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Epoxy resin is widely used in various fields of the national economy due to its excellent chemical and mechanical properties. Lignin is mainly derived from lignocelluloses as one of the most abundant renewable bioresources. Due to the diversity of lignin sources and the complexity as well as heterogeneity of its structure, the value of lignin has not been fully realized. Herein, we report the utilization of industrial alkali lignin for the preparation of low-carbon and environmentally friendly bio-based epoxy thermosetting materials. Specifically, epoxidized lignin with substituted petroleum-based chemical bisphenol A diglycidyl ether (BADGE) in various proportions was cross-linked to fabricate thermosetting epoxies. The cured thermosetting resin revealed enhanced tensile strength (4.6 MPa) and elongation (315.5%) in comparison with the common BADGE polymers. Overall, this work provides a practicable approach for lignin valorization toward tailored sustainable bioplastics in the context of a circular bioeconomy., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)

Objective: To assess outcomes in twin-twin transfusion syndrome (TTTS) according to middle cerebral artery pulsatility index (MCA-PI) prior to fetoscopic laser photocoagulation (FLPC) surgery., Methods: A retrospective cohort analysis of monochorionic-twin pregnancies complicated by TTTS who underwent FLPC at two fetal centers (2012-2021). The cohort was stratified according to abnormal MCA-PI of the donor twin, defined as below fifth centile for gestational age., Results: Abnormal MCA-PI of the donor twin was detected in 46 (17.7%) cases compared to 213 (83.3%) controls with no such abnormality. The abnormal PI group presented with higher rates of sFGR (56.5% vs. 36.8% in controls, p = 0.014) and lower donor survival rates within 48 h after FLPC (73.9 vs. 86.8%, p = 0.029). Donor twin survival rates at the time of delivery and 30 days after birth were lower in the abnormal MCA-PI. Multivariate logistic regression analysis controlling for sFGR and MCA-PI

Objectives: To evaluate the survival of twin-to-twin transfusion syndrome (TTTS) and concomitant twin anemia polycythemia sequence (TAPS) compared to TTTS without TAPS at the time of fetoscopic laser photocoagulation (FLP)., Methods: TTTS pregnancies undergoing FLP were divided to three groups including (i) traditional TAPS definition of middle cerebral artery (MCA) peak systolic velocity (PSV) < 1 multiple of the median (MoM) in recipient and > 1.5 MoM in the donor fetus, (ii) delta MCA-PSV > 0.5 MoM and (iii) delta MCA-PSV > 1.0 MoM., Results: A total of 353 monochorionic twins underwent FLP for TTTS. Based on the traditional definition, 335 (94.9 %) had TTTS only and 18 (5.1 %) had TTTS + TAPS. There were 245 (69.4 %) TTTS only and 108 (30.6 %) TTTS + TAPS considering delta MCA-PSV > 0.5 MoM and 339 (96 %) TTTS only and 14 (4 %) TTTS + TAPS considering delta MCA-PSV > 1.0 MoM. No significant differences in survival were noted at birth or 30-days after delivery between TTTS and TTTS with TAPS patients using the traditional definition, delta > 0.5 MoM or delta > 1.0 MoM., Conclusion: The rate of neonatal survival at birth or at 30-days of life following FLP for TTTS only and TTTS with TAPS were not different based on any of the clinically used TAPS definitions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Glycogen dysregulation is a hallmark of aging, and aberrant glycogen drives metabolic reprogramming and pathogenesis in multiple diseases. However, glycogen heterogeneity in healthy and diseased tissues remains largely unknown. Herein, we describe a method to define spatial glycogen architecture in mouse and human tissues using matrix-assisted laser desorption/ionization mass spectrometry imaging. This assay provides robust and sensitive spatial glycogen quantification and architecture characterization in the brain, liver, kidney, testis, lung, bladder, and even the bone. Armed with this tool, we interrogated glycogen spatial distribution and architecture in different types of human cancers. We demonstrate that glycogen stores and architecture are heterogeneous among diseases. Additionally, we observe unique hyperphosphorylated glycogen accumulation in Ewing sarcoma, a pediatric bone cancer. Using preclinical models, we correct glycogen hyperphosphorylation in Ewing sarcoma through genetic and pharmacological interventions that ablate in vivo tumor growth, demonstrating the clinical therapeutic potential of targeting glycogen in Ewing sarcoma., (© 2022 The Authors. Published under the terms of the CC BY 4.0 license.)

N-linked protein glycosylation in the brain is an understudied facet of glucose utilization that impacts a myriad of cellular processes including resting membrane potential, axon firing, and synaptic vesicle trafficking. Currently, a spatial map of N-linked glycans within the normal and Alzheimer's disease (AD) human brain does not exist. A comprehensive analysis of the spatial N-linked glycome would improve our understanding of brain energy metabolism, linking metabolism to signaling events perturbed during AD progression, and could illuminate new therapeutic strategies. Herein we report an optimized in situ workflow for enzyme-assisted, matrix-assisted laser desorption and ionization (MALDI) mass spectrometry imaging (MSI) of brain N-linked glycans. Using this workflow, we spatially interrogated N-linked glycan heterogeneity in both mouse and human AD brains and their respective age-matched controls. We identified robust regional-specific N-linked glycan changes associated with AD in mice and humans. These data suggest that N-linked glycan dysregulation could be an underpinning of AD pathologies., (© 2021 the Alzheimer's Association.)

Cancer cells are known for their ability to adapt variable metabolic programs depending on the availability of specific nutrients. Our previous studies have shown that uptake of fatty acids alters cellular metabolic pathways in colon cancer cells to favor fatty acid oxidation. Here, we show that fatty acids activate Drp1 to promote metabolic plasticity in cancer cells. Uptake of fatty acids (FAs) induces mitochondrial fragmentation by promoting ERK-dependent phosphorylation of Drp1 at the S616 site. This increased phosphorylation of Drp1 enhances its dimerization and interaction with Mitochondrial Fission Factor (MFF) at the mitochondria. Consequently, knockdown of Drp1 or MFF attenuates fatty acid-induced mitochondrial fission. In addition, uptake of fatty acids triggers mitophagy via a Drp1- and p62-dependent mechanism to protect mitochondrial integrity. Moreover, results from metabolic profiling analysis reveal that silencing Drp1 disrupts cellular metabolism and blocks fatty acid-induced metabolic reprograming by inhibiting fatty acid utilization. Functionally, knockdown of Drp1 decreases Wnt/β-catenin signaling by preventing fatty acid oxidation-dependent acetylation of β-catenin. As a result, Drp1 depletion inhibits the formation of tumor organoids in vitro and xenograft tumor growth in vivo. Taken together, our study identifies Drp1 as a key mediator that connects mitochondrial dynamics with fatty acid metabolism and cancer cell signaling., (© 2022. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare.)

Excessive discharge of inorganic and organic contaminants in water poses a serious threat to the ecosystems. However, most synthetic adsorbents lack cost-effectiveness in terms of preparation. Interestingly, loofah sponge (LS) was a natural absorbent that could effectively remove pollutions in wastewater, but its adsorption capacity is barely satisfactory. Herein, we present a novel strategy of TEMPO-oxidized loofah sponge (TOLS) to boost the adsorption performance of LS. The batch experiments demonstrated that the maximum removal capacity of TOLS for Pb(II) and methylene blue (MB) was 96.6 mg/g and 10.0 mg/g, respectively, which were 3.5 and 1.3 times that of pristine LS. Notably, the continuous-flow reaction testing of the mixed solution revealed that the elimination rate of Pb(II) and MB was still better than 90 % even after 16 h. Such excellent performance was benefit from the enhanced specific surface area and surface carboxyl content of TOLS. This work offers new insights into the rational development of multifunctional and inexpensive cellulose-based bio-adsorbents for wastewater remediation., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Classical swine fever virus (CSFV), a member of the Flaviviridae enveloped RNA virus family, results in an epidemic disease that brings serious economic losses to the pig industry worldwide. Valosin-containing protein (VCP/p97), a multifunctional active protein in cells, is related to the life activities of many viruses. However, the role of VCP in CSFV infection remains unknown. In this study, it was first found that treatment of VCP inhibitors impaired CSFV propagation. Furthermore, overexpression or knockdown of VCP showed that it was essential for CSFV infection. Moreover, confocal microscopy and immunoprecipitation assay showed that VCP was recruited for intracellular transport from early endosomes to lysosomes. Importantly, knockdown of VCP prevented CSFV to release from early endosomes, suggesting that VCP is a key factor for CSFV trafficking. Taken together, our findings first demonstrate that the endocytosis of CSFV into PK-15 cells requires the participation of VCP, providing the alternative approach for the discovery of novel anti-flaviviridae drugs., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction:  The Nuss procedure is the most common and preferred operative correction of pectus excavatum. Surgeon preference and patient factors can result in variations in Nuss procedure technique. We hypothesize that certain techniques are associated with increased risk of complications., Materials and Methods:  We performed a single-center retrospective review of Nuss operations from 2016 to 2020. Variations in intraoperative techniques included sternal elevator (SE) use, number of bars placed, and usage of bilateral stabilizing sutures. Patient demographics, intraoperative data, and postoperative outcomes were reported as median with interquartile ranges or percentages. Statistical significance ( p  < 0.05) was determined with Wilcoxon's rank-sum and chi-square tests. Multivariate analysis was performed to control for introduction of intercostal nerve cryoablation and surgeon volume, and reported as odds ratio with 95% confidence interval., Results:  Two hundred and sixty-five patients were identified. Patients repaired with two bars were older with a larger Haller index (HI). Patient demographics were not significantly different for SE or stabilizing suture use. Placement of two bars was associated with significantly increased risk of readmission. Similarly, SE use was associated with increased risk of pleural effusion and readmission. Finally, the use of bilateral stabilizing sutures resulted in less frequent slipped bars without statistical significance., Conclusion:  Older patients with a larger HI were more likely to need two bars placed to repair pectus excavatum. Placement of multiple bars and SE use are associated with significantly higher odds of certain complications., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: To analyze the mediating effect of work-occupation fit between occupational stress and anxiety symptoms in medical staff. Methods: Convenience sampling method was adopted to select participants of one general hospital and three specialized hospitals as respondents for a questionnaire survey in Henan Province from October 2020 to January 2021. A total of 2050 medical staff were investigated, and 1988 valid questionnaires were collected, and the effective rate of the questionnaire was 97.0% (1988/2050) . The "Depression-Anxiety-Stress Scale" and "Worker-Occupation Fit Inventory" were used to evaluate the occupational stress, anxiety symptoms and worker-occupation fit level of medical staff, and the mediation effect of work-occupation fit on the relationship between occupational stress and anxiety symptoms was analyzed using a mediating effect model. Results: The average age of the 1988 medical staff was (32.7±7.8) years old, the positive detection rates of occupational stress and anxiety symptoms were 42.5% (845/1988) and 56.7% (1127/1988) , respectively. Anxiety symptoms of medical staff were positively correlated with occupational stress, negatively correlated with worker-occupation fit ( r =0.831, -0.364, P <0.001) , work-occupation fit was negatively correlated with occupational stress ( r =-0.259, P <0.001) . The results of the mediation effect analysis showed that occupational stress had a direct effect on anxiety symptoms ( β =0.677, BCa 95% CI : 0.648-0.707) , and worker-occupation fit ( β =0.047, BCa 95% CI : 0.039-0.056) , characteristic fit ( β =0.089, BCa 95% CI : 0.074-0.104) , need-supply fit ( β =0.075, BCa 95% CI : 0.062-0.089) , and ability-demand fit ( β =0.035, BCa 95% CI : 0.026-0.044) mediated the association between occupational stress and anxiety symptoms in medical staff, with the mediating effect as a percentage of 6.5%, 12.3%, 10.3%, and 4.8%, respectively. Conclusion: Worker-occupation fit has a mediating effect between occupational stress and anxiety symptoms in medical staff, but mainly direct effect.

Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-22-292/coif). LLC reports stocks or stock options from Kojin Therapeutics. RCS reports personal fees and non-financial support from Maze Therapeutics. SKC reports personal fees and non-financial support from AbbVie, Sanofi. The other authors have no conflicts of interest to declare.

Objective: We sought to perform a meta-analysis of the predictive value of antenatal ultrasonographic markers of bowel dilation, gastric dilation, polyhydramnios and abdominal circumference that predict complex gastroschisis and adverse perinatal outcomes DATA SOURCES: PubMed, Web of Science, Scopus and Embase were searched for relevant articles up to December 2020. Studies reporting prenatal ultrasonographic markers including intra-abdominal bowel dilation (IABD), extra-abdominal bowel dilation (EABD), bowel wall thickness, polyhydramnios, abdominal circumference <5th percentile, gastric dilation (GD) and bowel dilation not otherwise specified (BD-NOS) were included. The primary outcome was prediction of complex gastroschisis; secondary outcomes were length of hospital stay for newborn, time to full enteral feeding, postnatal mortality rate, incidence of necrotising enterocolitis and short bowel syndrome., Results: Thirty-six studies were included in this meta-analysis. We found significant associations between complex gastroschisis and IABD (OR=5.42; 95% CI 3.24 to 9.06), EABD (OR=2.27; 95% CI 1.40 to 3.66), BD-NOS (OR=6.27; 95% CI 1.97 to 19.97), GD (OR=1.88; 95% CI 1.22 to 2.92) and polyhydramnios (OR=6.93; 95% CI 3.39 to 14.18). Second trimester IABD and EABD have greater specificity for the prediction of complex gastroschisis than third trimester values with specificity of 95.6% (95% CI 58.1 to 99.7) and 94.6% (95% CI 86.7 to 97.9) for the second trimester IABD and EABD, respectively., Conclusion: Prenatal ultrasonographic markers, especially the second trimester IABD and EABD, can identify fetuses that develop complex gastroschisis. Furthermore, these specific ultrasonographic markers can identify those babies at the highest risk for severe complications of this congenital anomaly and hence selected for future antenatal interventions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Congenital lung malformation (CLM) volume ratio (CVR) of ≥1.1 has been shown to be highly predictive of the need for urgent, perinatal surgical intervention. The purpose of this study was to utilize this information to propose a delivery planning and clinical management algorithm based on this threshold., Methods: A retrospective cohort study was performed for all fetuses evaluated at our fetal center between 5/2015 and 11/2020. Demographics, ultrasound findings, late gestation CVR (≥27 weeks gestational age), prenatal and postnatal treatment, and outcomes were analyzed with nonparametric univariate analysis based on late gestation CVR of 1.1. Receiver operating characteristic curve analysis was performed to evaluate association between late gestation CVR, hydrops, need for fetal intervention, and need for urgent perinatal surgery., Results: Of the 90 CLMs referred to our fetal center, 65 had late gestation CVR with a majority <1.1 (47/65, 72%). All patients with late gestation CVR ≥ 1.1 were managed with resection (18/18) with most resections requiring fetal intervention or urgent neonatal resection (13/18). Late gestation CVR < 1.1 were managed with elective resection (36/47, 77%) or non-operative observation (11/47, 23%). Late gestation CVR ≥ 1.1 had 100% sensitivity and NPV for hydrops, need for fetal intervention, and need for urgent perinatal surgery., Conclusion: CLM with CVR ≥ 1.1 were associated with urgent perinatal surgical intervention and expectant mothers should plan for delivery at centers equipped to manage neonatal resuscitation and potential urgent neonatal resection. Conversely, CLM with CVR < 1.1 may be safe to deliver at patient hospital of choice., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Pulmonary fibrosis (PF) is an abnormal remodeling of cellular composition and extracellular matrix that results in histological and functional alterations in the lungs. Apoptosis signal-regulating kinase-1 (ASK1) is a member of the mitogen-activated protein (MAP) kinase family that is activated by oxidative stress and promotes inflammation and apoptosis. Here we show that bleomycin-induced PF is reduced in Ask1 knockout mice (Ask1 -/- ) compared with wild-type (WT) mice, with improved survival and histological and functional parameters restored to basal levels. In WT mice, bleomycin caused activation of ASK1, p38, and extracellular signal-regulated kinase 1/2 (ERK1/2) in lung tissue, as well as changes in redox indicators (thioredoxin and heme-oxygenase-1), collagen content, and epithelial-mesenchymal transition markers (EMTs). These changes were largely restored toward untreated WT control levels in bleomycin-treated Ask1 -/- mice. We further investigated whether treatment of WT mice with an ASK1 inhibitor, selonsertib (GS-4997), during the fibrotic phase would attenuate the development of PF. We found that pharmacological inhibition of ASK1 reduced activation of ASK1, p38, and ERK1/2 and promoted the restoration of redox and EMT indicators, as well as improvements in histological parameters. Our results suggest that ASK1 plays a central role in the development of bleomycin-induced PF in mice via p38 and ERK1/2 signaling. Together, these data indicate a possible therapeutic target for PF that involves an ASK1/p38/ERK1/2 axis.

Purpose: The purpose of this study is to evaluate the relationship of social continence with patient centered outcomes, such as quality of life, in children with sarococcygeal teratoma (SCT). We hypothesize there is a correlation between social continence and patient-centered outcomes., Methods: A chart review and three surveys (Pediatric Quality of Life Inventory™ (PedsQL™), Baylor Continence Scale (BCS), and Impact on Family (IOF)) were performed for SCT patients who underwent resection at our institution from 2013 to 2018. PedsQL™ assesses quality of life, BCS evaluates global continence, and the IOF scale measures the impact of a child's illness on the family. Pearson correlation was used to examine the relationship between BCS, PedsQL™, and IOF., Results: Eighteen patients were identified with 72% (13/18) participating in the surveys with a median age at time of survey of 4.7 years (range 2.8-7.9). Patients with Altman IV were diagnosed postnatally and had smaller tumors. At the time of survey administration, a majority of children were toilet trained (54%, 7/13). Parents reported urinary incontinence (46%, 6/13) more frequently than bowel incontinence (15%, 2/13). Altman III/IV trended towards worse PedsQL™, BCS, and IOF surveys; however, it was not significant. The BCS correlated with the Total PedsQL™ (ρ = -0.56, p = 0.048) and IOF (ρ = 0.68, p = 0.011)., Conclusion: Children with SCT have a correlation between social continence, quality of life, and the impact on family. This study suggests interventions to screen and improve continence in children with SCT could also improve patient centered metrics., Study Design: Cross-sectional study LEVEL OF EVIDENCE: Level II, Prognosis Study., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To analyze the literature of related research reports on occupational hearing loss (ONIHL) , study the characteristics of the subject and determine the research hotspots. Methods: In December 2020, PubMed database was searched by bibliometrics for ONIHL published in PubMed database from January 1971 to December 2020. Bicomb 2.03 software was used to extract the subject. The publication year, publication country, source magazine and subject words were summarized and analyzed. Results: A total of 1 473 papers were included in this study, and the number of papers was 66 from 1971 to 1980, and 628 from 2011 to 2020, an increase of nearly 10 times. The top three countries were the United States, China and Germany, with 31.5% (464/1473) , 11.5% (171/1473) and 6.2% (91/1473) ; The cross-sectional study was the most applied type; The top five words for 2011-2020: Mental Illness, polymorphism, cardiovascular disease, high frequency hearing impairment and standards and regulations. Conclusion: Susceptibility Genes, Psychological Disorders, Cardiovascular Diseases and Risk Assessment are hot areas in ONIHL at present. Researchers should focus on major fields and grasp future trends as a whole.

Objective: To compare the perinatal outcomes of pregnancies complicated by chorioamniotic separation (CAS) vs septostomy following fetoscopic laser photocoagulation (FLP) for twin-twin transfusion syndrome (TTTS)., Methods: This was a retrospective cohort analysis of monochorionic diamniotic twin pregnancies with TTTS that underwent FLP at one of two university-affiliated tertiary medical centers between January 2012 and December 2020. CAS and septostomy were diagnosed either during the procedure or by ultrasonography within 24-48 h after FLP. Data on procedure and postprocedure parameters, pregnancy outcomes and survival were collected from the patients' electronic medical records. Pregnancies were stratified according to the presence of CAS, septostomy or neither. Patients diagnosed with both CAS and septostomy were analyzed separately., Results: Of the 522 women included in the cohort, 38 (7.3%) were diagnosed with CAS, 68 (13.0%) with septostomy and 23 (4.4%) with both CAS and septostomy. The remaining 393 (75.3%) women comprised the control group. Groups did not differ in demographic characteristics. The septostomy group had a lower rate of selective fetal growth restriction than did the CAS and control groups (24.2% vs 36.8% vs 42.7%, respectively; P = 0.017). Moreover, intertwin size discordance was lower in the septostomy group (15.1% vs 23.4% in the CAS group and 25.5% in the control group; P = 0.001). Median gestational age at FLP was significantly lower in the CAS group (19.3 weeks vs 20.4 weeks in controls and 20.9 weeks in the septostomy group; P = 0.049). The rate of delivery prior to 34 weeks was significantly higher in the CAS group (89.2%), followed by the septostomy group (80.9%), compared with the control group (69.0%) (P = 0.006). A secondary analysis demonstrated that patients with both CAS and septostomy presented the highest rates of delivery prior to 34 weeks (100%) and 32 weeks (68.2%)., Conclusions: CAS and septostomy following laser surgery for TTTS are independently associated with higher rates of preterm delivery. The presence of these two findings in the same patient enhances the risk of prematurity. © 2021 International Society of Ultrasound in Obstetrics and Gynecology., (© 2021 International Society of Ultrasound in Obstetrics and Gynecology.)

Fetus-in-fetu (FIF) is a rare congenital anomaly where a parasitic twin is within the body of a host twin. FIF is reported to occur in 1:500,000 live births. Herein, we report the first case of the medical and surgical treatment of a FIF patient who was born with extreme prematurity at 25-weeks gestation. With the multi-disciplinary coordination of neonatology, surgery, and interventional radiology, the patient was able to achieve a window of medical stability 4 weeks after birth. A decision was made at that time to proceed with an intra-abdominal and perineal resection of the FIF. The FIF was successfully resected and the patient was able to recover from the operation, with eventual discharge from the NICU. In conclusion, extreme prematurity and FIF may be amenable to surgical resection and a multi-disciplinary approach is crucial to achieve the desired outcome., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sun, Cheng, Shah, Lohmann, Cortes-Santiago, Ketwaroo, Keswani, King and Lee.)

As the important molecular machinery for membrane protein sorting in eukaryotic cells, the endosomal sorting and transport complexes (ESCRT-0/I/II/III and VPS4) usually participate in various replication stages of enveloped viruses, such as endocytosis and budding. The main subunit of ESCRT-I, Tsg101, has been previously revealed to play a role in the entry and replication of classical swine fever virus (CSFV). However, the effect of the whole ESCRT machinery during CSFV infection has not yet been well defined. Here, we systematically determine the effects of subunits of ESCRT on entry, replication, and budding of CSFV by genetic analysis. We show that EAP20 (VPS25) (ESCRT-II), CHMP4B and CHMP7 (ESCRT-III) regulate CSFV entry and assist vesicles in transporting CSFV from Clathrin, early endosomes, late endosomes to lysosomes. Importantly, we first demonstrate that HRS (ESCRT-0), VPS28 (ESCRT-I), VPS25 (ESCRT-II) and adaptor protein ALIX play important roles in the formation of virus replication complexes (VRC) together with CHMP2B/4B/7 (ESCRT-III), and VPS4A. Further analyses reveal these subunits interact with CSFV nonstructural proteins (NS) and locate in the endoplasmic reticulum, but not Golgi, suggesting the role of ESCRT in regulating VRC assembly. In addition, we demonstrate that VPS4A is close to lipid droplets (LDs), indicating the importance of lipid metabolism in the formation of VRC and nucleic acid production. Altogether, we draw a new picture of cellular ESCRT machinery in CSFV entry and VRC formation, which could provide alternative strategies for preventing and controlling the diseases caused by CSFV or other Pestivirus., Competing Interests: The authors have declared that no competing interests exist.

The tumor microenvironment contains a heterogeneous population of stromal and cancer cells that engage in metabolic crosstalk to ultimately promote tumor growth and contribute to progression. Due to heterogeneity within solid tumors, pooled mass spectrometry workflows are less sensitive at delineating unique metabolic perturbations between stromal and immune cell populations. Two critical, but understudied, facets of glucose metabolism are anabolic pathways for glycogen and N-linked glycan biosynthesis. Together, these complex carbohydrates modulate bioenergetics and protein-structure function, and create functional microanatomy in distinct cell populations within the tumor heterogeneity. Herein, we combine high-dimensionality reduction and clustering (HDRC) analysis with matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and demonstrate its ability for the comprehensive assessment of tissue histopathology and metabolic heterogeneity in human FFPE sections. In human lung adenocarcinoma (LUAD) tumor tissues, HDRC accurately clusters distinct regions and cell populations within the tumor microenvironment, including tumor cells, tumor-infiltrating lymphocytes, cancer-associated fibroblasts, and necrotic regions. In-depth pathway enrichment analyses revealed unique metabolic pathways are associated with each distinct pathological region. Further, we highlight the potential of HDRC analysis to study complex carbohydrate metabolism in a case study of lung cancer disparity. Collectively, our results demonstrate the promising potentials of HDRC of pixel-based carbohydrate analysis to study cell-type and regional-specific stromal signaling within the tumor microenvironment., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Histopathological detection and quantitation of glycogen in situ are important for the assessment of glycogen storage diseases and different types of cancer. The current standard method for defining the regionality of glycogen rely almost exclusively on Periodic Acid-Schiff (PAS) staining, a workflow that lacks specificity and sensitivity. Herein, we describe a new and much improved workflow to detect microenvironmental glycogen in situ using enzyme-assisted matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI). This method provides superior sensitivity and can elucidate the molecular features of glycogen structure, with 50 μm spatial resolution for a next-generation histopathological assessment of glycogen., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Recently, the high-value utilization of food wastes has attracted great interest in sustainable development. Focusing on the major application of electrochemical energy storage (ECES), light-weight lignin-based carbon nanofibers (LCNFs) were controllably fabricated as supercapacitors from melon seed shells (MSS) and peanut shells (PS) through electrospinning and carbonizing processes. As a result, the optimal specific capacitance of 533.7 F/g in three-electrode system, energy density of 69.7 Wh/kg and power density of 780 W/Kg in two-electrode system were achieved. Surprisingly, the LCNFs also presented a satisfied electromagnetic absorption property: The minimum reflection loss (RL) value reached -37.2 dB at an absorbing frequency of 7.98 GHz with an effective frequency (RL < 10 dB) of 2.24 GHz (6.88 to 9.12 GHz) at a thickness of 3.0 mm. These features make the multifunctional LCNFs highly attractive for light-weight supercapacitor electrodes and electromagnetic wave absorbers applications., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: Without fetal or perinatal intervention, congenital high airway obstruction syndrome (CHAOS) is a fatal anomaly. The ex utero intrapartum treatment (EXIT) procedure has been used to secure the fetal airway and minimize neonatal hypoxia but is associated with increased maternal morbidity., Case Presentation: A 16-year-old woman (gravida 1, para 0) was referred to our hospital at 31 weeks gestation with fetal anomalies, including echogenic lungs, tracheobronchial dilation, and flattened diaphragms. At 32 weeks, fetoscopic evaluation identified laryngeal stenosis, which was subsequently treated with balloon dilation and stent placement. The patient developed symptomatic and regular preterm contractions at postoperative day 7 with persistent sonographic signs of CHAOS, which prompted a repeat fetoscopy with confirmation of a patent fetal airway followed by Cesarean delivery under neuraxial anesthesia. Attempts to intubate through the tracheal stent were limited and resulted in removal of the stent. A neonatal airway was successfully established with rigid bronchoscopy. Direct laryngoscopy and bronchoscopy confirmed laryngeal stenosis with a small tracheoesophageal fistula immediately inferior to the laryngeal stenosis and significant tracheomalacia. A tracheostomy was then immediately performed for anticipated long-term airway and pulmonary management. The procedures were well tolerated by both mom and baby. The baby demonstrated spontaneous healing of the tracheoesophageal fistula by day of life 7 with discharge home with ventilator support at 3 months of life., Conclusion: Use of repeated fetoscopy in order to relieve fetal upper airway obstruction offers the potential to minimize neonatal hypoxia, while concurrently decreasing maternal morbidity by avoiding an EXIT procedure. Use of the tracheal stent in CHAOS requires further investigation. The long-term reconstruction and respiratory support of children with CHAOS remain challenging., (© 2022 S. Karger AG, Basel.)

Hydrothermal processes are an attractive clean technology and cost-effective engineering platform for biorefineries based in the conversion of biomass to biofuels and high-value bioproducts under the basis of sustainability and circular bioeconomy. The deep and detailed knowledge of the structural changes by the severity of biomasses hydrothermal fractionation is scientifically and technological needed in order to improve processes effectiveness, reactors designs, and industrial application of the multi-scale target compounds obtained by steam explosion and liquid hot water systems. The concept of the severity factor [log 10 (R o )] established>30 years ago, continues to be a useful index that can provide a simple descriptor of the relationship between the operational conditions for biomass fractionation in second generation of biorefineries. This review develops a deep explanation of the hydrothermal severity factor based in lignocellulosic biomass fractionation with emphasis in research advances, pretreatment operations and the applications of severity factor kinetic model., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

N-linked glycosylation is a complex, co- and post-translational series of events that connects metabolism to signaling in almost all cells. Metabolic assembly of N-linked glycans spans multiple cellular compartments, and early N-linked glycan biosynthesis is a central mediator of protein folding and the unfolded protein response (UPR). In the brain, N-linked glycosylated proteins participate in a myriad of processes, from electrical gradients to neurotransmission. However, it is less clear how perturbations in N-linked glycosylation impact and even potentially drive aspects of neurological disorders. In this review, we discuss our current understanding of the metabolic origins of N-linked glycans in the brain, their role in modulating neuronal function, and how aberrant N-linked glycosylation can drive neurological disorders., Competing Interests: Declaration of interests R.C.S. and M.S.G. are consultants for Maze Therapeutics, M.S.G. is a consultant for Enable Therapeutics, Glut1-Deficiency Syndrome Foundation, and Chelsea's Hope. M.S.G. and R.C.S. are founders of Atterogen, LLC., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Recent studies have shown intercostal cryoablation(IC) during the Nuss procedure decreases hospital length of stay(LOS) and opioid administration. However, few studies have also evaluated the risk of postoperative complications related to IC., Methods: We performed a single center retrospective analysis of all patients who underwent Nuss procedure by one surgeon from 2/2016 to 2/2020, comparing intraoperative IC to other pain management modalities(non-IC). Primary outcomes were postoperative complications, hospital LOS, and opioid administration. Multivariate analysis was performed with outcomes reported as regression coefficients(RC) or odds ratios(OR) with 95% confidence interval., Results: IC was associated with decreased hospital LOS (RC -1.91[-2.29 to -1.54], less hospital opioid administration (RC -4.28[-5.13 to -3.43]), and less discharge opioid administration (RC -3.82[-5.23 to -2.41]). With respect to postoperative complications, IC decreased the odds of urinary retention (OR 0.16[0.06 to 0.44]); however, increased the odds of slipped bars requiring reoperation (OR 36.65[5.04-266.39])., Conclusions: Our single surgeon experience controls for surgeon variability and demonstrates intraoperative IC for the Nuss procedure is an effective pain management modality that decreases hospital LOS and opioid use during hospitalization and at discharge; however, it is associated with increased odds of slipped bars requiring reoperation., Level of Evidence: III., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Lactate accumulation is a hallmark of solid cancers and is linked to the immune suppressive phenotypes of tumor-infiltrating immune cells. We report herein that interleukin-4 (IL-4)–induced M0 → M2 macrophage polarization is accompanied by interchangeable glucose- or lactate-dependent tricarboxylic acid (TCA) cycle metabolism that directly drives histone acetylation, M2 gene transcription, and functional immune suppression. Lactate-dependent M0 → M2 polarization requires both mitochondrial pyruvate uptake and adenosine triphosphate–citrate lyase (ACLY) enzymatic activity. Notably, exogenous acetate rescues defective M2 polarization and histone acetylation following mitochondrial pyruvate carrier 1 (MPC1) inhibition or ACLY deficiency. Lastly, M2 macrophage–dependent tumor progression is impaired by conditional macrophage ACLY deficiency, further supporting a dominant role for glucose/lactate mitochondrial metabolism and histone acetylation in driving immune evasion. This work adds to our understanding of how mitochondrial metabolism affects macrophage functional phenotypes and identifies a unique tumor microenvironment (TME)–driven metabolic-epigenetic link in M2 macrophages.

Objective: Monochorionic twins with twin-twin transfusion syndrome (TTTS) treated with fetoscopic laser photocoagulation (FLP) are at increased risk of neurodevelopmental impairment (NDI). This meta-analysis aimed to identify the prevalence of and perinatal risk factors for NDI in TTTS survivors treated with FLP., Methods: We performed a search in PubMed, EMBASE, Scopus and Web of Science, from inception to 13 February 2021, for studies evaluating perinatal risk factors for NDI in children diagnosed prenatally with TTTS managed by FLP. Data on severity of TTTS at the time of diagnosis, defined according to the Quintero staging system, FLP-related complications and perinatal outcomes were compared between children with a history of TTTS treated with FLP with and those without NDI, which was defined as performance on a cognitive or developmental assessment tool ≥ 2 SD below the mean or a defined motor or sensory disability. A random-effects model was used to pool the mean differences or odds ratios (OR) with the corresponding 95% CIs. Heterogeneity was assessed using the I 2 statistic., Results: Nine studies with a total of 1499 TTTS survivors were included. The overall incidence of NDI was 14.0% (95% CI, 9.0-18.0%). The occurrence of NDI in TTTS survivors was associated with later gestational age (GA) at FLP (mean difference, 0.94 weeks (95% CI, 0.50-1.38 weeks); P < 0.0001, I 2  = 0%), earlier GA at delivery (mean difference, -1.44 weeks (95% CI, -2.28 to -0.61 weeks); P = 0.0007, I 2  = 49%) and lower birth weight (mean difference, -343.26 g (95% CI, -470.59 to -215.92 g); P < 0.00001, I 2  = 27%). Evaluation of different GA cut-offs showed that preterm birth before 32 weeks was associated with higher risk for NDI later in childhood (OR, 2.25 (95% CI, 1.02-4.94); P = 0.04, I 2  = 35%). No statistically significant difference was found between cases with and those without NDI with respect to Quintero stage of TTTS, recipient or donor status, development of postlaser twin anemia-polycythemia sequence, recurrence of TTTS and incidence of small- for-gestational age or cotwin fetal demise., Conclusions: TTTS survivors with later GA at the time of FLP, earlier GA at delivery and lower birth weight are at higher risk of developing NDI. No significant association was found between Quintero stage of TTTS and risk of NDI. Our findings may be helpful for parental counseling and highlight the need for future studies to understand better the risk factors for NDI in TTTS survivors. © 2021 International Society of Ultrasound in Obstetrics and Gynecology., (© 2021 International Society of Ultrasound in Obstetrics and Gynecology.)

Introduction: A shortage of medical devices designed for children persists due to the smaller pediatric population and market factors. Furthermore, pediatric device development is challenging due to the limited available funding sources. We describe our experience with pediatric device projects that successfully received federal grant support towards commercializing the devices that can serve as a guide for future innovators., Methods: The developmental pathways of pediatric device projects at a tertiary-care children's hospital that received NIH SBIR/STTR funding between 2016-2019 were reviewed. The clinical problems, designs, specific aims, and development phase were delineated., Results: Pediatric faculty successfully secured NIH SBIR/STTR funding for five pediatric devices via qualified small business concerns (SBC's). Three projects were initiated in the capstone engineering design programs and developed further at two affiliated engineering schools, while the other two projects were developed in the faculty members' labs. Four projects received funding via established SBC's, while one was awarded funding via a newly established SBC., Conclusion: NIH SBIR/STTR grants are an essential source of external non-dilutive funding for pediatric device innovation and especially for academic-initiated projects. This funding can provide needed early-stage support to facilitate commercialization. In addition, these grants can serve as achievable accomplishments for pediatric faculty portfolios toward academic promotion. Our experience shows that it is possible to build a robust innovation ecosystem comprised of academic faculty (clinical/engineering) collaborating with local device development companies while jointly implementing a product development strategy leveraging NIH SBIR/STTR funding for critical translational research phases of pediatric device development., (Copyright © 2021. Published by Elsevier Inc.)

Objective: To evaluate laparoscopy-assisted fetoscopic laser photocoagulation (FLPC) of placental anastomoses in the treatment of twin-to-twin-transfusion syndrome (TTTS)., Study Design: We performed a retrospective cohort study analyzing pregnancies complicated by TTTS who underwent FLPC in a single university-affiliated tertiary medical-center. Outcomes were compared between patients who received laparoscopy-assisted FLPC (study group) and patients who underwent the conventional FLPC technique (control group). Baseline characteristics, sonographic findings, procedure details, and neonatal outcomes were compared between groups., Results: The cohort included 278 women with 31 in the study group and 247 in the control group. Sonographic parameters, including fetal biometry and TTTS stage, were comparable between study groups. Gestational age at delivery did not differ between the groups (29.22 ± 4.55 weeks in the study group vs. 30.62 ± 4.3 weeks in the control group, p = 0.09). There were no differences in neonatal survival rates at birth and at 30 days between both groups. A subanalysis comparing the laparoscopy-assisted group to only those patients with anterior placenta in the control group, showed a lower rate of incomplete Solomonization in the laparoscopy-assisted study group (3.4% vs. 33%, p = 0.01)., Conclusion: Laparoscopy-assisted FLPC is a reasonable and safe option that may be offered in cases of FLPC where an anterior placenta restricts adequate surgical access., (© 2021 John Wiley & Sons Ltd.)

Alzheimer's disease (AD) is an unremitting neurodegenerative disorder characterized by cerebral amyloid-β (Aβ) accumulation and gradual decline in cognitive function. Changes in brain energy metabolism arise in the preclinical phase of AD, suggesting an important metabolic component of early AD pathology. Neurons and astrocytes function in close metabolic collaboration, which is essential for the recycling of neurotransmitters in the synapse. However, this crucial metabolic interplay during the early stages of AD development has not been sufficiently investigated. Here, we provide an integrative analysis of cellular metabolism during the early stages of Aβ accumulation in the cerebral cortex and hippocampus of the 5xFAD mouse model of AD. Our electrophysiological examination revealed an increase in spontaneous excitatory signaling in the 5xFAD hippocampus. This hyperactive neuronal phenotype coincided with decreased hippocampal tricarboxylic acid (TCA) cycle metabolism mapped by stable 13 C isotope tracing. Particularly, reduced astrocyte TCA cycle activity and decreased glutamine synthesis led to hampered neuronal GABA synthesis in the 5xFAD hippocampus. In contrast, the cerebral cortex of 5xFAD mice displayed an elevated capacity for oxidative glucose metabolism, which may suggest a metabolic compensation in this brain region. We found limited changes when we explored the brain proteome and metabolome of the 5xFAD mice, supporting that the functional metabolic disturbances between neurons and astrocytes are early primary events in AD pathology. In addition, synaptic mitochondrial and glycolytic function was selectively impaired in the 5xFAD hippocampus, whereas non-synaptic mitochondrial function was maintained. These findings were supported by ultrastructural analyses demonstrating disruptions in mitochondrial morphology, particularly in the 5xFAD hippocampus. Collectively, our study reveals complex regional and cell-specific metabolic adaptations in the early stages of amyloid pathology, which may be fundamental for the progressing synaptic dysfunctions in AD., (© 2021. The Author(s).)

Prostate cancer is the most common cancer in men worldwide. Despite its prevalence, there is a critical knowledge gap in understanding factors driving disparities in survival among different cohorts of patients with prostate cancer. Identifying molecular features separating disparate populations is an important first step in prostate cancer research that could lead to fundamental hypotheses in prostate biology, predictive biomarker discovery, and personalized therapy. N-linked glycosylation is a cotranslational event during protein folding that modulates a myriad of cellular processes. Recently, aberrant N-linked glycosylation has been reported in prostate cancers. However, the full clinical implications of dysregulated glycosylation in prostate cancer has yet to be explored. Herein, we performed direct on-tissue analysis of N-linked glycans using matrix-assisted laser desorption ionization-mass spectrometry imaging (MALDI-MSI) from tissue microarrays of over 100 patient tumors with over 10 years of follow-up metadata. We successfully identified a panel of N-glycans that are unique between benign and prostate tumor tissue. Specifically, high-mannose as well as tri-and tetra-antennary N-glycans were more abundant in tumor tissue and increase proportionally with tumor grade. Further, we expanded our analyses to examine the N-glycan profiles of Black and Appalachian patients and have identified unique glycan signatures that correlate with recurrence in each population. Our study highlights the potential applications of MALDI-MSI for digital pathology and biomarker discovery for prostate cancer. IMPLICATIONS: MALDI-MSI identifies N-glycan perturbations in prostate tumors compared with benign tissue. This method can be utilized to predict prostate cancer recurrence and study prostate cancer disparities., (©2021 American Association for Cancer Research.)

Background: Cerebral glucose hypometabolism is consistently observed in individuals with Alzheimer's disease (AD), as well as in young cognitively normal carriers of the Ε4 allele of Apolipoprotein E (APOE), the strongest genetic predictor of late-onset AD. While this clinical feature has been described for over two decades, the mechanism underlying these changes in cerebral glucose metabolism remains a critical knowledge gap in the field., Methods: Here, we undertook a multi-omic approach by combining single-cell RNA sequencing (scRNAseq) and stable isotope resolved metabolomics (SIRM) to define a metabolic rewiring across astrocytes, brain tissue, mice, and human subjects expressing APOE4., Results: Single-cell analysis of brain tissue from mice expressing human APOE revealed E4-associated decreases in genes related to oxidative phosphorylation, particularly in astrocytes. This shift was confirmed on a metabolic level with isotopic tracing of 13 C-glucose in E4 mice and astrocytes, which showed decreased pyruvate entry into the TCA cycle and increased lactate synthesis. Metabolic phenotyping of E4 astrocytes showed elevated glycolytic activity, decreased oxygen consumption, blunted oxidative flexibility, and a lower rate of glucose oxidation in the presence of lactate. Together, these cellular findings suggest an E4-associated increase in aerobic glycolysis (i.e. the Warburg effect). To test whether this phenomenon translated to APOE4 humans, we analyzed the plasma metabolome of young and middle-aged human participants with and without the Ε4 allele, and used indirect calorimetry to measure whole body oxygen consumption and energy expenditure. In line with data from E4-expressing female mice, a subgroup analysis revealed that young female E4 carriers showed a striking decrease in energy expenditure compared to non-carriers. This decrease in energy expenditure was primarily driven by a lower rate of oxygen consumption, and was exaggerated following a dietary glucose challenge. Further, the stunted oxygen consumption was accompanied by markedly increased lactate in the plasma of E4 carriers, and a pathway analysis of the plasma metabolome suggested an increase in aerobic glycolysis., Conclusions: Together, these results suggest astrocyte, brain and system-level metabolic reprogramming in the presence of APOE4, a 'Warburg like' endophenotype that is observable in young females decades prior to clinically manifest AD., (© 2021. The Author(s).)

The hallmark of Lafora disease, a fatal neurodegenerative disorder, is the accumulation of intracellular glycogen aggregates called Lafora bodies. Until recently, it was widely believed that brain Lafora bodies were present exclusively in neurons and thus that Lafora disease pathology derived from their accumulation in this cell population. However, recent evidence indicates that Lafora bodies are also present in astrocytes. To define the role of astrocytic Lafora bodies in Lafora disease pathology, we deleted glycogen synthase specifically from astrocytes in a mouse model of the disease (malinKO). Strikingly, blocking glycogen synthesis in astrocytes-thus impeding Lafora bodies accumulation in this cell type-prevented the increase in neurodegeneration markers, autophagy impairment, and metabolic changes characteristic of the malinKO model. Conversely, mice that over-accumulate glycogen in astrocytes showed an increase in these markers. These results unveil the deleterious consequences of the deregulation of glycogen metabolism in astrocytes and change the perspective that Lafora disease is caused solely by alterations in neurons., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Lignin is recommended to a tempting alternative precursor of petroleum for fabricating carbon nanofibers (CNFs) due to its high carbon content, low-cost and renewable resources. However, the property of lignin-based carbon nanofibers (LCNFs) is inferior owing to the heterogeneity and 3D-network structure of lignin, which hinders its application in supercapacitors. The latest developments in fractionation technology have shown great potential for overcoming the aforementioned shortcomings. However, most of fractionation methods mainly rely on expensive chemicals and complex reaction process, such as enzymes, multiple solvents, membranes, and dialysis tubes. Herein, we proposed a controllable and effective strategy to fractionate lignin by only changing the ratio of ethanol/water (V/V) as mixture solvent. This gradient extraction method effectively removed the part of lignin with small molecular and branching structure, thus selectively getting the fractionated lignin with high molecular weight, narrow polydispersity index, and good linear structure. Fortunately, when the ratio of ethanol/water was 6:4, the corresponding LCNFs (LCNFs-L60) was obtained with large specific surface area, independent filamentous morphology networks and excellent electrochemical property. Its specific capacitance was up to 405.8 F/g. This way features controllable and sustainable for preparing high-quality LCNFs supercapacitors., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Glycosylation defects are a hallmark of many nervous system diseases. However, the molecular and metabolic basis for this pathology is not fully understood. In this study, we found that N-linked protein glycosylation in the brain is metabolically channeled to glucosamine metabolism through glycogenolysis. We discovered that glucosamine is an abundant constituent of brain glycogen, which functions as a glucosamine reservoir for multiple glycoconjugates. We demonstrated the enzymatic incorporation of glucosamine into glycogen by glycogen synthase, and the release by glycogen phosphorylase by biochemical and structural methodologies, in primary astrocytes, and in vivo by isotopic tracing and mass spectrometry. Using two mouse models of glycogen storage diseases, we showed that disruption of brain glycogen metabolism causes global decreases in free pools of UDP-N-acetylglucosamine and N-linked protein glycosylation. These findings revealed fundamental biological roles of brain glycogen in protein glycosylation with direct relevance to multiple human diseases of the central nervous system., Competing Interests: Declaration of interests M.S.G. is a consultant for Maze Therapeutics, Enable Therapeutics, Glut1-Deficiency Syndrome Foundation, and Chelsea's Hope. M.S.G., R.C.S., C.W.V.K., and R.C.B. are founders of Atterogen, LLC., (Copyright © 2021 Elsevier Inc. All rights reserved.)

As a common air pollutant, formaldehyde is widely present in nature, industrial production and consumer products. Endogenous formaldehyde is mainly produced through the oxidative deamination of methylamine catalysed by semicarbazide-sensitive amine oxidase (SSAO) and is ubiquitous in human body fluids, tissues and cells. Vascular endothelial cells and smooth muscle cells are rich in this formaldehyde-producing enzyme and are easily damaged owing to consequent cytotoxicity. Consistent with this, increasing evidence suggests that the cardiovascular system and stages of heart development are also susceptible to the harmful effects of formaldehyde. Exposure to formaldehyde from different sources can induce heart disease such as arrhythmia, myocardial infarction (MI), heart failure (HF) and atherosclerosis (AS). In particular, long-term exposure to high concentrations of formaldehyde in pregnant women is more likely to affect embryonic development and cause heart malformations than long-term exposure to low concentrations of formaldehyde. Specifically, the ability of mouse embryos to effect formaldehyde clearance is far lower than that of the rat embryos, more readily allowing its accumulation. Formaldehyde may also exert toxic effects on heart development by inducing oxidative stress and cardiomyocyte apoptosis. This review focuses on the current progress in understanding the influence and underlying mechanisms of formaldehyde on cardiovascular disease and heart development., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Inflammation and endothelial dysfunction are important participants and drivers in atherosclerosis. NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome activation and the resulting pyroptosis are involved in the initiation and vicious circle of chronic inflammation, thus playing an indispensable role in atherosclerosis. Accordingly, blocking the activation of NLRP3 inflammasome may be a promising treatment strategy to blunt the progression of atherosclerosis. In this study, it was demonstrated that miR-302c-3p exerted anti-pyroptosis effects by directly targeting NLRP3 in vivo and in vitro. In brief, the expression of miR-302c-3p was down-regulated whereas the expression of NLRP3 was up-regulated in human plaques and in vitro pyroptosis model of endothelial cells. Overexpression of miR-302c-3p suppressed endothelial cell pyroptosis by targeting specific sites of NLRP3. By comparison, down-regulation of endogenous miR-302c-3p led to the opposite results, which were reversed by silencing the expression of NLRP3. Finally, the up-regulation of miR-302c-3p inhibited the inflammation and pyroptosis of atherosclerosis mouse model. In conclusion, miR-302c-3p may be a powerful and attractive target for suppressing endothelial inflammation and pyroptosis, providing a novel strategy for preventing or alleviating the progression of atherosclerosis., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

High Glutaminase (GLS1) expression may have prognostic implications in colorectal and breast cancers; however, high quality data for expression in prostate cancer (PCa) are lacking. The purpose of this study is to investigate the status of GLS1 expression in PCa and correlated expression levels with clinicopathologic parameters. This study was conducted in two phases: an exploratory cohort analyzing RNA-Seq data for GLS1 from The Cancer Genome Atlas (TCGA) data portal (246 PCa samples) and a GLS1 immunohistochemical protein expression cohort utilizing a tissue microarray (TMA) (154 PCa samples; 41 benign samples) for correlation with clinicopathologic parameters. In the TCGA cohort, GLS1 mRNA expression did not show a statistically significant difference in disease-free survival (DFS) but did show a small significant difference in overall survival (OS). In the TMA cohort, there was no correlation between GLS1 expression and stage, Gleason score, DFS and OS. GLS1 expression did not significantly correlate with the clinical outcomes measured; however, GLS1 expression was higher in PCa cells compared to benign epithelium. Future studies are warranted to evaluate expression levels in greater numbers of high-grade and advanced PCa samples to investigate whether there is a rational basis for GLS1 targeted therapy in a subset of patients with prostate cancer.

Purpose of Review: Fetal hydronephrosis secondary to congenital anomalies of the kidney and urinary tract (CAKUT) can adversely affect neonates in the postnatal period with long-term consequences. A prenatal diagnosis of CAKUT can have an early fetal intervention to minimize these consequences. This review aims to provide an overview of the possible fetal intervention with severe hydronephrosis., Recent Findings: Clinical course and outcomes of CAKUT are predicted based on biochemical markers and radiological findings. In spite of advancements and accurately diagnosing the severity of hydronephrosis, there are many controversies surround on selection of cases with antenatal hydronephrosis (ANH) that will benefit from fetal intervention. Despite better diagnosis and techniques fetal intervention is limited to mainly lower urinary tract obstruction patients to improve amniotic fluid volume and assist in lung development., Summary: ANH can potentially detect the severity of congenital renal anomalies but unable to recognize a specific disease. A multidisciplinary approach is required to diagnose and properly stage cases of severe CAKUT and potential surgical intervention can be considered., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Fabricating lignin-based carbon nanofibers (LCNFs) with the lignin in spent coffee grounds (SCG) as raw material which are disposed as waste amounting to millions tons annual is benefit to promote economy and environmental protection. However, due to the heterogeneity and complex three-dimensional structure, the mechanic property is very poor. In this study, we propose a fractionating pretreatment method to overcome the above problems by regulating the structure of SCG lignin in which high-performance LCNFs were fabricated. On one hand, the linear structure of SCG lignin was optimized to fit the raw material of LCNFs by tuning the content of β-O-4 and C 5 -substituted condensed phenolic compounds. On the other hand, the carboxyl as the hydrophilic groups was removed so as to promote the mixing of lignin and polyacrylonitrile (PAN, blending agent) in organic solvents. Additionally, the heterogeneity was reduced by screening large molecular weight SCG lignin with low polydispersity index (PDI). Fortunately, with 1:1 mass ratio of the above fractionated lignin and PAN as substrate, the LCNFs could reach to comparable mechanic properties with those of pure PAN CNFs. This work can provide a new way to not only promote the utilization of SCG lignin but also accelerate the development of LCNFs., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2021. Published by Elsevier B.V.)

Doxorubicin (DOX) is a kind of representative anthracyclines. It has greatly prolonged lifespan of cancer patients. However, a long course of DOX chemotherapy could induce various forms of deaths of cardiomyocytes, such as apoptosis, pyroptosis and ferroptosis, contributing to varieties of cardiac complications called cardiotoxicity. It has become a major concern considering the large number of cancer patients' worldwide and increased survival rates after chemotherapy. Exosomes, a subgroup of extracellular vesicles (EVs), are secreted by nearly all cells and consist of lipid bilayers, nucleic acids and proteins. They can serve as mediators between intercellular communication via the transfer of bioactive molecules from secretory to recipient cells, modulating multiple pathophysiological processes. It has been proven that exosomes in body fluids can serve as biomarkers for doxorubicin-induced cardiotoxicity (DIC). Moreover, exosomes have attracted considerable attention because of their capacity as carriers of certain proteins, genetic materials (miRNA and lncRNA), and chemotherapeutic drugs to decrease the dosage of DOX and alleviate cardiotoxicity. This review briefly describes the characteristics of exosomes and highlights their clinical application potential as diagnostic biomarkers and drug delivery vehicles for DIC, thus providing a strategy for addressing it based on exosomes., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

The increasing prevalence of age-related diseases and resulting healthcare insecurity and emotional burden require novel treatment approaches. Several promising strategies seek to limit nutrients and promote healthy aging. Unfortunately, the human desire to consume food means this strategy is not practical for most people but pharmacological approaches might be a viable alternative. We previously showed that myriocin, which impairs sphingolipid synthesis, increases lifespan in Saccharomyces cerevisiae by modulating signaling pathways including the target of rapamycin complex 1 (TORC1). Since TORC1 senses cellular amino acids, we analyzed amino acid pools and identified 17 that are lowered by myriocin treatment. Studying the methionine transporter, Mup1, we found that newly synthesized Mup1 traffics to the plasma membrane and is stable for several hours but is inactive in drug-treated cells. Activity can be restored by adding phytosphingosine to culture medium thereby bypassing drug inhibition, thus confirming a sphingolipid requirement for Mup1 activity. Importantly, genetic analysis of myriocin-induced longevity revealed a requirement for the Gtr1/2 (mammalian Rags) and Vps34-Pib2 amino acid sensing pathways upstream of TORC1, consistent with a mechanism of action involving decreased amino acid availability. These studies demonstrate the feasibility of pharmacologically inducing a state resembling amino acid restriction to promote healthy aging.

N-glycans and lipids are structural metabolites that play important roles in cellular processes. Both show unique regional distribution in tissues; therefore, spatial analyses of these metabolites are crucial to our understanding of cellular physiology. Matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) is an innovative technique that enables in situ detection of analytes with spatial distribution. This workflow details a MALDI-MSI protocol for the spatial profiling of N-glycans and lipids from tissues following application of enzyme and MALDI matrix. For complete details on the use and execution of this protocol, please refer to Drake et al. (2018) and Andres et al. (2020)., Competing Interests: The authors declare no competing interests., (© 2021 The Author(s).)