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Exogenous ferrous chloride (FeCl2) suppressed in vitro growth of Ralstonia pseudosolanacearum, causing bacteria for tomato bacterial wilt. More than 50 μM of FeCl2 reduced the in vitro bacterial growth in dosedependent manners. Two to 200 μM of FeCl2 did not affect the fresh weight of detached tomato leaves at 3 and 5 days after the petiole dipping without the bacterial inoculation. The bacterial wilt of the detached tomato leaves was evaluated by inoculating two different inoculum densities of R. pseudosolanacearum (105 and 107 cfu/ml) in the presence of FeCl2. Bacterial wilt in the detached leaves by 105 cfu/ml was efficiently attenuated by 10–200 μM of FeCl2 at 3 and 5 days post-inoculation (dpi), but bacterial wilt by 107 cfu/ml was only reduced by 200 μM of FeCl2 at 3 and 5 dpi. These results suggest that iron nutrients can be included in the integrated disease management of tomato bacterial wilt.

Microglia are brain-resident macrophage-like cells that play critical roles in diverse pathophysiological conditions, including development, neurogenesis, tissue damage, and pathogenic infection. Identifying molecular switches that govern the fate and function of microglia would be valuable for maintaining brain homeostasis. Forkhead box protein O1 (FoxO1) is the first identified gene in the FoxO family and serves as a potent transcriptional regulator that participates in development, apoptosis, metabolism, and stress response. It has been recently reported that FoxO1 expression is downregulated in human microglia with age, but the role of FoxO1 has not been characterized so far. In the present study, we investigated the molecular function of FoxO1 in microglia by utilizing BV-2 cells. By generating FoxO1-deficient BV-2 microglia through Crispr/Cas9 system, we analyzed the influence of FoxO1 on redox status, metabolism, and polarization of microglia. Our data clearly showed that FoxO1 deficiency suppressed oxidative stress and cell death. In addition, FoxO1 level could modulate metabolic status and polarizing potential of BV-2 microglia. FoxO1 might be a critical element for the regulation of microglial cell physiology and the maintenance of the brain homeostasis.

Bacterial vaginosis (BV) is caused by a microbial imbalance in the vaginal ecosystem, which causes genital discomfort and a variety of potential complications in women. This study validated the potential of Lactobacillus helveticus HY7801 as a probiotic to benefit vaginal health. In vivo, HY7801 reduced the number of Gardnerella vaginalis (GV) and pro-inflammatory cytokines in the vagina of GV-induced BV mice and ameliorated vaginal histological changes. In vitro, HY7801 exhibited positive resistance to simulated gastrointestinal conditions, showed excellent adherence ability to the female genital epithelium, and had high lactic acid and H2O2 production capacity. Furthermore, it was found that HY7801 can alleviate BV because it can suppress the expression of virulence factor genes of GV involved in epithelial cell adhesion and biofilm formation along with antibacterial activity against GV. These results indicate that HY7801 can be used as a promising probiotic strain for the maintenance of a healthy vaginal physiological state.

Microbiota promotes or inhibits the pathogenesis of a range of immune-mediated disorders. Although recent studies have elucidated the role of gut microbiota in ocular disease, the effect of ocular microbiota remains unclear. Herein, we explored the role of ocular commensal bacteria in non-infectious corneal inflammation and angiogenesis in a mouse model of suture-induced corneal neovascularization. Results revealed that the ocular surface harbored a microbial community consisting mainly of Actinobacteria, Firmicutes and Proteobacteria. Elimination of the ocular commensal bacteria by oral broad-spectrum antibiotics or topical fluoroquinolone significantly suppressed corneal inflammation and neovascularization. Disease amelioration was associated with reduced numbers of CD11b

Context The number of women who achieve pregnancy through assisted reproductive technology (ART), including in vitro fertilisation and embryo transfer (IVF-ET), is increasing worldwide. Placenta-mediated diseases associated with ART, such as gestational hypertension, preeclampsia, disorders of placental implantation, and placental abruption, are also increasing. Aims To determine the association between placental pathologies and IVF-ET in women with preterm births. Methods This retrospective cohort study examined archived placenta specimens of women who achieved pregnancy through either spontaneous conception or IVF-ET. In total, 1677 women with singleton pregnancies who gave birth consecutively between 20 and 37 weeks of gestation at Seoul National University Bundang Hospital and underwent placental pathologic evaluation between April 2013 and October 2018 were included. Data from all pathologic reports were reviewed. Key results The IVF-ET group had a higher median maternal age and rate of nulliparity than the natural conception group. The incidence rate of obstetric complications, except preterm premature rupture of membranes and placenta previa, was similar in both groups. The IVF-ET group had a higher incidence rate of placental infarction than the natural conception group (26.4% vs 16.4%, P = 0.012). Multivariate logistic regression analysis indicated that IVF, hypertensive disorders, and fetal growth restriction were significantly associated with placental infarction. Conclusions IVF-ET was independently associated with the risk of placental infarction in women with preterm births. Implications The use of IVF-ET may cause abnormal placental formation with an increased risk of anatomical and vascular pathology, which are observed in preterm deliveries and may contribute to pregnancy complications.

Polyploidization is a process by which cells are induced to possess more than two sets of chromosomes. Although polyploidization is not frequent in mammals, it is closely associated with development and differentiation of specific tissues and organs. The liver is one of the mammalian organs that displays ploidy dynamics in physiological homeostasis during its development. The ratio of polyploid hepatocytes increases significantly in response to hepatic injury from aging, viral infection, iron overload, surgical resection, or metabolic overload, such as that from non-alcoholic fatty liver diseases (NAFLDs). One of the unique features of NAFLD is the marked heterogeneity of hepatocyte nuclear size, which is strongly associated with an adverse liver-related outcome, such as hepatocellular carcinoma, liver transplantation, and liver-related death. Thus, hepatic polyploidization has been suggested as a potential driver in the progression of NAFLDs that are involved in the control of the multiple pathogenicity of the diseases. However, the importance of polyploidy in diverse pathophysiological contexts remains elusive. Recently, several studies reported successful improvement of symptoms of NAFLDs by reducing pathological polyploidy or by controlling cell cycle progression in animal models, suggesting that better understanding the mechanisms of pathological hepatic polyploidy may provide insights into the treatment of hepatic disorders.

In this study, we aimed to comprehensively characterize the microbiomes of various samples from pregnant women and their neonates, and to explore the similarities and associations between mother-neonate pairs, sample collection sites, and obstetrical factors. We collected samples from vaginal discharge and amniotic fluid in pregnant women and umbilical cord blood, gastric liquid, and meconium from neonates. We identified 19,597,239 bacterial sequences from 641 samples of 141 pregnant women and 178 neonates. By applying rigorous filtering criteria to remove contaminants, we found evidence of microbial colonization in traditionally considered sterile intrauterine environments and the fetal gastrointestinal track. The microbiome distribution was strongly grouped by sample collection site, rather than the mother-neonate pairs. The distinct bacterial composition in meconium, the first stool passed by newborns, supports that microbial colonization occurs during normal pregnancy. The microbiome in neonatal gastric liquid was similar, but not identical, to that in maternal amnionic fluid, as expected since fetuses swallow amnionic fluid in utero and their urine returns to the fluid under normal physiological conditions. Establishing a microbiome library from various samples formed only during pregnancy is crucial for understanding human development and identifying microbiome modifications in obstetrical complications.

Background Cleansing of the vulva and perineum is recommended during preparation for vaginal delivery, and special attention is paid to cleansing before episiotomy because episiotomy is known to increase the risk of perineal wound infection and/or dehiscence. However, the optimal method of perineal cleansing has not been established, including the choice of antiseptic agent. To address this issue, we designed a randomized controlled trial to examine whether skin preparation with chlorhexidine-alcohol is superior to povidone-iodine for the prevention of perineal wound infection after vaginal delivery. Methods In this multicenter randomized controlled trial, term pregnant women who plan to deliver vaginally after episiotomy will be enrolled. The participants will be randomly assigned to use antiseptic agents for perineal cleansing (povidone-iodine or chlorhexidine-alcohol). The primary outcome is superficial or deep perineal wound infection within 30 days after vaginal delivery. The secondary outcomes are the length of hospital stay, physician office visits, or hospital readmission for infection-related complications, endometritis, skin irritations, and allergic reactions. Discussion This study will be the first randomized controlled trial aiming to determine the optimal antiseptic agent for the prevention of perineal wound infections after vaginal delivery. Trial registration ClinicalTrials.gov NCT05122169. First submitted date on 8 November 2021. First posted date on 16 November 2021

Background Mounting evidence suggests that the immune system plays detrimental or protective roles in nerve injury and repair. Main body Herein we report that both CD11bhiLy6Ghi and CD11bhiLy6ChiLy6Glo myeloid cells are required to protect corneal nerves against sterile corneal injury. Selective depletion of CD11bhiLy6Ghi or CD11bhiLy6ChiLy6Glo cells resulted in aggravation of corneal nerve loss, which correlated with IL-6 upregulation. IL-6 neutralization preserved corneal nerves while reducing myeloid cell recruitment. IL-6 replenishment exacerbated corneal nerve damage while recruiting more myeloid cells. In mice lacking Toll-like receptor 2 (TLR2), the levels of IL-6 and myeloid cells were decreased and corneal nerve loss attenuated, as compared to wild-type and TLR4 knockout mice. Corneal stromal fibroblasts expressed TLR2 and produced IL-6 in response to TLR2 stimulation. Conclusion Collectively, our data suggest that CD11bhiLy6Ghi and CD11bhiLy6ChiLy6Glo myeloid cells confer corneal nerve protection under sterile injury by creating a negative-feedback loop to suppress the upstream TLR2–IL-6 axis that drives corneal nerve loss.

PurposeTo investigate the potential of the Link_TSG6 polypeptide comprising the Link module of human TSG-6 (TNF-stimulated gene/protein-6) as a novel treatment for dry eye disease (DED).MethodsWe analyzed the therapeutic effects of topical application of Link_TSG6 in two murine models of DED, the NOD.B10.H2b mouse model and the desiccating stress model. The effects of Link_TSG6 on the ocular surface and DED were compared with those of full-length TSG-6 (FL_TSG6) and of 0.05% cyclosporine (Restasis®). Additionally, the direct effect of Link_TSG6 on wound healing of the corneal epithelium was evaluated in a mouse model of corneal epithelial debridement.ResultsTopical Link_TSG6 administration dose-dependently reduced corneal epithelial defects in DED mice while increasing tear production and conjunctival goblet cell density. At the highest dose, no corneal lesions remained in ∼50% of eyes treated. Also, Link_TSG6 significantly suppressed the levels of inflammatory cytokines at the ocular surface and inhibited the infiltration of T cells in the lacrimal glands and draining lymph nodes. Link_TSG6 was more effective in decreasing corneal epithelial defects than an equimolar concentration of FL_TSG6. Link_TSG6 was significantly more potent than Restasis® at ameliorating clinical signs and reducing inflammation. Link_TSG6 markedly and rapidly facilitated epithelial healing in mice with corneal epithelial debridement wounds.ConclusionLink_TSG6 holds promise as a novel therapeutic agent for DED through its effects on the promotion of corneal epithelial healing and tear secretion, the preservation of conjunctival goblet cells and the suppression of inflammation.Previous article in issueNext article in issueKeywordsDry eye diseaseLink_TSG6Link moduleTNF-Stimulated gene/protein-6TSG-6

Background: Breastfeeding is beneficial to infants. However, cesarean section is reported to be a risk factor for unsuccessful breastfeeding. Research Aims: (1) To extract discriminating data from texture analysis of breast ultrasound images in the immediate postpartum period; and (2) to compare the analysis results according to delivery mode. Methods: A cross-sectional, prospective non-experimental design with a questionnaire and observational components was used. Participants ( N = 30) were women who delivered neonates at a center from September 2020 to December 2020. The participants underwent ultrasound examination of bilateral breasts 7–14 days after delivery. Ultrasound images were collected for texture analysis. A questionnaire about breastfeeding patterns was given to the participants on the day of the ultrasound examination. Results: No significant differences were found in texture analysis between the breasts of participants who had undergone Cesarean section and vaginal deliveries. The mean volume of total human milk produced in 1 day was significantly greater in the vaginal delivery group than in the cesarean section group ( M = 350.87 ml, SD = 183.83 vs. M = 186.20 ml, SD = 184.02; p = .017). The pain score due to breast engorgement measured subjectively by participants was significantly lower in the vaginal delivery group than in the cesarean section group ( M = 2.8, SD = 0.86 vs. M = 3.4, SD = 0.63; p = .047). Conclusion: Texture analysis of breast ultrasound images did not demonstrate difference between the cesarean section and vaginal delivery groups in the immediate postpartum period; nevertheless, cesarean section was independently associated with less successful breastfeeding.

Objectives To evaluate the effect of maternal age to the cesarean section rate of twin pregnancies in late preterm and term gestation. Methods A retrospective study was performed on twin pregnancies delivered at Seoul National University Bundang Hospital from June 2003 to December 2020. Preterm births before 34 weeks of gestation were excluded, and only live births were analyzed. The patients were classified into four groups according to maternal age ( Results The median value of maternal body mass index, the rate of assisted reproductive technology, dichorionic twin pregnancy, preeclampsia, and gestational diabetes increased significantly according to the maternal age group (all p Conclusions The rate of cesarean section in twin pregnancies significantly increased as maternal age increased, even in multiparous women.

Objective To compare the frequency of Ureaplasma-positive gastric fluid (GF) cultures based on the cause and mode of delivery in preterm newborns. Design Retrospective cohort study. Setting A single university hospital in South Korea. Population Women with a singleton pregnancy who delivered prematurely (between 23+0 and 32+0 weeks of gestation, N=464). Methods The newborns’ GF was obtained on the day of birth via nasogastric intubation. The frequency of Ureaplasma-positive GF cultures was compared according to the cause and mode of delivery. Main outcome measures Ureaplasma spp.-positivity in GF cultures. Results Ureaplasma spp. was detected in 20.3% of the GF samples. The presence of Ureaplasma spp. was significantly higher in the spontaneous preterm birth group than in the indicated preterm birth group (30.2% vs 3.0%; P < 0.001). Additionally, Ureaplama spp. was more frequently found in the vaginal delivery group than in the cesarean delivery group, irrespective of the cause of preterm delivery [indicated preterm birth group (22.2% vs. 1.9%, P = 0.023); spontaneous preterm birth group (37.7% vs. 24.2%, P = 0.015)]. Conclusions Ureaplasma spp. were found in 20.3% of the GFs. However, only 1.9% of newborns in the indicated preterm birth group with cesarean delivery had a Ureaplasma-positive GF culture. Our findings support the view that the amniotic cavity is a sterile environment before the onset of parturition. Funding Ministry of Health & Welfare and Ministry of Science and ICT, Republic of Korea (Grant No. HI22C1859) and the Seoul National University Bundang Hospital Research Fund (Grant No. 14-2021-0025).

To evaluate the effect of continuous infusion of nicardipine on the management of uncontrolled blood pressure (BP) during postpartum period. This retrospective study included 209 women diagnosed in hospital with hypertensive disorders during pregnancy and had uncontrolled BP after delivery between January 2018 to December 2020 Uncontrolled BP was defined as persistent elevation of systolic BP ≥ 160 mm Hg or diastolic BP ≥ 110 mm Hg. Patients were divided into 2 groups: nicardipine (N = 53; continuous nicardipine infusion and additional bolus of labetalol or hydralazine) and control (N = 156; consecutive bolus of labetalol or hydralazine). BP data were analyzed using the Mann-Whitney U and χ2 tests by dividing the time interval of 4 hours by the delivery time. The highest BP trends showed that the mean values of both systolic and diastolic BP immediately before delivery were higher in the nicardipine group than in the control. After 8 to 12 hours following delivery, both systolic and diastolic BP were lower in the nicardipine group than in the control. Subsequently, 16 to 20 hours after delivery, both systolic and diastolic BP were significantly lower in the nicardipine group than in the control (137/80 vs 141/84 mm Hg). Initially, the proportions of uncontrolled BP in the nicardipine group were higher than those in the control; however, it then became lower at all time intervals 8 hours after delivery. The proportions of patients who received additional antihypertensive agents and the median cumulative dosages were lower in the nicardipine group than in the control. Continuous infusion of nicardipine can help manage uncontrolled BP during the postpartum period.

ObjectiveWe compared the efficacy and postoperative complications of tension-free vaginal tape (TVT)-abbrevo® (TVT-A) and TVT-obturator® (TVT-O) surgeries for the treatment of stress urinary incontinence (SUI).MethodsWe retrospectively analyzed the medical records of 143 female patients with SUI who underwent TVT-A or TVT-O surgery between January 2010 and December 2019 at the Asan Medical Center in Seoul. We evaluated intra- and postoperative complications such as bladder injury, groin pain, urinary retention, and mesh exposure. We also checked the success rate at 6 months after surgery.ResultsThere were no complications, including fever, hematuria, hematoma of the vulva, or bladder injury, immediately after surgery in either group. Postoperative complications 2 weeks post-surgery were groin pain (11.3%), urinary retention (4.9%), and mesh exposure (0.7%). Groin pain was not significantly different between the two groups at 2 weeks, 3 months, and 6 months after surgery (TVT-O vs. TVT-A after 2 weeks: 12.5% vs. 10.3%, P=0.791; 3 months: 0.0% vs. 1.4%, P=0.999; and 6 months: 0.0% vs. 0.0%, P=0.999). Over 90% of the patients reported cure or improved symptoms in both groups. In the univariate logistic analysis, the type of TVT (TVT-O or TVT-A) was not associated with the success rate (odds ratio, 3.21; 95% confidence interval, 0.59-17.40; P=0.175).ConclusionTVT-A surgery is comparable with TVT-O in terms of high success rate and low frequency of complications, including bladder injury and groin pain.

To identify potential plasma biomarkers associated with microbial invasion of the amniotic cavity (MIAC) and/or intraamniotic inflammation (IAI) in women with preterm premature rupture of membranes (PPROM). This retrospective cohort study included 182 singleton pregnant women with PPROM (23–33 weeks) who underwent amniocentesis. Plasma samples; all subjects were chosen from these participants and were analyzed using label-free liquid chromatography-tandem mass spectrometry for proteome profiling using a nested case–control study design (cases with MIAC/IAI vs. non-MIAC/IAI controls [n = 9 each]). Three identified target molecules for MIAC/IAI were further verified by ELISA in the study cohort (n = 182). Shotgun proteomic analysis revealed 17 differentially expressed proteins (P

Due to the increased morbidity and mortality by fungal infections and the emergence of severe antifungal resistance, there is an urgent need for new antifungal agents. Here, we screened for antifungal activity in our in-house library through the minimum inhibitory concentration test and derived two hit compounds with moderate antifungal activities. The hit compounds' antifungal activities and drug-like properties were optimized by substituting various aryl ring, alkyl chain, and methyl groups. Among the optimized compounds, 22h was the most promising candidate with good drug-like properties and exhibited potent fast-acting fungicidal antifungal effects against various fungal pathogens and synergistic antifungal activities with some known antifungal drugs. Additionally, 22h was further confirmed to disturb fungal cell wall integrity by activating multiple cell wall integrity pathways. Furthermore, 22h exerted significant antifungal efficacy in both the subcutaneous infection mouse model and ex vivo human nail infection model.

To develop a noninvasive scoring system to identify patients at high risk for intra-amniotic infection and/or inflammation, which would reduce the need for amniocentesis.This prospective cohort study comprised patients admitted with preterm labor and intact membranes (20-34 weeks of gestation) who underwent a transabdominal amniocentesis and for whom concentrations of quantitative cervical fetal fibronectin and of maternal serum C-reactive protein (CRP) were determined. Intra-amniotic infection was defined as a positive amniotic fluid culture for microorganisms. Intra-amniotic inflammation was defined as an amniotic fluid matrix metalloproteinase-8 concentration23 ng/mL. Multivariate logistic regression analysis was performed to identify intra-amniotic infection/inflammtion with noninvasive parameters that had a significant relationship with univariate analysis. With four parameters identified by multivariate analysis, we generated a noninvasive risk scoring system.Of the study population consisting of 138 singleton pregnant women, (1) the overall rate of intra-amniotic infection/inflammation was 28.3% (39/138); (2) four parameters were used to develop a noninvasive risk scoring system [i.e. cervical fetal fibronectin concentration (score 0-2), maternal serum CRP concentration (score 0-2), cervical dilatation (score 0-2), and gestational age at presentation (score 0-1)]; the total score ranges from 0 to 7; 3) the area under the curve of the risk score was 0.96 (95% confidence interval (CI), 0.92-0.99), significantly higher than that of each predictor in the identification of intra-amniotic infection/inflammation ((1) The combination of four parameters (concentrations of cervical fetal fibronectin and maternal serum CRP, cervical dilatation, and gestational age) was independently associated with intra-amniotic infection and/or inflammation; and (2) the risk scoring system comprised of the combination of 4 noninvasive parameters was sensitive and specific to identify the patients at risk for intra-amniotic infection and/or inflammation.

Background: Mounting evidence suggests that the immune system plays detrimental or protective roles in nerve injury and repair. Main body: Herein we report that both CD11bhiLy6Ghi and CD11bhiLy6ChiLy6Glo myeloid cells are required to protect corneal nerves against sterile corneal injury. Selective depletion of CD11bhiLy6Ghi or CD11bhiLy6ChiLy6Glo cells resulted in aggravation of corneal nerve loss, which correlated with IL-6 upregulation. IL-6 neutralization preserved corneal nerves while reducing myeloid cell recruitment. IL-6 replenishment exacerbated corneal nerve damage while recruiting more myeloid cells. In mice lacking Toll-like receptor 2 (TLR2), the levels of IL-6 and myeloid cells were decreased and corneal nerve loss attenuated, as compared to wild-type and TLR4 knockout mice. Corneal stromal fibroblasts produced IL-6 in response to TLR2 stimulation. Conclusion: Collectively, our data suggest that CD11bhiLy6Ghi and CD11bhiLy6ChiLy6Glo myeloid cells confer corneal nerve protection under injury by creating a negative-feedback loop to suppress the upstream TLR2-IL-6 axis that drives corneal nerve loss.

The global prevalence of non-alcoholic fatty liver disease (NAFLD) has rapidly increased over the last decade due to an elevated occurrence of metabolic syndromes. Importantly, the prevalence and severity of NAFLD is higher in men than in women. Therefore, in the present study we endeavored to identify the mechanistic disparity between male and female mice.Global gene transcriptomics analysis was done with the high-fat diet (HFD)-induced NAFLD model of male, female, and ovariectomized (OVX) female mice. The expression of CCL2, CXCL2, and CXCL10 in mRNA level and serum protein level was done by qPCR and ELISA each. Immunohistochemistry staining was used to observe hepatic immune cell infiltration. To analyzing portion of immune cells, flow cytometry was done with isolated liver cells from HFD-fed male and female mice. Primary mouse liver cells were isolated from male and female mice for in vitro studies.We identified sex differences in inflammatory chemokines, CCL2, CXCL2, and CXCL10, with the expression of these chemokines enhanced in male and OVX, but not in female, mice after HFD feeding. Resident Kupffer cells (KCs) were identified as the major source of production of CCL2, CXCL2, and CXCL10 in the mouse NAFLD model. Notably, KCs obtained from male mice expressed higher levels of chemokines than those from female mice, indicating that KCs may mediate the sex discrepancy in NAFLD progression.Our findings offer new insights into the pathology of sex-specific differences in NAFLD, involving chemokines and KCs.

We compared the mean interleukin-6 (IL-6) level in the amniotic fluid after rupture of membranes during labour at term pregnancy according to the delivery methods through prospective cohort study. Cases with premature rupture of membranes, multifetal pregnancy, and major congenital anomalies were excluded. Amniotic fluid was obtained from vaginal canal immediately after spontaneous rupture of membranes. A total of 47 cases were analysed, and 72.3% (34/47) had successful vaginal delivery. The mean concentration of IL-6 in the amniotic fluid was significantly higher in the vaginal delivery group than in the caesarean section group (5,229 pg/mL vs. 1,702 pg/mL

Mycobacterial acyl carrier protein (AcpM; Rv2244), a key protein involved in Mycobacterium tuberculosis (Mtb) mycolic acid production, has been shown to suppress host cell death during mycobacterial infection. This study reports that mycobacterial AcpM works as an effector to subvert host defense and promote bacterial growth by increasing microRNA (miRNA)-155-5p expression. In murine bone marrow-derived macrophages (BMDMs), AcpM protein prevented transcription factor EB (TFEB) from translocating to the nucleus in BMDMs, which likely inhibited transcriptional activation of several autophagy and lysosomal genes. Although AcpM did not suppress autophagic flux in BMDMs, AcpM reduced Mtb and LAMP1 co-localization indicating that AcpM inhibits phagolysosomal fusion during Mtb infection. Mechanistically, AcpM boosted the Akt-mTOR pathway in BMDMs by upregulating miRNA-155-5p, a SHIP1-targeting miRNA. When miRNA-155-5p expression was inhibited in BMDMs, AcpM-induced increased intracellular survival of Mtb was suppressed. In addition, AcpM overexpression significantly reduced mycobacterial clearance in C3HeB/FeJ mice infected with recombinant M. smegmatis strains. Collectively, our findings point to AcpM as a novel mycobacterial effector to regulate antimicrobial host defense and a potential new therapeutic target for Mtb infection.

Nontuberculous mycobacterial pulmonary diseases (NTM-PDs) are emerging as global health threats with issues of antibiotic resistance. Accumulating evidence suggests that the gut-lung axis may provide novel candidates for host-directed therapeutics against various infectious diseases. However, little is known about the gut-lung axis in the context of host protective immunity to identify new therapeutics for NTM-PDs. This study was performed to identify gut microbes and metabolites capable of conferring pulmonary immunity to NTM-PDs. Using metabolomics analysis of sera from NTM-PD patients and mouse models, we showed that the levels of l-arginine were decreased in sera from NTM-PD patients and NTM-infected mice. Oral administration of l-arginine significantly enhanced pulmonary antimicrobial activities with the expansion of IFN-γ-producing effector T cells and a shift to microbicidal (M1) macrophages in the lungs of NTM-PD model mice. Mice that received fecal microbiota transplants from l-arginine-treated mice showed increased protective host defense in the lungs against NTM-PD, whereas l-arginine-induced pulmonary host defense was attenuated in mice treated with antibiotics. Using 16S rRNA sequencing, we further showed that l-arginine administration resulted in enrichment of the gut microbiota composition with

We aimed to evaluate the correlation and agreement of interleukin (IL)-8 and matrix metalloproteinases (MMP-9) levels between cervicovaginal (CVF) and amniotic fluids (AF) in women with preterm labor (PTL) and to determine the clinical values of these proteins in CVF compared with those in AF. We designed a retrospective cohort study of 85 singleton pregnant women with PTL at 23 to 34 weeks, who underwent amniocentesis. The AF was cultured, and CVF samples were collected at the time of amniocentesis. Paired AF and CVF samples were assayed for IL-8 and MMP-9 by enzyme-linked immunoassay (ELISA) in duplicate on a single plate, using similar dilution ratios. A significant but weak correlation was found for IL-8 levels between AF and CVF (r = 0.333), while no correlation was found for MMP-9 levels between AF and CVF (r = -0.039). Intra-class correlation coefficient for the agreement of IL-8 levels between CVF and AF was 0.4335 and -0.279 for MMP-9, indicating a poor-to-fair level of agreement between the two measured values, respectively. IL-8 and MMP-9 levels in CVF were not associated with the risk of either microbial invasion of the amniotic cavity (MIAC) or spontaneous preterm delivery (SPTD) within 7 days, whereas those in AF provided good-to-excellent predictive values for these two outcomes (area under the curve [AUCs]: 0.82-0.95). AUCs for IL-8 and MMP-9 were significantly larger using AF rather than using CVF for the prediction of MIAC and SPTD. In women with PTL, IL-8 and MMP-9 levels in CVF do not precisely reflect the levels of the corresponding proteins in AF. IL-8 and MMP-9 levels in CVF had poor predictive values for the risk of MIAC and SPTD and were significantly inferior to those in AF.· IL-8 and MMP-9 levels in CVF do not precisely reflect levels of the corresponding proteins in AF.. · Diagnostic accuracy of IL-8 and MMP-9 in CVF alone is not sufficient to predict MIAC and SPTD.. · IL-8 and MMP-9 levels in AF provide good-to-excellent predictive values for these two outcomes..

Background Maternal-fetal attachment (MFA) has been reported to be associated with the postpartum mother-infant relationship. Seeing the fetus through ultrasound might influence MFA, and the effect could be increased by more realistic images, such as those generated in virtual reality (VR). Objective The aim was to determine the effect of fetal images generated in VR on MFA and depressive symptoms through a prenatal-coaching mobile app. Methods This 2-arm parallel randomized controlled trial involved a total of 80 pregnant women. Eligible women were randomly assigned to either a mobile app–only group (n=40) or an app plus VR group (n=40). The VR group experienced their own baby’s images generated in VR based on images obtained from fetal ultrasonography. The prenatal-coaching mobile app recommended health behavior for the pregnant women according to gestational age, provided feedback on entered data for maternal weight, blood pressure, and glucose levels, and included a private diary service for fetal ultrasound images. Both groups received the same app, but the VR group also viewed fetal images produced in VR; these images were stored in the app. All participants filled out questionnaires to assess MFA, depressive symptoms, and other basic medical information. The questionnaires were filled out again after the interventions. Results Basic demographic data were comparable between the 2 groups. Most of the assessments showed comparable results for the 2 groups, but the mean score to assess interaction with the fetus was significantly higher for the VR group than the control group (0.4 vs 0.1, P=.004). The proportion of participants with an increased score for this category after the intervention was significantly higher in the VR group than the control group (43% vs 13%, P=.005). The feedback questionnaire revealed that scores for the degree of perception of fetal appearance all increased after the intervention in the VR group. Conclusions The use of a mobile app with fetal images in VR significantly increased maternal interaction with the fetus. Trial Registration ClinicalTrials.gov NCT04942197; https://clinicaltrials.gov/ct2/show/NCT04942197