Gene associations of lipid traits, lipid-lowering drug-target genes and endometriosis.

RESEARCH QUESTION: Does the observed correlation between dyslipidaemia and endometriosis indicate a bidirectional causal association? DESIGN: Bidirectional Mendelian randomization was used to investigate the causal association between lipid traits and endometriosis. Drug-target Mendelian randomization was used to explore potential drug-target genes for managing endometriosis. In cases where lipid-mediated effects via specific drug targets were significant, aggregate analyses, such as summary-data-based Mendelian randomization and colocalization methods, were introduced to validate the outcomes. Mediation analyses supplemented these evaluations. RESULTS: The bidirectional Mendelian randomization results suggested that genetically predicted triglyceride (OR 1.15, 95% CI 1.08-1.23), high-density lipoprotein cholesterol (OR 0.87, 95% CI 0.81-0.94), low-density lipoprotein cholesterol (OR 1.20, 95% CI 1.06-1.34) and apolipoprotein A (OR 0.90, 95% CI 0.83-0.96) concentrations were causally associated with endometriosis. Reverse Mendelian randomization results revealed that genetically proxied endometriosis was causally associated with triglyceride concentration (OR 1.02, 95% CI 1.01-1.02). In drug-target Mendelian randomization, genetic mimicry in proprotein convertase subtilisin/kexin type 9 (PCSK9) (OR 1.40, 95% CI 1.13-1.72), apolipoprotein B (APOB) (OR 1.49, 95% CI 1.21-1.86) and angiopoietin-related protein 3 (ANGPTL3) (OR 1.57, 95% CI 1.14-2.16) was significantly associated with the risk of endometriosis stages 1-2. CONCLUSION: There is a potential bidirectional causal association between endometriosis and dyslipidaemia. Genetic mimicry of PCSK9, APOB and ANGPTL3 is associated with the risk of early-stage endometriosis. The development of lipid-lowering drugs to treat endometriosis is of potential clinical interest.

Oil-soluble contrast medium bathing attenuated endometrial inflammation and improved endometrial receptivity in women with recurrent implantation failure: a descriptive study.

BACKGROUND: The oil-soluble contrast medium used in hysterosalpingography has been shown to have a fertility-enhancing effect, but the underlying mechanism is unclear, especially regarding the role of window of implantation (WOI). This study aimed to assess the endometrial immunological impact of the WOI before and after bathing with the oil-soluble contrast medium in women with recurrent implantation failure (RIF). METHODS: This descriptive study involved two medical centers between December 18, 2019, and December 30, 2020. We included infertile women who underwent three or more transfer cycles, cumulative transplantation of at least four high-quality cleavage-stage embryos or three high-quality blastocysts without clinical pregnancy, and high-quality frozen embryos that were still available for implantation. Patients received 5 ml of ethiodized poppyseed oil bathing, endometrial biopsy around bathing, and frozen-thawed embryo transfer (FET) within four menstrual cycles after bathing. Patients were excluded if failure to complete anyone. Data on the baseline characteristics and clinical data of the FET cycles were collected, and endometrial biopsy specimens were collected in the luteal phase before and after bathing and subjected to immunohistochemistry. The number of CD56 and CD138 positive cells and H-score of expression of ανß-3 and HOXA10 in endometrium were collected. RESULTS: Thirty-four patients were initially enrolled in the study; ultimately, twelve patients with a median age of 32.5 years (range 27-40 years) completed the research. The median number of embryo transfer cycles was three (range 3-8). A total of 4 of 12 women (33.33%) were diagnosed with chronic endometritis before oil-soluble contrast bathing. After bathing, the median numbers of CD138-positive cells in endometrium decreased from 0.75 (range 0-13.5) to 0.65 (range 0-6), P = 0.035; additionally, the H-score of expression of ανß-3 in endometrium increased from 148.50 ± 31.63 to 175.58 ± 31.83, P < 0.001. The thickness of the endometrium also significantly increased (8.90 ± 1.45 mm vs.10.11 ± 1.98 mm, P = 0.005). However, no consistent changes were found in the expression of CD56 and HOXA10 in the endometrium. Five patients experienced biochemical pregnancies (41.67%), four had clinical pregnancies (33.33%), and three achieved live births following oil-soluble contrast bathing (25%). CONCLUSIONS: These results suggest that oil-soluble contrast medium bathing decreased CD138-positive cells and upregulated expression of ανß-3 during WOI in patients with RIF. This histological impact of endometrium may result in enhanced fertility during FET cycles. Investigating the ability of intrauterine bathing with lower-dosage oil-soluble contrast to improve pregnancy in the RIF population is warranted.

Exonuclease III-propelled DNAzyme walker: an electrochemical strategy for microRNA diagnostics.

MicroRNA detection is crucial for early infectious disease diagnosis and rapid cancer screening. However, conventional techniques like reverse transcription-quantitative polymerase chain reaction, requiring specialized training and intricate procedures, are less suitable for point-of-care analyses. To address this, we've developed a straightforward amplifier based on an exonuclease III (exo III)-propelled DNAzyme walker for sensitive and selective microRNA detection. This amplifier employs a specially designed hairpin probe with two exposed segments for strand recognition. Once the target microRNA is identified by the hairpin's extended single-strand DNA, exo III initiates its digestion, allowing microRNA regeneration and subsequent hairpin probe digestion cycles. This cyclical process produces a significant amount of DNAzyme, leading to a marked reduction in electrochemical signals. The biosensor exhibits a detection range from 10 fM to 100 pM and achieves a detection limit of 5 fM (3σ criterion). Importantly, by integrating an "And logic gate," our system gains the capacity for simultaneous diagnosis of multiple microRNAs, enhancing its applicability in RNA-based disease diagnostics.

Environmentally Controlled Oscillator with Triplex Guided Displacement of DNA Duplexes.

The use of DNA triplex association is advantageous for the reconfiguration of dynamic DNA nanostructures through pH alteration and can provide environmental control for both structural changes and molecular signaling. The combination of pH-induced triplex-forming oligonucleotide (TFOs) binding with toehold-mediated strand displacement has recently garnered significant attention in the field of structural DNA nanotechnology. While most previous studies use single-stranded DNA to displace or replace TFOs within the triplex, here we demonstrate that pH alteration allows a DNA duplex, with a toehold assistance, to displace TFOs from the components of another DNA duplex. We examined the dependence of this process on toehold length and show that the pH changes allow for cyclic oscillations between two molecular formations. We implemented the duplex/triplex design onto the surface of 2D DNA origami in the form outlining binary digits 0 or 1 and verified the oscillatory conformational changes between the two formations with atomic force microscopy.

Risk factors of immune checkpoint inhibitor-associated acute kidney injury: evidence from clinical studies and FDA pharmacovigilance database.

BACKGROUND: Several risk factors of immune checkpoint inhibitors (ICIs)-associated acute kidney injury (AKI) have been reported sporadically. To identify the risk factors of ICIs-associated AKI in a large-scale population, therefore we conducted a systematic review and a real-world retrospective study. METHODS: We search literature concerning risk factors of ICIs-associated AKI in ClinicalTrials.gov and electronic databases (PubMed, Cochrane Library, Embase) up to January 2022. Meta-analysis was performed by using odds ratios (ORs) with 95%CIs. In a separate retrospective pharmacovigilance study by extracting data from US FDA Adverse Event Reporting System (FAERS) database, disproportionality was analyzed using the reporting odds ratio (ROR). RESULTS: A total of 9 studies (5927 patients) were included in the meta-analysis. The following factors were associated with increased risk of ICIs-associated AKI, including proton pump inhibitors(PPIs) (OR = 2.07, 95%CI 1.78-2.42), angiotensin-converting enzyme inhibitors (ACEIs)/ angiotensin receptor blockers (ARBs) (OR = 1.56, 95%CI 1.24-1.95), nonsteroidal anti-inflammatory drugs (NSAIDs) (OR = 1.29, 95%CI 1.01-1.65), diuretics (OR = 2.00, 95%CI 1.38-2.89), diabetes mellitus (OR = 1.28, 95%CI 1.04-1.57), genitourinary cancer (OR = 1.46, 95%CI 1.15-1.85), combination therapy of ICIs (OR = 1.93, 95%CI 1.25-2.97) and extrarenal immune-related adverse events(irAEs) (OR = 2.51, 95%CI 1.96-3.20). Furthermore, analysis from FAERS database verified that concurrent exposures of PPIs (ROR = 2.10, 95%CI 1.91-2.31), ACEIs/ARBs (ROR = 3.25, 95%CI 2.95-3.57), NSAIDs (ROR = 3.06, 95%CI 2.81-3.32) or diuretics (ROR = 2.82, 95%CI 2.50-3.19) were observed significant signals associated with AKI in ICIs-treated patients. CONCLUSIONS: Concurrent exposures of PPIs, ACEIs/ARBs, NSAIDs or diuretics, diabetes mellitus, genitourinary cancer, combination therapy, and extrarenal irAEs seem to increase the risk of AKI in ICIs-treated patients.

Aflatoxin B1 impairs porcine oocyte quality via disturbing intracellular membrane system and ATP production.

Aflatoxin is the most common type of mycotoxins in contaminated corn, peanuts and rice, which affects the livestock and ultimately endangers human health. Aflatoxin is reported to have carcinogenicity, mutation, growth retardation, immunosuppression and reproductive toxicity. In present study we reported the causes for the declined porcine oocyte quality under aflatoxin exposure. We set up an in vitro exposure model and showed that aflatoxin B1 disturbed cumulus cell expansion and oocyte polar body extrusion. We found that aflatoxin B1 exposure disrupted ER distribution and elevated the expression of GRP78, indicating the occurrence of ER stress, and the increased calcium storage also confirmed this. Besides, the structure of cis-Golgi apparatus, another intracellular membrane system was also affected, showing with decreased GM130 expression. The oocytes under aflatoxin B1 exposure showed aberrant lysosome accumulation and higher LAMP2 expression, a marker for lysosome membrane protection, and this might be due to the aberrant mitochondria function with low ATP production and the increase of apoptosis, since we found that BAX expression increased, and ribosomal protein which is also an apoptosis-related factor RPS3 decreased. Taken together, our study revealed that aflatoxin B1 impairs intracellular membrane system ER, Golgi apparatus, lysosome and mitochondria function to affect porcine oocyte maturation quality.

Oil-based contrast for hysterosalpingography-regulated Th1/Th2-type cytokines and alleviated inflammation in rats with LPS-induced chronic endometritis.

AIM: The chronic endometritis (CE) prevalence in people experiencing infertility is 2.8-56.8%, pregnancy rates in patients with infertility increase after hysterosalpingography with oil-based contrast, but the effect and mechanism are not clear. Here, we analyzed the effects of intrauterine ethiodized poppyseed oil (EPO) bathing on a rat model of CE and the possible underlying mechanism. METHODS: CE rats were induced by lipopolysaccharide (LPS) exposure, and rats were subjected to intrauterine bathing with EPO or phosphate-buffered saline (PBS) after model verification. Serum and uterus levels of IFN-γ, IL-4, TNF-α, and IL-1ß were detected by ELISA kit, and the number of CD138+ and CD68+ cells and uterine IFN-γ, IL-4, TNF-α, IL-1ß, and NF-κB P65 expression were detected by immunohistochemistry after bathing. RESULTS: LPS exposure induced the typical CE phenotype with CD138+ phagocyte infiltration of the endometrial stroma. Compared with PBS bathing, bathing with EPO in CE rats showed decreases in the CD138+ and CD68+ cells populations and significant decreases in serum and uterine IFN-γ levels, moreover, uterine IL-4 levels were slightly higher, and the IFN-γ/IL-4(Th1/Th2-type cytokine ratio) in the uterus was significantly lower. Local IFN-γ, TNF-α, and NF-κB P65 expression in the endometrium was significantly downregulated, while IL-4 expression was upregulated. CONCLUSION: Intrauterine oil-based contrast bathing significantly alleviated local inflammation in the rat CE model by downregulating NF-κB P65 expression, reducing IFN-γ (Th1), increasing IL-4 levels (Th2) in the endometrium, and regulating the Th1/Th2-type cytokine trends toward Th2.

Andrographolide/Phospholipid/Cyclodextrin Complex-Loaded Nanoemulsion: Preparation, Optimization, in Vitro and in Vivo Evaluation.

Andrographolide (AG), a natural product with various pharmacological effects, exhibited low oral bioavailability owing to its poor solubility, stability, and low absorption. Previous studies have suggested that phospholipid (PC) and hydroxypropyl-ß-cyclodextrin (HPCD) could improve the drug solubility and absorption. Moreover, nanoemulsion (NE) has been confirmed as an appropriate enhancer for oral bioavailability. Therefore, AG/HPCD/PC complex (AHPC) was synthesized, and AHPC-loaded nanoemulsion (AHPC-NE) was optimized and prepared using central composite design combined response surface methodology. The average droplet size and polydispersity index (PDI) were 116.50 ± 5.99 and 0.29 ± 0.03 nm, respectively. AHPC-NE with a loading capacity of 0.32 ± 0.01% and an encapsulation efficiency of 96.43 ± 2.27% appeared round and uniformly dispersed based on transmission electron microscopy. In vivo release studies demonstrated that AHPC-NE had good sustained-release effects. Further, AHPC-NE significantly enhanced the absorption of AG with a relative bioavailability of 550.71% compared to AG suspension. Such findings reveal AHPC-NE as a potential strategy for sustained-release and oral bioavailability enhancement.

Serum homocysteine is associated with tubular interstitial lesions at the early stage of IgA nephropathy.

BACKGROUND: The association between homocysteine (Hcy) and IgA nephropathy (IgAN) is not well understood. We aimed to investigate the relationship between Hcy and clinicopathologic features in IgAN patients. METHODS: A total of 337 IgAN patients and 150 sex- and age- matched healthy controls were enrolled in this single-center retrospective study. According to Hcy ≤ 10 µmol/L or > 10 µmol/L, patients were divided into low and high Hcy groups. Multivariate logistic regression was performed to explore the risk factors for elevated Hcy. RESULTS: Serum Hcy was higher in IgAN patients than in healthy controls [11.6 (9.1,15.3) vs. 8.8 (7.5,10.6) µmol/L, P < 0.001], unanimously in the subgroup of 156 patients with a normal estimated glomerular filtration rate (eGFR) (≥ 90 ml/min/1.73 m2) [9.9 (7.6,12.4) vs. 8.8 (7.5,10.6) µmol/L, P < 0.001]. Compared to the low Hcy group, serum creatinine (Scr), blood urine nitrogen (BUN), uric acid (UA), endocapillary hypercellularity (E) and tubular atrophy/interstitial fibrosis lesion (T) were higher in the high Hcy group. Hcy levels were positively correlated with Scr, BUN, UA, 24-h urine protein, and E and T lesions, but negatively correlated with eGFR and superoxide dismutase (SOD). In the subgroup with normal eGFR, patients with higher Hcy were persistent with higher Scr, BUN and T lesions. A multivariate logistic regression model showed that the risk of elevated Hcy in patients with pathological T increased by 2.87-fold. T lesions could better predict high Hcy, with an odds ratio (OR) of 14.20 in the subgroup with normal eGFR. CONCLUSIONS: Pathologic T was an independent risk factor associated with elevated Hcy, especially at the early stage of IgAN.

Adenine base-editing-mediated exon skipping induces gene knockout in cultured pig cells.

Gene-knockout pigs have important applications in agriculture and medicine. Compared with CRISPR/Cas9, Adenine base editor (ABE) convert single A·T pairs to G·C pairs in the genome without generating DNA double-strand breaks, and this method has higher accuracy and biosafety in pig genetic modification. However, the application of ABE in pig gene knockout is limited by protospacer-adjacent motif sequences and the base-editing window. Alternative mRNA splicing is an important mechanism underlying the formation of proteins with diverse functions in eukaryotes. Spliceosome recognizes the conservative sequences of splice donors and acceptors in a precursor mRNA. Mutations in these conservative sequences induce exon skipping, leading to proteins with novel functions or to gene inactivation due to frameshift mutations. In this study, adenine base-editing-mediated exon skipping was used to expand the application of ABE in the generation of gene knockout pigs. We first constructed a modified "all-in-one" ABE vector suitable for porcine somatic cell transfection that contained an ABE for single-base editing and an sgRNA expression cassette. The "all-in-one" ABE vector induced efficient sgRNA-dependent A-to-G conversions in porcine cells during single base-editing of multiple endogenous gene loci. Subsequently, an ABE system was designed for single adenine editing of the conservative splice acceptor site (AG sequence at the 3' end of the intron 5) and splice donor site (GT sequence at the 5' end of the intron 6) in the porcine gene GHR; this method achieved highly efficient A-to-G conversion at the cellular level. Then, porcine single-cell colonies carrying a biallelic A-to-G conversion in the splice acceptor site in the intron 5 of GHR were generated. RT-PCR indicated exon 6 skipped at the mRNA level. Western blotting revealed GHR protein loss, and gene sequencing showed no sgRNA-dependent off-target effects. These results demonstrate accurate adenine base-editing-mediated exon skipping and gene knockout in porcine cells. This is the first proof-of-concept study of adenine base-editing-mediated exon skipping for gene regulation in pigs, and this work provides a new strategy for accurate and safe genetic modification of pigs for agricultural and medical applications.

Nonsymmetrical Segregation of Solutes in Periodic Misfit Dislocations Separated Tilt Grain Boundaries.

Interfacial segregation is ubiquitous in mulit-component polycrystalline materials and plays a decisive role in material properties. So far, the discovered solute segregation patterns at special high-symmetry interfaces are usually located at the boundary lines or are distributed symmetrically at the boundaries. Here, in a model Mg-Nd-Mn alloy, we confirm that elastic strain minimization facilitated nonsymmetrical segregation of solutes in four types of linear tilt grain boundaries (TGBs) to generate ordered interfacial superstructures. Aberration-corrected high-angle annular dark-field scanning transmission electron microscopy observations indicate that the solutes selectively segregate at substitutional sites at the linear TGBs separated by periodic misfit dislocations to form such two-dimensional planar structures. These findings are totally different from the classical McLean-type segregation which has assumed the monolayer or submonolayer coverage of a grain boundary and refresh understanding on strain-driven interface segregation behaviors.

Twin Boundary Superstructures Assembled by Periodic Segregation of Solute Atoms.

Twinning is a common deformation mechanism in metals, and twin boundary (TB) segregation of impurities/solutes plays an important role in the performances of alloys such as thermostability, mobility, and even strengthening. The occurrence of such segregation phenomena is generally believed as a one-layer coverage of solutes alternately distributed at extension/compression sites, in an orderly, continuous manner. However, in the Mn-free and Mn-containing Mg-Nd model systems, we reported unexpected three- and five-layered discontinuous segregation patterns of the coherent {101̅1} TBs, and not all the extension sites occupied by solutes larger in size than Mg, and even some larger sized solutes taking the compression sites. Nd/Mn solutes selectively segregate at substitutional sites and thus to generate two new types of ordered two-dimensional TB superstructures or complexions. These findings refresh the understanding of solute segregation in the perfect coherent TBs and provide a meaningful theoretical guidance for designing materials via targeted TB segregation.

Multivariate pattern analysis of electroencephalography data reveals information predictive of charitable giving.

Charitable donations are an altruistic behavior whereby individuals donate money or other resources to benefit others while the recipient is normally absent from the context. Several psychological factors have been shown to influence charitable donations, including a cost-benefit analysis, the motivation to engage in altruistic behavior, and the perceived psychological benefits of donation. Recent work has identified the ventral medial prefrontal cortex (MPFC) for assigning value to options in social decision making tasks, with other regions involved in empathy and emotion contributing input to the value computation (e.g. Hare et al., 2010; Hutcherson et al., 2015; Tusche et al., 2016). Most impressively, multivariate pattern analysis (MVPA) has been applied to fMRI data to predict donation behavior on a trial-by-trial basis from ventral MPFC activity (Hare et al., 2010) while identifying the contribution of emotional processing in other regions to the value computation (e.g. Tusche et al., 2016). MVPA of EEG data may be able to provide further insight into the timing and scalp topography of neural activity related to both value computation and emotional effects on donation behavior. We examined the effect of incidental emotional states and the perceived urgency of the charitable cause on donation behavior using support vector regression on EEG data to predict donation amount on a trial by trial basis. We used positive, negative, and neutral pictures to induce incidental emotional states in participants before they made donation decisions concerning two types of charities. One category of charity was oriented toward saving people from current suffering, and the other was to prevent future suffering. Behaviorally, subjects donated more money in a negative emotional state relative to other emotional states, and more money to alleviate current over future suffering. The data-driven multivariate pattern analysis revealed that the electrophysiological activity elicited by both emotion-priming pictures and charity cues could predict the variation in donation magnitude on a trial-by-trial basis.

Systematic review and subgroup analysis of the incidence of acute kidney injury (AKI) in patients with COVID-19.

BACKGROUND: Acute kidney injury (AKI) occurs among patients with coronavirus disease-19 (COVID-19) and has also been indicated to be associated with in-hospital mortality. Remdesivir has been authorized for the treatment of COVID-19. We conducted a systematic review to evaluate the incidence of AKI in hospitalized COVID-19 patients. The incidence of AKI in different subgroups was also investigated. METHODS: A thorough search was performed to find relevant studies in PubMed, Web of Science, medRxiv and EMBASE from 1 Jan 2020 until 1 June 2020. The systematic review was performed using the meta package in R (4.0.1). RESULTS: A total of 16,199 COVID-19 patients were included in our systematic review. The pooled estimated incidence of AKI in all hospitalized COVID-19 patients was 10.0% (95% CI: 7.0-12.0%). The pooled estimated proportion of COVID-19 patients who needed continuous renal replacement therapy (CRRT) was 4% (95% CI: 3-6%). According to our subgroup analysis, the incidence of AKI could be associated with age, disease severity and ethnicity. The incidence of AKI in hospitalized COVID-19 patients being treated with remdesivir was 7% (95% CI: 3-13%) in a total of 5 studies. CONCLUSION: We found that AKI was not rare in hospitalized COVID-19 patients. The incidence of AKI could be associated with age, disease severity and ethnicity. Remdesivir probably did not induce AKI in COVID-19 patients. Our systematic review provides evidence that AKI might be closely associated with SARS-CoV-2 infection, which should be investigated in future studies.

miR-20a-5p is enriched in hypoxia-derived tubular exosomes and protects against acute tubular injury.

Exosomes have been shown to effectively regulate the biological functions of target cells. Here, we investigated the protective effect and mechanism of hypoxia-induced renal tubular epithelial cells (TECs)-derived exosomes on acute tubular injury. We found that in vitro hypoxia-induced tubular exosomes (Hy-EXOs) were protective in acute tubular injury by promoting TECs proliferation and improving mitochondrial functions. By using exosome miRNA sequencing, we identified miR-20a-5p was abundant and was a key mechanism for the protective effect of Hy-EXOs on tubular injury as up-regulation of miR-20a-5p enhanced but down-regulation of miR-20a-5p inhibited the protective effect of Hy-EXOs on tubular injury under hypoxia conditions. Further study in a mouse model of ischemia-reperfusion-induced acute kidney injury (IRI-AKI) also confirmed this notion as pre-treating mice with the miR-20a-5p agomir 48 h prior to AKI induction was capable of inhibiting IRI-AKI by lowering serum levels of creatinine and urea nitrogen, and attenuating the severity of tubular necrosis, F4/80(+) macrophages infiltration and vascular rarefaction. Mechanistically, the protective effect of miR-20a-5p on acute kidney injury (AKI) was associated with inhibition of TECs mitochondrial injury and apoptosis in vitro and in vivo. In conclusion, miR-20a-5p is enriched in hypoxia-derived tubular exosomes and protects against acute tubular injury. Results from the present study also reveal that miR-20a-5p may represent as a novel therapy for AKI.

CD8+CD103+ iTregs Inhibit Chronic Graft-versus-Host Disease with Lupus Nephritis by the Increased Expression of CD39.

Many patients with systemic lupus erythematosus (SLE) have lupus nephritis, one of the severe complications of SLE. We previously reported that CD8+CD103+ T regulatory cells induced ex vivo with transforming growth factor ß (TGF-ß) (iTregs) inhibited immune cells responses to ameliorate excessive autoimmune inflammation. However, the molecular mechanism(s) underlying the role of these CD8+ iTregs is still unclear. Here we identified that CD39, which is highly expressed on CD8+ iTregs, crucially contributes to the immunosuppressive role of the CD8+CD103+ iTregs. We showed that adoptive transfer of CD8+CD103+ iTregs significantly relieves the chronic graft-versus-host disease with lupus nephritis and CD39 inhibitor mostly abolished the functional activities of these CD8+ iTregs in vitro and in vivo. CD39+ cells sorted from CD8+CD103+ iTregs were more effective in treating lupus nephritis than CD39- partner cells in vivo. Furthermore, human CD8+ iTregs displayed increased CD103 and CD39 expressions, and CD39 was involved in the suppressive function of human CD8+ iTregs. Thus, our data implicated a crucial role of CD39 in CD8+CD103+ iTregs in treating lupus nephritis, and CD39 could be a new phenotypic biomarker for the identification of highly qualified CD8+ Tregs. This subpopulation may have therapeutic potential in patients with SLE nephritis and other autoimmune diseases.

The incidence, risk factors, and long-term outcomes of acute kidney injury in hospitalized diabetic ketoacidosis patients.

BACKGROUND: Emerging evidence has demonstrated that acute kidney injury (AKI) is an important risk factor associated with increased morbidity and mortality in diabetic ketoacidosis (DKA) patients. The current study aimed to investigate the incidence rate, risk factors, long-term renal outcomes, and mortality in DKA patients with AKI. METHODS: A total of 179 patients diagnosed with DKA at Sun Yat-sen Memorial Hospital from January 2012 to January 2018 were included in the analysis. AKI was diagnosed according to the 2012 KDIGO criteria. Risk factors, long-term renal outcomes, and mortality were analyzed by logistic regression and Cox proportional hazards models. RESULTS: Among 179 DKA patients, 98 patients (54.75%) were diagnosed as AKI. Aging; increased blood glucose, serum uric acid and white blood cells; decreased serum pH and albumin; coma; and preexisting chronic kidney disease (CKD) were risk factors of AKI in patients with DKA. During follow-up, DKA patients with AKI showed more than a two-fold decline in eGFR within 1 year after discharge from the hospital when compared with non-AKI DKA patients. Furthermore, AKI was also an independent risk factor for poor long-term renal outcomes and mortality in DKA patients. CONCLUSIONS: Multiple risk factors contribute to the development of AKI in DKA patients. AKI and advanced AKI stage are associated with rapid progressive CKD and long-term mortality in patients with DKA.

Immunohistochemical expression of estrogen receptor α, Bcl-2 and NF-κB P65 in the polyps of patients with and without endometriosis.

AIM: To compare the expression of estrogen receptor α (ERα), Bcl-2 and NF-κB P65 in endometrial polyps from patients with and without endometriosis. METHODS: Immunohistochemistry was used to characterize the expression of ERα, Bcl-2 and NF-κB P65 in proliferative phase endometrial polyps from patients with and without endometriosis. H-Scores indicating the staining intensity for ERα, Bcl-2 and NF-κB P65 in the glandular epithelium and stroma were measured separately. Apoptotic cells were detected with the use of the dUTP nick-end labeling (TUNEL) assay. RESULTS: Bcl-2 was expressed in the cytoplasm of glandular epithelial cells, whereas ERα was expressed in the nuclei of both glandular epithelial and stromal cells. NF-κB P65 was observed in the cytoplasm of both glandular epithelial and stromal cells. The H-scores for Bcl-2 in the endometrial glands significantly higher in the endometriosis polyp group than in the non-endometriosis polyp group. The H-scores for ERα in both stromal and glandular epithelial cells were significantly higher in the endometriosis polyp group than in the non-endometriosis polyp group. The H-scores for Bcl-2 and ERα were positively correlated in all of the women examined. Apoptotic cells in the endometriosis polyp group were significantly less than that of the non-endometriosis polyp group. CONCLUSION: There expression levels of Bcl-2 and ERα, both of which were significantly increased in the polyps of endometriosis patients compared to those of patients without endometriosis, were positively correlated. These results suggested that imbalanced apoptosis secondary to abnormally high ERα expression was responsible for the high prevalence of polyps in endometriosis patients.

G-CSF-mobilized peripheral blood mononuclear cells combined with platelet-rich plasma accelerate restoration of ovarian function in cyclophosphamide-induced POI rats†.

Peripheral blood mononuclear cells (PBMCs) are rich in hematopoietic cells and mesenchymal stem cells. Platelet-rich plasma (PRP) is rich in various growth factors. PBMCs and PRP have been suggested, individually, to restore ovarian function by improving the local microenvironment. The current study investigated the effect of granulocyte colony-stimulating factor (G-CSF)-mobilized PBMCs combined with PRP on restoring ovarian function in rats with primary ovarian insufficiency (POI). Thirty adult female rats were randomly subdivided into five groups: normal control (control), cyclophosphamide (CTX) plus subsequent PBS (POI + PBS), CTX plus subsequent PRP (POI + PRP), CTX plus subsequent G-CSF-mobilized PBMCs (POI + PBMCs), and CTX plus subsequent G-CSF-mobilized PBMCs combined with PRP (POI + PBMCs + PRP). CTX exposure induced the typical POI phenotype with increased diestrus; shortened estrus; follicle arrest at all stages; decreased serum levels of estradiol-17ß (E2) and anti-Mullerian hormone (AMH); and increased levels of follicle-stimulating hormone (FSH). Transplantation of mobilized PBMCs with PRP resulted in a much earlier restoration of the estrous cycle, sex hormone levels, and preantral follicle growth in POI rats. Expression of the male-specific Sry gene in the ovarian tissues of POI + PBMCs + PRP female recipient rats was evident at 5, 10, and 20 days posttransplantation along with significant increases in the expression of angiogenesis markers CD34+ and VEGF and folliculogenesis markers AMH and FSHR. Additionally, PBMCs in combination with PRP mitigated granulosa cell apoptosis by downregulating BAX and upregulating BCL-2. These results demonstrate that G-CSF-mobilized PBMCs combined with PRP accelerate the restoration of ovarian function in POI rats by increasing ovarian neovascularization, reducing granulosa cell apoptosis, and promoting folliculogenesis.

mpg-C3N4/Ag2O Nanocomposites Photocatalysts with Enhanced Visible-Light Photocatalytic Performance.

To study the photocatalytic activity under visible light irradiation, a series of mesoporous graphitic carbon nitride (mpg-C3N4)/Ag2O photocatalysts were synthesized. The as-prepared photocatalysts were characterized with X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), N2 adsorption Brunauer-Emmett-Teller method (N2-BET), Fourier transform infrared spectroscopy (FT-IR), UV-vis diffuse reflectance spectra (DRS), and photoluminescence spectra (PL) methods to determine their phase structure, purity, morphology, spectroscopic and photoluminescence emission performance, respectively. Photocatalytic degradation of methyl orange (MO) aqueous solution under visible-light irradiation indicated that the mpg-C3N4/Ag2O-50 nanocomposite exhibited the best activity. The degradation rate of MO reached to 90.8% in 120 min onto the mpg-C3N4/Ag2O-50 nanocomposite, and as compared with the pure mpg-C3N4 and Ag2O samples, the photocatalytic activity of the mpg-C3N4/Ag2O-50 nanocomposite was greatly enhanced. The enhancement of photocatalytic activity was mainly ascribed to the enhanced visible-light absorption ability and the formation of p-n heterojunctions between counterparts of the nanocomposites, which promoted the generation and separation of charge carriers.