Abnormal Changes Research Articles

Tangeretin inhibits airway inflammatory responses by reducing early growth response 1 (EGR1) expression in mice exposed to cigarette smoke and lipopolysaccharide

BackgroundTangeretin, a natural polymethoxyflavone compound, possesses potent anti-inflammatory activity that improves respiratory inflammation in chronic obstructive pulmonary disease (COPD). However, the molecular mechanisms underlying the anti-COPD effects of tangeretin remain unclear. In this study, we aimed to investigate the key molecular mechanisms by which tangeretin suppresses COPD-related inflammatory responses. MethodsWe conducted the investigation in phorbol-12-myristate-13-acetate (PMA)-stimulated human airway epithelial cells (in vitro) and cigarette smoke (CS)/lipopolysaccharide (LPS)-exposed mice (in vivo). ResultsTangeretin decreased the release of inflammatory mediators, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and mucin 5AC (MUC5AC), by suppressing early growth response 1 (EGR1) expression in vitro. Tangeretin and EGR1 small interfering ribonucleic acid (siRNA) combination showed a synergistic reduction in MUC5AC and TNF-α secretion. Tangeretin administration significantly inhibited the levels of reactive oxygen species (ROS) production, elastase activity, TNF-α, IL-6, and monocyte chemoattractant protein-1 (MCP-1) secretion, and macrophage and neutrophil numbers in the bronchoalveolar lavage fluid of CS/LPS-exposed mice. Tangeretin also prevented CS/LPS-induced abnormal pathological changes and excessive MUC5AC and EGR1 expression in lung tissue. ConclusionComprehensively, tangeretin inhibits the lung inflammatory response associated with COPD by reducing EGR1 expression in PMA-induced human epithelial cells and in a CS/LPS-stimulated mouse model. This study shows that tangeretin has anti-COPD properties and can be a promising alternative (or complementary) treatment for inflammatory lung disease.

Identification of circulating microbial DNA and its association with kidney function in patients with diabetic kidney disease.

Recently, substantial studies have been accumulated to indicate the important role of gut microbiota in diabetic kidney disease (DKD). The abnormal change of bacterial-derived products could imply specific injuries or play beneficial or harmful roles in DKD progression. In this study, we examined the presence and contribution of the Klebsiella oxytoca gene in the circulation of patients with DKD. We enrolled a total of 16 healthy participants, 17 patients with DKD, 5 patients with DKD requiring haemodialysis (HD), and 7 patients with CKD without diabetes. Bacterial-derived DNA (16S rDNA and a specific K. oxytoca gene) in the blood was detected using droplet digital PCR, then investigated the relationship with clinical characteristics. We identified an increase in K. oxytoca genes in the blood of DKD patients. Interestingly, blood K. oxytoca copies and K. oxytoca/ 16S DNA ratio correlated with higher blood creatinine and BUN levels together with lower eGFR in DKD patients. K. oxytoca levels were also associated with higher neutrophil percentage, lower lymphocyte frequency, and increased neutrophil-to-lymphocyte ratio. Collectively, the presence of the K. oxytoca gene in the circulation could serve as a biomarker reflecting reduced renal function in DKD patients.

Gentiopicroside Attenuates Lithium/Pilocarpine-Induced Epilepsy Seizures by Down-Regulating NR2B/CaMKII/CREB and TLR4/NF-κB Signaling Pathways in the Hippocampus of Mice.

Background: Epilepsy is a prevalent and disabling neurological condition characterized by recurrent seizures. Approximately 50% of adults with active epilepsy have at least one comorbidity and they are at a greater risk of premature death than the general population. Gentiopicroside (Gent) is a primary component of Gentiana macrophylla Pall. that has been shown to have diverse pharmacological properties. However, its role in epileptic seizures in adult mice and its underlying mechanism of action remain obscure. We aimed to explore the anti-epileptic effect and mechanism of Gent on lithium/pilocarpine (Pilo)-induced epilepsy seizures in mice. Methods: In this study, we established a lithium/Pilo-induced epilepsy model, and Gent was first given to mice 30 min before Pilo administration. Then, we detected behavioral and histopathological changes through electrocorticographic (ECoG) measurements, Nissl staining, Fluoro-Jade B (FJB) staining, and immunohistochemical staining. We then used molecular biology techniques, such as Western blotting, quantitative polymerase chain reaction (qPCR) analysis, and the enzyme-linked immunosorbent assay (ELISA) to investigate the mechanisms of Gent in lithium/Pilo-induced epileptic seizures in mice and lipopolysaccharide (LPS)-induced inflammatory astrocytes. Results: We confirmed that Gent could prevent abnormal ECoG activity, behavioral changes, and neurodegeneration. Subsequently, we found Gent could downregulate the factors that could promote apoptosis (i.e., the NR2B/CaMKII/CREB signaling cascade) and neuroinflammatory-related factors (i.e., the TLR4/NF-κB signaling cascade). Conclusions: Gent could be a potential therapeutic agent for epilepsy, offering possibilities for both prevention and treatment. Our research establishes a preliminary experimental framework for ongoing studies into Gent's efficacy as a treatment for epilepsy.

Consolidation in the right middle lobe in pediatric bronchial-pulmonary artery shunt: radiology's Aunt Minnie?

By retrospectively studying the chest computed tomography (CT) data of children with bronchial artery (BA)-pulmonary artery fistula, this study summarizes the characteristic imaging features of the disease and provides imaging support for the diagnosis and clinical treatment of these children. Digital subtraction angiography and CT angiography data were collected from 74 children with pulmonary hemorrhage following BA embolization. Bronchial-pulmonary shunt was present in 30 cases. Of the 74 children with pulmonary hemorrhage in this study, seven exhibited signs of consolidation in the middle lobe of the right lung, and bronchial-pulmonary shunt existed in all of them. A total of 30 children with BA-pulmonary artery shunt (PAS) had BA tortuosity and thickening. Regarding primary BA-PAS, the middle lobe and lower lobe of the right lung were involved in 94.1% (16) of the children. Those with a fistula located in the middle lobe of the right lung accounted for 58.8% (10 cases), of which 40.0% (four cases) presented consolidation. In this study, 41.2% (seven) of the children with primary BA-PAS exhibited no abnormal changes on chest CT, and 58.8% (10 cases) exhibited abnormal changes in the unilateral lung. For children with pulmonary hemorrhage who have consolidation in the right middle lobe, the formation of BA-PAS should be anticipated. The possibility of primary BA-PAS should not be disregarded in children with pulmonary hemorrhage with tortuosity and dilation of BAs, despite no apparent abnormalities on lung CT, or ground-glass density or consolidation on only one side. The chest CT of patients with pulmonary hemorrhage showed consolidation of the right middle lobe of the lung, which was highly likely to indicate BA-PAS.

Yigong San improves learning and memory functions of APP/PS1 transgenic mice by regulating brain fluid metabolism

To explore the mechanism by which Yigong San (YGS) improves learning and memory abilities of APP/PS1 transgenic mice in light of cerebral fluid metabolism regulation. Three-month-old male APP/PS1 transgenic mice and wild-type C57BL/6 mice were both randomized into control group, model group, donepezil (1.67 mg/kg) group, and YGS (7.5 g/kg) group and received the corresponding treatments via gavage once daily for one month. After the treatments, the mice were assessed for learning and memory functions using Morris water maze test and examined for hippocampal and cortical pathologies and amyloid plaques using HE, immunohistochemical and thioflavin S staining; ELISA and Evans blue method were used for detecting Aβ1-40 and Aβ1-42 levels in the brain tissue and serum and assessing blood-brain barrier (BBB) integrity. Immunofluorescence colocalization was used to investigate AQP4 polarization on astrocytes. Western blotting was performed to detect the expressions of VE-cadherin, ZO-1, occludin, β-amyloid precursor protein (APP), BACE1, insulin-degrading enzyme (IDE), LRP1, RAGE, and AQP4 proteins. Compared with the control mice, APP/PS1 mice showed significant impairment of learning and memory abilities, increased degeneration or necrosis of hippocampal and cortical neurons, pathological scores, Aβ-positive plaques, elevated Aβ1-40 and Aβ1-42 levels in the brain tissue and serum, increased BBB permeability, upregulated RAGE expression, lowered expressions of VE-cadherin, LRP1, ZO-1, occludin, and AQP4 proteins, and reduced AQP4- expressing GFAP-positive cells. YGS treatment significantly improved the performance of the transgenic mice in Morris water maze test, reduced hippocampal and cortical pathologies and Aβ-positive plaques, and ameliorated the abnormal changes in Aβ1-40 and Aβ1-42 levels, BBB permeability, protein expressions of RAGE, VE-cadherin, LRP1, ZO-1, occludin and AQP4, and the number of AQP4-expressing GFAP-positive cells. YGS improves learning and memory changes in APP/PS1 mice by ameliorating neuronal damage and Aβ pathology in the brain and regulating brain fluid metabolism.

H2S improves hippocampal synaptic plasticity in SPS rats via PI3K/AKT signaling pathway

Post-traumatic stress disorder (PTSD) is a severe mental illness that could impose heavy burdens on individuals and society, but effective and precise treatment modalities are unknown. The level of hydrogen sulfide (H2S) in the brain plays an important role in psychiatric diseases. However, it is still unclear whether PTSD exposure could affect the level of H2S and whether there is a correlation between H2S levels and the pathogenesis of PTSD. In this study, we selected single prolonged stress (SPS) as a PTSD model and found that SPS exposure decreased the endogenous H2S content accompanied by abnormal behavioral changes and dysregulation of the hippocampal synaptic plasticity in SPS rats. We further found that the exogenous administration of H2S could alleviate PTSD-like behaviors and improve hippocampal synaptic plasticity in SPS rats. In addition, we further used the phosphatidylinositol-3 kinase (PI3K) inhibitor LY294002 to interfere with the PI3K/AKT/BDNF signaling pathway. It was found that LY294002 significantly blocked the anti-anxiety effect and the improvement in synaptic plasticity derived from the exogenous administration of H2S in SPS rats. These results suggested that the endogenous H2S content was decreased in SPS rats, and that the exogenous administration of H2S could ameliorate abnormal disorders and improve hippocampal synaptic plasticity by mediating the PI3K/AKT pathway.

Adaptive Ransomware Detection Using Similarity-Preserving Hashing

Crypto-ransomware is a type of ransomware that encrypts the victim’s files and demands a ransom to return the files. This type of attack has been on the rise in recent years, as it offers a lucrative business model for threat actors. Research into developing solutions for detecting and halting the spread of ransomware is vast, and it uses different approaches. Some approaches rely on analyzing system calls made via processes to detect malicious behavior, while other methods focus on the affected files by creating a file integrity monitor to detect rapid and abnormal changes in file hashes. In this paper, we present a novel approach that utilizes hashing and can accommodate large files and dynamically take into account the amount of change within each file. Mainly, our approach relies on dividing each file into partitions and then performing selective hashing on those partitions to rapidly detect encrypted partitions due to ransomware. Our new approach addresses the main weakness of a previous implementation that relies on hashing files, not file partitions. This new implementation strikes a balance between the detection time and false positives based on the partition size and the threshold of partition changes before issuing an alert.

Double umbilical artery converging into a single umbilical artery: A case report.

The normal structure and Doppler parameters of the umbilical cord are closely related to many diseases, including fetal infection, chromosomal abnormalities, hypoxia, and growth and development restrictions. We report a case of bilateral umbilical artery confluence resulting in the formation of a single umbilical artery in the free segment of the fetal umbilical cord, diagnosed at 24 weeks and 4 days gestation. The fetus was born prematurely after premature membrane rupture at 31 weeks and 3 days gestation. The Toxoplasma, Others, Rubellavirus, Cytomegalovirus, Herpesvirus test showed positive results for Toxoplasma gondii, rubella virus, and herpes simplex virus IgG antibodies. A 36-year-old woman had vaginal discharge for > 1 hour at 31 weeks + 3 days gestation and came to our obstetrics department for treatment. The pregnant woman sought treatment due to premature membrane rupture and vaginal discharge for > 1 hour. The vaginal discharge was caused by Escherichia coli. After cesarean section, the Toxoplasma, Others, Rubellavirus, Cytomegalovirus, Herpesvirus test revealed positive results for the following: T gondii, rubella virus, and herpes simplex virus IgG antibodies. The patient underwent 2 ultrasound examinations and was diagnosed with umbilical artery malformation (the free segment of the umbilical cord on the fetal side converged into a single umbilical artery), which may have been related to fetal infection. The patient received anti-inflammatory and fetal lung maturation treatment for 2 days before undergoing a cesarean section. The mother and newborn received anti-inflammatory, symptomatic, and supportive treatment and were discharged after 1 week of improvement. After 1 month, 6 months, and 1 year of follow-up after birth, the growth and development of the infant (height and weight) were significantly lower than those of her peers, and her responses to sound and light were slightly delayed. Umbilical artery malformation is extremely rare and may be related to intrauterine parasitic and viral infections. Ultrasound has the advantages of being noninvasive and cost-effective and can be used to dynamically observe umbilical artery structure. An abnormal change in umbilical artery structure found during ultrasound examination can indicate intrauterine infection risk, which provides clinical guidance for further examination of pregnant women, early diagnosis, timely targeted treatment, and fetal prognosis improvement.

Ghrelin in Depression: A Promising Therapeutic Target.

Depression is a widespread disease affecting over 300 million individuals of various ethnicities and socioeconomic backgrounds globally. It frequently strikes early in life and becomes a chronic or recurring lifelong illness. Out of the various hypotheses for the pathophysiology of depression, the gut-brain axis and stress hypothesis are the ones that need to be researched, as psychological stress impairs one or more pathways of the brain-gut axis and is likely to cause brain-gut axis dysfunction and depression. A dysfunctional reciprocal gut-brain relationship may contribute to many diseases, including inflammatory disorders, abnormal stress responses, impaired behavior, and metabolic changes. The hormone ghrelin is a topic of interest concerning the gut-brain axis as it interacts with the gut-brain axis indirectly via the central nervous system or via crossing the blood-brain barrier. Ghrelin release is also affected by the gut microbes, which has also been discussed in the review. This review elaborates on Ghrelin's role in depression and its effect on various aspects like neurogenesis, HPA axis, and neuroinflammation. Furthermore, this review focuses on ghrelin as a potential target for alleviation of depressive symptoms.

Awareness of Diabetic Retinopathy Among Patients With Diabetes Mellitus in the Ernakulam District, South India: A Hospital-Based Cross-Sectional Study.

Introduction India is currently experiencing a significant burden of diabetes mellitus, characterized by its high prevalence and associated complications. Diabetic retinopathy (DR) is a major microvascular complication of diabetes, leading to blindness. Awareness regarding this ocular complication of diabetes can help prevent vision loss due to early screening and diagnosis. However, awareness of DR among diabetes patients remains low, especially among developing nations, which affects the smooth functioning of health programs and interventions. This study aimed to determine the independent predictors of awareness regarding DR among patients with diabetes mellitus in the Ernakulam district of Kerala state in South India. Methods A hospital-based cross-sectional study was conducted from June 2024 to July 2024 among patients with diabetes mellitus attending a tertiary care hospital in Kerala. A pre-tested, structured questionnaire was used to collect the data. The patients' responses regarding awareness of DR were scored on a two-point scale, with correct responses receiving a score of 2 and incorrect responses receiving a score of 1. The total score ranged from 20 to 40. The data were entered into Microsoft Excel (Microsoft® Corp., Redmond, WA, USA), numerically coded, and analyzed using IBM SPSS Statistics for Windows, Version 26 (Released 2019; IBM Corp., Armonk, NY, USA). Descriptive analysis was carried out to characterize the study participants and was expressed in frequencies, percentages, and mean (±standard deviation (SD)). Independent samples t-test and one-way analysis of variance (ANOVA) were used for bivariate analyses. A multivariable linear regression model was used to determine the independent predictors of DR awareness score. A p-value <0.05 was considered statistically significant. Results The study included a total of 253 patients. The mean ± SD age of the study participants was 58.74 ± 12.51 years, and the majority (55.7%) were females. While 161 (63.6%, 95% CI: 57.71-69.56) patients were not aware that DR was due to the abnormal changes in the blood vessels of the retina, 219 (86.6%, 95% CI: 82.36-90.76) patients were aware that DR screening includes evaluation of the retina by dilating the eye. The independent predictors that had a positive impact on DR awareness scores were: (1) age (B = 1.46; 95% CI: 1.18-2.35), (2) education (B = 4.32; 95% CI: 3.57-5.06), and (3) family history of diabetes (B = 1.04; 95% CI: -1.79 to -0.29). The independent predictor that had a negative impact on DR awareness scores was the occupation of the patients: (a) semi-professional, skilled, unskilled (B = -1.24; 95% CI: -2.26 to -0.21), and (b) unemployed, retired (B = -1.32; 95% CI: -2.43 to -0.21). Conclusion It is crucial to evaluate the awareness of DR among patients with diabetes in the Ernakulam district of Kerala, South India. Age, graduate and post-graduate levels of education, as well as family history of diabetes, were the positive predictors of awareness, while lower-level occupations, including unemployment and retirement, were the negative predictors. This information is crucial for developing effective strategies for the early detection, treatment, and prevention of this ocular complication of diabetes. Future research should include longitudinal studies coupled with in-depth interviews, which would provide valuable insights into public perception and attitudes toward DR.

Integrated serum pharmacochemistry, 16S rDNA sequencing, and metabolomics to reveal the material basis and mechanism of Shouhui Tongbian capsule against diphenoxylate-induced slow transit constipation in rats

BackgroundSlow transit constipation (STC) is highly prevalent and has rising incidence. Shouhui Tongbian capsule (SHTB) is a traditional Chinese Medicine formula with extensive and highly efficacious usage in STC treatment, however, its mechanism of action, especially the regulation of microbiome and lipid metabolites, remains unclear.MethodsAfter quality control of SHTB using LC‒MS to obtain its material basis, we tried to elucidate the cohesive modulatory network of SHTB against STC using hyphenated methods from microbiomics, lipidomics, mass spectrometry imaging (MSI) and molecular methods.ResultsSHTB could repair intestinal barrier damage, reduce systemic inflammation and increase intestinal motility in a diphenoxylate-induced STC rat model. Based on 16S rDNA sequencing results, SHTB rehabilitated the abnormal changes in Alloprevotella, Coprococcus, Marvinbryantia, etc., which were associated with STC symptoms. Meanwhile, microbial functional prediction showed that lipid metabolism was improved with SHTB administration. The differential lipids, including fatty acids, lysophosphatidylcholine, phosphatidylcholine, sphingomyelin triglyceride and ceramide, that are closely related to STC disease and SHTB efficacy. Furthermore, SHTB significantly reversed the abnormal expression of these key target enzymes in colon samples, including CTP-phosphocholine cytidylyltransferase, CTP-phosphoethanolamine cytidylyltransferase, phosphatidic acid phosphatase, acid sphingomyelinase etc.ConclusionsCombined analysis demonstrated that SHTB reducing lipid accumulation and recovery of intestinal microbial homeostasis was the critical mechanism by which SHTB treats STC.

Multi-omics approach to reveal follicular metabolic changes and their effects on oocyte competence in PCOS patients.

Polycystic ovary syndrome (PCOS) is a common heterogeneous disorder linked with endocrine and metabolic disturbances. The underlying mechanism of PCOS, especially its effect on oocyte competence, remains unclear. The study aimed to identify abnormal follicular metabolic changes using a multi-omics approach in follicular fluid from PCOS patients and to determine their effects on oocyte competence. A total of 36 women with PCOS and 35 women without PCOS who underwent in vitro fertilization and embryo transfer were included in the study. Cumulus cells and follicular fluid samples were collected. Follicular fluid samples underwent metabolomic analysis, while cumulus cell clusters from the same patients were assessed using transcriptomic analysis. Clinical information of patients and assisted reproductive technology (ART) results were recorded. Transcriptomics and metabolomics were integrated to identify disrupted pathways, and receiver operation characteristics (ROC) analysis was conducted to identify potential diagnostic biomarkers for PCOS. Pearson correlation analysis was conducted to assess the relationship between metabolites in follicular fluid and oocyte competence (fertilization and early embryo development potential). Through multi-omics analysis, we identified aberrantly expressed pathways at both transcriptional and metabolic levels, such as the citrate cycle (TCA cycle), oxidative phosphorylation, the cAMP signaling pathway, the mTOR signaling pathway, and steroid hormone biosynthesis. Ten candidate metabolites were identified based on metabolic profiling data from these altered pathways. Phytic acid, succinic acid, 2'-deoxyinosine triphosphate, and 4-trimethylammoniobutanoic acid in the follicular fluid exhibited high specificity and sensitivity in distinguishing PCOS. Among these metabolites, L-arginine showed a negative correlation with the 2PN fertilization rate and cleavage rate, while estrone sulfate showed a negative correlation with the high-quality embryo rate in the in-vitro fertilization (IVF) cycle. We have conducted a preliminary study of a novel metabolic signature in women with PCOS using a multi-omics approach. The alterations in key metabolic pathways may enhance our understanding of the pathogenesis of PCOS.

Cold Storage Temperature Monitoring with Trilinear Interpolation

The Internet of Things (IoT) is widely applied in agriculture and in-dustry. This article proposes a 3-dimensional temperature monitoring model for cold storage, enhancing the ability to observe and detect abnormal temperature changes within the storage. Using real-time temperature acquisition and applying trilinear interpolation techniques, this model determines temperatures at all loca-tions in the storage. It accepts temperature values and sensor locations, appropri-ately segmenting the cold storage space to apply trilinear interpolation and deter-mine the temperature value at every location in the storage. The model was tested based on different number of sensors and different sensor locations. Based on that, we provide an optimal solution for the number of sensors needed for cold storage.

A highly specific two-photon fluorescent probe for real-time monitoring of acetylcholinesterase in neurogenic disorders in vivo

Acetylcholinesterase (AChE) hydrolyses choline into thiocholine, which is essential for cholinergic neurons to revert to their resting state following activation. Abnormal changes in AChE activity can directly affect nervous system function. Thus, the specific detection of AChE activity is urgently needed for elucidating the function of the nervous system and diagnosing AChE-related diseases. Current methods for detecting AChE activity have several limitations, including strong background interference and poor tissue penetration. Thus, we designed and synthesized a two-photon (TP) excited fluorescent probe, WZ-AChE, for the specific detection of AChE. Briefly, a carbamate bond was chosen to specifically recognize AChE, which can also be cleaved by AChE. The product, WZ, released strong deep red fluorescence signal under TP excitation at 800 nm. Our results showed that WZ-AChE can detect AChE activity in PC12 cells with both superior sensitivity and selectivity. In addition, we successfully applied WZ-AChE to a C. elegans Parkinson's disease (PD) model and a mouse model of depression. The findings revealed that AChE activity was greater in both disease models than in the control group. To summarize, a novel tool was created to investigate the mechanisms underlying PD and depression.

Abnormal changes in neuropsychological function, brain structure and cerebral perfusion in patients with unruptured intracranial aneurysms.

Patients with unruptured intracranial aneurysms (UIAs) often experience emotional changes and cognitive impairments. However, the specific mechanisms underlying these impairments are still not fully understood. In the present study, voxel-based morphometry (VBM) and surface-based morphometry (SBM) were employed to investigate structural alterations in 49 patients diagnosed with UIAs compared with 50 healthy controls. Additionally, this study aimed to analyze the correlations among cortical morphological indices, cerebral blood perfusion values and neuropsychological test results. Compared with control group, UIA patients exhibited increased gray matter volume in the right anterior orbitofrontal cortex and decreased gray matter volume in the left thalamus pulvinar and hippocampus. Furthermore, the fractal dimension was lower in the right postcentral gyrus and entorhinal cortex. The cerebral perfusion values in the abnormal brain regions demonstrated a downward trend, which was associated with a reduction in gray matter volume in the left thalamus pulvinar and hippocampus, elevated anxiety levels and impaired executive function. UIA patients are prone to cognitive impairment and emotional dysregulation, which are accompanied by subtle changes in local gray matter volume and decreases in fractal dimension and cerebral blood flow. These findings provide new insights into the potential mechanisms underlying the cognitive impairment observed in UIA patients.

Maternal infection with SARS-CoV-2 during early pregnancy induces hypoxia at the maternal-fetal interface.

The coronavirus disease 2019 (COVID-19) pandemic increases the risk of adverse fetal outcomes during pregnancy. Maternal infection during pregnancy, particularly with cytomegalovirus (CMV), hepatitis B and C virus, and human immunodeficiency virus can have detrimental effects on both mother and fetus, potentially leading to adverse outcomes such as spontaneous abortion or neonatal infection. However, the impact of severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection on the maternal-fetal interface remains poorly understood. In this study, we initially utilised immunofluorescence and immunohistochemical to investigate placental samples from pregnant women who were infected with SARS-CoV-2 during the first trimester. Our data indicate that infection in the first trimester induces an upregulation of hypoxia inducible factor (HIF) levels at the maternal-fetal interface. Subsequently, single-cell RNA sequencing and metabolomics sequencing analyses reveal alterations in maternal-fetal interface. Remarkably, immune cells exhibited low expression levels of HIF possibly associated with immune activation. Furthermore, our findings demonstrate a gradual reduction in transcriptome and metabolic changes as gestation progressed beyond 12-16 weeks compared to samples obtained at 6-8 weeks gestation. Overall, our study suggests that early-stage SARS-CoV-2 infection during the first trimester leads to severe hypoxia and aberrant cell metabolism at the maternal-fetal interface which gradually resolves as pregnancy progresses. Nevertheless, these abnormal changes may have long-term implications for maternal-fetal interface development.

ANALYZING THE RELATIONSHIP AMONG CLINICAL SYMPTOMS, X-RAY RESULTS, AND CARTILAGE WEAR PATTERNS IN KNEE OSTEOARTHRITIS USING T2 MAPPING MRI

Objectives: Osteoarthritis (OA) is a condition that causes joint pain, varying degrees of functional limitations, and a decrease in overall quality of life. The purpose of this study was to examine the progression of cartilage degeneration in knees affected by symptomatic OA and determine its relationship with X-ray and T2 map MRI findings. Methods: This study was conducted at a Tertiary Care Teaching Institute in India and involved 40 patients. It was an observational type of study. For our assessment, we utilized the Western Ontario and McMaster University (WOMAC) osteoarthrosis index to evaluate function, quality of life, and joint pain. Medical imaging technique A standing AP view of the affected knee joint was taken using plain radiographs. Once the X-rays were obtained, they were graded using the Kellgren–Lawrence Classification, which ranges from 0 to 4 grades. Results: Out of the total patients, 6.0% were &lt;40 years old, 21.2% were between 41 and 50 years old, 27.2% were between 51 and 60 years old, 39.3% were between 61 and 70 years old, and 6.0% were above 70 years old. In this study, there were 21 females (63.6%) and 12 males (36.4%). In this study, the researchers found that there was no distinction between the sides of the limb affected. Both the left and right sides were involved in 13 cases each, accounting for 39.39% of the total cases. In addition, 7 cases, or 21.21%, reported experiencing bilateral knee pain. Merchant grade reported that out of the knees examined, 17.5% had Grade 0, 45% had Grade 1, 27.5% had Grade 2, 10% had Grade 3, and none had Grade 4. Conclusion: The findings of this study suggest that T2 map MRI has the ability to accurately measure abnormal cartilage changes in conditions that affect the mechanical properties of the knee joint. It is crucial to have non-invasive methods that can assess early cartilage matrix changes. These methods are important for initiating early treatment, monitoring disease progression, planning operative procedures, and following up on operative cartilage repair.

Near-infrared probes based on the phenanthridinium for dynamic monitoring of viscosity fluctuations during mitophagy

Abnormal changes in the mitochondrial microenvironment can cause a variety of diseases. Consequently, based on the twisted intramolecular charge transfer (TICT) theory, three hemicyanine fluorescent probes 1a-c were designed and developed by linking the phenanthridine group with different electron donor groups for the dynamic detection of mitochondrial viscosity in this paper. They have the advantages of near-infrared emission, excellent pH stability and viscosity sensitivity. Optical experiments showed that the maximum absorption and emission wavelengths of the probes in different solvents located at 411 − 529 nm and 623 − 684 nm with large Stokes shifts of 133 – 230 nm. In addition, when the viscosity increased from 0.89 cP to 856 cP, their fluorescence intensities in glycerol enhanced by 115-fold, 83-fold and 303-fold compared with water, respectively. The fluorescence intensities of probes showed excellent fit to the Forster Hoffmann equation, and exhibited nearly OFF-ON response to viscosity. Moreover, the probe 1a with good photostability and low cytotoxicity could target mitochondria. It was verified that 1a also could detect variation in mitochondrial viscosity during autophagy by modelling starvation and drug-induced (rapamycin and nystatin) in HeLa cells. Therefore, this study provides a useful probe for the analysis of mitophagy process in HeLa cells by the viscosity variation of mitochondria.

Characterizing the allele-specific gene expression landscape in high hyperdiploid acute lymphoblastic leukemia with BASE.

Somatic copy number variations (CNVs), including abnormal chromosome numbers and structural changes leading to gain or loss of genetic material, play a crucial role in initiation and progression of cancer. CNVs are believed to cause gene dosage imbalances and modify cis-regulatory elements, leading to allelic expression imbalances in genes that influence cell division and thereby contribute to cancer development. However, the impact of CNVs on allelic gene expression in cancer remains unclear. Allele-specific expression (ASE) analysis, a potent method for investigating genome-wide allelic imbalance profiles in tumors, assesses the relative expression of two alleles using high-throughput sequencing data. However, many existing methods for gene-level ASE detection rely on only RNA sequencing data, which present challenges in interpreting the genetic mechanisms underlying ASE in cancer. To address this issue, we developed a robust framework that integrates allele-specific copy number calls into ASE calling algorithms by leveraging paired genome and transcriptome data from the same sample. This integration enhances the interpretability of the genetic mechanisms driving ASE, thereby facilitating the identification of driver events triggered by CNVs in cancer. In this study, we utilized BASE to conduct a comprehensive analysis of ASE in high hyperdiploid acute lymphoblastic leukemia (HeH ALL), a prevalent childhood malignancy characterized by gains of chromosomes X, 4, 6, 10, 14, 17, 18, and 21. Our analysis unveiled the comprehensive ASE landscape in HeH ALL. Through a multi-perspective examination of HeH ASEs, we offer a systematic understanding of how CNVs impact ASE in HeH, providing valuable insights to guide ASE studies in cancer.

Excretory urography can track down morphological changes in the urinary bladder associated with urachal anomalies in calves for early diagnosis.

To investigate radiographic detection by excretory urography of morphological changes in the urinary bladder associated with urachal anomalies in calves. Excretory urography was performed to detect morphological changes in the urinary bladder of 13 calves, of which 6 were nondysuric with swelling of umbilical region and 7 were dysuric without clinical umbilical swelling from November 2022 through April 2024. The urinary bladder was delineated in all 13 calves after excretory urography. The aspect ratios (length:height), which objectively evaluate the shape of the urinary bladder, ranged from 1.08 to 2.43 (1.90 in average) and 1.34 to 11.89 (4.75 in average) in nondysuric and dysuric calves, respectively. The ratios of calves with nondysuric were significantly lower than those of dysuric (P < .05). Excretory urography could play an important role in evaluating abnormal morphological changes due to urachus anomalies in the urinary bladder of calves. Among calves with dysuria, urachal anomaly should be included in the differential diagnosis. Excretory urography is proposed as an alternative option for early diagnosis among calves presenting with dysuria to improve livestock productivity.