Spock2 Functions as a Key Time-Series Gene of Endothelial Cells in Sepsis-Induced Cardiomyopathy.

ABSTRACT: The study aimed to investigate the pathogenesis of sepsis-induced cardiomyopathy, a leading cause of mortality in septic patients. Transcriptome data from cecal ligation and puncture-induced septic mice were analyzed at different time points (24, 48, and 72 hours) using GSE171546 data. Through weighted gene co-expression network analysis, time series, and differential expression analyses, key time-series differentially expressed genes were identified. In addition, single-cell sequencing data (GSE207363) were used for both differential and pseudotime analyses to pinpoint differentially expressed genes specific to endothelial cells. The study highlighted Spock2, S100a9, S100a8, and Xdh as differential genes specific to endothelial cells in a time-dependent manner. Immunofluorescence validation confirmed the increased expression of SPOCK2 in the endothelial cells of cecal ligation and puncture-induced septic mice. Furthermore, in vitrostudies showed that deletion of Spock2 significantly increased LPS-induced apoptosis and necrosis in human umbilical vein endothelial cells. In conclusion, SPOCK2 expression was increased in septic cardiac endothelial cells and LPS-induced human umbilical vein endothelial cells and may play a protective role.

Warming-Induced Vegetation Greening May Aggravate Soil Mercury Levels Worldwide.

Mercury, a neurotoxic substance, circulates globally, significantly stored in soils through atmospheric deposition and plant decay. Despite being deposited, mercury can be remobilized and released into the atmosphere and water, enhancing its global cycle. Recent research suggests that climate warming may amplify the remobilization of soil mercury, facilitating its incorporation into food webs that humans exploit. However, the potential geospatial feedback of soil mercury levels in response to warming remains unclear. By leveraging up-to-date soil measurements and observation-driven models, we determined the amount of mercury stored in global 0-100 cm soils to be 4.3 Tg (interquartile range: 2.5-6.3 Tg). Furthermore, our analysis indicates that warming likely aggravates global soil mercury levels, particularly in many temperate areas in East Asia, North Europe, and North America (>20 ng g-1 increase by 2100) due to warming-induced vegetation greening. Critically, observation-driven models raise the possibility that implementing ambitious mercury-emission-control schemes alone may be insufficient to counterbalance the positive feedback of soil mercury concentration, while process-based biogeochemical modeling demonstrates consistent patterns that reinforce this concern. These findings hold broad implications; for example, such feedback may catalyze mercury remobilization in land-ocean continuums and exacerbate human risks, stressing the necessity for continued reductions in greenhouse gas and mercury emissions.

Finite immune imprinting on neutralizing antibody responses to Omicron subvariants by repeated vaccinations.

OBJECTIVE: To investigate the effects of repeated vaccination with ancestral SARS-CoV-2 (Wuhan-hu-1)-based inactivated, recombinant protein subunit or vector-based vaccines on the neutralizing antibody response to Omicron subvariants. METHODS: Individuals who received four-dose vaccinations with the Wuhan-hu-1 strain, individuals who were infected with the BA.5 variant alone without prior vaccination, and individuals who experienced a BA.5 breakthrough infection following receiving 2-4 doses of the Wuhan-hu-1 vaccine were enrolled. Neutralizing antibodies against D614G, BA.5, XBB.1.5, EG.5.1, and BA.2.86 were detected using a pseudovirus-based neutralization assay. Antigenic cartography was used to analyze cross-reactivity patterns among D614G, BA.5, XBB.1.5, EG.5.1, and BA.2.86 and sera from individuals. RESULTS: The highest neutralizing antibody titers against D614G were observed in individuals who only received four-dose vaccination and those who experienced BA.5 breakthrough infection, which was also significantly higher than the antibody titers against XBB.1.5, EG.5.1, and BA.2.86. In contrast, only BA.5 infection elicited comparable neutralizing antibody titers against the tested variants. While neutralizing antibody titers against D614G or BA.5 were similar across the cohorts, the neutralizing capacity of antibodies against XBB.1.5, EG.5.1, and BA.2.86 was significantly reduced. BA.5 breakthrough infection following heterologous booster induced significantly higher neutralizing antibody titers against the variants, particularly against XBB.1.5 and EG.5.1, than uninfected vaccinated individuals, only BA.5 infected individuals, or those with BA.5 breakthrough infection after primary vaccination. CONCLUSIONS: Our findings suggest that repeated vaccination with the Wuhan-hu-1 strain imprinted a neutralizing antibody response toward the Wuhan-hu-1 strain with limited effects on the antibody response to the Omicron subvariants.

A novel variant in the keratin 12 gene in a four-generation Chinese family with high myopia.

BACKGROUND: High myopia is a major cause of visual impairment, and genetic factors play crucial roles in the pathogenesis. We performed this study to identify candidate genes for the development of high myopia in a four-generation Chinese family with myopia. METHODS: All family members with myopia and 100 healthy participants were included in this study. Data were obtained on demographics, disease history, and ocular examination results. We performed whole exome sequencing of the genomic DNA and Sanger sequencing to verify the variants. Functional analyses of the variant were performed using software programmes. RESULTS: Nine of thirteen family members were found to have high myopia, amongst which two members were also diagnosed keratoconus. A missense variant in the keratin 12 gene (KRT12, p.Val410Gly) was detected in all high myopia cases but not in other family members without high myopia or the controls. The variant was predicted to be benign by online software programmes. However, modelling of the three-dimensional structure of the protein clearly revealed conformational changes caused by the mutation. CONCLUSIONS: A missense mutation in the KRT12 gene was identified in this Chinese family, which may be associated with the pathogenesis of high myopia.

Development and evaluation of a PICC virtual simulator in neonatal nursing: A randomized controlled trial.

BACKGROUND: Peripherally Inserted Central Catheter (PICC) is essential in neonatal care, especially for critically ill infants. Traditional training for neonatal PICC insertion faces challenges such as high costs and limited practice opportunities. Virtual simulation technology has emerged as a potential training tool, providing a realistic, risk-free learning environment. OBJECTIVES: The study aimed to assess the effectiveness of a virtual simulation teaching system in neonatal PICC care training, focusing on improving nursing students' knowledge， skills and interest in pediatric nursing. DESIGN: A quasi-experimental design was used, with assessments conducted before and after the activity. PARTICIPANTS: The study involved 58 graduate nursing students from China Medical University, divided into experimental and control groups. METHODS: The System Usability Scale (SUS) was utilized to assess teachers' experiences with the PICC virtual simulation software. Students' perceptions of the software and their interest in pediatric nursing were measured using Self-Administered Questionnaires. Furthermore, Theoretical and Operational Assessments were applied to determine the extent of students' knowledge and practical skills before and after experimentation. RESULTS: Teachers and students have favorably evaluated the software system, with notable improvements in theoretical scores following testing. While the virtual simulation system does not enhance practical skills, it does increase student interest in pediatric nursing and employment. CONCLUSIONS: This neonatal virtual simulation software serves as a complement to, rather than a replacement for, traditional clinical training. Its integration into educational programs significantly enhances learning outcomes.

Occurrence, distribution, and genetic diversity of faba bean viruses in China.

With worldwide cultivation, the faba bean (Vicia faba L.) stands as one of the most vital cool-season legume crops, serving as a major component of food security. China leads global faba bean production in terms of both total planting area and yield, with major production hubs in Yunnan, Sichuan, Jiangsu, and Gansu provinces. The faba bean viruses have caused serious yield losses in these production areas, but previous researches have not comprehensively investigated this issue. In this study, we collected 287 faba bean samples over three consecutive years from eight provinces/municipalities of China. We employed small RNA sequencing, RT-PCR, DNA sequencing, and phylogenetic analysis to detect the presence of viruses and examine their incidence, distribution, and genetic diversity. We identified a total of nine distinct viruses: bean yellow mosaic virus (BYMV, Potyvirus), milk vetch dwarf virus (MDV, Nanovirus), vicia cryptic virus (VCV, Alphapartitivirus), bean common mosaic virus (BCMV, Potyvirus), beet western yellows virus (BWYV, Polerovirus), broad bean wilt virus (BBWV, Fabavirus), soybean mosaic virus (SMV, Potyvirus), pea seed-borne mosaic virus (PSbMV, Potyvirus), and cucumber mosaic virus (CMV, Cucumovirus). BYMV was the predominant virus found during our sampling, followed by MDV and VCV. This study marks the first reported detection of BCMV in Chinese faba bean fields. Except for several isolates from Gansu and Yunnan provinces, our sequence analysis revealed that the majority of BYMV isolates contain highly conserved nucleotide sequences of coat protein (CP). Amino acid sequence alignment indicates that there is a conserved NAG motif at the N-terminal region of BYMV CP, which is considered important for aphid transmission. Our findings not only highlight the presence and diversity of pathogenic viruses in Chinese faba bean production, but also provide target pathogens for future antiviral resource screening and a basis for antiviral breeding.

Enzymatic cascade reactors on carbon nanotube transistor detecting trace prostate cancer biomarker.

Biosensors based on carbon nanotube field-effect transistors (CNT-FETs) have shown great potential in biomarker detection due to their high sensitivity because of appreciable semiconducting electrical properties. However, background signal interferences in complex mediums may results in low signal-to-noise ratio, which may impose challenges for precise biomarker detection in physiological fluids. In this work, we develop an enzymatic CNT-FET, with scalable production at wafer scale, for detection of trace sarcosine that is a biopsy-correlated biomarker of prostate cancer. Enzymatic cascade rectors are constructed on the CNT to improve the reaction efficiency, thereby, enhancing the signal transduction. As such, a limit of detection as low as 105 zM is achieved in buffer solution. Owing to the enhanced reaction efficiency, the testing of clinical serum samples yields significant signal difference to discriminate the prostate cancer (PCa) samples from the benign prostatic hyperplasia (BPH) samples (P = 1.07 × 10-5), demonstrating immense potential in practical applications.

Effect of Remote Ischemic Conditioning on Organ Transplantation: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Remote ischemic conditioning (RIC) has shown great advantages in protecting organs from ischemia-reperfusion loss and applied research on RIC continues to increase. We performed a systematic review and meta-analysis to comprehensively investigate the value of RIC for different organ transplantation. METHODS: We searched PubMed, EMBASE, and the Cochrane Library from inception to November 1, 2023, for randomized controlled trials investigating whether RIC has an advantage in organ transplantation (including heart, lung, liver, and kidney) compared with controls. The primary outcomes varied according to the transplanted organ, including liver transplantation (graft loss, early allograft dysfunction, acute kidney injury, days in hospital, and mortality); kidney transplantation (delayed graft function, acute rejection (AR), graft loss, 50% decrease in serum creatinine, glomerular filtration rate, days in hospital, and mortality); heart and lung transplantation (AR, mortality). Two investigators independently selected suitable trials, assessed trial quality, and extracted the data. RESULTS: A total of 11 randomized controlled trials were included in this study, including six kidney transplants, three liver transplants, and one heart and lung transplant each, with 561 RIC cases and 564 controls, and a total of 1125 patients. The results showed that RIC did not reduce mortality in transplant patients compared with controls (liver transplant: RR0.9, 95% confidence interval [0.31-2.66]; kidney transplant: RR 0.76, 95% confidence interval [0.17-3.33]), graft failure rate (liver transplantation: RR 0.3, 95% confidence interval [0.07, 1.19]; kidney transplantation: RR 0.89, 95% confidence interval [0.35, 2.27]), length of hospital stay (liver transplantation: standard mean difference [SMD] 0.14, 95% confidence interval [-0.15, 0.42]; kidney transplantation: SMD -0.1, 95% confidence interval [-0.3, 0.11]). In addition, RIC did not improve early liver function after liver transplantation (RR 0.97, 95% confidence interval [0.55,1.7]), acute kidney injury after liver transplantation (RR 1.17 95% confidence interval [0.9, 1.54]), delayed functional recovery after renal transplantation (RR 0.84, 95% confidence interval [0.62, 1.15]), AR rate (RR 1.04, 95% confidence interval [0.72, 1.49]), 50% serum creatinine decline rate (RR 1.1, 95% confidence interval [0.88, 1.37]), glomerular filtration rate 3 months after surgery (SMD 0.13, 95% confidence interval [-0.05, 0.31]) and postoperative 12 months glomerular filtration rate (SMD 0.13, 95% confidence interval [-0.06, 0.31]). CONCLUSION: Remote ischemic modulation does not improve clinical outcomes in patients undergoing organ transplantation (heart, lung, liver, and kidney).

Retraction note to: RNA-binding protein CPSF6 regulates IBSP to affect pyroptosis in gastric cancer.

[This retracts the article on p. 1531 in vol. 15, PMID: 37746647.].

Inflammatory Reprogramming Mediates Changes in Three-Dimensional Strain Capacity and Cardiac Function in Beagle Dogs with Doxorubicin-Related Cardiomyopathy.

Background: The cardiotoxicity of doxorubicin (DOX) limits its use in cancer treatment. To address this limitation, we developed a novel animal model that uses beagle dogs to investigate DOX-induced cardiac disorders. Unfortunately, the lack of effective cardioprotection strategies against DOX-induced cardiotoxicity poses a significant challenge. To establish a canine model for low-mortality DOX-induced cardiac dysfunction and explore the relationship between inflammatory reprogramming and DOX-related cardiotoxicity. Methods: Twenty male beagle dogs aged two years were randomly assigned into the DOX (N = 10) and control (CON) (N = 10) groups. DOX was infused (1.5 mg/kg) every two weeks until doses cumulatively reached 12 mg/kg. Serum biomarkers and myocardial pathology were evaluated, while real-time fluorescence-based quantitative polymerase chain reaction (RTFQ-PCR), two- and three-dimensional echocardiography (2DE and RT3DE), functional enrichment, and matrix correlation were also performed. Results: In the DOX group, high-sensitive cardiac troponin T (hs cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) were significantly increased. Myocardial pathology indicated early to medium myocardial degeneration via a decreased cardiomyocyte cross-sectional area (CSA). Increased levels of inflammatory gene transcripts (interleukin 6 (IL6), tumor necrosis factor (TNF), transforming growth factor ß (TGF ß ), intercellular adhesion molecule 1 (ICAM1), interleukin 1 (IL1), interleukin 1 ß (IL1 ß ), and interleukin 8 (IL8)), of collagen metabolism and deposition regulatory genes (matrix metalloproteinase (MMP) family and tissue inhibitor of matrix metalloproteinase (TIMP) family), and the natriuretic peptide family (NPS) (natriuretic peptide A, B and C (NPPA, NPPB, and NPPC)) were observed. Strain abnormalities in the right ventricular longitudinal septal strain (RVLSS), right ventricular longitudinal free-wall strain (RVLFS), left ventricular global longitudinal strain (LVGLS), and left ventricular global circumferential strain (LVGCS) were detected at week 28 (vs. week 0 or CON group, p < 0.05, respectively). A significant decline in RVLSS and RVLFS occurred at week 16, which was earlier than in the corresponding left ventricular areas. A significant right ventricular ejection fraction (RVEF) decline was noted at week 16 (vs. week 0, 33.92 ± 3.59% vs. 38.58 ± 3.58%, p < 0.05), which was 12 weeks earlier than for the left ventricular ejection fraction (LVEF), which occurred at week 28 (vs. week 0, 49.02 ± 2.07% vs. 54.26 ± 4.38%, p < 0.01). The right ventricular strain and functional damages correlated stronger with inflammatory reprogramming (most R from 0.60 to 0.90) than the left ones (most R from 0.30 to 0.65), thereby indicating a more pronounced correlation. Conclusions: Inflammatory reprogramming mediated disorders of strain capacity and cardiac function predominantly in the right side of the heart in the newly established DOX-related cardiomyopathy beagle dog model.

Oncogenic and immunological role of EDIL3 in human tumours: From pan-cancer analysis to validation in gastric cancer.

Background: Epidermal growth factor-like repeats and discoidin I-like domains 3 (EDIL3) is a secreted extracellular matrix protein implicated in diverse physiological and pathological processes including embryonic development, angiogenesis, and anti-inflammatory responses. Recent reports have indicated that EDIL3 play critical roles in carcinogenesis and progression of many cancers. Herein, we performed a pan-cancer investigation to study the potential functions of EDIL3 in various cancers and experimentally validate its function in gastric cancer (GC). Methods: We analysed EDIL3 expression profiles in different tumours using The Cancer Genome Atlas database. The Kaplan-Meier Plotter was used to investigate the prognostic value of EDIL3, while receiver operating characteristic curve was performed to analyze its diagnostic efficacy. Several bioinformatics tools were used to study the association between EDIL3 and promoter methylation, gene enrichment analysis, immune infiltration, immune-related genes, and drug sensitivity. Molecular biology experiments were conducted to validate the tumorigenic effects of EDIL3. Results: EDIL3 is variably expressed in different cancers and is closely associated with clinical outcomes. An inverse correlation between EDIL3 and DNA methylation has been observed in 13 cancers. Enrichment analysis indicated that EDIL3 is correlated with many cellular pathways such as extracellular matrix receptor interactions and focal adhesion. EDIL3 was tightly associated with immune infiltration and immune checkpoints. EDIL3 knockdown can promote GC calls apoptosis while preventing proliferation, migration, and invasion in vitro. Conclusion: EDIL3 is a promising prognostic, diagnostic, and immunological biomarker in various cancers, which could be applied as a new target for cancer therapy.

Pathogenic fungi synergistically cooperate with Serratia marcescens to increase cockroach mortality.

The abuse of chemical insecticides has led to strong resistance in cockroaches, and biopesticides with active ingredients based on insect pathogens have good development prospects; however, their slow effect has limited their practical application, and improving their effectiveness has become an urgent problem. In this study, the interaction between Serratia marcescens and Metarhizium anisopliae enhanced their virulence against Blattella germanica and exhibited a synergistic effect. The combination of S. marcescens and M. anisopliae caused more severe tissue damage and accelerated the proliferation of the insect pathogen. The results of high-throughput sequencing demonstrated that the gut microbiota was dysbiotic, the abundance of the opportunistic pathogen Weissella cibaria increased, and entry into the hemocoel accelerated the death of the German cockroaches. In addition, the combination of these two agents strongly downregulated the expression of Imd and Akirin in the IMD pathway and ultimately inhibited the expression of antimicrobial peptides (AMPs). S. marcescens released prodigiosin to disrupted the gut homeostasis and structure, M. anisopliae released destruxin to damaged crucial organs, opportunistic pathogen Weissella cibaria overproliferated, broke the gut epithelium and entered the hemocoel, leading to the death of pests. These findings will allow us to optimize the use of insect pathogens for the management of pests and produce more effective biopesticides.

Variant-specific antibody response following repeated SARS-CoV-2 vaccination and infection.

The ongoing emergence of SARS-CoV-2 variants poses challenges to the immunity induced by infections and vaccination. We conduct a 6-month longitudinal evaluation of antibody binding and neutralization of sera from individuals with six different combinations of vaccination and infection against BA.5, XBB.1.5, EG.5.1, and BA.2.86. We find that most individuals produce spike-binding IgG or neutralizing antibodies against BA.5, XBB.1.5, EG.5.1, and BA.2.86 2 months after infection or vaccination. However, compared to ancestral strain and BA.5 variant, XBB.1.5, EG.5.1, and BA.2.86 exhibit comparable but significant immune evasion. The spike-binding IgG and neutralizing antibody titers decrease in individuals without additional antigen exposure, and <50% of individuals neutralize XBB.1.5, EG.5.1, and BA.2.86 during the 6-month follow-up. Approximately 57% of the 107 followed up individuals experienced an additional infection, leading to improved binding IgG and neutralizing antibody levels against these variants. These findings provide insights into the impact of SARS-CoV-2 variants on immunity following repeated exposure.

Comparative metabolic profiling of the mycelium and fermentation broth of Penicillium restrictum from Peucedanum praeruptorum rhizosphere.

Microorganisms in the rhizosphere, particularly arbuscular mycorrhiza, have a broad symbiotic relationship with their host plants. One of the major fungi isolated from the rhizosphere of Peucedanum praeruptorum is Penicillium restrictum. The relationship between the metabolites of P. restrictum and the root exudates of P. praeruptorum is being investigated. The accumulation of metabolites in the mycelium and fermentation broth of P. restrictum was analysed over different fermentation periods. Non-targeted metabolomics was used to compare the differences in intracellular and extracellular metabolites over six periods. There were significant differences in the content and types of mycelial metabolites during the incubation. Marmesin, an important intermediate in the biosynthesis of coumarins, was found in the highest amount on the fourth day of incubation. The differential metabolites were screened to obtain 799 intracellular and 468 extracellular differential metabolites. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that the highly enriched extracellular metabolic pathways were alanine, aspartate and glutamate metabolism, glyoxylate and dicarboxylate metabolism, and terpenoid backbone biosynthesis. In addition, the enrichment analysis associated with intracellular and extracellular ATP-binding cassette transporter proteins revealed that some ATP-binding cassette transporters may be involved in the transportation of certain amino acids and carbohydrates. Our results provide some theoretical basis for the regulatory mechanisms between the rhizosphere and the host plant and pave the way for the heterologous production of furanocoumarin.

Development and verification of machine learning model based on anogenital distance, penoscrotal distance, and 2D:4D finger ratio before puberty to predict hypospadias classification.

Objectives: To describe the anatomical abnormalities of hypospadias before puberty using current commonly used anthropometric index data and predict postoperative diagnostic classification. Methods: Children with hypospadias before puberty who were initially treated at Sichuan Provincial People's Hospital from April 2021 to September 2022 were selected. We recorded their preoperative penoscrotal distance, anogenital distance, 2D:4D finger ratio, and postoperative hypospadias classification. The receiver operating character curve was used for univariate analysis of the diagnostic predictive value of each index for hypospadias classification in the training set. Binary logistic regression, random forest, and support vector machine models were constructed. In addition, we also prospectively collected data from October 2022 to September 2023 as a test set to verify the constructed machine learning models. Results: This study included 389 cases, with 50 distal, 167 midshaft, and 172 proximal cases. In the validation set, the sensitivity of the binary LR, RF, and SVM was 17%, 17% and 0% for identifying the distal type, 61%, 55% and 64% for identifying the midshaft type, and 56%, 60% and 48% for identifying the proximal type, respectively. The sensitivity of the three-classification RF and SVM models was 17% and 17% for distal type, 64% and 73% for midshaft type, 60% and 60% for proximal type, respectively. In the Testing set, the sensitivity of the binary LR, RF and SVM was 6%, 0% and 0% for identifying the distal type, 64%, 55% and 66% for identifying the midshaft type, and 48%, 62% and 39% for identifying the proximal type, respectively. The sensitivity of the three-classification RF and SVM models was 12% and 0% for distal type, 57% and 77% for midshaft type, and 65% and 53% for proximal type, respectively. Compared with binary classification models, the sensitivity of the three-classification models for distal type was not improved. Conclusion: Anogenital distance and penoscrotal distance have a favorable predictive value for midshaft and proximal hypospadias, among which AGD2, with higher test efficiency and stability, is recommended as the preferred anogenital distance indicator. The 2D:4D finger ratio (RadioL, RadioR) has little predictive value for hypospadias classification.

Artificial Tactile Receptor System for Sensitive Pressure-Neural Spike Conversion.

An artificial tactile receptor is crucial for e-skin in next-generation robots, mimicking the mechanical sensing, signal encoding, and preprocessing functionalities of human skin. In the neural network, pressure signals are encoded in spike patterns and efficiently transmitted, exhibiting low power consumption and robust tolerance for bit error rates. Here, we introduce a highly sensitive artificial tactile receptor system integrating a pressure sensor, axon-hillock circuit, and neurotransmitter release device to achieve pressure signal coding with patterned spikes and controlled neurotransmitter release. Owing to the heightened sensitivity of the axon-hillock circuit to pressure-mediated current signals, the artificial tactile receptor achieves a detection limit of 10 Pa that surpasses the human tactile receptors, with a wide response range from 10 to 5 × 105 Pa. Benefiting from the appreciable pressure-responsive performance, the potential application of an artificial tactile receptor in robotic tactile perception has been demonstrated, encompassing tasks such as finger touch and human pulse detection.

Comparison of short­term outcomes and 3-year overall survival between robotic and laparoscopic gastrectomy for gastric cancer: a propensity score matching analysis.

BACKGROUND: Despite the increasing use of robotic gastrectomy (RG) as an alternative to laparoscopic gastrectomy (LG) in treating gastric cancer, controversy remains over the advantages of RG compared to LG and there is a paucity of studies comparing the two techniques regarding patient survival. METHODS: In this retrospective cohort study, 675 patients undergoing minimally invasive gastrectomy were recruited from January 2016 to January 2018 (LG: n = 567; RG: n = 108). A one-to-one propensity score matching (PSM) analysis was applied to minimize the selection bias due to confounding factors, yielding 104 patients in each of the RG and LG groups. After matching, the short-term outcomes and 3-year overall survival were compared in the two groups. RESULTS: The PSM cohort analysis showed a similar 3-year overall survival between RG and LG groups (p = .249). Concerning the short-term outcomes, the RG compared to LG resulted in lower blood loss (p = .01), lower postoperative complications (p = .001), lower postoperative pain (p = .016), earlier initiation of soft diet (p = .011), shorter hospital stay |(p = .012), but higher hospitalization expenses (p = .001). CONCLUSION: Our findings suggest that RG may offer advantages in terms of blood loss, surgical complications, recovery time, and pain management compared to LG while maintaining similar overall survival rates. However, RG is associated with higher hospital costs, potentially limiting its wider adoption. Further research, including large, multi-center randomized controlled trials with longer patient follow-up, particularly for advanced gastric cancer, is needed to confirm these findings.

Moxibustion ameliorates chronic inflammatory visceral pain via spinal circRNA-miRNA-mRNA networks: a central mechanism study.

This study aimed to unveil the central mechanism of moxibustion treating chronic inflammatory visceral pain (CIVP) from the angle of circRNA-miRNA-mRNA networks in the spinal cord. The rat CIVP model was established using a mixture of 5% (w/v) 2,4,6-trinitrobenzene sulfonic acid and 50% ethanol at a volume ratio of 2:1 via enema. Rats in the moxibustion group received herb-partitioned moxibustion at Tianshu (ST25, bilateral) and Qihai (CV6) points. The abdominal withdrawal reflex (AWR), mechanical withdrawal threshold (MWT), and thermal withdrawal latency (TWL) were adopted for pain behavior observation and pain sensitivity assessment. The circRNA, miRNA, and mRNA expression profiles were detected using the high-throughput sequencing technique. Relevant databases and bioinformatics analysis methods were used to screen for differentially expressed (DE) RNAs and build a circRNA-miRNA-mRNA (competing endogenous RNA) ceRNA regulatory network. The real-time quantitative PCR was employed to verify the sequencing result. CIVP rat models had a significantly higher AWR and lower TWL and MWT than normal rats. Between normal and model rats, there were 103 DE-circRNAs, 16 DE-miRNAs, and 397 DE-mRNAs in the spinal cord. Compared with the model group, the moxibustion group had a lower AWR and higher TWL and MWT; between these two groups, there were 118 DE-circRNAs, 15 DE-miRNAs, and 804 DE-mRNAs in the spinal cord. Two ceRNA networks were chosen to be verified. As a result, moxibustion's analgesic effect on visceral pain in CIVP rats may be associated with regulating the circRNA_02767/rno-miR-483-3p/Gfap network in the spinal cord and improving central sensitization.

Genetic blockade of the activation of 26S proteasomes by PKA is well tolerated by mice at baseline.

OBJECTIVE: Proteasome activation by the cAMP-dependent protein kinase (PKA) was long suggested and recent studies using both cell cultures and genetically engineered mice have established that direct phosphorylation of RPN6/PSMD11 at Serine14 (pS14-RPN6) mediates the activation of 26S proteasomes by PKA. Genetic mimicry of pS14-RPN6 has been shown to be benign at baseline and capable of protecting against cardiac proteinopathy in mice. Here we report the results from a comprehensive baseline characterization of the Rpn6S14A mice (S14A), the first animal model of genetic blockade of the activation of 26S proteasomes by PKA. METHOD: Wild type and homozygous S14A littermate mice were subjected to serial M-mode echocardiography at 1 through 7 months of age, to left ventricular (LV) catheterization via the carotid artery for assessment of LV mechanical performance, and to cardiac gravimetric analyses at 26 weeks of age. Mouse mortality and morbidity were monitored daily for up to one year. Males and females were studied in parallel. RESULTS: Mice homozygous for S14A were viable and fertile and did not show discernible developmental abnormalities or increased mortality or morbidity compared with their Rpn6 wild type littermates by at least one year of age, the longest cohort observed thus far. Neither serial echocardiography nor hemodynamic assessments detected a remarkable difference in cardiac morphometry and function between S14A and wild type littermate mice. No cardiac gravimetric difference was observed. CONCLUSION: The findings of the present study indicate that genetic blockade of the activation of 26S proteasomes by PKA is well tolerated by mice at baseline. Therefore, the S14A mouse provides a desirable genetic tool for further investigating the in vivo pathophysiological and pharmacological significance of pS14-RPN6.