Megakaryocytic IGF1 coordinates activation and ferroptosis to safeguard hematopoietic stem cell regeneration after radiation injury.

BACKGROUND: Hematopoietic stem cell (HSC) regeneration underlies hematopoietic recovery from myelosuppression, which is a life-threatening side effect of cytotoxicity. HSC niche is profoundly disrupted after myelosuppressive injury, while if and how the niche is reshaped and regulates HSC regeneration are poorly understood. METHODS: A mouse model of radiation injury-induced myelosuppression was built by exposing mice to a sublethal dose of ionizing radiation. The dynamic changes in the number, distribution and functionality of HSCs and megakaryocytes were determined by flow cytometry, immunofluorescence, colony assay and bone marrow transplantation, in combination with transcriptomic analysis. The communication between HSCs and megakaryocytes was determined using a coculture system and adoptive transfer. The signaling mechanism was investigated both in vivo and in vitro, and was consolidated using megakaryocyte-specific knockout mice and transgenic mice. RESULTS: Megakaryocytes become a predominant component of HSC niche and localize closer to HSCs after radiation injury. Meanwhile, transient insulin-like growth factor 1 (IGF1) hypersecretion is predominantly provoked in megakaryocytes after radiation injury, whereas HSCs regenerate paralleling megakaryocytic IGF1 hypersecretion. Mechanistically, HSCs are particularly susceptible to megakaryocytic IGF1 hypersecretion, and mTOR downstream of IGF1 signaling not only promotes activation including proliferation and mitochondrial oxidative metabolism of HSCs, but also inhibits ferritinophagy to restrict HSC ferroptosis. Consequently, the delicate coordination between proliferation, mitochondrial oxidative metabolism and ferroptosis ensures functional HSC expansion after radiation injury. Importantly, punctual IGF1 administration simultaneously promotes HSC regeneration and hematopoietic recovery after radiation injury, representing a superior therapeutic approach for myelosuppression. CONCLUSIONS: Our study identifies megakaryocytes as a last line of defense against myelosuppressive injury and megakaryocytic IGF1 as a novel niche signal safeguarding HSC regeneration.

Hematopoietic Stem Cells as an Integrative Hub Linking Lifestyle to Cardiovascular Health.

Despite breakthroughs in modern medical care, the incidence of cardiovascular disease (CVD) is even more prevalent globally. Increasing epidemiologic evidence indicates that emerging cardiovascular risk factors arising from the modern lifestyle, including psychosocial stress, sleep problems, unhealthy diet patterns, physical inactivity/sedentary behavior, alcohol consumption, and tobacco smoking, contribute significantly to this worldwide epidemic, while its underpinning mechanisms are enigmatic. Hematological and immune systems were recently demonstrated to play integrative roles in linking lifestyle to cardiovascular health. In particular, alterations in hematopoietic stem cell (HSC) homeostasis, which is usually characterized by proliferation, expansion, mobilization, megakaryocyte/myeloid-biased differentiation, and/or the pro-inflammatory priming of HSCs, have been shown to be involved in the persistent overproduction of pro-inflammatory myeloid leukocytes and platelets, the cellular protagonists of cardiovascular inflammation and thrombosis, respectively. Furthermore, certain lifestyle factors, such as a healthy diet pattern and physical exercise, have been documented to exert cardiovascular protective effects through promoting quiescence, bone marrow retention, balanced differentiation, and/or the anti-inflammatory priming of HSCs. Here, we review the current understanding of and progression in research on the mechanistic interrelationships among lifestyle, HSC homeostasis, and cardiovascular health. Given that adhering to a healthy lifestyle has become a mainstream primary preventative approach to lowering the cardiovascular burden, unmasking the causal links between lifestyle and cardiovascular health from the perspective of hematopoiesis would open new opportunities to prevent and treat CVD in the present age.

Ferroptosis heterogeneity within the tumor microenvironment revealed a genetic blueprint of breast cancer.

The tumor microenvironment (TME) significantly influences disease progression through immune infiltration, while ferroptosis, a recently discovered cell death mechanism, plays a crucial role in tumor suppression. However, its role in breast cancer is not clear. In this study, we analyzed bulk RNA and single-cell RNA sequencing data from 1217 samples, including 1104 breast cancer patients and 113 controls, to identify ferroptosis-related genes (FRGs) and construct a prognostic model. Using univariate cox regression, LASSO regression, and multivariate cox regression analysis, we discovered 21 FRGs and 3 TME-related immune cell types with prognostic value. Dimensionality reduction clustering and visualization were performed using the UMAP method, while the immune infiltration process was calculated with the TIP online tool. We employed GSEA enrichment analysis, WGCNA clustering analysis, and correlation analysis to examine functional differences, and the mutation analysis of the best and worst prognosis groups was conducted using the maftools package. Our findings revealed that knocking down the expression of the hub gene SLC39A7 significantly impacted cancer cell apoptosis and combining ferroptosis and TME scores yielded high prognostic power. Epithelial cells and B cells exhibited higher ferroptosis scores, which were independently associated with immune checkpoint blockade (ICB) response and ICB gene expression. This study provides a foundation for further exploration of the relationship between ferroptosis and ICB response in breast cancer. In conclusion, we developed a prognostic model based on ferroptosis and infiltrated immune cells that effectively stratified breast cancer patients and demonstrated the role of SLC39A7 in breast cancer pathogenesis through the regulation of apoptosis.

Effect of Pelvic Floor Muscle Training With Smartphone Reminders on Women in the Postpartum Period: A Randomized Controlled Trial.

IMPORTANCE: Standard postpartum pelvic floor muscle training (PFMT) can effectively reduce the incidence of pelvic floor dysfunction diseases. OBJECTIVE: This study aimed to evaluate the adherence of PFMT with smartphone application reminders on women in the postpartum period. STUDY DESIGN: We conducted a randomized controlled trial. This single-center randomized (1:1) controlled study included primiparous women admitted to Tongji Hospital between March 2022 and June 2022 (ChiCTR2200059157). Every puerpera was given pelvic floor muscle (PFM) assessment and PFMT guidance at 6 weeks after delivery. After randomization, women in the intervention group received daily training reminders from the smartphone application WeChat. Adherence to PFMT, a symptom of stress urinary incontinence, and PFM characteristics were measured 3 months later. RESULTS: A total of 148 participants were included in the final analysis (76 in the intervention group and 72 in the control group). The adherence rate of daily PFMT was higher in the intervention group than in the control group (53.9% vs 20.8%, P = 0.00) at 3-month follow-up. In addition, participants in the intervention group showed higher peak surface electromyography of PFMs (39.8 ± 6.2 vs 37.5 ± 5.9 µV, P = 0.03) and longer PFM endurance (8.1 ± 2.0 vs 7.3 ± 2.0 seconds, P = 0.01) than in the control group, whereas there was no difference between the 2 groups in International Consultation on Incontinence Questionnaire-Short Form ( P = 0.60) and the Patient Global Impression of Improvement scores ( P = 1.00). CONCLUSIONS: Smartphone application-based PFMT could increase adherence and improves electromyography of PFMs in the short term but did not affect stress urinary incontinence symptoms in women in the postpartum period.

Association of epidural analgesia during labor and early postpartum urinary incontinence among women delivered vaginally: a propensity score matched retrospective cohort study.

BACKGROUND: Although epidural analgesia is considered the gold standard for pain relief during labor and is safe for maternity and fetus, the association between the epidural analgesia and pelvic floor disorders remains unclear. Thus we estimate the association between epidural analgesia and early postpartum urinary incontinence (UI). METHODS: A propensity score-matched retrospective cohort study was conducted at a university-affiliated hospital in Shanghai, China. Primiparous women with term, singleton, and vaginal delivery between December 2020 and February 2022 were included. UI was self-reported by maternity at 42 to 60 days postpartum and was classified by International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF). Using logistic regression models, the associations between epidural analgesia and early postpartum UI were assessed. RESULTS: Among 5190 participants, 3709 (71.5%) choose epidural anesthesia during labor. Analysis of the propensity-matched cohort (including 1447 maternal pairs) showed epidural anesthesia during labor was independently associated with UI in early postpartum period (aOR 1.50, 95% CI 1.24-1.81). This association was mainly contributed to stress UI (aOR 1.38, 95% CI 1.12-1.71) rather than urge UI (aOR 1.45, 95% CI 0.99-2.15) and mixed UI (aOR 1.52, 95% CI 0.95-2.45). Furthermore, we observed that the association between epidural anesthesia and UI was more pronounced among older women (≥ 35 y) and women with macrosomia (infant weight ≥ 4000 g), compared with their counterparts (both P for interaction < 0.01). After further analysis excluding the women with UI during pregnancy, the results remained largely consistent with the main analysis. CONCLUSIONS: The findings support that epidural anesthesia was associated with SUI in the early postpartum period.

Application of interface treatment at different positionp-nc-Si:H hole collector of silicon heterojunction cells.

The hole collector in silicon heterojunction cells serves not only as an integral component of thep/njunction, determining the strength of the built-in electric field, but also as a layer responsible for hole transport, thereby affecting carrier transport capacity. To enhance carrier extraction and transport properties of the hole collector, various interface treatments have been employed onp-type nanocrystalline (p-nc-Si:H) hole collectors. Through an examination of characteristics such as dark conductivity, crystallinity, and contact resistance, the impact of interface treatment onp-nc-Si:H hole collectors is clarified. Furthermore, considering distinct requirements for the hole collector at different locations, interface treatment processes are optimized accordingly. The introduction of interface treatment onp-nc-Si:H hole collectors has demonstrated significant enhancement of both front and rear junction cell efficiencies, which increased from 17.74% to 21.61% and from 16.83% to 20.92%, respectively.

Abdominal wall hernia repair: from prosthetic meshes to smart materials.

Hernia reconstruction is one of the most frequently practiced surgical procedures worldwide. Plastic surgery plays a pivotal role in reestablishing desired abdominal wall structure and function without the drawbacks traditionally associated with general surgery as excessive tension, postoperative pain, poor repair outcomes, and frequent recurrence. Surgical meshes have been the preferential choice for abdominal wall hernia repair to achieve the physical integrity and equivalent components of musculofascial layers. Despite the relevant progress in recent years, there are still unsolved challenges in surgical mesh design and complication settlement. This review provides a systemic summary of the hernia surgical mesh development deeply related to abdominal wall hernia pathology and classification. Commercial meshes, the first-generation prosthetic materials, and the most commonly used repair materials in the clinic are described in detail, addressing constrain side effects and rational strategies to establish characteristics of ideal hernia repair meshes. The engineered prosthetics are defined as a transit to the biomimetic smart hernia repair scaffolds with specific advantages and disadvantages, including hydrogel scaffolds, electrospinning membranes, and three-dimensional patches. Lastly, this review critically outlines the future research direction for successful hernia repair solutions by combing state-of-the-art techniques and materials.

Study on Enhanced Oil Recovery Mechanism of CO2 Miscible Flooding in Heterogeneous Reservoirs under Different Injection Methods.

The mechanism by which oil recovery can be enhanced by different injection methods of CO2 miscible flooding to alleviate the influence of heterogeneous reservoirs was studied to optimize the injection methods, further improving oil recovery. According to the reservoir heterogeneity characteristics of the TI oil formation group in Lunnan Oilfield, a 1 m double-layer long core was designed and prepared for four CO2 miscible displacement experiments with different injection methods. By analyzing the variation in the injection-production parameters, the displacement effects of different injection methods were compared, and the mechanism of enhanced oil recovery (EOR) was summarized. The results indicate the following. ① The displacement efficiency of the different injection methods lies in the following order. Alternate CO2-water injection, continuous CO2 flooding, cyclic CO2 flooding, and alternate CO2-hydrocarbon gas injection. ② The recovery of crude oil via CO2 miscible flooding in heterogeneous reservoirs relies on both convective diffusion and miscible mass transfer. Convective diffusion depends mainly on control of the displacement pressure differential and the plugging of preferential seepage channels in high-permeability areas, while miscible mass transfer depends mainly on the swept range of the convective diffusion and the degree of miscibility between CO2 and crude oil. ③ To improve the recovery efficiency of CO2 miscible flooding in heterogeneous reservoirs, it is necessary to choose an injection method that optimizes these two aspects.

Construct of an Electrodeposited Cobalt-Molybdenum Film and Evaluation of Its Efficiency in Hydrogen Evolution.

Hydrogen is a valuable clean energy source, and electrolysis to produce hydrogen from water is a crucial component. However, a major problem of hydrogen generation by electrolysis is its large overpotential and poor economics. To reduce the overpotential, we mainly use nickel foam and Co-Mo ions as feedstock and create an efficient catalytic material by electrodeposition. The Co-Mo interaction improves the current efficiency. In 1 mol/L NaOH solution, the overpotential of the Co-Mo-NF composites was low when the current density is -10 mA/cm2, with the best value reaching 45.3 mV, which is less than those of Co-NF (94.4 mV) and Mo-NF (88.2 mV). All deposits had similar Tafel slopes in the 77.9 mV/decade range. The catalyst does not just have a favorable effect on hydrogen formation but also has a surprisingly high double-layer capacitance (up to 180 mF/cm2) and good stability. This research provides an impactful approach for developing a non-precious metal HER catalyst for industrial hydrogen production.

Microscopic Production Characteristics of Pore Crude Oil and Influencing Factors during Enhanced Oil Recovery by Air Injection in Shale Oil Reservoirs.

High-pressure air injection (HPAI) is one of the effective methods to improve shale oil recovery after the primary depletion process. However, the seepage mechanisms and microscopic production characteristics between air and crude oil are complicated in porous media during the air flooding process. In this paper, an online nuclear magnetic resonance (NMR) dynamic physical simulation method for enhanced oil recovery (EOR) by air injection in shale oil was established by combining high-temperature and high-pressure physical simulation systems with NMR. The microscopic production characteristics of air flooding were investigated by quantifying fluid saturation, recovery, and residual oil distribution in different sizes of pores, and the air displacement mechanism of shale oil was discussed. On this basis, the effects of air oxygen concentration, permeability, injection pressure, and fracture on recovery were studied, and the migration mode of crude oil in fractures was explored. The results show that the shale oil is mainly found in <0.1 µm (small pores), followed by 0.1-1 µm (medium pores), and 1-10 µm (macropores); thus, it is critical to enhancing oil recovery in pores less than 0.1 and 0.1-1 µm. The low-temperature oxidation (LTO) reaction can occur by injecting air into depleted shale reservoirs, which has a certain effect on oil expansion, viscosity reduction, and thermal mixing phases, thereby greatly improving shale oil recovery. There is a positive relationship between air oxygen concentration and oil recovery; the recoveries of small pores and macropores can increase by 3.53 and 4.28%, respectively, and they contribute 45.87-53.68% of the produced oil. High permeability means good pore-throat connectivity and greater oil recovery, and the production degree of crude oil in three types of pores can be increased by 10.36-24.69%. Appropriate injection pressure is beneficial to increasing the oil-gas contact time and delaying gas breakthrough, but high injection pressure will result in early gas channeling, which causes the crude oil in small pores to be difficult to produce. Notably, the matrix can supply oil to fractures due to the mass exchange between matrix fractures and the increase of the oil drainage area, and the recoveries of medium pores and macropores in fractured cores increased by 9.01 and 18.39%, respectively; fractures can act as bridges for matrix crude oil migration, which means that proper fracturing before gas injection can make the EOR better. This study provides a new idea and a theoretical basis for improving shale oil recovery and clarifies the microscopic production characteristics of shale reservoirs.

Case report: Transvaginal single-port extraperitoneal laparoscopic sacrospinous ligament fixation for apical prolapse: A single-center case series.

Background: Sacrospinous ligament fixation (SSLF) is a minimally invasive and effective procedure for the treatment of apical prolapse. Because intraoperative exposure of the sacrospinous ligament is difficult, SSLF is difficult. The aim of our article is to determine the safety and feasibility of single-port extraperitoneal laparoscopic SSLF for apical prolapse. Methods: This single-center, single-surgeon case series study included 9 patients with pelvic organ prolapse quantification (POP-Q) III or IV apical prolapse who underwent single-port laparoscopic SSLF. Additionally, transobturator tension-free vaginal tap (TVT-O) was performed in 2 patients, and anterior pelvic mesh reconstruction was performed in 1 patient. Results: The operative time ranged from 75 to 105 (mean, 88.9 ± 10.2) min, and blood loss ranged from 25 to 100 (mean, 43.3 ± 22.6) ml. No serious operative complications, blood transfusions, visceral injuries, or postoperative gluteal pain were reported for these patients. After 2-4 months of follow-up, no recurrence of POP, gluteal pain, urinary retention/incontinence, or other complications was observed. Conclusion: Transvaginal single-port SSLF is a safe, effective, and easy-to-master operation for apical prolapse.

The association between the interdelivery interval and early postpartum urinary incontinence in women who had consecutive vaginal deliveries: a retrospective cohort study.

Background: Urinary incontinence (UI) is associated with obstetric-related factors; however, the association between the timing of deliveries and UI remains unclear. We examined the association between the interdelivery interval (IDI) and early postpartum UI. Methods: This retrospective cohort study included 2,492 parous women who had consecutive singleton, full-term, and vaginal deliveries. UI was self-reported by the participants from 42 to 60 days postpartum and was classified using the International Consultation on Incontinence Questionnaire-Urinary Incontinence-Short Form. The IDI was measured as the number of months between 2 consecutive live births, and the participants were divided into 4 groups based on the IDI quartiles. The associations between the IDI and early postpartum UI were assessed using multiple logistic regression models. Results: The median [interquartile range] IDI for the entire cohort was 62 [40-90] months at the baseline. In general, the restricted cubic splines showed a U-shaped curve association between the IDI and the incidence of early postpartum UI. After fully adjusting for potential confounders, a longer IDI was associated with a lower adjusted odds ratio (aOR) of postpartum UI. Among the 4 groups, the Quartile 3 IDI group had the lowest aOR [aORQuartile 1-Quartile 2: 0.48 (95% CI: 0.36-0.63); aORQuartile 1-Quartile 3: 0.37 (95% CI: 0.27-0.49); aORQuartile 1-Quartile 4: 0.40 (95% CI: 0.28-0.57); the P value for the trend was <0.001). The association between the IDI and UI was more pronounced in the younger women (<35 years old) and the women with a pre-pregnancy body mass index of <25 kg/m2 (the P values for both interactions were <0.01). Conclusions: We found that the IDI was independently associated with the incidence of early postpartum UI in parous women. IDI ≥41 months was associated with a lower risk of postpartum UI compared to IDI <41 months.

H2O2-responsive polymer prodrug nanoparticles with glutathione scavenger for enhanced chemo-photodynamic synergistic cancer therapy.

The combination of chemotherapy and photodynamic therapy (PDT) based on nanoparticles (NPs) has been extensively developed to improve the therapeutic effect and decrease the systemic toxicity of current treatments. However, overexpressed glutathione (GSH) in tumor cells efficiently scavenges singlet oxygens (1O2) generated from photosensitizers and results in the unsatisfactory efficacy of PDT. To address this obstacle, here we design H2O2-responsive polymer prodrug NPs with GSH-scavenger (Ce6@P(EG-a-CPBE) NPs) for chemo-photodynamic synergistic cancer therapy. They are constructed by the co-self-assembly of photosensitizer chlorin e6 (Ce6) and amphiphilic polymer prodrug P(EG-a-CPBE), which is synthesized from a hydrophilic alternating copolymer P(EG-a-PD) by conjugating hydrophobic anticancer drug chlorambucil (CB) via an H2O2-cleavable linker 4-(hydroxymethyl)phenylboronic acid (PBA). Ce6@P(EG-a-CPBE) NPs can efficiently prevent premature drug leakage in blood circulation because of the high stability of the PBA linker under the physiological environment and facilitate the delivery of Ce6 and CB to the tumor site after intravenous injection. Upon internalization of Ce6@P(EG-a-CPBE) NPs by tumor cells, PBA is cleaved rapidly triggered by endogenous H2O2 to release CB and Ce6. Ce6 can effectively generate abundant 1O2 under 660 nm light irradiation to synergistically kill cancer cells with CB. Concurrently, PBA can be transformed into a GSH-scavenger (quinine methide, QM) under intracellular H2O2 and prevent the depletion of 1O2, which induces the cooperatively strong oxidative stress and enhanced cancer cell apoptosis. Collectively, such H2O2-responsive polymer prodrug NPs loaded with photosensitizer provide a feasible approach to enhance chemo-photodynamic synergistic cancer treatment.

Influence of Different Obstetric Factors on Early Postpartum Pelvic Floor Function in Primiparas After Vaginal Delivery.

Purpose: This study sought to explore the obstetric factors affecting early postpartum pelvic floor function of primiparas after vaginal delivery. Patients and Methods: We included 3362 primiparas who underwent postpartum re-examination in International Peace Maternity and Child Health Hospital at 42-60 days after delivery. The Glazer Protocol was used to evaluate their pelvic floor function, and univariate and multivariate logistic regression analyses were performed to identify obstetric factors that might affect it. Results: Forceps-assisted delivery significantly increased the risk of the decline in fast- and slow-twitch muscle strength in the early postpartum period when compared with natural vaginal delivery (P < 0.05). Women with a pre-pregnancy body mass index (BMI) of ≥18.5 kg/m2 had a decreased risk of decline in fast-twitch muscle strength than those with a pre-pregnancy BMI of <18.5 kg/m2 (P < 0.05). Women who had a pre-pregnancy BMI of 24.0 to <28.0 kg/m2 bore a decreased risk of decline in slow-twitch muscle strength than those with a pre-pregnancy BMI of <18.5 kg/m2 (P < 0.05). The risk of decline in fast-twitch muscle strength and slow-twitch muscle in women with anemia during pregnancy was significantly increased (P < 0.05); women with second-stage labors of >2 h had an increased risk of fast-twitch and slow-twitch muscle strength decline than those with <2 h (P < 0.05). Conclusion: Both pre-pregnancy underweight and obesity may cause impairment of early postpartum pelvic floor function. Forceps delivery, anemia during pregnancy, and the length of second stage of labor are independent factors leading to pelvic floor function impairment.

Establishment and validation of a simple nomogram for predicting early postpartum stress urinary incontinence among women with vaginal delivery: a retrospective study.

BACKGROUND: Stress urinary incontinence (SUI) is a common public health issue that negatively impacts the quality of life for women worldwide, of which early detection and rehabilitation are consequently pivotal. The aim of this study is to establish a simple nomogram for identifying women at risk of postpartum SUI. METHODS: A retrospective study was conducted in a tertiary specialized hospital in Shanghai, China. The study included only women with singleton, full-term, and vaginal deliveries. 2,441 women who delivered from July 2019 to November 2019 were included in the training cohort, and 610 women who delivered from January 2022 to February 2022 were included in the validation cohort. SUI was determined by the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI-SF). Univariate and multifactorial logistical regression were used to identify independent risk factors for postpartum SUI and further construct the nomogram accordingly. Based on concordance statistics (C-statistics), calibration curves, and decision curve analyses, we evaluated the performance of the nomogram in the training cohort and the validation cohort. In addition, the model was validated internally in the training cohort through cross-validation. RESULTS: There were no significant statistically differences in important baseline data such as age, pre-pregnancy BMI, and parity between the training and validation cohorts. SUI was observed in 431 (17.6%) and 125 (20.5%) women in the training and validation cohorts, respectively. According to the regression analysis, age, parity, second stage of labor, infant weight, and forceps delivery were included in the nomogram. The nomogram had a C-statistic of 0.80 (95% confidence interval [CI] 0.74-0.85) for predicting SUI. C-statistics were stable in both internally cross-validated training cohort (mean 0.81) and validation cohort (0.83 [95% CI 0.79-0.87]). The nomogram's calibration curve was near the ideal diagonal line. Additionally, the model exhibited a positive net benefit from the decision curve analysis. CONCLUSION: We have created a nomogram that can be utilized to quantify the risk of postpartum SUI for women with vaginal delivery. The model might contribute to predicting early postpartum SUI, thereby facilitating the management of SUI.

De novo synthesis of nervonic acid and optimization of metabolic regulation by Yarrowia lipolytica.

Nervonic acid, a natural fatty acid compound and also a core component of nerve fibers and nerve cells, has been widely used to prevent and treat related diseases of the brain nervous system. At present, fatty acids and their derivatives are mainly obtained by natural extraction or chemical synthesis which are limited by natural resources and production costs. In this study, the de novo synthetic pathway of nervonic acid was constructed in Yarrowia lipolytica by means of synthetic biology, and the yield of nervonic acid was further improved by metabolic engineering and fermentation optimization. Specially, heterologous elongases and desaturases derived from different organism were successfully expressed and evaluated for their potential for the production of nervonic acid in Y. lipolytica. Meanwhile, we overexpressed the genes involved in the lipid metabolism to increase the nervonic acid titer to 111.6 mg/L. In addition, the potential of adding oil as auxiliary carbon sources for nervonic acid production by the engineered Y. lipolytica was analyzed. The results indicated that supplementation with colleseed oil as an auxiliary carbon source can be beneficial for the nervonic acid productivity, which led to the highest concentration of 185.0 mg/L in this work. To summarize, this study describes that the Y. lipolytica can be used as a promising platform for the production of nervonic acid and other very long-chain fatty acids.

Iterative gene integration mediated by 26S rDNA and non-homologous end joining for the efficient production of lycopene in Yarrowia lipolytica.

Because of its potent antioxidant effects, lycopene has been used in various industries including, but not limited to, food, medical, and cosmetic industries. Yarrowia lipolytica, a non-conventional yeast species, is a promising chassis due to its natural mevalonate (MVA) pathway, abundant precursor acetyl coenzyme A content, and oleaginous properties. Several gene editing tools have been developed for Y. lipolytica along with engineering strategies for tetraterpenoid production. In this study, we engineered Y. lipolytica following multi-level strategies for efficient lycopene accumulation. We first evaluated the performance of the key lycopene biosynthetic genes crtE, crtB, and crtI, expressed via ribosomal DNA (rDNA) mediated multicopy random integration in the HMG1- and GGS1-overexpressing background strain. Further improvement in lycopene production was achieved by overexpressing the key genes for MVA synthesis via non-homologous end joining (NHEJ) mediated multi-round iterative transformation. Efficient strategies in the MVA and lipid synthesis pathways were combined to improve lycopene production with a yield of 430.5 mg/L. This strain produced 121 mg/g dry cell weight of lycopene in a 5-L fed-batch fermentation system. Our findings demonstrated iterative gene integration mediated by 26S rDNA and NHEJ for the efficient production of lycopene in Y. lipolytica. These strategies can be applied to induce Y. lipolytica to produce other tetraterpenoids.

Differential Effects of Intrauterine Balloon Tamponade Indications on Postpartum Hemorrhage Outcomes.

Objective: To determine whether the indication of intrauterine balloon tamponade (IUBT) was associated with postpartum hemorrhage (PPH) outcomes. Methods: Patients with PPH who underwent IUBT between January 2013 and November 2021 were included in a cohort study. PPH outcomes in patients who had IUBT for indications of uterine atony were compared to those who had IUBT for indications of placental site bleeding. PPH outcomes included uterine artery embolization (UAE) or hysterectomy after IUBT, estimated blood loss (EBL) after balloon placement, and blood transfusion. Statistical analysis was performed using multivariate logistic regression. Results: IUBT was performed on 603 cases, with 121 (20.1%) undergoing it for placental site bleeding and 482 (79.9%) for uterine atony. In general, IUBT was a reliable treatment for PPH, but the specific efficacy varied depending on the indication for placement. After controlling for confounding variables, compared to the indication of uterine atony, the indication of placental site bleeding increased the risk of transfusion of ≥4 units of PRBCs (aOR 2.47, 95%CI 1.32-3.98), EBL ≥ 300 ml after IUBT (aOR 3.78, 95%CI 2.22-5.33), and UAE or hysterectomy (aOR 2.52, 95%CI 1.20-6.01), respectively. Other factors associated with adverse PPH outcomes were lower antenatal hemoglobin, higher IUBT volume, longer duration of IUBT and larger shock index values. Conclusions: IUBT was less effective in treating PPH patients with indications of placental site bleeding than with indications of uterine atony. Follow-up monitoring of PPH patients with placental site bleeding should be intensified.

Effect of hydroxyl and carboxyl-functionalized carbon nanotubes on phase morphology, mechanical and dielectric properties of poly(lactide)/poly(butylene adipate-co-terephthalate) composites.

A series of poly(lactide)/poly(butylene adipate-co-terephthalate) (PLA/PBAT) composites containing different types of multi-walled carbon nanotubes (CNTs) such as hydroxyl and carboxyl-functionalized CNTs were fabricated using the melt blending method. The multifunctional epoxy oligomer (ADR) was selected as a chain extender in order to enhance the compatibility between PBAT and PLA. It was revealed that the addition of ADR could induce CNTs-OH to locate at the PLA/PBAT interface. But the inhibition effect of CNTs-COOH on chain extension reaction in PLA/PBAT blend system led to a decrease in the interaction force between PLA and PBAT owing to the high efficiency of the reaction between CNTs-COOH and ADR. The ε' of PLA/PBAT/4CNTs-OH composite was greater than that of PLA/PBAT/4CNTs-COOH composite because of the strong interaction between fillers and polymer matrix in PLA/PBAT/4CNTs-OH composite. The PLA/PBAT/4CNTs-OH composite showed a high ε' (24.9) and a low tan δ (0.23), respectively. The adjacent CNTs-OH could act as assemble microcapacitors electrodes and the polymer acted as a dielectric to, which greatly increased the interfacial polarization. The PLA/PBAT/4CNTs-OH composite has excellent mechanical and dielectric properties.