Genetic evidence strengthens the connection between gut microbiota and gingivitis: a two-sample Mendelian randomization study.

Introduction: The oral cavity and gut tract, being interconnected and rich in microbiota, may have a shared influence on gingivitis. However, the specific role of distinct gut microbiota taxa in gingivitis remains unexplored. Utilizing Mendelian Randomization (MR) as an ideal method for causal inference avoiding reverse causality and potential confounding factors, we conducted a comprehensive two-sample MR study to uncover the potential genetic causal impact of gut microbiota on gingivitis. Methods: Instrumental variables were chosen from single nucleotide polymorphisms (SNPs) strongly associated with 418 gut microbiota taxa, involving 14,306 individuals. Gingivitis, with 4,120 cases and 195,395 controls, served as the outcome. Causal effects were assessed using random-effect inverse variance-weighted, weighted median, and MR-Egger methods. For replication and meta-analysis, gingivitis data from IEU OpenGWAS were employed. Sensitivity analyses included Cochran's Q tests, funnel plots, leave-one-out analyses, and MR-Egger intercept tests. This study aimed to assess the genetic correlation between the genetically predicted gut microbiota and gingivitis using linkage disequilibrium score regression (LDSC). Results: Three gut microbiota taxa (class Actinobacteria id.419, family Defluviitaleaceae id.1924, genus Defluviitaleaceae UCG011 id.11287) are predicted to causally contribute to an increased risk of gingivitis (P< 0.05). Additionally, four gut microbiota taxa (class Actinobacteria id.419, genus Escherichia Shigella id.3504, genus Ruminococcaceae UCG002 id.11360) potentially exhibit inhibitory causal effects on the risk of gingivitis (P< 0.05). No significant evidence of heterogeneity or pleiotropy is detected. Our findings indicate a suggestive genetic correlation between class Actinobacteria id.419, class Bacteroidia id.912, family Defluviitaleaceae id.1924, genus Escherichia Shigella id.3504 and gingivitis. Conclusion: Our study establishes the genetic causal effect of 418 gut microbiota taxa on gingivitis, offering insights for clinical interventions targeting gingivitis. Subsequent research endeavors are essential to corroborate the findings of our present study.

Transcriptome Sequencing on Treatment of Kidney Deficiency and Blood Stasis-thin Endometrium in Rats with Bushen Huoxue Prescription Through Enema / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Bushen Huoxue enema in treating the rat model of kidney deficiency and blood stasis-thin endometrium （KDBS-TE） by transcriptome sequencing. MethodThe rat model of KDBS-TE was established by administration of tripterygium polyglycosides tablets combined with subcutaneous injection of adrenaline. The pathological changes of rat endometrium in each group were then observed. Three uterine tissue specimens from each of the blank group， model group， and Bushen Huoxue enema group were randomly selected for transcriptome sequencing. The differentially expressed circRNAs， lncRNAs， and miRNAs were screened， and the disease-related specific competitive endogenous RNA （ceRNA） regulatory network was constructed. Furthermore， the gene ontology （GO） functional annotation and the Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment were performed for the mRNAs in the network. ResultCompared with the blank group， the model group showed endometrial dysplasia， decreased endometrial thickness and endometrial/total uterine wall thickness ratio （P<0.01）， and differential expression of 18 circRNAs， 410 lncRNAs， and 7 miRNAs. Compared with the model group， the enema and estradiol valerate groups showed improved endometrial morphology and increased endometrial thickness and ratio of endometrial to total uterine wall thickness （P<0.05）. In addition， 21 circRNAs， 518 lncRNAs， and 17 miRNAs were differentially expressed in the enema group. The disease-related specific circRNA-miRNA-mRNA regulatory network composed of 629 nodes and 664 edges contained 2 circRNAs， 34 miRNAs， and 593 mRNAs. The lncRNA-miRNA-mRNA regulatory network composed of 180 nodes and 212 edges contained 5 lncRNAs， 10 miRNAs， and 164 mRNAs. The mNRAs were mainly enriched in Hippo signaling pathway， autophagy-animal， axon guidance， etc. ConclusionBushen Huoxue enema can treat KDBS-TE in rats by regulating specific circRNAs， lncRNAs， and miRNAs in the uterus and the ceRNA network.

[Distribution Characteristics and Environmental Driving Factors of Cyanobacteria Community in Impounded Lakes and Reservoirs in Shandong on the East Route of South-to-North Water Diversion Project].

To investigate the distribution characteristics of the cyanobacteria community and the driving factors in impounded lakes and reservoirs in Shandong on the east route of the South-to-North Water Diversion Project, monthly samples of phytoplankton and the aquatic environment from Nansi Lake, Dongping Lake, Datun Reservoir, Donghu Reservoir, and Shuangwangcheng Reservoir were collected from May to November during 2010 to 2019. A total of 44 planktonic cyanobacteria taxa were identified with 23 filamentous cyanobacteria taxa. Pseudanabaena limnetica, Cylindrospermopsis raciborskii, Microcystis aeruginosa, and Microcystis wesenbergii were the dominant harmful cyanobacteria species, with a high detection frequency and abundance in all lakes and reservoirs. By analyzing the distribution characteristics of the cyanobacteria community in impounded lakes and reservoirs, we found that filamentous cyanobacteria had growth advantages in the water with large hydraulic disturbances, which should be the key points of cyanobacteria prevention and control in the future. Pearson correlation analysis and generalized linear fitting curve results showed that total nitrogen, total phosphorus, water temperature, and water depth played a key role in affecting the growth of P. limnetica, C. raciborskii, M. aeruginosa, and M. wesenbergii. The nitrogen and phosphorus nutrients could promote the growth of harmful cyanobacteria. Due to the good temperature adaptability, P. limnetica could still become the dominant species in early summer and late autumn, and C. raciborskii, M. aeruginosa, and M. wesenbergii had growth advantages when the water temperature was higher than 25℃. In addition, shallow water was more conducive to the growth of C. raciborskii. It was suggested that based on strengthening of the control of nitrogen and phosphorus nutrient input in lakes and reservoirs, the key monitoring of P. limnetica in lakes should be conducted in early summer and late autumn, and the growth of C. raciborskii in shallow water areas should be paid close attention in the high temperature period to ensure the safety of water quality.

Effects of ivabradine on ventricular electrophysiological remodeling after myocardial infarction in rats.

Introduction: This study aims to investigate the effects of ivabradine (IVA) on ventricular electrophysiological remodeling after myocardial infarction (MI) in rats. Material and methods: A total of 60 male Sprague-Dawley rats were randomly divided into five groups: an MI group, an IVA group, a metoprolol (MET) group, an IVA + MET group, and a sham group. After a four-week intervention, the ventricular electrophysiological parameters were detected by multichannel electrophysiological polygraph. Then, the morphological characteristics were evaluated using hematoxylin and eosin (H&E) and Masson's staining, and the expression of phosphorylated connexin 43 (p-Cx43) in the left ventricular wall was detected through immunohistochemistry and the Western blot test. Results: The electrophysiological examination revealed that the induction rate and fatality rate of ventricular tachycardia (VT)/ventricular fibrillation (VF) were lower in both the IVA and the MET group, compared with the MI group (6/12, 6/12 vs. 10/11; and 1/12, 1/12 vs. 5/11; all p < 0.05), as well as the IVA + MET group (1/11 vs. 10/11, p < 0.01; and 1/11 vs. 5/11, p < 0.05). The induction rate of VT/VF was lower in the IVA + MET group, compared to the MET group (1/11 vs. 6/12, p < 0.05). H&E and Masson's staining revealed that compared with the MI group, the left ventricular infarction area was lower in the IVA, MET, and IVA + MET groups (p < 0.05, p < 0.05, and p < 0.01, respectively), while collagen volume fraction (CVF) also was lower in the other groups (all p < 0.01). The left ventricular infarction area and CVF both were lower in the IVA + MET group, compared to the MET group (p < 0.05 and p < 0.01, respectively). The immunohistochemistry and Western blot revealed that p-Cx43 expression was higher in the treatment groups, compared with the MI group (all p < 0.01). Conclusions: IVA can reduce the incidence of ventricular arrhythmia after MI in male rats by improving both structural and electrical remodeling, and the combination of IVA and MET is even more effective.

Disruption of RCAN1.4 expression mediated by YY1/HDAC2 modulates chronic renal allograft interstitial fibrosis.

Chronic allograft dysfunction (CAD) is a major factor that hinders kidney transplant survival in the long run. Epithelial-mesenchymal transition (EMT) has been confirmed to significantly contribute to interstitial fibrosis/tubular atrophy (IF/TA), which is the main histopathological feature of CAD. Aberrant expression of the regulator of calcineurin 1 (RCAN1), recognized as an endogenous inhibitor of the calcineurin phosphatase, has been shown to be extensively involved in various kidney diseases. However, it remains unclear how RCAN1.4 regulates IF/TA formation in CAD patients. Herein, an in vivo mouse renal transplantation model and an in vitro model of human renal tubular epithelial cells (HK-2) treated with tumor necrosis factor-α (TNF-α) were employed. Our results proved that RCAN1.4 expression was decreased in vivo and in vitro, in addition to the up-regulation of Yin Yang 1 (YY1), a transcription factor that has been reported to convey multiple functions in chronic kidney disease (CKD). Knocking in of RCAN1.4 efficiently attenuated chronic renal allograft interstitial fibrosis in vivo and inhibited TNF-α-induced EMT in vitro through regulating anti-oxidative stress and the calcineurin/nuclear factor of activated T cells cytoplasmic 1 (NFATc1) signaling pathway. In addition, suppression of YY1 mediated by shRNA or siRNA alleviated TNF-α-induced EMT through abolishing reactive species partly in an RCAN1.4-dependent manner. Notably, we confirmed that YY1 negatively regulated RCAN1.4 transcription by directly interacting with the RCAN1.4 promoter. In addition, histone deacetylase 2 (HDAC2) interacted with YY1 to form a multi-molecular complex, which was involved in TNF-α-induced RCAN1.4 transcriptional repression. Therefore, RCAN1.4 is suggested to be modulated by the YY1/HDAC2 transcription repressor complex in an epigenetic manner, which is a mediated nephroprotective effect partly through modulating O2⋅- generation and the calcineurin/NFATc1 signaling pathway. Thus, the YY1-RCAN1.4 axis constitutes an innovative target for IF/TA treatment in CAD patients.

Macrophage polarization induces endothelium-to-myofibroblast transition in chronic allograft dysfunction.

Our research explores the role of M1 macrophage polarization in endothelium-to-myofibroblast transition (EndMT) and chronic allograft dysfunction (CAD). GSE21374 transcriptome sequencing data were obtained. Transplanted nephrectomy specimens from CAD patients were collected and studied to explore the infiltration of M1 and M2 macrophages using immunofluorescence, PCR, and Western blotting (WB). A co-culture model of M1 macrophages, polarized from mouse bone marrow-derived macrophages (BMDM) or Raw264.7, and aortic endothelial cells was established, and EndMT was tested using PCR and WB. RNA-sequencing was performed on the macrophages from the mouse BMDM. The TNF-α secreted from the polarized M1 macrophages was verified using ELISA. Based on the GEO public database, it was observed that macrophages were significantly infiltrated in CAD allograft tissues, with CD68(+) iNOS(+) M1 macrophages significantly infiltrating the glomeruli of allograft tissues, and CD68(+)CD206(+) M2 macrophages notably infiltrating the allograft interstitial area. The mRNA expression of the M1 macrophage marker inducible nitric oxide synthase (iNOS) was significantly increased (p < 0.05) and M1 macrophages were found to significantly promote the EndMT process in vitro. RNA-Sequencing analysis revealed that TNF signaling could be involved in the EndMT induced by M1 macrophages, and in vitro studies confirmed that TNF-α in the supernatant was significantly higher. The renal allograft tissues of CAD patients were found to be significantly infiltrated by M1 macrophages and could promote the progression of CAD by secreting the cytokine TNF-α to induce EndMT in endothelial cells.

Mineral and bone disorder after kidney transplantation: a single-center cohort study.

BACKGROUND: The assessment and prevention of mineral and bone disorder (MBD) in kidney transplant recipients (KTRs) have not been standardized. This study aimed to evaluate MBD one year after kidney transplantation (KT) and identify the influencing factors of MBD. METHODS: A total of 95 KTRs in our center were enrolled. The changes in bone mineral density (BMD) and bone metabolism biochemical markers, including serum calcium (Ca), phosphorus(P), 25-hydroxyvitamin D(25(OH)vitD), intact parathyroid hormone (iPTH), bone alkaline phosphatase, osteocalcin (OC), type I collagen N-terminal peptide and type I collagen C-terminal peptide (CTx), over one year after KT were assessed. The possible influencing factors of BMD were analyzed. The relationships between bone metabolism biochemical markers were evaluated. The indicators between groups with or without iPTH normalization were also compared. RESULTS: MBD after KT was manifested as an increased prevalence of hypophosphatemia and bone loss, persistent 25(OH)vitD deficiency, and partially decreased PTH and bone turnover markers (BTMs). Femoral neck BMD was positively correlated with body mass index (BMI) and postoperative 25(OH)vitD, and negatively correlated with postoperative PTH. Lumbar spine BMD was positively correlated with BMI and preoperative TG, and negatively correlated with preoperative OC and CTx. BMD loss was positively associated with glucocorticoid accumulation. Preoperative and postoperative iPTH was negatively correlated with postoperative serum P and 25(OH)vitD, and positively correlated with postoperative Ca and BTMs. The recipients without iPTH normalization, who accounted for 41.0% of all KTRs, presented with higher Ca, lower P, higher BTMs, advanced age, and a higher prevalence of preoperative parathyroid hyperplasia. CONCLUSIONS: MBD persisted after KT, showing a close relationship with hyperparathyroidism, high bone turnover, and glucocorticoid accumulation.

"Disease-syndrome-therapy" Spontaneous Abortion Models and Application Trends of Single-cell Multimodal Omics： A Review / 中国实验方剂学杂志

The incidence of spontaneous abortion （SAB） has been increasing year by year， and its etiology is complex， with limited treatment options， which poses a serious threat to social stability. The "disease-syndrome-therapy" research model can significantly improve the clinical efficacy of traditional Chinese medicine （TCM） for preventing miscarriage， but there has always been a lack of key and recognized diagnostic and treatment evaluation markers， which need to be further explored to establish a scientific and unified evaluation standard system. It is proposed to collect existing "disease-syndrome-therapy" SAB animal models， transplant and improve the model evaluation indicators， evaluate the degree of match between SAB animal models and the clinical characteristics of TCM and Western medicine diseases and syndromes， and compare the advantages and disadvantages of different SAB animal models in terms of construction methods， target selection， and evaluation indicators. In addition， the frontiers of TCM experimental research will be explored. In view of the current status and related bottlenecks of molecular biomarkers research on SAB TCM animal models， a single-cell multimodal omics research strategy will be proposed to break through the related evaluation defects of the "disease-syndrome-therapy" SAB and analyze the differences in various cell types， cell subpopulations， spatiotemporal trajectories， and gene expression in the mother-fetal interface tissue at the single-cell level. This will provide accurate guidance and model animal platform support for the in-depth study of disease-syndrome models， Zang-fu biology， and novel targeted drugs. It will also provide a basis for establishing a stable and repeatable "disease-syndrome-therapy" SAB animal model and evaluation indicator system， which is beneficial for the long-term development of TCM reproductive animal model research.

Effect of improved management of placenta accreta spectrum disorders on maternal and infant outcomes / 中华围产医学杂志

Objective:To evaluate the role of improved management procedures in placenta accreta spectrum disorders (PAS) and its impact on maternal and infant outcomes.Methods:This retrospective study involved 164 pregnant women who were diagnosed with PAS complicated with placenta previa and delivered at Nanjing Drum Tower Hospital, Nanjing University Medical School from January 2019 to December 2022. All subjects were allocated to pre-improvement group (January 2019 to December 2020, n=96) and post-improvement group (January 2021 to December 2022, n=68). The management was improved in the following five aspects: (1) The time for scheduled delivery was postponed to 37 weeks from 34-36 weeks;(2) Intraoperative cell salvage was encouraged despite autologous blood donation during pregnancy;(3) Original surgical incision was utilized instead of mid-longitudinal incision in the lower abdomen to reduce operative trauma; (4) A lower segment incision of the uterus was not prohibited based on pre-operative PAS classification and intra-operative situation to enter the uterine cavity, even through the placenta instead of pass-by;(5) The interface between lower uterine segment and bladder was dissected before instead of after the baby was born and uterine blood supply was stopped by tourniquet or Scharr forceps. Statistical methods such as t-test, Chi-square test or Fisher exact probability method were used to compare the difference in maternal and infant outcomes between the two groups. Results:After the improvement, the delivery rate beyond 37 weeks decreased significantly [83.3% (80/96) vs 69.1% (47/68), χ 2=4.60, P=0.038]. There was no significant difference in the distribution of elective, subemergency and emergency surgeries before and after the improvement ( χ 2=0.36, P=0.834). Compared to the pre-improvement group, the proportion of women who underwent cesarean section through previous abdominal incisions increased significantly [74.0% (71/96) vs 91.1% (64/68), χ 2=11.11, P=0.001] in the post-improvement group, while the proportion of application of abdominal longitudinal incision and classical cesarean section decreased significantly [84.3% (81/96) vs 57.3% (39/68), χ 2=14.81, P<0.001; 83.3% (80/96) vs 61.8% (42/68), χ 2=9.72, P=0.003]. No significant difference was found between the two groups in terms of the transfusion rate of allogeneic red blood cell, platelet and other blood components, pre-discharge hemoglobin level, subtotal hysterectomy rate, bladder injury, thrombus event, the admission rate of intensive care unit and unplanned reoperation rate (all P>0.05). The incidence of admission in neonatal intensive care unit (NICU) and necrotizing enterocolitis decreased significantly after improvement [24.7% (24/97) vs 11.8% (8/68), χ 2=4.31, P=0.038; 4.1% (4/97) vs 0.0% (0/68), χ 2=58.06, P<0.001]. The incidence of respiratory distress syndrome, mechanical ventilation, and neonatal septicemia also decreased, but without statistical difference. Conclusions:After adopting a series of improvement measures, such as delaying planned delivery to 37 weeks of gestation, individualized cesarean section plan, and changing the method of obtaining autoblood, the number of premature infants and the NICU admission rate decreased significantly without increasing the risk of maternal complications and emergency operation. Furthermore, the incidence of adverse events such as maternal organ injury, unplanned reoperation, and re-admission remains at a low level. Therefore, this improved management is feasible.

Establishment of a machine learning model for the diagnosis of clinically significant prostate cancer based on transrectal contrast-enhanced ultrasound parameters and clinical data / 中华超声影像学杂志

Objective:To establish a machine learning model for the diagnosis of clinically significant prostate cancer based on transrectal contrast-enhanced ultrasound parameters and clinically relevant data.Methods:A retrospective analysis was performed on 151 patients in Chongqing University Cancer Hospital who underwent transrectal contrast-enhanced ultrasonography and transrectal ultrasound-guided needle biopsy from November 2018 to September 2021. The time intensity curve was drawn using VueBox software and 12 parameters such as rise time, peak time, average transit time, peak intensity, and rising slope were quantitatively analyzed. Age, total prostate-specific antigen, free prostate-specific antigen, free prostate-specific antigen ratio, volume, prostate-specific antigen density, and transrectal contrast-enhanced ultrasonography parameters, a total of 18 characteristic parameters, were analyzed and screened through relevant attribute values and information gain attribute values. The screening features were trained and tested by the machine learning single algorithm and integrated algorithm, and then the model was evaluated by the F1 value and the area under the ROC curve(AUC).Results:Using the related attribute value and the information gain attribute value, 12 variables and 5 variables were screened out respectively to establish a machine learning model. The model established by the ensemble algorithm was better than the single algorithm. For the two variable selection methods, the AUC (0.810 vs 0.789) and F1 values (0.748 vs 0.742) of the Bagging ensemble algorithm model, which basic algorithm was decision tree, were the highest, followed by Logistic regression and support vector machine(SVM) in order of AUC and F1 values.Conclusions:Based on transrectal contrast-enhanced ultrasound parameters and clinical data, the Bagging ensemble model based on decision tree has the best performance in diagnosing clinically significant prostate cancer.

Progress on enteral nutrition therapy for acute pancreatitis / 中华临床营养杂志

Acute pancreatitis (AP) is an acute inflammatory disease of various severity, characterized by upper abdominal pain, elevated pancreatic enzymes, and changes in imaging features of the pancreas. According to the degree of pancreatic injury and the presence and duration of systemic organ failure, AP is classified into mild, moderate, or severe disease. Most AP patients experience mild disease and recover quickly, while up to 20% progress to moderate or severe disease, with an estimated risk of death as high as 30%. Severe acute pancreatitis (SAP) is a clinical emergency with a critical condition and poor prognosis, especially in patients with pancreatic and/or peripancreatic tissue infection and necrosis. AP is essentially an inflammatory process that can lead to protein catabolism and increased metabolic rates, further resulting in negative nitrogen balance. The goal of nutritional support therapy for AP is to correct negative nitrogen balance, reduce inflammation, and improve prognosis. Enteral nutrition therapy is an important component of clinical treatment of SAP. This review aims to summarize the nutritional support treatment in AP based on the existing clinical data and experience.

Effect of uridine on mitochondrial function / 生物工程学报

Uridine is one of the essential nutrients in organisms. To maintain normal cell growth and intracellular metabolism, the uridine must be maintained at certain concentration. Recent studies have shown that uridine can reduce inflammatory response in organisms, participate in glycolysis, and regulate intracellular protein modification, such as glycosylation and acetylation. Furthermore, it can protect cells from hypoxic injury by reducing intracellular oxidative stress, promoting high-energy compounds synthesis. Previous studies have shown that the protective effects of uridine are closely related to its effect on mitochondria. This review summarizes the effect of uridine on mitochondrial function.

[Study on protective effect of Chaihu Shugan Powder against liver injury in rats with intrahepatic cholestasis by regulating FXR/Nrf2/ARE pathway].

This study aims to investigate the effect of Chaihu Shugan Powder(CHSG) on liver injury in rats with intrahepatic cholestasis by regulating farnesoid X receptor(FXR)/nuclear factor erythroid-2-related factor(Nrf2)/antioxidant response element(ARE) pathway. Eighty-four SD rats were classified into normal group, model group, CHSG-L group(0.5 g·kg~(-1)), CHSG-H group(2.5 g·kg~(-1)), ursodeoxycholic acid group(UDCA group, 100 mg·kg~(-1)), CHSG-H+sh-NC group(2.5 g·kg~(-1) CHSG+subcutaneous injection of sh-NC lentivirus), CHSG-H+sh-FXR group(2.5 g·kg~(-1) CHSG+subcutaneous injection of sh-FXR lentivirus), with 12 rats in each group. Rats were treated with corresponding drugs except for the normal group and the model group, once a day, for 7 days. On 5 th day, rats, except the normal group, were given α-naphthalene isothiocyanate(ANIT) at a dose of 100 mg·kg~(-1), once a day for 3 days to induce intrahepatic cholestasis, and the normal group was given the same amount of normal saline. Rats were anesthetized 1 h after the last administration and the 2 h bile flow was measured. Aeroset chemistry analyzer was employed to detect the levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), total bilirubin(TBIL), and total bile acid(TBA) in rat serum. Based on hematoxylin and eosin(HE) staining, the pathological changes of rat liver tissue were observed. Glutathione peroxidase(GSH-Px), superoxide dismutase(SOD), and malondialdehyde(MDA) in rat liver tissue homogenate were monitored with corresponding kits. Western blot was used to detect the expression of FXR, Nrf2, and heme oxygenase-1(HO-1) proteins in rat liver tissue. Compared with the normal group, the model group showed many spots or concentrated necrotic areas in the liver tissue, infiltration of a large number of inflammatory cells, swelling liver cells with nuclear shrinkage. The 2 h bile flow, levels of GSH-Px and SOD, and relative expression of FXR, Nrf2, and HO-1 proteins were significantly lower, and the levels of ALT, AST, TBIL, TBA and MDA were significantly higher in the model group than in the normal group. Compared with the model group, CHSG-L group, CHSG-H group, and UDCA group demonstrated significant alleviation of pathological damage of the liver tissue, significantly high 2 h bile flow, levels of GSH-Px and SOD, and expression of FXR, Nrf2 and HO-1 proteins, and significantly low levels of ALT, AST, TBIL, TBA and MDA. Compared with the CHSG-H group, the CHSG-H+sh-FXR group had worse liver pathological damage, significantly low levels of 2 h bile flow, levels of GSH-Px and SOD, and expression of FXR, Nrf2, and HO-1 proteins, and significantly high levels of ALT, AST, TBIL, TBA, and MDA. CHSG may protect against liver injury in rats with intrahepatic cholestasis by activating the FXR/Nrf2/ARE pathway.

IRF1/ZNF350/GPX4-mediated ferroptosis of renal tubular epithelial cells promote chronic renal allograft interstitial fibrosis.

Renal interstitial fibrosis and tubular atrophy are essential pathological characteristics of chronic renal allograft dysfunction (CAD). Herein, we revealed that ferroptosis of renal tubular epithelial cells (RTECs) might contribute to renal tubular injury in CAD. Mechanistically, TNF-α induced ferroptosis by inhibiting GPX4 transcription through upregulating IRF1 in RTECs. IRF1 could bind with ZNF350 to form a transcription factor complex, which directly binds to the GPX4 promoter region to inhibit GPX4 transcription. Ferroptotic RTECs might secrete profibrotic factors, including PDGF-BB and IL-6, to activate neighboring fibroblasts to transform into myofibroblasts or induce EMT in adjacent RTECs. In conclusion, our results confirmed a novel role of ferroptosis in renal tubular injury and interstitial fibrosis, thereby providing insights into the pathogenesis of chronic renal allograft interstitial fibrosis during CAD.

Ovarian Auto-Transplantation of Cryopreserved Tissue on Muscle Surface Compared With Subrenal Capsular in Rats.

BACKGROUND: Fertility protection and ovarian function preservation are important to those undergoing radiation therapy to fight female reproductive cancers. The aim of this study was to explore a new ovarian transplantation position, the surface of thigh muscle, which was biceps femoris muscle in rats. METHODS: We hypothesized that this procedure was comparable to traditional subrenal capsular transplantation and realized a normal ovarian function. The ovarian tissue, after cryopreservation, were transplanted to surface of biceps femoris muscle by suturing. RESULTS: Histologic examination indicated that the transplanted tissues would survive and support a lower level of follicle growth compared with subrenal capsular (17 ± 2.6 vs 8.9 ± 4; P = .0018). According to weight gaining record, muscle surface transplantation supported appropriate weight gain although the ß-estradiol levels did not completely recover. This new procedure could support a basic normal estrous cycle. CONCLUSION: Ovarian transplantation through this procedure partly rebuilt ovarian function, which was more likely to be an alternative way for those not suitable for subrenal capsular transplantation.

Increasing phosphorus inhibits the retention and prevention of cadmium by iron plaque and promotes cadmium accumulation in rice plants.

Iron (Fe) plaque is an important component of rice roots because it influences the uptake and transport of cadmium (Cd) in rice. In this study, a hydroponic experiment was developed to investigate the influence of phosphorus (P) on the formation of iron plaque on the root surface as well as the influence on Cd uptake in rice plants. Three important results were obtained, as follows. (1) During the formation of iron plaque induced by exogenous Fe, P supply was beneficial for the iron plaque formation, but it restrained the Cd retention capability, resulting in a decrease in Cd in iron plaque by 35.48-61.93%, and leading to an increase in Cd in rice roots from 72.13 mg kg-1 to 112.78 mg kg-1 (2) After the iron plaque induction, the formation of iron plaque was inhibited by P supply, resulting in the amount of iron plaque decreasing by 18.46-54.57%, and the Cd in iron plaque decreased by 3.93-31.78%. Then, the Cd retention capability and the prevention effect simultaneously decreased, and as a result, the Cd in rice roots increased from 100.83 mg kg-1 to 146.03 mg kg-1 (3) Without exogenous Fe induction, P sufficiency continued to increase the amount of iron plaque and decrease the Cd in iron plaque, and increase the Cd in rice plants. These results suggested that P supply increases the amount of iron plaque, which is ineffective for Cd retention, such as non-reddish-brown iron plaque (NIP), and then decreases the capacity of iron plaque to retain Cd. Additionally, the P supply decreased the amount of formed iron plaque, causing the decreasing prevention effect. Therefore, excessive application of P fertilizer should be avoided in Cd-contaminated paddy fields.

Novel fabrication of hydrophobic/oleophilic human hair fiber for efficient oil/water separation through one-pot dip-coating synthesis route.

Frequent oil spill accidents and industrial wastewater discharge has always been one of the most severe worldwide environmental problems. To cope with this problem, many fluorine-containing and high-cost materials with superwettability have been extensively applied for oil-water separation, which hinders its large-scale application. In this work, a novel human hair fiber (HHF)-polymerized octadecylsiloxane (PODS) fiber was fabricated with a facile one-pot dip-coating synthesis approach, inspired by the self-assembly performance and hydrophobicity of OTS modification. The benefits of prominent hydrophobic/lipophilic behavior lie in the low surface energy, and a rough PODS coating was rationally adhered on the surface of HHF. Driven solely by gravity and capillary force, the HHF-PODS showed excellent oil/water separation efficiency (> 99.0%) for a wide range of heavy and light oil/water mixtures. In addition, HHF-PODS demonstrated durability toward different harsh environments like alkaline, acid, and salty solutions.

Iguratimod Attenuates Macrophage Polarization and Antibody-Mediated Rejection After Renal Transplant by Regulating KLF4.

Background: This study aimed to explore the effect and mechanism of iguratimod (IGT) on M1 macrophage polarization and antibody-mediated rejection (ABMR) after renal transplant. Methods: Bioinformatics analysis was performed using three public databases derived from the GEO database. Sprague-Dawley (SD) rats were pre-sensitized with donors of Wistar rats in skin transplantation and a rat renal transplant ABMR model was established from the donors to skin pre-sensitized recipients. Subsequently, IGT was treated on the ABMR model. Routine staining and immunofluorescence (IF) staining were performed to observe the pathological changes in each group and flow cytometry was performed to detect the changes of DSA titers in peripheral blood. In addition, bone-marrow-derived macrophage (BMDM) was extracted and interfered with IGT to explore the effect of IGT in vivo. PCR, IF staining, and Western blot were used to detect the expression of related genes and proteins. Results: Bioinformatics analysis revealed that several immune cells were significantly infiltrated in the ABMR allograft, while M1 macrophage was noticed with the most significance. Results of IF staining and PCR proved the findings of the bioinformatics analysis. Based on this, IGT was observed to significantly attenuate the degree of peritubular capillary vasculitis and arteriolitis in the rat renal transplant ABMR model, whereas it decreases the expression of C4d and reduces the titer of DSA. Results in vitro suggested that M1 macrophage-related transcripts and proteins were significantly reduced by the treatment of IGT in a dose- and time-dependent manner. Furthermore, IGT intervention could remarkably decrease the expression of KLF4. Conclusion: Polarization of M1 macrophages may aggravate ABMR after renal transplant by promoting DSA-mediated endothelial cell injury, and IGT may attenuate the pathogenesis of ABMR by targeting KLF4.

Posterior cruciate ligament reconstruction with independent internal brace reinforcement: surgical technique and clinical outcomes with a minimum two year follow-up.

PURPOSE: We developed an augmentation technique for PCL reconstruction with independent internal brace reinforcement and evaluated the functional outcome after PCL reconstruction employing autologous hamstrings augmented with an internal brace system for patients with isolated or combined grade 3 posterior instability who were treated with this technique. METHODS: From January 2016 to January 2018, patients with isolated or combined grade 3 PCL tears who underwent single-bundle PCL reconstruction using autologous hamstrings augmented with independent internal braces were studied. The function of the operated knee was evaluated according to the International Knee Documentation Committee (IKDC) score, Lysholm score, and Tegner activity score. The patients were asked the level of returned to their previous sport. Posterior knee laxity was examined with a KT-1000 arthrometer, and data on range of motion (ROM), re-operation, and other complications were collected. RESULTS: A total of 33 consecutive patients who received single-bundle PCL reconstruction using autologous hamstrings augmented with independent internal braces with a minimum two years follow-up were included in this study. Two patients had undergone this procedure during the study period and were not included in this study (one had combined bone fractures, and one patient had previous meniscus surgery). Thirty-one patients were available for final analysis. The mean follow-up was 45.35 ± 10.88 months (range 29-66 months). The average IKDC subjective knee evaluation scores from 51.65 ± 12.35 to 84.52 ± 6.42, the Lysholm score from 53.90 ± 11.86 to 85.68 ± 4.99, and the Tegner score from 2.81 ± 0.79 to 6.71 ± 1.83 (P < 0.05 for all). The mean total posterior side-to-side difference in knee laxity, assessed using a KT-1000 arthrometer, decreased from 12.13 ± 2.66 mm pre-operatively to 1.87 ± 0.56 mm post-operatively at 70° (P < 0.05). Most patients (29/31) had normal or near normal knee ROM post-operatively; two patients revealed a 6-15° loss of knee flexion compared with the contralateral knee. Twenty-nine patients (93.55%) returned to a normal daily exercise level. Twenty-three patients (74.19%) returned to competitive sports with high-level sports (Tegner score of 6 or above; eleven patients (35.48%) reported to be on the same level as well as the Tegner level); six patients (19.35%) returned to recreational sports (Tegner score of 4 or 5). Two patients had Tegner scores of 2 and 3, indicating poor function level. No patient needed PCL revision surgery during the follow-up period. CONCLUSION: Single-bundle PCL reconstruction with internal brace augmentation for PCL injury exhibited satisfactory posterior stability and clinical outcomes in patients with isolated or combined grade 3 PCL injuries at a minimum two year follow-up.

Biological Characteristics and Predictive Model of Biopsy-Proven Acute Rejection (BPAR) After Kidney Transplantation: Evidences of Multi-Omics Analysis.

Objectives: Early diagnosis and detection of acute rejection following kidney transplantation are of great significance for guiding the treatment and improving the prognosis of renal transplant recipients. In this study, we are aimed to explore the biological characteristics of biopsy-proven acute rejection (BPAR) and establish a predictive model. Methods: Gene expression matrix of the renal allograft samples in the GEO database were screened and included, using Limma R package to identify differentially expressed transcripts between BPAR and No-BPAR groups. Then a predictive model of BPAR was established based on logistic regression of which key transcripts involved in the predictive model were further explored using functional enrichment analyses including Gene Ontology analysis (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and Gene Set Enrichment Analysis (GSEA). Results: A total of four studies (GSE129166, GSE48581, GSE36059, and GSE98320) were included for extensive analysis of differential expression. 32 differential expressed transcripts were observed to be significant between two groups after the pooled analysis. Afterward, a predictive model containing the five most significant transcripts (IDO1, CXCL10, IFNG, GBP1, PMAIP1) showed good predictive efficacy for BPAR after kidney transplantation (AUC = 0.919, 95%CI = 0.902-0.939). Results of functional enrichment analysis showed that The functions of differential genes are mainly manifested in chemokine receptor binding, chemokine activity, G protein-coupled receptor binding, etc. while the immune infiltration analysis indicated that immune cells mainly related to acute rejection include Macrophages. M1, T cells gamma delta, T cells CD4 memory activated, eosinophils, etc. Conclusion: We have identified a total of 32 differential expressed transcripts and based on that, a predictive model with five significant transcripts was established, which was suggested as a highly recommended tool for the prediction of BPAR after kidney transplantation. However, an extensive study should be performed for the evaluation of the predictive model and mechanism involved.