Exploring regulatory network of icariin synthesis in Herba Epimedii through integrated omics analysis.

Herba Epimedii's leaves are highly valued in traditional Chinese medicine for their substantial concentration of flavonoids, which play a crucial role in manifesting the plant's therapeutic properties. This study investigated the metabolomic, transcriptomic and proteomic profiles of leaves from two Herba Epimedii cultivars, Epipremnum sagittatum (J) and Epipremnum pubescens (R), at three different developmental stages. Metabolite identification and analysis revealed a total of 1,412 and 1,421 metabolites with known structures were found. Flavonoids made up of 33%, including 10 significant accumulated icariin analogues. Transcriptomic analysis unveiled totally 41,644 differentially expressed genes (DEGs) containing five encoded genes participated in icariin biosynthesis pathways. Totally, 9,745 differentially expressed proteins (DEPs) were found, including Cluster-47248.2.p1 (UDP-glucuronosy/UDP-glucosyltransferase), Cluster-30441.2.p1 (O-glucosyltransferase), and Cluster-28344.9.p1 (anthocyanidin 3-O-glucoside 2 "-O-glucosyltransferase-like) through proteomics analysis which are involved to icariin biosynthesis. Protein-protein interaction (PPI) assay exhibited, totally 12 proteins showing a strong relationship of false discovery rate (FDR) <0.05 with these three proteins containing 2 leucine-rich repeat receptor kinase-like protein SRF7, and 5 methyl jasmonate esterase 1. Multi-omics connection networks uncovered 237 DEGs and 72 DEPs exhibited significant associations with the 10 icariin analogues. Overall, our integrated omics approach provides comprehensive insights into the regulatory network underlying icariin synthesis in Herba Epimedii, offering valuable resources for further research and development in medicinal plant cultivation and pharmaceutical applications.

Celastrol reduces lung inflammation induced by multiwalled carbon nanotubes in mice via NF-κb-signaling pathway.

Multiwalled carbon nanotubes (MWCNTs) have numerous applications in the field of carbon nanomaterials. However, the associated toxicity concerns have increased significantly because of their widespread use. The inhalation of MWCNTs can lead to nanoparticle deposition in the lung tissue, causing inflammation and health risks. In this study, celastrol, a natural plant medicine with potent anti-inflammatory properties, effectively reduced the number of inflammatory cells, including white blood cells, neutrophils, and lymphocytes, and levels of inflammatory cytokines, such as IL-1ß, IL-6, and TNF-α, in mice lungs exposed to MWCNTs. Moreover, celastrol inhibited the activation of the NF-κB-signaling pathway. This study confirmed these findings by demonstrating comparable reductions in inflammation upon exposure to MWCNTs in mice with the deletion of NF-κB (P50-/-). These results indicate the utility of celastrol as a promising pharmacological agent for preventing MWCNT-induced lung tissue inflammation.

Clinicopathological characteristics and prognosis of synchronous brain metastases from non-small cell lung cancer compared with metachronous brain metastases.

Purpose: Brain metastasis (BM) from non-small cell lung cancer (NSCLC) is a serious complication severely affecting patients' prognoses. We aimed to compare the clinicopathological features and prognosis of synchronous and metachronous BM from NSCLC. Methods: Clinical data of 461 patients with brain metastases from NSCLC who visited the Cancer Hospital of China Medical University from 2005 to 2017 were retrospectively collected. We analyzed the pathophysiological characteristics of synchronous and metachronous BM from NSCLC and survival rates of the patients. Propensity score matching analysis was used to reduce bias between groups. In addition, we used the Kaplan-Meier method for survival analysis, log-rank test to compare survival rates, and Cox proportional hazards regression model for multivariate prognosis analysis. Results: Among 461 patients with BM, the number of people who met the inclusion criteria was 400 cases, and after 1:2 propensity score matching,130 had synchronous BM and 260 had metachronous BM. The survival time was longer for metachronous BM in driver mutation-negative patients with squamous cell carcinoma than synchronous BM. Conversely, metachronous and synchronous BM with gene mutations and adenocarcinoma showed no differences in survival time. Multivariate analysis showed that metachronous BM was an independent prognostic factor for overall survival. Furthermore, the pathological type squamous cell carcinoma and Karnofsky Performance Status score <80 were independent risk factors affecting overall survival. Conclusion: BM status is an independent factor influencing patient outcome. Moreover, synchronous and metachronous BM from NSCLC differ in gene mutation profile, pathological type, and disease progression and hence require different treatments.

[Effects of Different Forms of Nitrogen Addition on Soil Physical and Chemical Properties and Microbial Community Structure of Perennial Alpine Cultivated Grassland].

This study aimed to investigate the impact of different nitrogen forms on soil physicochemical properties and microbial community structure in perennial alpine cultivated grasslands, in order to provide scientific basis for developing nitrogen addition strategies for perennial alpine cultivated grasslands. In June 2022, a 4-year-old Qinghai grassland mixed with Poa pratensis Qinghai and Festuca sinensis Qinghai was established at the Bakatai Farm in Gonghe County, Hainan Tibetan Autonomous Prefecture, Qinghai Province. The study was conducted without fertilization as a control (CK), and three different forms of nitrogen treatments were set up, namely, U:urea (amide nitrogen), A:ammonium sulfate (ammonium nitrogen), and N:calcium nitrate (nitrate nitrogen); the nitrogen application rate for each treatment was 67.5 kg·(hm2·a)-1, and the composition and diversity of soil nutrients and microbial communities under different treatments were analyzed. The results showed that the input of exogenous ammonium nitrogen significantly increased NH4+-N content, AP content, and EC; amide nitrogen input significantly increased SOC content and TN content; and nitrate nitrogen input significantly increased NO3--N content, AN content, and TC content. Exogenous nitrogen input changed the structure of soil bacterial and fungal communities, as well as the relative abundance of dominant phyla and genera, but it did not significantly affect the alpha diversity of bacterial and fungal communities. Principal coordinate analysis (PCoA) showed that different forms of nitrogen addition had a significant impact on the Beta diversity of bacterial communities, whereas the impact on fungal communities was not significant. Redundancy analysis (RDA) indicated that nitrogen addition mainly changed the composition and structure of microbial communities through soil ammonium nitrogen. Overall, ammonium nitrogen fertilizer should be given priority in the soil remediation process of perennial cultivated grasslands in the Qinghai Tibet Plateau.

Microcystin-LR Induces Estrogenic Effects at Environmentally Relevant Concentration in Black-Spotted Pond Frogs (Pelophylax nigromaculatus): In Situ, In Vivo, In Vitro, and In Silico Investigations.

Harmful cyanobacterial blooms are frequent and intense worldwide, creating hazards for aquatic biodiversity. The potential estrogen-like effect of Microcystin-LR (MC-LR) is a growing concern. In this study, we assessed the estrogenic potency of MC-LR in black-spotted frogs through combined field and laboratory approaches. In 13 bloom areas of Zhejiang province, China, the MC-LR concentrations in water ranged from 0.87 to 8.77 µg/L and were correlated with sex hormone profiles in frogs, suggesting possible estrogenic activity of MC-LR. Tadpoles exposed to 1 µg/L, an environmentally relevant concentration, displayed a female-biased sex ratio relative to controls. Transcriptomic results revealed that MC-LR induces numerous and complex effects on gene expression across multiple endocrine axes. In addition, exposure of male adults significantly increased the estradiol (E2)/testosterone (T) ratio by 3.5-fold relative to controls. Downregulation of genes related to male reproductive endocrine function was also identified. We also showed how MC-LR enhances the expression of specific estrogen receptor (ER) proteins, which induce estrogenic effects by activating the ER pathway and hypothalamic-pituitary-gonadal (HPG) axis. In aggregate, our results reveal multiple lines of evidence demonstrating that, for amphibians, MC-LR is an estrogenic endocrine disruptor at environmentally relevant concentrations. The data presented here support the need for a shift in the MC-LR risk assessment. While hepatoxicity has historically been the focus of MC-LR risk assessments, our data clearly demonstrate that estrogenicity is a major mode of toxicity at environmental levels and that estrogenic effects should be considered for risk assessments on MC-LR going forward.

Correction: Fang et al. Study on Dispersion, Adsorption, and Hydration Effects of Polycarboxylate Superplasticizers with Different Side Chain Structures in Reference Cement and Belite Cement. Materials 2023, 16, 4168.

In the original publication [...].

Clinical Characteristics and Diagnosis of Ph-Positive Mixed Phenotype Acute Leukemia.

BACKGROUND: The goal was to improve the clinical cognition of Ph-positive mixed phenotype acute leukemia and avoid misdiagnosis or delayed diagnosis. METHODS: The clinical manifestations and laboratory results (bone marrow cell morphology, multiparameter flow cytometry, and cytogenetics) of a case of Ph-positive mixed phenotype acute leukemia were analyzed, and related literature was reviewed. RESULTS: Blood routine: WBC 386.35 x 109/L, HGB 117.00 g/L, PLT 31 x 109/L; 80% of the original cells can be seen by artificial classification. Morphological examination of bone marrow cells showed that the proliferation of nucleated cells was obviously active, and the original cells accounted for 76%. The size of the original cells was somewhat uniform, most of the cells had less mass, were stained light grayish blue, the cytoplasm particles were not obvious, the nuclei were mostly round or quasi-round, some of them showed distortion and nuclear notch, and the chromatin was coarse. Some of the cells were rich in mass, small azurin granules were seen, the nuclei were regular, most of them were round, the chromatin was fine, the myeloperoxidase and esterase staining were negative, the eosinophils accounted for 2.5%, and the basophils accounted for 0.5%. Flow cytometry immunotyping: Two groups of abnormal cells were seen in the bone marrow. 1. A group included 12.32% of nuclear cells and showed abnormal myeloid primitive cell phenotype. Main expression: CD117, CD34, CD38, HLA-DR, CD33, CD64, CD123, weak expression: CD13, CD19. 2. The other group included 45.61% of the nuclear cells and had a B-lymphoblastic phenotype. Main expression: CD34, CD38, HLA-DR, CD123, CD19, CD10, CD9, cCD79a, TDT, weak expression of CD13, CD22. Mixed phenotype acute leukemia (M/B) immunophenotype was considered. Chromosome: 46,XY,t(9; 22)(q34;q11.2) [20]. BCR-ABL (P210) fusion gene was positive. CONCLUSIONS: Mixed phenotype acute leukemia (MPAL) is a rare type of malignant hematologic disease. Its diagnosis is based on the comprehensive evaluation of bone marrow cell morphology, immunophenotype, molecular and cytogenetic features.

Drug Analysis of Voriconazole Combined with Granulocyte Colony Stimulating Factor.

BACKGROUND: The aim of the study was to improve the clinical cognition of leukemia-like reaction caused by voriconazole and granulocyte colony-stimulating factor and to avoid misdiagnosis or delayed diagnosis. METHODS: A case of drug analysis of Voriconazole combined with granulocyte colony stimulating factor was retrospectively analyzed and related literature was reviewed. RESULTS: Blood routine of the patient on July 29: WBC 13.48 x 109/L, neutrophil 85.3%, lymphocyte 13.4%, hemoglobin 111 g/L, platelet 285 x 109/L. Vancomycin was given to prevent intracranial infection. Lumbar puncture was performed on July 30, cerebrospinal fluid was sent for routine and biochemical examination, leukocytes were 0.15 x 109/L, monocytes 45%, polynuclear cells 55%, protein 1.172 g/L, Acinetobacter baumannii and Candida clorbicus were detected in sputum culture, vancomycin and meropenem static sites were given to prevent intracranial secondary infection. Fungi were detected in urine culture, and voriconazole was given to prevent fungal infection. Blood routine: White blood cell 0.61 x 109/L, neutrophil 23%, lymphocyte 73.8%, red blood cell 2.65 x 1012/L, hemoglobin 77 g/L, platelet 17 x 109/L, bone marrow was extracted after medication. Bone marrow images show poor myelodysplasia, with granulocytes dominated by protoearly cells. Subsequent flow cytometry, chromosomal karyotype, and fusion gene analysis were performed to exclude the possibility of leukemia. Flow cytometry showed that the proportion of myeloid primordial cells was not high, the granulocytes were mainly at the early and young stage, no abnormal phenotype was observed in erythrocytes, monocytes and NK cells, no obvious mature B lymphocytes were observed, and the ratio of CD4+/CD8+ was decreased. Karyotype results showed that there was no mitotic phase. The results of fusion gene analysis showed that the fusion gene was negative or lower than the detection sensitivity. Voliconazole was stopped first, and granulocyte colony stimulating factor was stopped 3 days later. Two weeks later, blood and bone marrow images basically recovered, white blood cell 7.88 x 109/L, neutrophil 46.3%, lymphocyte 48.2%, hemoglobin 126 g/L, platelet 142 x 109/L, bone marrow hyperplasia active. The proportion of three series is roughly normal. CONCLUSIONS: The reason for the occurrence of leukemia-like reaction in this patient was considered to be related to voriconazole and granulocyte colony stimulating factor, cessation of voriconazole and granulocyte colony stimulating factor, and recovery of blood and bone marrow images. In the clinical use of voriconazole and granulocyte colony stimulating factor, close attention should be paid to the drug interaction and individualized medication should be carried out to ensure the safety of medication.

Association between ideal cardiovascular health and abnormal glucose metabolism in the elderly: evidence based on real-world data.

BACKGROUND: Limited information is available on the effect of ideal cardiovascular health (CVH) and abnormal glucose metabolism in elderly people. We aimed to analyze the prevalence of CVH behaviors, abnormal glucose metabolism, and their correlation in 65 and older people. METHODS: In this study, randomized cluster sampling, multivariate logistic regression, and mediating effects analysis were used. Recruiting was carried out between January 2020 and December 2020, and 1984 participants aged 65 years or older completed the study. RESULTS: The prevalence of abnormal glucose metabolism in this group was 26.7% (n = 529), among which the prevalence of impaired fasting glucose (IFG) was 9.5% (male vs. female: 8.7% vs 10.1%, P = 0.338), and the prevalence of type 2 diabetes mellitus (T2DM) was 19.0% (male vs. female: 17.8 vs. 19.8%, P = 0.256). The ideal CVH rate (number of ideal CVH metrics ≥ 5) was only 21.0%. The risk of IFG and T2DM decreased by 23% and 20% with each increase in one ideal CVH metrics, with OR (95%CI) of 0.77(0.65-0.92) and 0.80(0.71-0.90), respectively (P -trend < 0.001). TyG fully mediated the ideal CVH and the incidence of T2DM, and its mediating effect OR (95%CI) was 0.88(0.84-0.91). CONCLUSIONS: Each increase in an ideal CVH measure may effectively reduce the risk of abnormal glucose metabolism by more than 20%.

Ideal cardiovascular health index and high-normal blood pressure in elderly people: evidence based on real-world data.

Limited information is available on the cardiovascular health (CVH) index and risk of high-normal blood pressure (HNBP) in elderly people. Randomized cluster sampling, multivariate logistic regression, and mediating effects analysis were used in this study analyze the relationship between CVH index and HNBP in the elderly. 1089 non-hypertensive residents aged 65 years or older completed the study. The positive rate of HNBP was 75.85% (male vs. female: 76.13% vs. 75.64%, P = 0.852); The ideal rate of CVH (ideal CVH index ≥ 5 items) was 14.51% (male vs. female: 15.91% vs. 13.46%, P = 0.256). Compared with people with 0-2 ideal CVH index, the risk of HNBP in people with 4 ideal indexes and ≥ 5 ideal indexes decreased by 50% and 63%, respectively, and their OR (95% CI) were 0.50 (0.31, 0.81) and 0.37 (0.21, 0.66), respectively. The results of the trend test showed that the risk of HNBP decreased by 32% for every increase in the ideal CVH index (trend P < 0.001) and TyG index does not play a mediating role in this relationship. That is, increasing the number of ideal CVH index may effectively reduce the risk of HNBP in elderly by one-third.

Suanzaoren decoction exerts its antidepressant effect via the CaMK signaling pathway.

Calmodulin-dependent protein kinases (CaMKs) are widely regarded as "memory molecules" due to their role in controlling numerous neuronal functions in the brain, and the CaMK signaling pathway plays a crucial role in controlling synaptic plasticity. Suanzaoren decoction (SZRD) can improve depression-like behavior and thus has potential benefits in the clinical treatment of depression; however, its mechanism of action is not fully understood. In this study, we found that key proteins in the CaMK signaling pathway were regulated by the decoction used to treat depression. The purpose of this research was to ascertain if the SZRD's therapeutic efficacy in the treatment of depression is associated with the modulation of key proteins in the CaMK signaling pathway. A rat model of depression was created by exposing the animals to chronic, unexpected, mild stress. Model rats were given intragastric administration of SZRD or fluoxetine every morning once a day. Protein and mRNA relative expression levels of CaM, CaMK I, and CaMK IV in the hippocampus were measured by Western blot, quantitative polymerase chain reaction, and immunohistochemistry in the hippocampus. Our findings demonstrated that SZRD significantly improved the mood of depressed rats. This indicates that SZRD, by modulating the CaMK signaling system, may alleviate depressive symptoms and lessen work and life-related pressures.

Effectiveness of Detailed Operating Room Quality Care on the Quality of Operating Room Care and Patient Satisfaction.

Objective: The current study was performed to assess the effectiveness of detailed operating room quality care on the quality of operating room care and patient satisfaction. Methods: A total of 102 patients who underwent surgery in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology between October 2020 and April 2022 were recruited and assigned to receive either conventional operating room care (conventional group) or detailed operating room quality care (quality group), with 51 cases in each group. Outcome measures for the evaluation of the detailed quality care included quality of operating room care, safe operation, incidence of errors in instrument preparation, loss of parts, incidence of intraoperative adverse reactions, and patient satisfaction. Results: Patients who received quality care showed higher scores for information acquisition ability, communication ability, standardization of nursing process, and professionalism of nursing service than those who received conventional care (P = .021, .032, .003, .043). Detailed operating room quality care resulted in significantly higher standardization of anesthesia disinfection, promptness of instrument preparation, instrument and equipment management, effectiveness of auxiliary cooperation, and standardization of medical records scores versus conventional care (P = .004, .022, .036, .004, .002). Detailed operating room quality care was associated with a lower incidence of instrument preparation errors, lost parts, and intraoperative adverse reactions than conventional care (P < .05). Patients were more satisfied with quality care (49/51, 96.1%) than with conventional care (39/51, 76.5%) (P = .004). Conclusion: Detailed operating room quality care can significantly improve patient satisfaction, enhance the quality of operating room care and safe operation, and reduce the risk of instrument preparation errors, lost parts, and intraoperative complications in the operating room.

Case report: Report of a rare encounter: metastasis of renal cell carcinoma to the thyroid.

Renal cell carcinoma (RCC) is the most common renal tumor, with lung, bone, and liver being the primary sites of metastasis. Thyroid metastasis, on the other hand, is relatively uncommon. Metastatic tumors in the thyroid gland typically manifest as multiple or isolated nodules, which can be easily overlooked due to the lack of specific clinical and imaging features. However, the identification of thyroid metastasis suggests the presence of systemic metastasis and is indicative of a poor prognosis for patients. In this paper, we present two cases of thyroid metastasis following nephrectomy, with the objective of enhancing understanding among medical community regarding the diagnosis and treatment of thyroid metastasis originating from renal cell carcinoma. By raising awareness about this phenomenon, we emphasize the importance of early detection and diagnosis to improve patient prognoses. The implementation of standardized treatment protocols at the earliest possible stage is also emphasized. Through this research, we aim to contribute to the early identification and management of thyroid metastasis in patients with renal cell carcinoma, ultimately leading to improved outcomes.

A DIRIGENT Gene GmDIR26 Regulates Pod Dehiscence in Soybean.

Pod dehiscence brings much loss for modern agricultural production, and multiple pod dehiscence components have been identified in many plant species. However, the pod dehiscence regulation factors in soybean are limited. In this study, we investigate the function of GmDIR26, a close homologues gene of pod dehiscence genes GmPdh1, PvPdh1, and CaPdh1, in the regulation of pod dehiscence in soybean. The secondary and tertiary structure analysis reveals that GmDIR26 protein has a similar structure with GmPdh1, PvPdh1, and CaPdh1 proteins. Synteny analysis of soybean and chickpea genomes shows that the genomic region surrounding GmDIR26 and CaPdh1 might be evolved from the same ancestor, and these two genes might have similar function. GmDIR26 shows an increased expression pattern during pod development and reaches a peak at beginning seed stage. Meanwhile, GmDIR26 exhibits high expression levels in dorsal suture and pod wall, but low expression pattern in ventral suture. In addition, GmDIR26 shows higher expression levels in pod dehiscence genotype than that in pod indehiscence accessions. Overexpression of GmDIR26 in soybean increases pod dehiscence in transgenic plants, of which the lignin layer in inner sclerenchyma pods is thicker and looser. The expression levels of several pod dehiscence genes are altered. Our study provides important information for further modification of pod dehiscence resistance soybean and characterization of soybean pod dehiscence regulation network.

Dose-response association between Chinese visceral adiposity index and cardiovascular disease: a national prospective cohort study.

Background: Chinese visceral adiposity index (CVAI) is a reliable visceral obesity index, but the association between CVAI and risk of cardiovascular disease (CVD) remains unclear. We explored the associations of CVAI with incident CVD, heart disease, and stroke and compared the predictive power of CVAI with other obesity indices based on a national cohort study. Methods: The present study included 7,439 participants aged ≥45 years from China Health and Retirement Longitudinal Study (CHARLS). Cox regression models were applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Restricted cubic splines analyses were adopted to model the dose-response associations. Receiver operator characteristic (ROC) analyses were used to compare the predictive ability of different obesity indices (CVAI, visceral adiposity index [VAI], a body shape index [ABSI], conicity index [CI], waist circumference [WC], and body mass index [BMI]). Results: During 7 years' follow-up, 1,326 incident CVD, 1,032 incident heart disease, and 399 stroke cases were identified. The HRs (95% CI) of CVD, heart disease, and stroke were 1.50 (1.25-1.79), 1.29 (1.05-1.57), and 2.45 (1.74-3.45) for quartile 4 versus quartile 1 in CVAI. Linear associations of CVAI with CVD, heart disease, and stroke were observed (P nonlinear >0.05) and per-standard deviation (SD) increase was associated with 17% (HR 1.17, 1.10-1.24), 12% (1.12, 1.04-1.20), and 31% (1.31, 1.18-1.46) increased risk, respectively. Per-SD increase in CVAI conferred higher risk in participants aged<60 years than those aged ≥60 years (P interaction<0.05). ROC analyses showed that CVAI had higher predictive value than other obesity indices (P<0.05). Conclusions: CVAI was linearly associated with risk of CVD, heart disease, and stroke and had best performance for predicting incident CVD. Our findings indicate CVAI as a reliable and applicable obesity index to identify higher risk of CVD.

Experimental Study of Interference in Calcitonin Testing: A Case Report and Literature Review.

BACKGROUND: Calcitonin (CT) is a sensitive serum marker of medullary thyroid carcinoma usually detected via immunoassays; however, its levels are easily disturbed by several endogenous factors. OBJECTIVE: The study aimed to discuss a case of suspected interference resulting in aberrant CT values and review previous reports of CT interference. METHODS: A female patient visited our clinic with a physical ultrasound examination showing a slightly enlarged thyroid gland with small nodules. She had elevated CT levels, inconsistent with the clinical presentation and other findings. We evaluated the results by retesting using the same platform, platform validation, multiplex dilution, Polyethylene Glycol (PEG) precipitation, heterophilic blocking tubes, and RET gene analysis. RESULTS: Retesting CT using the same platform confirmed the high value obtained. However, serial dilution of the sample produced nonlinear results, suggesting some interference. While PEG precipitation did not significantly reduce the CT level, incubating the sample in HBTs normalized the CT value, indicating interference from heterophilic antibodies. Gene sequencing revealed no RET mutations. CONCLUSION: In cases where elevated CT levels are inconsistent with clinical presentations and other findings, the laboratory technicians should communicate with clinicians, analyze the reasons for the inconsistent results, and use different methods to verify the results. Accurate testing provides realistic and reliable data for doctors and patients and helps to avoid unnecessary procedures.

Cytochrome P450 enzymes in the black-spotted frog (Pelophylax nigromaculatus): molecular characterization and upregulation of expression by sulfamethoxazole.

Cytochrome P450 (CYP) enzymes are crucial for the detoxification of xenobiotics, cellular metabolism, and homeostasis. This study investigated the molecular characterization of CYP enzymes in the black-spotted frog, Pelophylax nigromaculatus, and examined the regulation of CYP expression in response to chronic exposure to the antibiotic sulfamethoxazole (SMX) at various environmental concentrations (0, 1, 10, and 100 µg/L). The full-length cDNA of Pn-CYP26B1 was identified. The sequence included open reading frames of 1,536 bp, encoding proteins comprising 511 amino acids. The signature motif, FxxGxxxCxG, was highly conserved when compared with a number of selected animal species. SMX significantly upregulated the expression of the protein CYP26B1 in frog livers at concentrations of 1 and 10 µg/L. SMX showed an affinity for CYP26B1 of -7.6 kcal/mol, indicating a potential mechanism for SMX detoxification or adaptation of the frog. These findings contributed to our understanding of the environmental impact of antibiotics on amphibian species and underscored the importance of CYP enzymes in maintaining biochemical homeostasis under exposure to xenobiotic stress.

Immunoglobulin G4 (IgG4) Positive Associated Liver Disease.

BACKGROUND: The goal was to explore the cognition of diagnosis and treatment level of IgG4-related diseases mainly involving lymph nodes. METHODS: The clinical manifestations, laboratory indicators, histopathology, and therapeutic effects of a patient with IgG4-RD suspected of lymphoma were analyzed and the relevant literature was reviewed. RESULTS: Lymph node biopsy showed reactive hyperplasia of lymph node tissue. The liver biochemical indexes were abnormal and the bone marrow smear showed atypical lymphocytes. Lymph node section: IgG4+ cells > 100/HPF (IgG4/IgG > 40%). The serum IgG4 level was 17,200 mg/L, and the diagnosis was IgG4-RD. Oral glucocorticoids took effect after 2 weeks, and no significant enlargement of lymph nodes was observed. CONCLUSIONS: For the diagnosis of IgG4-RD, at present, histopathology is still the gold standard, but a single result cannot diagnose the disease. Comprehensive judgment should be made by combining clinical symptoms, serum IgG4 level and imaging results to prevent misdiagnosis and missed diagnosis, and to avoid over-diagnosis. Short-term hormonal diagnostic therapy may be used in highly suspected patients who cannot be diagnosed. Once diagnosed, standardized medication, adhere to follow-up, regular review, to prevent recurrence and adverse drug reactions.

Inhibition of METTL3 in macrophages provides protection against intestinal inflammation.

Inflammatory bowel disease (IBD) is prevalent, and no satisfactory therapeutic options are available because the mechanisms underlying its development are poorly understood. In this study, we discovered that increased expression of methyltransferase-like 3 (METTL3) in macrophages was correlated with the development of colitis and that depletion of METTL3 in macrophages protected mice against dextran sodium sulfate (DSS)-induced colitis. Mechanistic characterization indicated that METTL3 depletion increased the YTHDF3-mediated expression of phosphoglycolate phosphatase (PGP), which resulted in glucose metabolism reprogramming and the suppression of CD4+ T helper 1 (Th1) cell differentiation. Further analysis revealed that glucose metabolism contributed to the ability of METTL3 depletion to ameliorate colitis symptoms. In addition, we developed two potent small molecule METTL3 inhibitors, namely, F039-0002 and 7460-0250, that strongly ameliorated DSS-induced colitis. Overall, our study suggests that METTL3 plays crucial roles in the progression of colitis and highlights the potential of targeting METTL3 to attenuate intestinal inflammation for the treatment of colitis.

Paternal exposures to endocrine-disrupting chemicals induce intergenerational epigenetic influences on offspring: A review.

Endocrine-disrupting chemicals (EDCs) are ubiquitous in ecological environments and have become a great issue of public health concern since the 1990 s. There is a deep scientific understanding of the toxicity of EDCs. However, recent studies have found that the abnormal physiological functions of the parents caused by EDCs could be transmitted to their unexposed offspring, leading to intergenerational toxicity. We questioned whether sustained epigenetic changes occur through the male germline. In this review, we (1) systematically searched the available research on the intergenerational impacts of EDCs in aquatic and mammal organisms, including 42 articles, (2) summarized the intergenerational genetic effects, such as decreased offspring survival, abnormal reproductive dysfunction, metabolic disorders, and behavioral abnormalities, (3) summarized the mechanisms of intergenerational toxicity through paternal interactions, and (4) propose suggestions on future research directions to develop a deeper understanding of the ecological risk of EDCs.