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Abstract The life cycle of genome builds spans interlocking pillars of assembly, annotation, and comparative genomics to drive biological insights. While tools exist to address each pillar separately, there is a growing need for tools to integrate different pillars of a genome project holistically. For example, comparative approaches can provide quality control of assembly or annotation; genome assembly, in turn, can help to identify artifacts that may complicate the interpretation of genome comparisons. The JCVI library is a versatile Python‐based library that offers a suite of tools that excel across these pillars. Featuring a modular design, the JCVI library provides high‐level utilities for tasks such as format parsing, graphics generation, and manipulation of genome assemblies and annotations. Supporting genomics algorithms like MCscan and ALLMAPS are widely employed in building genome releases, producing publication‐ready figures for quality assessment and evolutionary inference. Developed and maintained collaboratively, the JCVI library emphasizes quality and reusability.

Abstract Myxofibrosarcoma (MFS) is a malignant fibroblastic/myofibroblastic neoplasm with a prominent myxoid area. It has the clinical features of frequent local recurrence (LR) and occasional distant metastasis. Robust epidemiological data on MFS in China are lacking. The aim of this retrospective analysis was to determine the natural history of MFS, identify prognostic factors for recurrence and describe the real-life outcomes of MFS. We reviewed 52 patients with primary MFS from the First Affiliated Hospital of Nanjing Medical University diagnosed between 2016 and 2020. All tumors were subjected to retrospective univariate analysis for prognostic factors of the disease, including tumor size, grade, location and sex; patient age; planned operation; surgical margin; and laboratory results. The significant factors identified by univariate analysis were subsequently analyzed via multivariate analysis. Overall survival (OS), post-treatment LR and metastatic-free survival were assessed as outcomes. The median age was 61 years (range, 13–93). Fourteen (26.92%) patients exhibited low grade disease, and 38 (73.08%) exhibited high grade disease. Among the 29 males, and 23 females, 15 (28.85%) had tumors in the trunk, 37 (71.15%) had tumors in the extremities, 26 had undergone planned surgery, and 26 had unexpected unplanned operation. The margin was negative in 39 (75%) patients and positive in 13 patients (25%). The serum creatine kinase (CK) concentration was high level in 33 (63.46%) patients and low level in 19 (36.54%) patients. The serum lactate dehydrogenase (LDH) levels were low in 23 (44.23%) patients and high in 29 (55.77%) patients. LR was observed in 25 patients (48.08%), and 4 patients developed metastasis. A worse LR rate was found for patients with a low CK level (84.21%) than for those with a high CK level (27.27%) at 5 years (p

The fetal liver (FL) is the key erythropoietic organ during fetal development, but knowledge on human FL erythropoiesis is very limited. In this study, we sorted primary erythroblasts from FL cells and performed RNA sequencing (RNA-seq) analyses. We found that temporal gene expression patterns reflected changes in function during primary human FL terminal erythropoiesis. Notably, the expression of genes enriched in proteolysis and autophagy was up-regulated in orthochromatic erythroblasts (OrthoEs), suggesting the involvement of these pathways in enucleation. We also performed RNA-seq of in vitro cultured erythroblasts derived from FL CD34+ cells. Comparison of transcriptomes between the primary and cultured erythroblasts revealed significant differences, indicating impacts of the culture system on gene expression. Notably, the expression of lipid metabolism-related genes was increased in cultured erythroblasts. We further immortalized erythroid cell lines from FL and cord blood (CB) CD34+ cells (FL-iEry and CB-iEry, respectively). FL-iEry and CB-iEry were immortalized at the proerythroblast stage and can be induced to differentiate into OrthoEs, but their enucleation ability was very low. Comparison of the transcriptomes between OrthoEs with and without enucleation capability revealed the down-regulation of pathways involved in chromatin organization and mitophagy in OrthoEs without enucleation capacity, indicating that defects in chromatin organization and mitophagy contribute to the inability of OrthoEs to enucleate. Additionally, the expression of HBE1, HBZ, and HBG2 was up-regulated in FL-iEry compared with CB-iEry, and such up-regulation was accompanied by down-regulated expression of BCL11A and up-regulated expression of LIN28B and IGF2BP1. Our study provides new insights into human FL erythropoiesis and rich resources for future studies.

Capillary flow-related hydrovoltaic technology is an emerging research field for sustainable electricity generation. Despite great progress in the last decade, the mechanisms behind electricity generation remain unclear. In this review, we provide an overview of the current proposed mechanisms for electricity generation induced by water evaporation and moisture absorption. We explore key mechanisms, including streaming potential, ion concentration gradient, microbial electricity, ionovoltaic effect, pseudo-streaming, evaporating potential, and upstream proton diffusion. Each offers distinct insights and faces specific challenges that require further study. Unlike previous reviews, we focus specifically on the detailed mechanistic understanding of capillary flow-related electricity generation and highlight the interplay of different mechanisms. Additionally, we identify critical gaps in current research, particularly the need for empirical validation through advanced characterization techniques, such as spectroscopy, microscopy, and electrochemical analysis. Moreover, we discuss the practical applications of capillary flow-related hydrovoltaic technology in energy harvesting systems and self-powered sensors, highlighting its potential to convert water evaporation and environmental moisture into sustainable energy. We believe this review can serve as a starting point for further efforts aimed at addressing these challenges, thus paving the way for the commercialization of this technology and its contribution to sustainable development goals.

Abstract Background Urinary ascites represents a scarcely observed pseudo-acute kidney injury in clinical settings. Protracted or missed diagnosis may hold grave ramifications for patient outcomes. Case presentation We reported a case involving an elderly female patient experiencing pseudo-acute kidney injury accompanied by ascites, wherein her renal dysfunction persisted despite medical intervention and hemodialysis. Urinary ascites was identified via a methylene blue test and by contrasting creatinine levels in serum and ascites. This patient’s kidney function was multiple typified by a marked elevation in serum creatinine/Cystatin C ratio (> 2 L/dL), potentially serving as a clue for the clinical diagnosis of pseudo-acute kidney injury engendered by urinary ascites. Conclusions This case suggested the potential diagnostic value of an asynchronous increase in serum creatinine and serum CysC (or an increased ratio of blood creatinine to blood CysC) in patients with pseudo-acute kidney injury.

Objective: The purpose of this experiment is to study the effects of Curcumin (Cur) on the proliferation, apoptosis and cell cycle of human hepatocellular carcinoma HepG2 cells, and to explore its mechanism of inhibiting the proliferation of HepG2 cells. Methods: The experiment was divided into control group and Cur group. The HepG2 cultured human hepatoma cells were treated with Cur solution of different concentrations. The inhibitory effect of Cur on the proliferation of HepG2 cells was detected by MTT assay. The apoptosis rate and cell cycle distribution of CUR-induced HepG2 cells were detected by flow cytometry. Results: Compared with the control group, the growth of HepG2 cells was inhibited by Cur in a concentration-dependent manner. Apoptosis by flow cytometry. Results: Compared with the control group, the growth of HepG2 cells was inhibited by Cur in a concentration-dependent manner. Flow cytometry showed that the apoptosis rates of the control group and the Cur group were 0.3%, 18.0%, 24.7% and 86.9%, respectively, showing a dose-dependent relationship. Cell cycle detection showed that in the control group and Cur concentration groups, the proportion of S phase was 24.11%, 32.68%, 37.75%, 42.10%, respectively. The apoptosis percentage was most obvious in S phase, and cells were blocked in S phase. Compared with control group, with the increase of Cur concentration. Conclusion: Curcumin may inhibit the proliferation of human hepatoma cells HepG2 by preventing cell division and inducing cell apoptosis.

Abstract Granulation, an ancient metal processing technique mainly applied to gold, has originated from West Asia, and later appeared at many different archaeological sites across the Eurasia. The distribution of granulated gold ornaments bearing diverse soldering techniques reveal the long-distance human interaction across the Eurasia. This paper presents the scientific analysis of the surface morphology and elemental composition of two granulated gold ornaments from Tushan Tomb No.2 pit in Xuzhou, Jiangsu Province, which approximately dated to the first century CE of Han Dynasty. Multiple non-destructive analytical methods including Ultra-Depth Three-Dimensional Microscope, Energy dispersive X-ray fluorescence spectrometer (XRF) and Scanning electron microscope with energy dispersive X-Ray spectrometer (SEM-EDS) were conducted to obtain analytical data. The result indicates that tin-participated soldering technique has been adopted to accomplish the granulation. Although the usage of tin has been mentioned in a former study as “a secret of Etruscan granulation”, the lack of quantitative analyses leaves this assumption unconvinced. Our findings on Tushan ornaments throw light on this issue by illustrating the regular distribution pattern of the tin content at the joints, which appears to be intentionally added for certain amount. Although tiny in size, the gold granules record the secret of soldering techniques used in China and many other regions across the Eurasia during the ancient time, complementing the study of granulation techniques and reflecting the transmission and innovation along with the technological and cultural contacts.

The LGS1 (Large grain size 1) gene, also known as GS2/GL2/OsGRF4, is involved in regulating grain size and quality in rice, but the mechanism governing grain size has not been elucidated. We performed transcriptomic, proteomic, and phosphoproteomic analyses of young rice panicles in Samba (a wild-type cultivar with extra-small grain) and NIL-LGS1 (a nearly isogenic line of LGS1 with large grain in the Samba genetic background) at three developmental stages (4–6) to identify internal dynamic functional networks determining grain size that are mediated by LGS1. Differentially expressed proteins formed seven highly functionally correlated clusters. The concordant regulation of multiple functional clusters may be key features of the development of grain length in rice. In stage 5, 16 and 24 phosphorylated proteins were significantly up-regulated and down-regulated, and dynamic phosphorylation events may play accessory roles in determining rice grain size by participating in protein–protein interaction networks. Transcriptomic analysis in stage 5 showed that differentially expressed alternative splicing events and dynamic gene regulatory networks based on 39 transcription factors and their highly correlated target genes might contribute to rice grain development. Integrative multilevel omics analysis suggested that the regulatory network at the transcriptional and posttranscriptional levels could be directly manifested at the translational level, and this analysis also suggested a regulatory mechanism, regulation of protein translation levels, in the biological process that extends from transcript to protein to the development of grain. Functional analysis suggested that biological processes including MAPK signaling, calcium signaling, cell proliferation, cell wall, energy metabolism, hormone pathway, and ubiquitin-proteasome pathway might be involved in LGS1-mediated regulation of grain length. Thus, LGS1-mediated regulation of grain size is affected by dynamic transcriptional, posttranscriptional, translational and posttranslational changes.

BackgroundNeurological manifestations in patients with COVID-19 have been reported previously as outcomes of the infection. The purpose of current study was to investigate the occurrence of neurological signs and symptoms in COVID-19 patients, in the county of Östergötland in southeastern Sweden.MethodsThis is a retrospective, observational cohort study. Data were collected between March 2020 and June 2020. Information was extracted from medical records by a trained research assistant and physician and all data were validated by a senior neurologist.ResultsSeventy-four percent of patients developed at least one neurological symptom during the acute phase of the infection. Headache (43%) was the most common neurological symptom, followed by anosmia and/or ageusia (33%), confusion (28%), hallucinations (17%), dizziness (16%), sleep disorders in terms of insomnia and OSAS (Obstructive Sleep Apnea) (9%), myopathy and neuropathy (8%) and numbness and tingling (5%). Patients treated in the ICU had a higher male presentation (73%). Several risk factors in terms of co-morbidities, were identified. Hypertension (54.5%), depression and anxiety (51%), sleep disorders in terms of insomnia and OSAS (30%), cardiovascular morbidity (28%), autoimmune diseases (25%), chronic lung diseases (24%) and diabetes mellitus type 2 (23%) founded as possible risk factors.ConclusionNeurological symptoms were found in the vast majority (74%) of the patients. Accordingly, attention to neurological, mental and sleep disturbances is warranted with involvement of neurological expertise, in order to avoid further complications and long-term neurological effect of COVID-19. Furthermore, risk factors for more severe COVID-19, in terms of possible co-morbidities that identified in this study should get appropriate attention to optimizing treatment strategies in COVID-19 patients.

Objective: We report that lumbar puncture (LP) with removal of cerebrospinal fluid (CSF) induced rebound intracranial hypertension with increased papilledema as monitored by optical coherence tomography (OCT). Background: Severe papilledema causes visual field loss and central vision damage if untreated. Fundoscopy is a key to diagnose papilledema, but is not sensitive enough to monitor therapeutic effects. Methods: OCT was applied to follow a 24-year-old woman with headache, visual dysfunction, severe bilateral papilledema, and elevated CSF opening pressure. She was first treated with serial LP, which led to symptom deterioration, increased CSF pressure, and increased the retinal nerve fiber layer (RNFL) thickness. She was then successfully treated with acetazolamide and furosemide. Results: OCT showed reduction of RNFL thickness directly after LP with CSF removal, accompanied with reduced CSF pressure. Increased RNFL thickness accompanied with worsened headache, visual dysfunction, and increased CSF pressure was observed on the next day after LP. Less than 24 h after start of medication, the symptoms had reversed and RNFL thickness was reduced. The patient was symptom-free 2 weeks after starting on medical treatment. Papilledema had vanished on fundoscopy 6 weeks after the therapy, and RNFL thickness was normalized at 3 months of follow-up. Conclusion: This case provides evidence that OCT is an objective and sensitive tool to monitor papilledema and its response to therapy, and thereby important to help in correct clinical decision-making.

Abstract Background Structural variants (SVs) significantly drive genome diversity and environmental adaptation for diverse species. Unlike the prevalent small SVs (< kilobase-scale) in higher eukaryotes, large-size SVs rarely exist in the genome, but they function as one of the key evolutionary forces for speciation and adaptation. Results In this study, we discover and characterize several megabase-scale presence-absence variations (PAVs) in the maize genome. Surprisingly, we identify a 3.2 Mb PAV fragment that shows high integrity and is present as complete presence or absence in the natural diversity panel. This PAV is embedded within the nucleolus organizer region (NOR), where the suppressed recombination is found to maintain the PAV against the evolutionary variation. Interestingly, by analyzing the sequence of this PAV, we not only reveal the domestication trace from teosinte to modern maize, but also the footprints of its origin from Tripsacum, shedding light on a previously unknown contribution from Tripsacum to the speciation of Zea species. The functional consequence of the Tripsacum segment migration is also investigated, and environmental fitness conferred by the PAV may explain the whole segment as a selection target during maize domestication and improvement. Conclusions These findings provide a novel perspective that Tripsacum contributes to Zea speciation, and also instantiate a strategy for evolutionary and functional analysis of the “fossil” structure variations during genome evolution and speciation.

Abstract Studies have greatly explored the role of microRNAs (miRNAs) in cerebral ischemia/reperfusion injury (CI/RI). But the specific mechanism of miR-326-5p in CI/RI is still elusive. Hence, this study was to unmask the mechanism of miR-326-5p/signal transducer and activator of transcription-3 (STAT3) axis in CI/RI. Two models (oxygen and glucose deprivation [OGD] in primary rat cortical neurons and middle cerebral artery occlusion [MCAO] in Sprague–Dawley rats) were established to mimic CI/RI in vitro and in vivo, respectively. Loss- and gain-of function assays were performed with OGD-treated neurons and with MCAO rats. Afterward, viability, apoptosis, oxidative stress and mitochondrial membrane potential in OGD-treated neurons were tested, as well as pathological changes, apoptosis and mitochondrial membrane potential in brain tissues of MCAO rats. Mitofusin-2 (Mfn2), miR-326-5p and STAT3 expression in OGD-treated neurons and in brain tissues of MCAO rats were detected. Mfn2 and miR-326-5p were reduced, and STAT3 was elevated in OGD-treated neurons and brain tissues of MCAO rats. miR-326-5p targeted and negatively regulated STAT3 expression. Restoring miR-326-5p or reducing STAT3 reinforced viability, inhibited apoptosis and oxidative stress, increased mitochondrial membrane potential and increased Mfn2 expression in OGD-treated neurons. Up-regulating miR-326-5p or down-regulating STAT3 relieved pathological changes, inhibited apoptosis and elevated mitochondrial membrane potential and Mfn2 expression in brain tissues of rats with MCAO. This study elucidates that up-regulated miR-326-5p or down-regulated STAT3 protects against CI/RI by elevating Mfn2 expression.

Chalkiness is one of several major restricting factors for the improvement of rice quality. Although many chalkiness-related quantitative trait loci have been mapped, only a small number of genes have been cloned to date. In this study, the candidate gene GSE5 of a major quantitative trait locus (QTL) for rice chalkiness, qDEC5, was identified by map-based cloning. Phenotyping and haplotype analysis of proActin:GSE5 transgenic line, gse5-cr mutant, and 69 rice varieties further confirmed that GSE5 had the pleiotropic effects and regulated both chalkiness and grain shape. Genetic analysis showed GSE5 was a dominant gene for grain length and a semi-dominant gene for grain width and chalkiness. The DNA interval closely linked to GSE5 was introgressed to Zhenshan 97B (ZB) based on molecular marker-assisted selection, and the improved ZB showed lower chalkiness and longer but smaller grains, which showed that GSE5 played an important role in breeding rice varieties with high yield and good quality. Transcriptomics, proteomics, and qRT-PCR analyses showed that thirty-nine genes associated with carbon and protein metabolism are regulated by GSE5 to affect the formation of chalkiness, including some newly discovered genes, such as OsCESA9, OsHSP70, OsTPS8, OsPFK04, OsSTA1, OsERdj3A, etc. The low-chalkiness lines showed higher amino sugar and nucleotide sugar metabolism at 10 days after pollination (DAP), lower carbohydrate metabolism at 15 DAP, and lower protein metabolism at 10 and 15 DAP. With heat shock at 34/30°C, rice chalkiness increased significantly; OsDjC10 and OsSUS3 were upregulated at 6 and 12 DAP, respectively, and OsGSTL2 was downregulated at 12 DAP. Our results identified the function and pleiotropic effects of qDEC5 dissected its genetic characteristics and the expression profiles of the genes affecting the chalkiness formation, and provided a theoretical basis and application value to harmoniously pursue high yield and good quality in rice production.

Kinkéliba (Combretum micranthum, Seh-Haw in Wolof) is a popular bush tea in West African countries. Although the kinkéliba plant’s leaves have been widely consumed for its nutritional and medicinal properties, its benefits on skin health potential have been practically untouched. In human epidermal primary keratinocytes, vitexin and isovitexin-rich kinkéliba extract treatment significantly (p < 0.001) enhanced up to 39.6% of the cell survival rate decreased by UV radiation irritation. The treatment of kinkéliba leaf extracts also reduced the production of UV-induced pro-inflammatory cytokines IL-6 and IL-8 by 57.6% and 42.5%, respectively (p < 0.001), which cause skin redness and skin barrier dysfunction, as well as wrinkles and collagen degradation. The anti-inflammation efficacy of kinkéliba leaf extracts might involve significant inhibition on the levels of cellular reactive oxygen species (ROS) (−70.8%, p < 0.001) and nitrotyrosine (−56.9%, p < 0.05). Further topical applications of kinkéliba leaf extract gel were found to reduce sodium lauryl sulfate (SLS)-induced skin inflammation: at D7, the skin trans-epidermal water loss (TEWL) and skin redness (a* value) were both reduced by 59.81% (p < 0.001) and 22.4% (p < 0.001), compared with D0. In vitro and in vivo data support a new topical application of the kinkéliba leaf as an effective active ingredient for the treatment of skin inflammation, as well as subsequent barrier dysfunction and inflammaging.

Abstract Background Accumulating evidence indicates that aberrant microRNA (miRNA) expression contributes to osteosarcoma progression. This study aimed to elucidate the association between miR-624-5p expression and osteosarcoma (OS) development and to investigate its underlying mechanism. Methods We analyzed GSE65071 from the GEO database and found miR-624-5p was the most upregulated miRNA. The expression of miR-624-5p and its specific target gene were determined in human OS specimens and cell lines by RT-PCR and western blot. The effects of miR-624-5p depletion or ectopic expression on OS proliferation, migration and invasion were evaluated in vitro using CCK-8 proliferation assay, colony formation assay, transwell assay, would-healing assay and 3D spheroid BME cell invasion assay respectively. We investigated in vivo effects of miR-624-5p using a mouse tumorigenicity model. Besides, luciferase reporter assays were employed to identify interactions between miR-624-5p and its specific target gene. Results miR-624-5p expression was upregulated in OS cells and tissues, and overexpressing miR-624-5p led to a higher malignant level of OS, including cell proliferation, migration and invasion in vitro and in vivo. Protein tyrosine phosphatase receptor type B (PTPRB) was negatively correlated with miR-624-5p expression in OS tissues. Using the luciferase reporter assay and Western blotting, PTPRB was confirmed as a downstream target of miR-624-5p. PTPRB restored the effects of miR-624-5p on OS migration and invasion. The Hippo signaling pathway was identified as being involved in the miR-624-5p/PTPRB axis. Conclusions In conclusion, our results suggest that miR-624-5p is a negative regulator of PTPRB and a risk factor for tumor metastasis in OS progression.

Polyarylene ether nitrile (PEN) is a novel high-performance engineering plastic with various applications, particularly in thermoresistance-required fields. In this study, a well-known stimuli-response polydiacetylene monomer, 10, 12-pentacosadiynoic acid (PCDA), was encapsulated within electrospun PEN nanofibers to fabricate a colorimetric membrane with satisfactory thermal and corrosion resistance. To optimize the compatibility with PCDA, two PENswith distinct molecular chains were utilized: PEN−PPL and PEN−BPA. The chemical structure and elemental mapping analysis revealed that the PCDA component was successfully incorporated into the PEN fibrous. The PCDA bound significantly better to the PEN−PPL than to the PEN−BPA; due to the carboxyl groups present on the side chains of PEN−PPL, the surface was smooth and the color changed uniformly as the temperature rose. However, owing to its poor compatibility with PEN−BPA, the PCDA formed agglomerations on the fibers. The thermal analysis demonstrated that the membranes obtained after PCDA compounding maintained their excellent heat resistance. The 5% weight loss temperatures of composite nanofibrous membranes manufactured by PEN−PPL and PEN−BPA were 402 °C and 506 °C, respectively, and their glass transition temperatures were 219 °C and 169 °C, respectively, indicating that the blended membranes can withstand high temperatures. The evaluation of application performance revealed that the composite membranes exhibited good dimensional stability upon high thermal and corrosive situations. Specifically, the PEN−P−PCDA did not shrink at 170 °C. Both composite membranes were dimensionally stable when exposed to the alkali aqueous solution. However, PEN−P−PCDA is more sensitive to OH−, exhibiting color transition at pH > 8, whereas PEN−B−PCDA exhibited color transition at high OH− concentrations (pH ≥ 13), with enhanced alkali resistance stability owing to its nanofibrous architecture. This exploratory study reveals the feasibility of PEN nanofibers functionalized using PCDA as a desirable stimulus-response sensor even in high-temperature and corrosive harsh environments.

Abstract Introduction Stroke is the most common cause of homonymous visual field defects (VFD). About half of the stroke patients recover from VFD. However, relationship between VFD and retinal changes remains elusive. Purpose To investigate the association between occurrence of VFD, changes of macular ganglion cell and inner plexiform layer (GCIPL) and its axon retinal nerve fiber layer (RNFL) detected with optical coherence tomography (OCT). Patients and methods The study consists of retrospective review of medical records and follow‐up examinations. Patients with acute occipital stroke were registered. VFD was identified with confrontation and/or perimetry tests at the onset. At follow‐up, the patients were examined with visual field tests and OCT measurements. Results Thirty‐six patients met the inclusion criteria. At onset, 26 patients (72%) had VFD. At follow‐up >1 year after stroke, 13 patients (36%) had remaining VFD: 5 had homonymous hemianopia, 5 had homonymous quadrantanopia, and 3 had homonymous scotomas. Average thickness of GCIPL and RNFL were significantly reduced in each eye in patients with VFD compared to non‐VFD (NVFD) (p < .01 for all comparisons). Thickness of superior and inferior RNFL quadrants was significantly reduced in VFD compared to NVFD (p < .01 for both). Among these 13 patients, 4 had characteristic homonymous quadrant‐GCIPL thinning, 2 had characteristic homonymous hemi‐GCIPL thinning, and 7 had diffuse GCIPL thinning. Conclusion GCIPL and RNFL thinning were observed in the patients with VFD. GCIPL thinning appears in two forms: atypical diffuse thinning, or homonymous hemi‐GCIPL thinning. Examining GCIPL and RNFL provides easy and reliable objective measures and is therefore proposed to be of predictive value on visual function.

Abstract Background The anther cuticle, which is primarily composed of lipid polymers, is crucial for pollen development and plays important roles in sexual reproduction in higher plants. However, the mechanism underlying the biosynthesis of lipid polymers in maize (Zea mays. L.) remains unclear. Results Here, we report that the maize male-sterile mutant shrinking anther 1 (sa1), which is allelic to the classic mutant male sterile 33 (ms33), displays defective anther cuticle development and premature microspore degradation. We isolated MS33 via map-based cloning. MS33 encodes a putative glycerol-3-phosphate acyltransferase and is preferentially expressed in tapetal cells during anther development. Gas chromatography-mass spectrometry revealed a substantial reduction in wax and cutin in ms33 anthers compared to wild type. Accordingly, RNA-sequencing analysis showed that many genes involved in wax and cutin biosynthesis are differentially expressed in ms33 compared to wild type. Conclusions Our findings suggest that MS33 may contribute to anther cuticle and microspore development by affecting lipid polyester biosynthesis in maize.

Lung adenocarcinoma (LUAD) accounts for ~30% of all lung cancers and is one of the causes of cancer-related death worldwide. As the role of monoamine oxidase A (MAOA) in LUAD remains unclear, in this study, we examine how MAOA affects LUAD cell proliferation. Analyses of both public data and our data reveal that the expression of MAOA is downregulated in LUAD compared with non-tumor tissue. In addition, the expression of MAOA in tumors correlates with clinicopathologic features, and the expression of MAOA serves as an independent biomarker in LUAD. In addition, the overexpression of MAOA inhibits LUAD cell proliferation by inducing G1 arrest in vitro. Further mechanistic studies show that MAOA abrogates aerobic glycolysis in LUAD cells by decreasing hexokinase 2 (HK2). Finally, the expression of HK2 shows a negative correlation with MAOA in LUAD, and high HK2 predicts poor clinical outcome. In conclusion, our findings indicate that MAOA functions as a tumor suppressor in LUAD. Our results indicate that the MAOA/HK2 axis could be potential targets in LUAD therapy.

Abstract: Anemia is the defining feature in most patients with myelodysplastic syndromes (MDS), yet defects in erythropoiesis have not been well characterized. We examined freshly obtained bone marrow (BM) samples for stage-specific abnormalities during terminal erythroid differentiation (TED) from 221 samples (MDS, n = 205 from 113 unique patients; normal, n = 16) by measuring the surface expression of glycophorin A, band 3, and integrin α-4. Clinical and biologic associations were sought with presence or absence of TED and the specific stage of erythroid arrest. In 27% of MDS samples (56/205), there was no quantifiable TED documented by surface expression of integrin α-4 and band 3 by terminally differentiating erythroblasts. Absence of quantifiable TED was associated with a significantly worse overall survival (56 vs 103 months, P = .0001) and SRSF2 mutations (7/23, P < .05). In a multivariable Cox proportional hazards regression analysis, absence of TED remained independently significant across International Prognostic Scoring System-Revised (IPSS-R) categories, myeloid/erythroid ratio, and mutations in several genes. In 149/205 MDS samples, the proportion of cells undergoing TED did not follow the expected 1:2:4:8:16 doubling pattern in successive stages. Absence of TED emerged as a powerful independent prognostic marker of poor overall survival across all IPSS-R categories in MDS, and SRSF2 mutations were more frequently associated with absence of TED.

Abstract Background SF3B1 is a core component of splicing machinery. Mutations in SF3B1 are frequently found in myelodysplastic syndromes (MDS), particularly in patients with refractory anemia with ringed sideroblasts (RARS), characterized by isolated anemia. SF3B1 mutations have been implicated in the pathophysiology of RARS; however, the physiological function of SF3B1 in erythropoiesis remains unknown. Methods shRNA-mediated approach was used to knockdown SF3B1 in human CD34+ cells. The effects of SF3B1 knockdown on human erythroid cell differentiation, cell cycle, and apoptosis were assessed by flow cytometry. RNA-seq, qRT-PCR, and western blot analyses were used to define the mechanisms of phenotypes following knockdown of SF3B1. Results We document that SF3B1 knockdown in human CD34+ cells leads to increased apoptosis and cell cycle arrest of early-stage erythroid cells and generation of abnormally nucleated late-stage erythroblasts. RNA-seq analysis of SF3B1-knockdown erythroid progenitor CFU-E cells revealed altered splicing of an E3 ligase Makorin Ring Finger Protein 1 (MKRN1) and subsequent activation of p53 pathway. Importantly, ectopic expression of MKRN1 rescued SF3B1-knockdown-induced alterations. Decreased expression of genes involved in mitosis/cytokinesis pathway including polo-like kinase 1 (PLK1) was noted in SF3B1-knockdown polychromatic and orthochromatic erythroblasts comparing to control cells. Pharmacologic inhibition of PLK1 also led to generation of abnormally nucleated erythroblasts. Conclusions These findings enabled us to identify novel roles for SF3B1 in human erythropoiesis and provided new insights into its role in regulating normal erythropoiesis. Furthermore, these findings have implications for improved understanding of ineffective erythropoiesis in MDS patients with SF3B1 mutations.

Transmembrane protein 30A (Tmem30a) is the β-subunit of P4-ATPases which function as flippase that transports aminophospholipids such as phosphatidylserine from the outer to the inner leaflets of the plasma membrane to maintain asymmetric distribution of phospholipids. It has been documented that deficiency of Tmem30a led to exposure of phosphatidylserine. However, the role of Tmem30a in vivo remains largely unknown. Here we found that Vav-Cre-driven conditional deletion of Tmem30a in hematopoietic cells led to embryonic lethality due to severe anemia by embryonic day 16.5. The numbers of erythroid colonies and erythroid cells were decreased in the Tmem30a deficient fetal liver. This was accompanied by increased apoptosis of erythroid cells. Confocal microscopy analysis revealed an increase of localization of erythropoietin receptor to areas of membrane raft microdomains in response to erythropoietin stimulation in Ter119−erythroid progenitors, which was impaired in Tmem30a deficient cells. Moreover, erythropoietin receptor (EPOR)-mediated activation of the STAT5 pathway was significantly reduced in Tmem30a deficient fetal liver cells. Consistently, knockdown of TMEM30A in human CD34+ cells also impaired erythropoiesis. Our findings demonstrate that Tmem30a plays a critical role in erythropoiesis by regulating the EPOR signaling pathway through the formation of membrane rafts in erythroid cells.

Poly(arylene ether nitrile)s with sulfonic and carboxylic groups (SCPEN) were synthesized to investigate their electrical properties. This new series of copolymers were prepared by copolymerization of phenolphthalein, potassium hydroquinonesulfonate, and 2,6-difluorobenzonitrile, in different mole ratios. Their thermal, mechanical and dielectric properties were investigated in detail. By adjusting the composition of sulfonic and carboxylic groups, it can be concluded that the dielectric constant increases with the increase of sulfonic groups, and mechanical and thermal properties improve with the increase of carboxylic groups. The as-prepared SCPEN films show potential applications in electronic storage materials, which provide insights into the correlation of SCPEN electrical properties with its chemical structure. The structure−property relationship is established to broaden the application of functionalized PEN. Furthermore, SCPEN with rich polar groups may also be used as the polymer matrix to increase the interaction with the filler surface, ensuring a better dispersion of filler in the matrix. This provides a reference for the development of high dielectric materials.

Metal-organic frameworks (MOFs) are considered as good materials for the adsorption of many environmental pollutants. In this study, magnetic Fe3O4/MIL-88A composite was prepared by modification of MIL-88A with magnetic nanoparticles using the coprecipitation method. The structures and magnetic property of magnetic Fe3O4/MIL-88A composite were characterized and the adsorption behavior and mechanism for Bromophenol Blue (BPB) were evaluated. The results showed that magnetic Fe3O4/MIL-88A composite maintained a hexagonal rod-like structure and has good magnetic responsibility for magnetic separation (the maximum saturation magnetization was 49.8 emu/g). Moreover, the maximum adsorption amount of Fe3O4/MIL-88A composite for BPB was 167.2 mg/g and could maintain 94% of the initial adsorption amount after five cycles. The pseudo-second order kinetics and Langmuir isotherm models mostly fitted to the adsorption for BPB suggesting that chemisorption is the rate-limiting step for this monomolecular-layer adsorption. The adsorption capacity for another eight dyes (Bromocresol Green, Brilliant Green, Brilliant Crocein, Amaranth, Fuchsin Basic, Safranine T, Malachite Green and Methyl Red) were also conducted and the magnetic Fe3O4/MIL-88A composite showed good adsorption for dyes with sulfonyl groups. In conclusion, magnetic Fe3O4/MIL-88A composite could be a promising adsorbent and shows great potential for the removal of anionic dyes containing sulfonyl groups.

The purpose of this study was to investigate the effects of leaf extract from Lithocarpus polystachyus Rehd. on type II diabetes mellitus (T2DM) and the active ingredients of this effect. In addition, this study determined, for the first time, the underlying molecular and pharmacological mechanisms of the extracts on hyperglycemia using long-term double high diet-fed and streptozotocin (STZ) induced type II diabetic mice. In the present study, leaf extract, phloridzin and trilobatin were assessed in vivo (gavage) and in vitro (non-invasive micro-test technique, NMT) in experimental T2DM mice. The biochemical parameters were measured including blood glucose and blood lipid level, liver biochemical indexes, and hepatic glycogen. The relative expression of glycometabolism-related genes was detected. The effect of leaf extracts on physiological glucose flux in liver tissue from control and T2DM mice was also investigated. Body weight of experimental T2DM mice increased significantly after the first week, but stabilized over the subsequent three weeks; body weight of all other groups did not change during the four weeks' study. After four weeks, all treatment groups decreased blood glucose, and treatment with leaf extract had numerous positive effects: a) promoted in glucose uptake in liver, b) increased synthesis of liver glycogen, c) reduced oxidative stress, d) up-regulation of glucokinase (GK), glucose transporter 2 (GLUT2), insulin receptor (IR) and insulin receptor substrate (IRS) expression in liver, e) down-regulation of glucose-6-phosphatase (G-6-P) expression, and f) ameliorated blood lipid levels. Both treatment with trilobatin or phloridzin accelerated liver glycogen synthesis, decreased oxidative stress and increased expression of GK. IRS and phosphoenolpyruvate carboxykinase (PEPCK) were both up-regulated after treatment with trilobatin. Expression of GLUT2, PEPCK and G-6-P were also increased in liver tissue after treatment with phloridzin. Our data indicate that leaf extract from L. polystachyus Rehd. has a preferable hypoglycemic effects than trilobatin or phloridzin alone. Leaf extract significantly increased glucose uptake and hepatic glycogen synthesis while also inducing a decline of hepatic gluconeogenesis and oxidative stress in T2DM mice. From this study, we draw conclusions that L. polystachyus promoted glycogen synthesis in T2DM mice, and that the active compounds were not only the trilobatin or phloridzin.

The mitogenic effects of periodic mechanical stress on chondrocytes have been studied extensively but the mechanisms whereby chondrocytes sense and respond to periodic mechanical stress remain a matter of debate. We explored the signal transduction pathways of chondrocyte proliferation and matrix synthesis under periodic mechanical stress. In particular, we sought to identify the role of the MEK1/2-ERK1/2 signaling pathway in chondrocyte proliferation and matrix synthesis following cyclic physiologic mechanical compression. Under periodic mechanical stress, both rat chondrocyte proliferation and matrix synthesis were significantly increased (P < 0.05) and were associated with increases in the phosphorylation of Src, PLCγ1, MEK1/2, and ERK1/2 (P < 0.05). Pretreatment with the MEK1/2-ERK1/2 selective inhibitor, PD98059, and shRNA targeted to ERK1/2 reduced periodic mechanical stress-induced chondrocyte proliferation and matrix synthesis (P < 0.05), while the phosphorylation levels of Src-Tyr418 and PLCγ1-Tyr783 were not inhibited. Proliferation, matrix synthesis and phosphorylation of MEK1/2-Ser217/221 and ERK1/2-Thr202/Tyr204 were inhibited after pretreatment with the PLCγ1 inhibitor U73122 in chondrocytes in response to periodic mechanical stress (P < 0.05), while the phosphorylation site of Src-Tyr418 was not affected. Inhibition of Src activity with PP2 and shRNA targeted to Src abrogated chondrocyte proliferation and matrix synthesis (P < 0.05) and attenuated PLCγ1, MEK1/2 and ERK1/2 activation in chondrocytes subjected to periodic mechanical stress (P < 0.05). These findings suggest that periodic mechanical stress promotes chondrocyte proliferation and matrix synthesis in part through the Src-PLCγ1-MEK1/2-ERK1/2 signaling pathway, which links these three important signaling molecules into a mitogenic cascade.

To obtain a proton exchange membrane (PEM) with high proton conductivity and low methanol permeability, a novel amino-sulfo-bifunctionalized GO (NSGO) was synthesized and explored as a filler for sulfonated poly(arylene ether nitrile) (SPEN). The result indicated that the microstructure of composite membranes was rearranged by NSGO and strong acid–base interactions were formed between fillers and the SPEN matrix, affording enhanced thermal, mechanical, and dimensional stabilities. Moreover, it was found that NSGO fillers were uniformly dispersed in the SPEN matrix, generating efficient proton-conducting paths along the SPEN/NSGO interface. Meanwhile, the sulfonic and amino groups of NSGO served as additional proton hopping sites to connect the ionic clusters in the SPEN matrix, creating interconnected and long-range ionic pathways. In such a way, proton-conducting highways with low energy barriers are constructed, which enhance the proton conductivity of the composite membranes via the Grotthuss mechanism. Furthermore, the composite membranes also effectively prevent methanol permeation, and therefore high selectivity (the ratio of proton conductivity and methanol permeability) is endowed. Compared to SPEN membrane, a 3.6-fold increase in selectivity is obtained for the optimal composite membrane. This study will provide a new strategy for the preparation of high-performance PEM.

This study aimed to assess whether Ginsenoside Rg1 (Rg1) inhibits inflammatory responses in human chondrocytes and reduces articular cartilage damage in a rat model of osteoarthritis (OA). Gene expression and protein levels of type II collagen, aggrecan, matrix metalloproteinase (MMP)‐13 and cyclooxygenase‐2 (COX‐2) were determined in vitro by quantitative real‐time‐polymerase chain reaction and Western blotting. Prostaglandin E2 (PGE2) amounts in the culture medium were determined by enzyme‐linked immunosorbent assay (ELISA). For in vivo assessment, a rat model of OA was generated by anterior cruciate ligament transection (ACLT). Four weeks after ACLT, Rg1 (30 or 60 mg/kg) or saline was administered by gavage once a day for eight consecutive weeks. Joint damage was analyzed by histology and immunohistochemistry. Ginsenoside Rg1 inhibited Interleukin (IL)‐1β‐induced chondrocyte gene and protein expressions of MMP‐13, COX‐2 and PGE2, and prevented type II collagen and aggrecan degradation, in a dose‐dependent manner. Administration of Ginsenoside Rg1 to OA rats attenuated cartilage degeneration, and reduced type II collagen loss and MMP‐13 levels. These findings demonstrated that Ginsenoside Rg1 can inhibit inflammatory responses in human chondrocytes in vitro and reduce articular cartilage damage in vivo, confirming the potential therapeutic value of Ginsenoside Rg1 in OA.

Strigolactones (SLs) are recently identified plant hormones that inhibit shoot branching and control various aspects of plant growth, development and interaction with parasites. Previous studies have shown that plant D10 protein is a carotenoid cleavage dioxygenase that functions in SL biosynthesis. In this work, we used an allelic SL-deficient d10 mutant XJC of rice (Oryza sativa L. spp. indica) to investigate proteins that were responsive to SL treatment. When grown in darkness, d10 mutant seedlings exhibited elongated mesocotyl that could be rescued by exogenous application of SLs. Soluble protein extracts were prepared from d10 mutant seedlings grown in darkness in the presence of GR24, a synthetic SL analog. Soluble proteins were separated on two-dimensional gels and subjected to proteomic analysis. Proteins that were expressed differentially and phosphoproteins whose phosphorylation status changed in response to GR24 treatment were identified. Eight proteins were found to be induced or down-regulated by GR24, and a different set of 8 phosphoproteins were shown to change their phosphorylation intensities in the dark-grown d10 seedlings in response to GR24 treatment. Analysis of these proteins revealed that they are important enzymes of the carbohydrate and amino acid metabolic pathways and key components of the cellular energy generation machinery. These proteins may represent potential targets of the SL signaling pathway. This study provides new insight into the complex and negative regulatory mechanism by which SLs control shoot branching and plant development.

The title compound, C18H18N3O+·PF6−, is a chiral bicyclic 1,2,4-triazolium salt which contains four rings, viz. a triazolium, a morpholine and two phenyl rings. Analysis of bond lengths shows that the N—CH—N group in the triazolium ring conforms to a typical three-center/four-electron bond (also known as the Pimentel–Rundle three-center model). The structure is completed by a disordered PF6− counter-ion [occupancies of F atoms 0.678 (8):0.322 (8)], which interacts with the main molecule through weak intermolecular P—F...π interactions.