle by ultrasound, muscle strength using an isokinetic multi-joint module and functional fitness, such as 2-min step test, 30-s chair stand, chair sit-and-reach, TUG and single-legged closed-eyed standing test. The morphology, strength, and functional fitness were compared using ANCOVA or Mann-Whitney U test to study the effects of 12 weeks WBDA. Results: Among all recruited participants, 33 completed all tests. After 12 weeks, the thickness of the vastus intermedius (F = 17.85, P < 0.01) and quadriceps (F = 15.62, P < 0.01) was significantly increased in the intervention group compared to the control group, along with a significant increase in the torque/weight of the knee flexor muscles (F = 4.47, P = 0.04). Similarly, the intervention group revealed a significant improvement in the single-legged closed-eyed standing test (z = -2.16, P = 0.03) compared to the control group. Conclusion: The study concluded that compared to the non-exercising control group, 12-week WBDA was shown to thicken vastus intermedius, increase muscle strength, and improve physical function in older women. In addition, this study provides a reference exercise program for older women.

Common intentional binding effects across diverse sensory modalities in touch-free voluntary actions.

The intentional binding effect refers to the phenomenon where the perceived temporal interval between a voluntary action and its sensory consequence is subjectively compressed. Prior research revealed the importance of tactile feedback from the keyboard on this effect. Here we examined the necessity of such tactile feedback by utilizing a touch-free key-press device without haptic feedback, and explored how initial/outcome sensory modalities (visual/auditory/tactile) and their consistency influence the intentional binding effect. Participants estimated three delay lengths (250, 550, or 850 ms) between the initial and outcome stimuli. Results showed that regardless of the combinations of sensory modalities between the initial and the outcome stimuli (i.e., modal consistency), the intentional binding effect was only observed in the 250 ms delay condition. This findings indicate a stable intentional binding effect both within and across sensory modalities, supporting the existence of a shared mechanism underlying the binding effect in touch-free voluntary actions.

SNX32 Regulates Sorting and Trafficking of Activated EGFR to the Lysosomal Degradation Pathway.

SNX32 is a member of the evolutionarily conserved Phox (PX) homology domain- and Bin/Amphiphysin/Rvs (BAR) domain- containing sorting nexin (SNX-BAR) family of proteins, which play important roles in sorting and membrane trafficking of endosomal cargoes. Although SNX32 shares the highest amino acid sequence homology with SNX6, and has been believed to function redundantly with SNX5 and SNX6 in retrieval of the cation-independent mannose-6-phosphate receptor (CI-MPR) from endosomes to the trans-Golgi network (TGN), its role(s) in intracellular protein trafficking remains largely unexplored. Here, we report that it functions in parallel with SNX1 in mediating epidermal growth factor (EGF)-stimulated postendocytic trafficking of the epidermal growth factor receptor (EGFR). Moreover, SNX32 interacts directly with EGFR, and recruits SNX5 to promote sorting of EGF-EGFR into multivesicular bodies (MVBs) for lysosomal degradation. Thus, SNX32 functions distinctively from other SNX-BAR proteins to mediate signaling-coupled endolysosomal trafficking of EGFR.

Zinc finger transcription factor ZFP1 is associated with growth, conidiation, osmoregulation, and virulence in the Polygonatum kingianum pathogen Fusarium oxysporum.

Rhizome rot is a destructive soil-borne disease of Polygonatum kingianum and adversely affects the yield and sustenance of the plant. Understanding how the causal fungus Fusarium oxysporum infects P. kingianum may suggest effective control measures against rhizome rot. In germinating conidia of infectious F. oxysporum, expression of the zinc finger transcription factor gene Zfp1, consisting of two C2H2 motifs, was up-regulated. To characterize the critical role of ZFP1, we generated independent deletion mutants (zfp1) and complemented one mutant with a transgenic copy of ZFP1 (zfp1 tZFP1). Mycelial growth and conidial production of zfp1 were slower than those of wild type (ZFP1) and zfp1 tZFP1. Additionally, a reduced inhibition of growth suggested zfp1 was less sensitive to conditions promoting cell wall and osmotic stresses than ZFP1 and zfp1 tZFP1. Furthermore pathogenicity tests suggested a critical role for growth of zfp1 in infected leaves and rhizomes of P. kingianum. Thus ZFP1 is important for mycelial growth, conidiation, osmoregulation, and pathogenicity in P. kingianum.

Comparison of totally robotic and totally laparoscopic gastrectomy for gastric cancer: a propensity score matching analysis.

BACKGROUND: With the improvements in laparoscopic or robotic surgical techniques and instruments, a growing number of surgeons have attempted to complete all digestive tract reconstruction intracorporeally; these procedures include totally robotic gastrectomy (TRG) and totally laparoscopic gastrectomy (TLG). This study aimed to evaluate the safety and feasibility of the TRG and compare the short-term outcomes of the TRG and TLG in patients with gastric cancer. METHODS: Between January 2018 and June 2023, 346 consecutive patients who underwent TRG or TLG at a high-volume academic gastric cancer specialty center were included. 1:1 propensity score matching (PSM) was performed to reduce confounding bias. The surgical outcomes, postoperative morbidity, and surgical burden were compared in PSM cohort. RESULTS: After PSM, a well-balanced cohort of 194 patients (97 in each group) was included in the analysis. The total operation time of the TRG group was significantly longer than that of the TLG group (244.9 vs. 213.0 min, P < 0.001). There was no significant difference in the effective operation time between the 2 groups (217.8 vs. 207.2 min, P = 0.059). The digestive tract reconstruction time of the TRG group was significantly shorter than that of the TLG group (39.4 vs. 46.7 min, P < 0.001). The mean blood loss in the TRG group was less than that in the TLG group (101.1 vs. 126.8 mL, P = 0.014). The TRG group had more retrieved lymph nodes in the suprapancreatic area than that in the TLG group (16.6 vs 14.2, P = 0.002). The TRG group had a lower surgery task load index (38.9 vs. 43.1, P < 0.001) than the TLG group. No significant difference was found in terms of postoperative morbidity between the 2 groups (14.4% vs. 16.5%, P = 0.691). CONCLUSION: This study demonstrated that TRG is a safe and feasible procedure, and is preferable to TLG in terms of invasion and ergonomics. The TRG may maximize the superiority of robotic surgical systems and embodies the theory of minimally invasive surgery.

Discovery of novel 1,8-naphthalimide piperazinamide based benzenesulfonamides derivatives as potent carbonic anhydrase IX inhibitors and ferroptosis inducers for the treatment of triple-negative breast cancer.

A novel series of 1,8-naphthalimide piperazinamide based benzenesulfonamides derivatives were designed and synthesized as carbonic anhydrase IX (CA IX) inhibitors and ferroptosis inducers for the treatment of triple-negative breast cancer (TNBC). The representative compound 9o exhibited more potent inhibitory activity and selective against CA IX over off-target CA II, compared with positive control SLC-0111. Molecular docking study was also performed to gain insights into the binding interactions of 9o in the binding pocket of CAIX. Moreover, compound 9o exhibited superior antitumor activities against breast cancer cells under hypoxia than that of normoxia conditions. Mechanism studies revealed that compound 9o could act as DNA intercalator and effectively suppressed cell migration, arrested the cell cycle at G1/S phase and induced apoptosis in MDA-MB-231 cells, while inducing ferroptosis accompanied by the dissipation of MMP and the elevation intracellular levels of ROS. Notably, in vivo studies demonstrated that 9o effectively inhibited tumor growth and metastasis in a highly metastatic murine breast cancer 4 T1 xenograft model. Taken together, this study suggests that compound 9o represents a potent and selective CA IX inhibitor and ferroptosis inducer for the treatment of TNBC.

Prognostic value of miR-223 for pregnancy outcomes in patients with in vitro fertilisation and intracytoplasmic sperm injection.

BACKGROUND: This study aimed to analyse the expression of microRNA-223 (miR-223) in embryo culture medium and its correlation with pregnancy outcomes. METHODS: Two hundred and two patients undergoing in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) were divided into clinical pregnancy group (n = 101) and non-pregnant group (n = 101). The baseline data, clinical indicators, and the expression level of miR-223 in the embryo medium were compared between the two groups. Logistic regression analysis was used to analyse the relationship between each index and the pregnancy outcome. Receiver operator characteristic curve was carried out to evaluate the differential ability of miR-223 in pregnancy status. Bioinformatics methods were used to identify the target genes of miR-223 and elucidate their functions. RESULTS: Compared with pregnancy group, the non-pregnancy group exhibited a reduction in miR-223 expression (p < 0.001). Multivariate analysis revealed that miR-223 reduction was an independent factor for pregnancy failure (p < 0.05). The ROC curve demonstrated the discriminative capability of miR-223 in distinguishing pregnancy and non-pregnancy. In addition, bioinformatics analysis indicated that the target genes of miR-223 were predominantly located in the endocytic vesicle membrane and were primarily enriched in adenosine monophosphate-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) signalling pathways. CONCLUSION: In this study, levels of miR-223 in the embryo culture medium predicted pregnancy outcomes in subjects undergoing IVF/ICSI. Low expression of miR-223 was a risk factor for adverse pregnancy outcomes in subjects.

In this study, 202 patients who underwent IVF/ICSI were retrospectively analysed and categorised into pregnant and non-pregnant groups based on their pregnancy status. The examination of embryo culture medium samples from both groups revealed that the non-pregnant group exhibited lower miR-223 expression compared to the pregnant group. Subsequent ROC analysis demonstrated the clinical relevance of miR-223 in effectively distinguishing between pregnant and non-pregnant states. Multi-factor analysis further established that the diminished expression of miR-223 independently influenced the likelihood of successful pregnancy.

The effect of systematic couple group therapy on families with depressed juveniles: a pilot trial.

Background: Depression is a primary cause of illness and disability among teenagers, and the incidence of depression and the number of untreated young people have increased in recent years. Effective intervention for those youths could decrease the disease burden and suicide or self-harm risk during preadolescence and adolescence. Objective: To verify the short efficacy of the systemic couple group therapy (SCGT) on youths' depression changes and families with depressed adolescents. Methods: The study was a self-control trial; only within-group changes were evaluated. Participants were couples with a depressed child who was resistant to psychotherapy; they were recruited non-randomly through convenient sampling. The paired-sample t-test and Wilcoxon signed-rank test were used to compare differences before and after interventions. The effect sizes were also estimated using Cohen's d. Spearman's correlation analysis was used to examine associations between changes. Results: A downward trend was seen in depressive symptoms after treatment, and Cohen's d was 0.33 (p = 0.258). The adolescents perceived fewer interparental conflicts, and the effect sizes were medium for perceived conflict frequency (0.66, p = 0.043), conflict intensity (0.73, p = 0.028), conflict solutions (0.75, p = 0.025), coping efficacy (0.68, p = 0.038), and perceived threat (0.57, p = 0.072). For parents, global communication quality, constructive communication patterns, and subjective marital satisfaction significantly improved after interventions, with large effect sizes (1.11, 0.85, and 1.03, respectively; all p < 0.001). Other destructive communication patterns such as demand/withdraw (p = 0.003) and mutual avoidance (p = 0.018) and communication strategies like verbal aggression (p = 0.012), stonewalling (p = 0.002), avoidance-capitulation (p = 0.036), and child involvement (p = 0.001) also reduced, with medium effect sizes (0.69, 0.52, 0.55, 0.71, 0.46, and 0.79, respectively). Meanwhile, the associations between depression changes and changes in interparental conflicts (p < 0.001) and marital satisfaction (p = 0.001) were significant. Conclusions and clinical relevance: The SCGT offers the possibility for the treatment of families with depressed children who are unwilling to seek treatment. Helping parents improve communication and marital quality may have benefits on children's depressive symptoms.

The Oncolytic virus VT1092M and an Anti-PD-L1 antibody synergize to induce systemic antitumor immunity in a murine bilateral tumor model.

This study investigated the synergistic potential of an oncolytic herpes simplex virus armed with interleukin 12 (VT1092M) in combination with immune checkpoint inhibitors for enhancing antitumor responses. The potential of this combination treatment to induce systemic antitumor immunity was assessed using bilateral subcutaneous tumor and tumor re-challenge mouse models. The antitumor efficacy of various OV and ICI treatment combinations and the underlying mechanisms were explored through diverse analytical techniques, including flow cytometry and RNA sequencing. Using VT1092M, either alone or in combination with an anti-PD-L1 antibody, significantly reduced the sizes of both the injected and untreated abscopal tumors in a bilateral tumor mouse model. The combination therapy demonstrated superior antitumor efficacy to the other treatment conditions tested, which was accompanied by an increase in T cell numbers and CD8+T cell activation. Results from the survival and tumor re-challenge experiments showed that the combination therapy elicited long-term, tumor-specific immune responses, which were associated with tumor clearance and prolonged survival. Immune cell depletion assays identified CD8+T cells as the crucial mediators of systemic antitumor immunity during combination therapy. In conclusion, the combination of VT1092M and PD-L1 blockade emerged as a potent inducer of antitumor immune responses, surpassing the efficacy of each monotherapy. This synergistic approach holds promise for achieving robust and sustained antitumor immunity, with potential implications for preventing tumor metastasis in patients with cancer.