A new method of pancreaticojejunostomy in laparoscopic pancreaticoduodenectomy: A retrospective analysis of 93 cases.

INTRODUCTION: Pancreaticojejunostomy have been studied and modified for more than a hundred years. We investigated a new method of pancreaticojejunostomy to explore its value in laparoscopic pancreaticoduodenectomy. PATIENTS AND METHODS: A retrospective analysis was conducted on the clinical data of 93 patients who underwent laparoscopic pancreaticoduodenectomy with 'Shunt-block combined' pancreaticojejunostomy at Ningbo Medical Center Lihuili Hospital from April 2017 to February 2023. RESULTS: All patients successfully completed the surgery, with two cases requiring conversion to open surgery. The average operation time was 328.5 (180-532) min, the average intraoperative blood loss was 182.9 (50-1000) mL and the average laparoscopic pancreaticojejunostomy time was 29.6 (20-39) min. There were no cases of grade C pancreatic fistula postoperatively, 10 cases of grade B pancreatic fistula, 43 cases of biochemical fistula and 40 cases without detected pancreatic fistula. CONCLUSION: 'Shunt-block combined' pancreaticojejunostomy was a safe and effective method for pancreaticojejunostomy in laparoscopic pancreaticoduodenectomy.

Epithelial Membrane Protein 2 (EMP2) Blockade Attenuates Pathological Neovascularization in Murine Oxygen-Induced Retinopathy.

Purpose: Retinopathy of prematurity (ROP) results from postnatal hyperoxia exposure in premature infants and is characterized by aberrant neovascularization of retinal blood vessels. Epithelial membrane protein-2 (EMP2) regulates hypoxia-inducible factor (HIF)-induced vascular endothelial growth factor (VEGF) production in the ARPE-19 cell line and genetic knock-out of Emp2 in a murine oxygen-induced retinopathy (OIR) model attenuates neovascularization. We hypothesize that EMP2 blockade via intravitreal injection protects against neovascularization. Methods: Ex vivo choroid sprouting assay was performed, comparing media and human IgG controls versus anti-EMP2 antibody (Ab) treatment. In vivo, eyes from wild-type (WT) mice exposed to hyperoxia from postnatal (P) days 7 to 12 were treated with P12 intravitreal injections of control IgG or anti-EMP2 Abs. Neovascularization was assessed at P17 by flat mount imaging. Local and systemic effects of anti-EMP2 Ab treatment were assessed. Results: Choroid sprouts treated with 30 µg/mL of anti-EMP2 Ab demonstrated a 48% reduction in vessel growth compared to control IgG-treated sprouts. Compared to IgG-treated controls, WT OIR mice treated with 4 µg/g of intravitreal anti-EMP2 Ab demonstrated a 42% reduction in neovascularization. They demonstrated down-regulation of retinal gene expression in pathways related to vasculature development and up-regulation in genes related to fatty acid oxidation and tricarboxylic acid cycle respiratory electron transport, compared to controls. Anti-EMP2 Ab-treated OIR mice did not exhibit gross retinal histologic abnormalities, vision transduction abnormalities, or weight loss. Conclusions: Our results suggest that EMP2 blockade could be a local and specific treatment modality for retinal neovascularization in oxygen-induced retinopathies, without systemic adverse effects.

Multi-omic characterization of allele-specific regulatory variation in hybrid pigs.

Hybrid mapping is a powerful approach to efficiently identify and characterize genes regulated through mechanisms in cis. In this study, using reciprocal crosses of the phenotypically divergent Duroc and Lulai pig breeds, we perform a comprehensive multi-omic characterization of regulatory variation across the brain, liver, muscle, and placenta through four developmental stages. We produce one of the largest multi-omic datasets in pigs to date, including 16 whole genome sequenced individuals, as well as 48 whole genome bisulfite sequencing, 168 ATAC-Seq and 168 RNA-Seq samples. We develop a read count-based method to reliably assess allele-specific methylation, chromatin accessibility, and RNA expression. We show that tissue specificity was much stronger than developmental stage specificity in all of DNA methylation, chromatin accessibility, and gene expression. We identify 573 genes showing allele specific expression, including those influenced by parent-of-origin as well as allele genotype effects. We integrate methylation, chromatin accessibility, and gene expression data to show that allele specific expression can be explained in great part by allele specific methylation and/or chromatin accessibility. This study provides a comprehensive characterization of regulatory variation across multiple tissues and developmental stages in pigs.

From macroautophagy to mitophagy: Unveiling the hidden role of mitophagy in gastrointestinal disorders.

In this editorial, we comment on an article titled "Morphological and biochemical characteristics associated with autophagy in gastrointestinal diseases", which was published in a recent issue of the World Journal of Gastroenterology. We focused on the statement that "autophagy is closely related to the digestion, secretion, and regeneration of gastrointestinal cells". With advancing research, autophagy, and particularly the pivotal role of the macroautophagy in maintaining cellular equilibrium and stress response in the gastrointestinal system, has garnered extensive study. However, the significance of mitophagy, a unique selective autophagy pathway with ubiquitin-dependent and independent variants, should not be overlooked. In recent decades, mitophagy has been shown to be closely related to the occurrence and development of gastrointestinal diseases, especially inflammatory bowel disease, gastric cancer, and colorectal cancer. The interplay between mitophagy and mitochondrial quality control is crucial for elucidating disease mechanisms, as well as for the development of novel treatment strategies. Exploring the pathogenesis behind gastrointestinal diseases and providing individualized and efficient treatment for patients are subjects we have been exploring. This article reviews the potential mechanism of mitophagy in gastrointestinal diseases with the hope of providing new ideas for diagnosis and treatment.

Sex Differences in the Expression of Cardiac Remodeling and Inflammatory Cytokines in Patients with Obstructive Sleep Apnea and Atrial Fibrillation.

Although there is a link between obstructive sleep apnea (OSA) and atrial fibrillation (AF) and numerous investigations have examined the mechanism of AF development in OSA patients, which includes cardiac remodeling, inflammation, and gap junction-related conduction disorder, there is limited information regarding the differences between the sexes. This study analyzes the impact of sex differences on the expression of cardiac remodeling, inflammatory cytokines, and gap junctions in patients with OSA and AF. A total of 154 individuals diagnosed with sleep-related breathing disorders (SRBDs) were enrolled in the study and underwent polysomnography and echocardiography. Significant OSA was defined as an apnea-hypopnea index (AHI) of ≥15 per hour. Exosomes were purified from the plasma of all SRBD patients and incubated in HL-1 cells to investigate their effects on inflammatory cytokines and GJA1 expression. The differences in cardiac remodeling and expression of these biomarkers in both sexes were analyzed. Of the 154 enrolled patients, 110 patients were male and 44 patients were female. The LA sizes and E/e' ratios of male OSA patients with concomitant AF were greater than those of control participants and those without AF (all p < 0.05). Meanwhile, female OSA patients with AF had a lower left ventricular ejection fraction than those OSA patients without AF and control subjects (p < 0.05). Regarding the expression of inflammatory cytokines and GJA1, the mRNA expression levels of GJA1 were lower and those of IL-1ß were higher in those male OSA patients with AF than in those male OSA patients without AF and control subjects (p < 0.05). By contrast, mRNA expression levels of HIF-1α were higher in those female OSA patients with and without AF than in control subjects (p < 0.05). In conclusion, our study revealed sex-specific differences in the risk factors and biomarkers associated with AF development in patients with OSA.

Impact of repetitive transcranial magnetic stimulation on cortical activity: a systematic review and meta-analysis utilizing functional near-infrared spectroscopy evaluation.

BACKGROUND: Repeated transcranial magnetic stimulation (rTMS) could induce alterations in cortical excitability and promote neuroplasticity. To precisely quantify these effects, functional near-infrared spectroscopy (fNIRS), an optical neuroimaging modality adept at detecting changes in cortical hemodynamic responses, has been employed concurrently alongside rTMS to measure and tailor the impact of diverse rTMS protocols on the brain cortex. OBJECTIVE: This systematic review and meta-analysis aimed to elucidate the effects of rTMS on cortical hemodynamic responses over the primary motor cortex (M1) as detected by fNIRS. METHODS: Original articles that utilized rTMS to stimulate the M1 cortex in combination with fNIRS for the assessment of cortical activity were systematically searched across the PubMed, Embase, and Scopus databases. The search encompassed records from the inception of these databases up until April, 2024. The assessment for risk of bias was also conducted. A meta-analysis was also conducted in studies with extractable raw data. RESULTS: Among 312 studies, 14 articles were eligible for qualitative review. 7 studies were eligible for meta-analysis. A variety of rTMS protocols was employed on M1 cortex. In inhibitory rTMS, multiple studies observed a reduction in the concentration of oxygenated hemoglobin [HbO] at the ipsilateral M1, contrasted by an elevation at the contralateral M1. Meta-analysis also corroborated this consistent trend. Nevertheless, certain investigations unveiled diminished [HbO] in bilateral M1. Several studies also depicted intricate inhibitory or excitatory interplay among distinct cortical regions. CONCLUSION: Diverse rTMS protocols led to varied patterns of cortical activity detected by fNIRS. Meta-analysis revealed a trend of increasing [HbO] in the contralateral cortices and decreasing [HbO] in the ipsilateral cortices following low frequency inhibitory rTMS. However, due to the heterogeneity between studies, further research is necessary to comprehensively understand rTMS-induced alterations in brain activity.

Association between physical activity, body composition, and cognitive performance among female office workers.

Regular physical activity can potentially prevent cognitive decline. While most studies focused on the general decline of the elderly and child and adolescent population, aging is a gradual process and cognitive decline can commence in middle age. Other than the middle-aged working population, gender-specific nuances are another overlooked area regarding the relationship between physical activity and cognitive performance. Therefore, this study examines the associations and benefits of maintaining regular physical activity habits with cognitive function and body composition in middle-aged female office workers. The results show that middle-aged females exhibited age-related declines in working memory, while no significant age-related changes are observed in reaction time and executive function. However, the regular exercise group demonstrates the ability to maintain their cognitive performance across age, unlike the sedentary group, who experiences declines in reaction time and executive function with age. Our findings highlight the significant impact of age on specific cognitive functions in middle-aged females and the positive influence of regular exercise on cognitive performance. Furthermore, this study demonstrates the potential of "the Brain Gym" App for efficient cognitive function assessment. The findings underscore the importance of regular exercise for cognitive well-being in middle-aged females and provide valuable insights into the relationship between body composition and cognitive function.

A polygenic risk score for the QT interval is an independent predictor of drug-induced QT prolongation.

Drug-induced QT prolongation (diLQTS), and subsequent risk of torsade de pointes, is a major concern with use of many medications, including for non-cardiac conditions. The possibility that genetic risk, in the form of polygenic risk scores (PGS), could be integrated into prediction of risk of diLQTS has great potential, although it is unknown how genetic risk is related to clinical risk factors as might be applied in clinical decision-making. In this study, we examined the PGS for QT interval in 2500 subjects exposed to a known QT-prolonging drug on prolongation of the QT interval over 500ms on subsequent ECG using electronic health record data. We found that the normalized QT PGS was higher in cases than controls (0.212±0.954 vs. -0.0270±1.003, P = 0.0002), with an unadjusted odds ratio of 1.34 (95%CI 1.17-1.53, P<0.001) for association with diLQTS. When included with age and clinical predictors of QT prolongation, we found that the PGS for QT interval provided independent risk prediction for diLQTS, in which the interaction for high-risk diagnosis or with certain high-risk medications (amiodarone, sotalol, and dofetilide) was not significant, indicating that genetic risk did not modify the effect of other risk factors on risk of diLQTS. We found that a high-risk cutoff (QT PGS ≥ 2 standard deviations above mean), but not a low-risk cutoff, was associated with risk of diLQTS after adjustment for clinical factors, and provided one method of integration based on the decision-tree framework. In conclusion, we found that PGS for QT interval is an independent predictor of diLQTS, but that in contrast to existing theories about repolarization reserve as a mechanism of increasing risk, the effect is independent of other clinical risk factors. More work is needed for external validation in clinical decision-making, as well as defining the mechanism through which genes that increase QT interval are associated with risk of diLQTS.

Enhancing Meibography Image Analysis Through Artificial Intelligence-Driven Quantification and Standardization for Dry Eye Research.

Purpose: This study enhances Meibomian gland (MG) infrared image analysis in dry eye (DE) research through artificial intelligence (AI). It is comprised of two main stages: automated eyelid detection and tarsal plate segmentation to standardize meibography image analysis. The goal is to address limitations of existing assessment methods, bridge the curated and real-world dataset gap, and standardize MG image analysis. Methods: The approach involves a two-stage process: automated eyelid detection and tarsal plate segmentation. In the first stage, an AI model trained on curated data identifies relevant eyelid areas in non-curated datasets. The second stage refines the eyelid area in meibography images, enabling precise comparisons between normal and DE subjects. This approach also includes specular reflection removal and tarsal plate mask refinement. Results: The methodology achieved a promising instance-wise accuracy of 80.8% for distinguishing meibography images from 399 DE and 235 non-DE subjects. By integrating diverse datasets and refining the area of interest, this approach enhances meibography feature extraction accuracy. Dimension reduction through Uniform Manifold Approximation and Projection (UMAP) allows feature visualization, revealing distinct clusters for DE and non-DE phenotypes. Conclusions: The AI-driven methodology presented here quantifies and classifies meibography image features and standardizes the analysis process. By bootstrapping the model from curated datasets, this methodology addresses real-world dataset challenges to enhance the accuracy of meibography image feature extraction. Translational Relevance: The study presents a standardized method for meibography image analysis. This method could serve as a valuable tool in facilitating more targeted investigations into MG characteristics.

Genetic variants in UNC93B1 predispose to childhood-onset systemic lupus erythematosus.

Rare genetic variants in toll-like receptor 7 (TLR7) are known to cause lupus in humans and mice. UNC93B1 is a transmembrane protein that regulates TLR7 localization into endosomes. In the present study, we identify two new variants in UNC93B1 (T314A, located proximally to the TLR7 transmembrane domain, and V117L) in a cohort of east Asian patients with childhood-onset systemic lupus erythematosus. The V117L variant was associated with increased expression of type I interferons and NF-κB-dependent cytokines in patient plasma and immortalized B cells. THP-1 cells expressing the variant UNC93B1 alleles exhibited exaggerated responses to stimulation of TLR7/-8, but not TLR3 or TLR9, which could be inhibited by targeting the downstream signaling molecules, IRAK1/-4. Heterozygous mice expressing the orthologous Unc93b1V117L variant developed a spontaneous lupus-like disease that was more severe in homozygotes and again hyperresponsive to TLR7 stimulation. Together, this work formally identifies genetic variants in UNC93B1 that can predispose to childhood-onset systemic lupus erythematosus.

Imipenem reduces the efficacy of vancomycin against Elizabethkingia species.

BACKGROUND: Elizabethkingia spp. are emerging as nosocomial pathogens causing various infections. These pathogens express resistance to a broad range of antibiotics, thus requiring antimicrobial combinations for coverage. However, possible antagonistic interactions between antibiotics have not been thoroughly explored. This study aimed to evaluate the effectiveness of antimicrobial combinations against Elizabethkingia infections, focusing on their impact on pathogenicity, including biofilm production and cell adhesion. METHODS: Double-disc diffusion, time-kill, and chequerboard assays were used for evaluating the combination effects of antibiotics against Elizabethkingia spp. We further examined the antagonistic effects of antibiotic combinations on biofilm formation and adherence to A549 human respiratory epithelial cells. Further validation of the antibiotic interactions and their implications was performed using ex vivo hamster precision-cut lung sections (PCLSs) to mimic in vivo conditions. RESULTS: Antagonistic effects were observed between cefoxitin, imipenem and amoxicillin/clavulanic acid in combination with vancomycin. The antagonism of imipenem toward vancomycin was specific to its effects on the genus Elizabethkingia. Imipenem further hampered the bactericidal effect of vancomycin and impaired its inhibition of biofilm formation and the adhesion of Elizabethkingia meningoseptica ATCC 13253 to human cells. In the ex vivo PCLS model, vancomycin exhibited dose-dependent bactericidal effects; however, the addition of imipenem also reduced the effect of vancomycin. CONCLUSIONS: Imipenem reduced the bactericidal efficacy of vancomycin against Elizabethkingia spp. and compromised its capacity to inhibit biofilm formation, thereby enhancing bacterial adhesion. Clinicians should be aware of the potential issues with the use of these antibiotic combinations when treating Elizabethkingia infections.

Characterizing substructure via mixture modeling in large-scale genetic summary statistics.

Genetic summary data are broadly accessible and highly useful including for risk prediction, causal inference, fine mapping, and incorporation of external controls. However, collapsing individual-level data into groups masks intra- and inter-sample heterogeneity, leading to confounding, reduced power, and bias. Ultimately, unaccounted substructure limits summary data usability, especially for understudied or admixed populations. Here, we present Summix2, a comprehensive set of methods and software based on a computationally efficient mixture model to estimate and adjust for substructure in genetic summary data. In extensive simulations and application to public data, Summix2 characterizes finer-scale population structure, identifies ascertainment bias, and identifies potential regions of selection due to local substructure deviation. Summix2 increases the robust use of diverse publicly available summary data resulting in improved and more equitable research.

Genotoxicity and cytotoxicity in male reproductive cells caused by sediment pollutants.

In recent years, mounting evidence has highlighted a global decline in male semen quality, paralleling an increase in male infertility problems. Such developments in the male reproductive system are likely due to a range of environmental factors, which could negatively affect the outcomes of pregnancy, reproductive health, and the well-being of fetuses. Different environmental contaminants ultimately accumulate in riverbed sediments due to gravity, so these sediments are frequently considered hotspots for pollutants. Therefore, understanding the detrimental effects of river sediment pollution on human reproductive health is crucial. This study indicates male germ cells' high vulnerability to environmental contaminants. There is a strong positive correlation between the concentration of complex accumulated pollutants from human activities and the reproductive toxicity observed in human testicular embryonic cell lines NCCIT and NTERA-2. This toxicity is characterized by increased levels of reactive oxygen species, disruption of critical cellular functions, genotoxic impacts, and the induction of cell apoptosis. This research marks a significant step in providing in vitro evidence of the damaging effects of environmental pollutants on the human male germline.

The Peptidoglycan Recognition Protein 1 confers immune evasive properties on pancreatic cancer stem cells.

OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) has limited therapeutic options, particularly with immune checkpoint inhibitors. Highly chemoresistant 'stem-like' cells, known as cancer stem cells (CSCs), are implicated in PDAC aggressiveness. Thus, comprehending how this subset of cells evades the immune system is crucial for advancing novel therapies. DESIGN: We used the KPC mouse model (LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx-1-Cre) and primary tumour cell lines to investigate putative CSC populations. Transcriptomic analyses were conducted to pinpoint new genes involved in immune evasion. Overexpressing and knockout cell lines were established with lentiviral vectors. Subsequent in vitro coculture assays, in vivo mouse and zebrafish tumorigenesis studies, and in silico database approaches were performed. RESULTS: Using the KPC mouse model, we functionally confirmed a population of cells marked by EpCAM, Sca-1 and CD133 as authentic CSCs and investigated their transcriptional profile. Immune evasion signatures/genes, notably the gene peptidoglycan recognition protein 1 (PGLYRP1), were significantly overexpressed in these CSCs. Modulating PGLYRP1 impacted CSC immune evasion, affecting their resistance to macrophage-mediated and T-cell-mediated killing and their tumourigenesis in immunocompetent mice. Mechanistically, tumour necrosis factor alpha (TNFα)-regulated PGLYRP1 expression interferes with the immune tumour microenvironment (TME) landscape, promoting myeloid cell-derived immunosuppression and activated T-cell death. Importantly, these findings were not only replicated in human models, but clinically, secreted PGLYRP1 levels were significantly elevated in patients with PDAC. CONCLUSIONS: This study establishes PGLYRP1 as a novel CSC-associated marker crucial for immune evasion, particularly against macrophage phagocytosis and T-cell killing, presenting it as a promising target for PDAC immunotherapy.

Fractionation of cassava pectins and their detailed structural analyses using various pectinolytic enzymes.

In this study, we analyzed the pectin structure within the pulp of cassava. Cassava pectin, derived from cassava pulp treatment at 120 °C for 90 min, was separated into four fractions (CP-P, CP-SD1, CP-SD2F, and CP-SD2R) based on variations in water solubility, electrical properties, and molecular weights. Sugar composition analysis demonstrated an abundance of homogalacturonan (HG) in CP-P and CP-SD2F, rhamnogalacturonan I (RG-I) in CP-SD2R, and neutral sugars in CP-SD1. Because RG-I possesses a complex structure, we analyzed CP-SD2R using various pectinolytic enzymes. Galactose was the major sugar in CP-SD2R accounting for 49 %, of which 65 % originated from arabinogalactan I, 9 % from galactose and galactooligosaccharides, 5 % from arabinogalactan II, and 11 % from galactoarabinan. Seventy-four percent of arabinose in CP-SD2R was present as galactoarabinan. The methylation (DM) and acetylation (DAc) degrees of cassava pectin were 11 and 15 %, respectively. The HG and RG-I regions exhibited DAc values of 5 and 44 %, respectively, signifying the high DAc of RG-I compared to HG. Information derived from the structural analysis of cassava pectin will enable efficient degradation of pectin and cellulose, leading to the use of cassava pulp as a raw material for biorefineries.

Myopic Regression after FS-LASIK and SMILE.

PURPOSE: To compare the degree of myopic regression after myopia correction with either femtosecond laser-assisted in situ keratomileusis (FS-LASIK) or small-incision lenticule extraction (SMILE) over 18 months. METHODS: Patients undergoing FS-LASIK or SMILE surgery for myopia correction were retrospectively recruited. The propensity scores were used to match patients by age and preoperative manifest spherical equivalent (SEQ) from these 2 groups. Myopic regression was analyzed using the Cox proportional hazard model. RESULTS: A total of 416 eyes of 416 patients undergoing FS-LASIK and 416 eyes of 416 patients undergoing SMILE were matched. Using 1-month SEQ as baseline, the SEQ regression values after FS-LASIK were 0D, -0.17 ± 0.69D, -0.24 ± 0.65D, -0.31 ± 0.65D, -0.32 ± 0.63D, and -0.33 ± 0.62D and the SEQ regression values after SMILE were 0D, -0.07 ± 0.75D, -0.18 ± 0.77D, -0.23 ± 0.82 D, -0.21 ± 0.77D, and -0.24 ± 0.68D at 1, 3, 6, 9, 12, and 18 months, respectively. The Cox proportional hazard model showed that preoperative manifest SEQ (P = 0.021) and designed optical zone (P = 0.048) are significant predictors. The selected surgical procedure had no significant effect on predicting myopic regression (P = 0.470). The cumulative survival rates of myopic regression were 54.74% and 42.10% in the FS-LASIK group and 58.66% and 43.83% in the SMILE group, at 12 and 18 months, respectively (log-rank test, P = 0.11). CONCLUSIONS: After matching based on age and preoperative manifest SEQ, we found that higher myopia and a smaller optical zone contribute significantly to the development of myopic regression after undergoing FS-LASIK or SMILE surgery at 18 months. The selected surgical procedure, however, does not affect the likelihood of myopic regression.

A critical role for the nuclear protein Akirin in larval development in Henosepilachna vigintioctopunctata.

Akirin is a nuclear protein that controls development in vertebrates and invertebrates. The function of Akirin has not been assessed in any Coleopteran insects. We found that high levels of akirin transcripts in Henosepilachna vigintioctopunctata, a serious Coleopteran potato defoliator (hereafter Hvakirin), were present at prepupal, pupal and adult stages, especially in larval foregut and fat body. RNA interference (RNAi) targeting Hvakirin impaired larval development. The Hvakirin RNAi larvae arrested development at the final larval instar stage. They remained as stunted larvae, gradually blackened and finally died. Moreover, the remodelling of gut and fat body was inhibited in the Hvakirin depleted larvae. Two layers of cuticles, old and newly formed, were noted in the dsegfp-injected animals. In contrast, only a layer of cuticle was found in the dsakirin-injected beetles, indicating the arrest of larval development. Furthermore, the expression of three transforming growth factor-ß cascade genes (Hvsmox, Hvmyo and Hvbabo), a 20-hydroxyecdysone (20E) receptor gene (HvEcR) and six 20E response genes (HvHR3, HvHR4, HvE75, HvBrC, HvE93 and Hvftz-f1) was significantly repressed, consistent with decreased 20E signalling. Conversely, the transcription of a juvenile hormone (JH) biosynthesis gene (Hvjhamt), a JH receptor gene (HvMet) and two JH response genes (HvKr-h1 and HvHairy) was greatly enhanced. Our findings suggest a critical role of Akirin in larval development in H. vigintioctopunctata.

O-GlcNAcylation in ischemic diseases.

Protein glycosylation is an extensively studied field, with the most studied forms being oxygen or nitrogen-linked N-acetylglucosamine (O-GlcNAc or N-GlcNAc) glycosylation. Particular residues on proteins are targeted by O-GlcNAcylation, which is among the most intricate post-translational modifications. Significantly contributing to an organism's proteome, it influences numerous factors affecting protein stability, function, and subcellular localization. It also modifies the cellular function of target proteins that have crucial responsibilities in controlling pathways related to the central nervous system, cardiovascular homeostasis, and other organ functions. Under conditions of acute stress, changes in the levels of O-GlcNAcylation of these proteins may have a defensive function. Nevertheless, deviant O-GlcNAcylation nullifies this safeguard and stimulates the advancement of several ailments, the prognosis of which relies on the cellular milieu. Hence, this review provides a concise overview of the function and comprehension of O-GlcNAcylation in ischemia diseases, aiming to facilitate the discovery of new therapeutic targets for efficient treatment, particularly in patients with diabetes.

Association between concentrations of rare earth elements in chorionic villus and risk for unexplained spontaneous abortion.

Rare earth elements (REEs) exposure during pregnancy may increase the risk of unexplained spontaneous abortion. However, the association between REEs intrauterine exposure and unexplained spontaneous abortion had yet to be studied. In order to conduct this large case-control study, we thus collected chorionic villus from 641 unexplained spontaneous abortion and 299 control pregnant women and detected the concentrations of 15 REEs by inductively coupled plasma mass spectrometer (ICP-MS). Because the detection rates of 10 REEs were less than 80%, the remaining 5 REEs, which were lanthanum (La), cerium (Ce), praseodymium (Pr), neodymium (Nd) and yttrium (Y), underwent to further analysis. The association between 5 REEs and unexplained spontaneous abortion was assessed by using the logistic regression, bayesian kernel regression (BKMR) and weighted quantile sum regression (WQS) models. In the adjusted logistic regression model, Pr, Nd and Y enhanced the incidence of unexplained spontaneous abortion in a dose-dependent way and Ce increased the risk only at high concentration group. The result of BKMR model demonstrated that the risk of unexplained spontaneous abortion increased as the percentile of five mixed REEs increased. Y and Nd were both significantly associated with an increased incidence of unexplained spontaneous abortion, but La was correlated with a decrease in the risk of unexplained spontaneous abortion. Pr was substantially associated with an increase in the risk of unexplained spontaneous abortion when other REEs concentrations were fixed at the 25th and 50th percentiles. According to WQS regression analysis, the WQS index was significantly associated with unexplained spontaneous abortion (OR = 3.75, 95% CI:2.40-5.86). Y had the highest weight, followed by Nd and Pr, which was consistent with the analysis results of our other two models. In short, intrauterine exposure to REEs was associated with an increased risk of unexplained spontaneous abortion, with Y, Nd and Pr perhaps playing an essential role.