The role of ncRNA regulatory mechanisms in diseases-case on gestational diabetes.

Non-coding RNAs (ncRNAs) are a class of RNA molecules that do not have the potential to encode proteins. Meanwhile, they can occupy a significant portion of the human genome and participate in gene expression regulation through various mechanisms. Gestational diabetes mellitus (GDM) is a pathologic condition of carbohydrate intolerance that begins or is first detected during pregnancy, making it one of the most common pregnancy complications. Although the exact pathogenesis of GDM remains unclear, several recent studies have shown that ncRNAs play a crucial regulatory role in GDM. Herein, we present a comprehensive review on the multiple mechanisms of ncRNAs in GDM along with their potential role as biomarkers. In addition, we investigate the contribution of deep learning-based models in discovering disease-specific ncRNA biomarkers and elucidate the underlying mechanisms of ncRNA. This might assist community-wide efforts to obtain insights into the regulatory mechanisms of ncRNAs in disease and guide a novel approach for early diagnosis and treatment of disease.

iRice-MS: An integrated XGBoost model for detecting multitype post-translational modification sites in rice.

Post-translational modification (PTM) refers to the covalent and enzymatic modification of proteins after protein biosynthesis, which orchestrates a variety of biological processes. Detecting PTM sites in proteome scale is one of the key steps to in-depth understanding their regulation mechanisms. In this study, we presented an integrated method based on eXtreme Gradient Boosting (XGBoost), called iRice-MS, to identify 2-hydroxyisobutyrylation, crotonylation, malonylation, ubiquitination, succinylation and acetylation in rice. For each PTM-specific model, we adopted eight feature encoding schemes, including sequence-based features, physicochemical property-based features and spatial mapping information-based features. The optimal feature set was identified from each encoding, and their respective models were established. Extensive experimental results show that iRice-MS always display excellent performance on 5-fold cross-validation and independent dataset test. In addition, our novel approach provides the superiority to other existing tools in terms of AUC value. Based on the proposed model, a web server named iRice-MS was established and is freely accessible at http://lin-group.cn/server/iRice-MS.

Aldehyde Dehydrogenase 2 Preserves Mitochondrial Function in the Ischemic Heart: A Redox-dependent Mechanism for AMPK Activation by Thioredoxin-1.

ABSTRACT: Aldehyde dehydrogenase 2 (ALDH2) protects the ischemic heart by activating adenosine 5'-monophosphate-activated protein kinase (AMPK) signaling. However, the molecular mechanisms linking ALDH2 and AMPK signaling are not fully understood. This study aimed to explore the potential mechanisms linking ALDH2 and AMPK in myocardial ischemic injury. An ischemic model was established by ligating the left anterior descending coronary artery in rats. The overexpression or knockdown of ALDH2 in H9c2 cells treated with oxygen-glucose deprivation was obtained through lentivirus infection. Transferase-mediated dUTP nick-end labeling was used to evaluate apoptosis in an ischemic rat model and oxygen-glucose deprivation cells. ALDH2 activity, mitochondrial oxidative stress markers, adenosine triphosphate, respiratory control ratio, and cell viability in H9c2 cells were evaluated using a biological kit and 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide. Protein expression of ALDH2 , 4-hydroxynonenal, thioredoxin-1 (Trx-1), and AMPK-proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) signaling pathway was detected through Western blotting. ALDH2 activation reduced ischemic-induced myocardial infarct size and apoptosis. ALDH2 protected mitochondrial function by enhancing mitochondrial respiratory control ratio and adenosine triphosphate production, alleviated mitochondrial oxidative stress, and suppressed myocardial apoptosis. Moreover, ALDH2 attenuated ischemia-induced oxidative stress and maintained Trx-1 levels by reducing 4-hydroxynonenal, thereby promoting AMPK-PGC-1α signaling activation. Inhibiting Trx-1 or AMPK abolished the cardioprotective effect of ALDH2 on ischemia. ALDH2 alleviates myocardial injury through increased mitochondrial biogenesis and reduced oxidative stress, and these effects were achieved through Trx1-mediating AMPK-PGC1-α signaling activation.

Safety and efficacy of non-reduced use of caspofungin in patients with Child-Pugh B or C cirrhosis: a real-world study.

BACKGROUND AND PURPOSE: The need for dose adjustment of caspofungin in patients with hepatic impairment is controversial, especially for those with Child-Pugh B or C cirrhosis. The purpose of this study was to investigate the safety and efficacy of standard-dose caspofungin administration in Child-Pugh B and C cirrhotic patients in a real-world clinical setting. PATIENTS AND METHODS: The electronic medical records of 258 cirrhotic patients, including 67 Child-Pugh B patients and 191 Child-Pugh C patients, who were treated with standard-dose of caspofungin at the Second Affiliated Hospital of Chongqing Medical University, China, from March 2018 to June 2023 were reviewed retrospectively. The white blood cells (WBC), hepatic, renal and coagulation function results before administration and post administration on days 7, 14 and 21 were collected, and the efficacy was assessed in all patients at the end of caspofungin therapy. RESULTS: Favorable responses were achieved in 137 (53.1%) patients while 34 (13.2%) patients died. We observed that some patients experienced an increase of prothrombin time (PT) or international normalized ratio (INR), or a decrease of WBC, but no exacerbation of hepatic or renal dysfunction were identified and no patient required dose interruption or adjustment because of an adverse drug reaction during treatment with caspofungin. CONCLUSIONS: Standard-dose of caspofungin can be safely and effectively used in patients with Child-Pugh B or C cirrhosis, and we appealed to re-assess the most suitable dosing regimen in this population to avoid a potential subtherapeutic exposure.

A novelty strategy for AMD prevention by biogas slurry: Acetate acid inhibition effect on chalcopyrite biooxidation and leachate.

With the widespread application of anaerobic digestion technology, biogas slurry become the main source of organic amendments in practice. Comprehensive studies into the inhibitory effects of low molecular weight (LMW) organic acids, essential components in biogas slurry, on the sulfide minerals biooxidation and its bioleaching (AMD) have been lacking. In this study, acetic acid (AA) served as a representative of LMW organic acids in biogas slurry to investigate its impact on the inhibition of chalcopyrite biooxidation by Acidithiobacillus ferrooxidans (A. ferrooxidans). It was shown that AA could slow down the chalcopyrite biooxidation and inhibit the jarosite formation on the mineral surface. Compared with the control group (0 ppm AA), the sulfate increment in the leachate of the 50 ppm, 100 ppm, and 200 ppm AA-treated groups decreased by 36.4%, 66.8%, and 69.0%, respectively. AA treatment (≥50 ppm) could reduce the oxidation of ferrous ions in the leachate by one order of magnitude. At the same time, the bacterial concentration of the leachate in the 50 ppm, 100 ppm, and 200 ppm AA-treated groups decreased by 70%, 93%, and 94%, respectively. These findings provide a scientific basis for new strategies to utilize biogas slurry for mine remediation and contribute to an enhanced comprehension of organic amendments to prevent AMD in situ in mining soil remediation.

Analysis of Enrichment Pathway, Hub Gene, and Protein-Protein Interaction Network in Rheumatoid Arthritis and Construction of Molecular Subtypes in Peripheral Blood.

Objective: To analyze the enrichment pathway, hub gene, and Protein-protein interaction (PPI) network of rheumatoid arthritis (RA) and construct peripheral blood subtypes based on integrated bioinformatics analysis. Methods: Suitable datasets were screened from the GEO database based on titles and abstracts, batch positive analysis was performed using R language, and KEGG enrichment analysis and GO enrichment analysis were performed. After screening the differential genes, the PPI network was constructed, and the hubba plug-in of Cytoscape software was used to obtain the top 10 hub genes(key regulatory genes). hub genes were used as the typing condition to identify the molecular subtypes of synovial tissue and peripheral blood of arthritis. Results: GSE12021 and GSE93272 have been chosen for analysis. GSE12021 presents the transcriptome analysis of human joint synovial tissue, comprising 12 samples from patients with rheumatoid arthritis and 9 samples from normal healthy individuals. On the other hand, GSE93272 includes human peripheral blood samples, comprising 232 samples from patients with rheumatoid arthritis and 43 samples from normal healthy individuals. The main results of GSE12021 KEGG enrichment were Parathyroid hormone synthesis, Relaxin signaling pathway, TNF signaling pathway, Rheumatoid arthritis, T cell receptor signaling pathway, Th1 and Th2 cell differentiation, Th17 cell differentiation, Toll-like receptor signaling pathway and so on. The main results of GSE12021 GO enrichment were regulation of feeding behavior, regulation of neuron death, positive regulation of cell-cell adhesion, and positive regulation of leukocyte activation. The top 10 hub genes were CD8A, JUN, CTLA4, CD19, LCK, FOS, CCL5, IL7R, CCR7 and CD247. Synovial tissue and peripheral blood subtypes of rheumatoid arthritis showed that the two classification methods maintained consistency. Conclusion: Identifying the Hub gene in peripheral blood helps screen molecular subtypes of rheumatoid arthritis.

Biomass-Derived Carbonaceous Materials with Graphene/Graphene-Like Structures: Definition, Classification, and Environmental Applications.

Biomass-derived carbonaceous materials with graphene/graphene-like structures (BGS) have attracted tremendous attention in the field of environmental remediation. The introduction of graphene/graphene-like structures into raw biochars can effectively improve their properties, such as electrical conductivity, surface functional groups, and catalytic activity. In 2021, the International Organization for Standardization defined graphene as a "single layer of carbon atoms with each atom bound to three neighbours in a honeycomb structure". Considering this definition, several studies have incorrectly referred to BGS (e.g., biomass-derived few-layer graphene or porous graphene-like nanosheets) as "graphene". The definitions and classifications of BGS and their applications in environmental remediation have not been assessed critically thus far. Comprehensive analysis and sufficient and robust evidence are highly desired to accurately determine the specific structures of BGS. In this perspective, we provide a systematic framework to define and classify the BGS. The state-of-the-art methods currently used to determine the structural properties of BGS are scrutinized. We then discuss the design and fabrication of BGS and how their distinctive features could improve the applicability of biomass-derived carbonaceous materials, particularly in environmental remediation. The environmental applications of these BGS are highlighted, and future research opportunities and needs are identified. The fundamental insights in this perspective provide critical guidance for the further development of BGS for a wide range of environmental applications.

Influence of systolic blood pressure trajectory on in-hospital mortality in patients with sepsis.

BACKGROUND: Numerous studies have investigated the mean arterial pressure in patients with sepsis, and many meaningful results have been obtained. However, few studies have measured the systolic blood pressure (SBP) multiple times and established trajectory models for patients with sepsis with different SBP trajectories. METHODS: Data from patients with sepsis were extracted from the Medical Information Mart for Intensive Care-III database for inclusion in a retrospective cohort study. Ten SBP values within 10 h after hospitalization were extracted, and the interval between each SBP value was 1 h. The SBP measured ten times after admission was analyzed using latent growth mixture modeling to construct a trajectory model. The outcome was in-hospital mortality. The survival probability of different trajectory groups was investigated using Kaplan-Meier (K-M) analysis, and the relationship between different SBP trajectories and in-hospital mortality risk was investigated using Cox proportional-hazards regression model. RESULTS: This study included 3034 patients with sepsis. The median survival time was 67 years (interquartile range: 56-77 years). Seven different SBP trajectories were identified based on model-fit criteria. The in-hospital mortality rates of the patients in trajectory classes 1-7 were 25.5%, 40.5%, 11.8%, 18.3%, 23.5%, 13.8%, and 10.5%, respectively. The K-M analysis indicated that patients in class 2 had the lowest probability of survival. Univariate and multivariate Cox regression analysis indicated that, with class 1 as a reference, patients in class 2 had the highest in-hospital mortality risk (P < 0.001). Subgroup analysis indicated that a nominal interaction occurred between age group and blood pressure trajectory in the in-hospital mortality (P < 0.05). CONCLUSION: Maintaining a systolic blood pressure of approximately 140 mmHg in patients with sepsis within 10 h of admission was associated with a lower risk of in-hospital mortality. Analyzing data from multiple measurements and identifying different categories of patient populations with sepsis will help identify the risks among these categories.

Deep-4mCW2V: A sequence-based predictor to identify N4-methylcytosine sites in Escherichia coli.

N4-methylcytosine (4mC) is a type of DNA modification which could regulate several biological progressions such as transcription regulation, replication and gene expressions. Precisely recognizing 4mC sites in genomic sequences can provide specific knowledge about their genetic roles. This study aimed to develop a deep learning-based model to predict 4mC sites in the Escherichia coli. In the model, DNA sequences were encoded by word embedding technique 'word2vec'. The obtained features were inputted into 1-D convolutional neural network (CNN) to discriminate 4mC sites from non-4mC sites in Escherichia coli genome. The examination on independent dataset showed that our model could yield the overall accuracy of 0.861, which was about 4.3% higher than the existing model. To provide convenience to scholars, we provided the data and source code of the model which can be freely download from https://github.com/linDing-groups/Deep-4mCW2V.

Diterpenoids from Euphorbia fischeriana with Kv1.3 Inhibitory Activity.

Euphorbia diterpenoids possess inhibitory effects of Kv1.3 ion channel, but most of this research has focused on diterpenoids with jatrophane-related or ingenane-related skeletons. In the present study, nine undescribed (1-9) and 16 known (10-25) diterpenoids, based on jatrophane, lathyrane, ingenane, abietane, and atisane skeletons, were identified from the methanol extract of the aerial parts of Euphorbia fischeriana. The structures were established by analysis of the spectroscopic data as well as by single-crystal X-ray diffraction analysis. Among the isolated diterpenoids, macrocyclic jatrophanes and lathyranes exerted Kv1.3 blocking activity. Compound 8 exhibited good selectivity on the inhibition of the Kv 1.3 channel rather than hERG channel, with a selectivity index over 7.0. The selective activity of lathyrane diterpenoids indicates that macrocyclic diterpenoids have the potential to be further investigated as therapeutic agents for the treatment of autoimmune diseases.

Trends in deaths and disability-adjusted life-years of stroke attributable to low physical activity worldwide, 1990-2019.

BACKGROUND: Low physical activity (LPA) is linked to the risk of stroke, but the disease burden of stroke attributable to LPA needs to be understood to develop effective preventive strategies. We aim to assess spatiotemporal trends in the global burden of stroke attributable to LPA from 1990 to 2019. METHODS: Based on the Global Burden of Disease, Injuries, and Risk Factors Study, our research examined deaths, the Disability-Adjusted Life Years (DALYs), the Age-Standardized Mortality Rate (ASMR), the Age-Standardized DALY Rate (ASDR), and the Estimated Annual Percentage Change (EAPC) for stroke attributable to LPA. RESULTS: Deaths and DALYs were on the rise worldwide from 1990 to 2019, with increases of 72.72% for the former and 67.41% for the latter; ASMR and ASDR decreased, with the ASMR-related EAPC of -1.61 (95% CI:-1.71--1.5) and ASDR-related EAPC of -1.35 (95% CI:-1.43--1.27); females had more numbers of deaths and DALYs, and the majorities of deaths and DALYs were shared by those aged ≥ 70. The highest burden rates were shared by North Africa, the Middle East, and Tropical Latin America; the ASMR-related EAPC was associated with the ASMR in 1990 (R = -0.26, P < 0.001) and the Socio-Demographic Index (SDI) across different countries in 2019 (R = -0.61, P < 0.001), respectively, and such patterns were similar to what ASDR and the ASDR-related EAPC had; the Human Development Index (HDI) in 2019 was associated with the ASMR-related EAPC (R = 0.63, P < 0.001) and the ASDR-related EAPC across different countries (R = -0.62, P < 0.001), respectively. CONCLUSIONS: Globally, deaths and DALYs of stroke attributable to LPA were on the rise, although their age-standardized rates presented downward over the past three decades; the burden of stroke attributable to LPA showed upward trends especially in those aged ≥ 70 and females in the regions of East Asia, North Africa, and the Middle East, which need more attention to the effects of physical activity on health interventions.

New pathogenic variants of ALMS1 gene in two Chinese families with Alström Syndrome.

PURPOSE: Alström Syndrome (AS) is an autosomal recessive hereditary disease with the characteristics of multiorgan dysfunction. Due to the heterogeneity of clinical manifestations of AS, genetic testing is crucial for the diagnosis of AS. Herein, we used whole-exome sequencing (WES) to determine the genetic causes and characterize the clinical features of three affected patients in two Chinese families with Alström Syndrome. MATERIALS AND METHODS: Three affected patients (initially diagnosed as achromatopsia). and five asymptomatic members were recruited for both genetic and clinical tests. The complete ophthalmic examinations and systemic examinations were performed on all participants. Whole exome sequencing (WES) was performed for mutation detection. The silico analysis was also applied to predict the pathogenesis of identified pathogenic variants. RESULTS: In family 1, the proband showed low vision, hyperopia, photophobia, nystagmus, and total color blindness. DNA analysis revealed that she carried a compound heterozygote with two novel pathogenic variants in the ALMS1 gene NM_015120.4:c.10379del (NP_055935.4:p.(Asp2252Tyr)) and NM_015120.4:c.11641_11642del (NP_055935.4:p.(Val3881ThrfsTer11)). Further systemic examinations showed short stature, acanthosis nigricans, and sensorineural hearing loss. In family 2, two affected siblings presented the low vision, hyperopia, photophobia, nystagmus, and total color blindness. DNA analysis revealed that they carried a same compound heterozygote with two novel pathogenic variants in the ALMS1 gene NM_015120.4:c.10379del (NP_055935.4:p.(Asn3460IlefsTer49)), NM_015120.4:c.10819C > T (NP_055935.4:p.(Arg3607Trp)). Further systemic examinations showed obesity and mild abnormalities of lipid metabolism. According to the genetic testing results and further systemic analysis, the three affected patients were finally diagnosed as Alström Syndrome (AS). CONCLUSIONS: We found two new compound heterozygous pathogenic variants of the ALMS1 gene and determined the diagnosis as Alström Syndrome in three patients of two Chinese families. Our study extends the genotypic and phenotypic spectrums for ALMS1 -AS and emphasizes the importance of gene testing in assisting the clinical diagnosis for cases with phenotypic diversities, which would help the AS patients with early diagnosis and treatment to reduce future systemic damage.

Surgical treatment of renal cell carcinoma with inferior vena cava tumor thrombus.

PURPOSE: The present report discusses the indications of cardiopulmonary bypass (CPB) in open nephrectomy and surgical outcomes of conventional and minimally invasive surgical techniques for treating advanced renal cell carcinoma with inferior vena cava tumor thrombus. METHODS: The present study involved a comprehensive retrieval of pertinent literature from the most recent two decades. RESULTS: Comparisons between radical nephrectomy procedures in terms of open, laparoscopic and robotic-assisted surgeries revealed that open surgery had more blood loss, a longer operation time and higher mortality rates than laparoscopic and robotic-assisted surgeries. Furthermore, surgery with CPB was associated with more blood loss than non-CPB surgery. Rates of early and late deaths were much higher in patients with CPB than in those without CPB. CONCLUSIONS: Different surgical techniques had different indications in terms of levels of inferior vena cava tumor thrombus. The laparoscopic, robotic-assisted, open surgical techniques and CPB with deep hypothermic circulatory arrest were indicated for Levels I, II, III and III-IV inferior vena cava tumor thrombus, respectively. Laparoscopic and robotic-assisted surgeries cause less trauma than open surgery but require more complicated equipments to support the procedure. CPB should be avoided in radical nephrectomy whenever possible. The increased application of laparoscopic and robotic techniques in the future is anticipated.

Novel homozygous truncating variants in ZMYND15 causing severe oligozoospermia and their implications for male infertility.

Sequence variants of ZMYND15 cause azoospermia in humans, but they have not yet been reported in infertile men with severe oligozoospermia (SO). We performed whole-exome and Sanger sequencing to identify suspected causative variants in 414 idiopathic participating infertile men with SO or azoospermia. Three novel homozygous truncating variants in ZMYND15 were identified in three of the 219 (1.37%) unrelated patients with SO, including c.1209T>A(p.Tyr403*), c.1650delC (p.Glu551Lysfs*75), and c.1622_1636delinsCCAC (p.Leu541Profs*39). In silico bioinformatic analyses as well as in vivo and in vitro experiments showed that the ZMYND15 variants carried by the affected subjects might be the underlying cause for their infertility. One patient accepted intracytoplasmic sperm injection therapy, using his ejaculated sperm, and his wife successfully became pregnant. Our findings expand the disease phenotype spectrum by indicating that ZMYND15 variants cause SO and male infertility and suggest a possible correlation between the severity of male infertility caused by ZMYND15 variants and male age.

Hydrogen-rich water alleviates cyclosporine A-induced nephrotoxicity via the Keap1/Nrf2 signaling pathway.

Oxidative stress induced by long-term cyclosporine A (CsA) administration is a major cause of chronic nephrotoxicity, which is characterized by tubular atrophy, tubular cell apoptosis, and interstitial fibrosis in the progression of organ transplantation. Although hydrogen-rich water (HRW) has been used to prevent various oxidative stress-related diseases, its underlying mechanisms remain unclear. This study investigated the effects of HRW on CsA-induced nephrotoxicity and its potential mechanisms. After administration of CsA (25 mg/kg/day), rats were treated with or without HRW (12 mL/kg) for 4 weeks. Renal function and vascular activity were investigated. Histological changes in kidney tissues were analyzed using Masson's trichrome and terminal deoxynucleotidyl transferase dUTP nick-end labeling stains. Oxidative stress markers and the activation of the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway were also measured. We found that CsA increased the levels of reactive oxygen species (ROS) and malonaldehyde (MDA), but it reduced glutathione (GSH) and superoxide dismutase (SOD) levels. Such alterations induced vascular dysfunction, tubular atrophy, interstitial fibrosis, and tubular apoptosis. This was evident secondary to an increase in urinary protein, serum creatinine, and blood urea nitrogen, ultimately leading to renal dysfunction. Conversely, HRW decreased levels of ROS and MDA while increasing the activity of GSH and SOD. This was accompanied by an improvement in vascular and renal function. Moreover, HRW significantly decreased the level of Keap1 and increased the expression of Nrf2, NADPH dehydrogenase quinone 1, and heme oxygenase 1. In conclusion, HRW restored the balance of redox status, suppressed oxidative stress damage, and improved kidney function induced by CsA via activation of the Keap1/Nrf2 signaling pathway.

Fetal Intrapericardial Teratomas: An Update.

Fetal intrapericardial teratomas are rare and benign cardiac tumors. By comprehensive literature retrieval of the pertinent articles published since 2000, 49 articles with 61 cases of intrapericadial teratomas were recruited into this study. The intrapericardial teratomas were found during pregnancy in 55 cases (fetal group), while the tumors were detected until neonatal period in 6 cases (neonatal group). In the fetal group, 15 cases were critical with fetal/neonatal respiratory distress or cardiac tamponade. Antenatal treatments including centesis, shunt placement, open fetal surgery and the ex utero intrapartum treatment were required in 24 (43.6%) fetal cases. Postnatal intubation was required in 19 cases with 18 of them having immediate intubation after birth. Postnatal tumor resection was performed in 41 (95.3%) cases. In neonatal group, 4 neonates had respiratory distress and/or cardiac tamponade. Neonatal intubation was required in 1 (16.7%) patient. Surgical tumor resection was performed in all 6 patients. A comparison between the fetal and neonatal groups revealed that the fetal group was associated with higher refractory effusions while the neonatal group had a higher incidence of respiratory distress. Although the all cause death rate was higher in the fetal group than in the neonatal (25.5 vs. 0%), but lack of a statistical significance. Antenatal treatments for fetal intrapericardial teratomas are feasible but carry higher risks in comparison to neonatal cases.

[Transcriptome analysis of "Langmei" fruits and key enzyme genes structure and function prediction involved in citric acid biosynthesis].

Prunus mume "Langmei" is a relict tree species, which fruit has good medicinal value. To understand the biosynthesis pathway of citric acid, the Illumina HiSeq XTen high-throughput sequencing technology was used to get the transcriptome from "Langmei". A total of 38 936 unigenes were obtained by assembling the fruit transcripts, of which 28 311 unigenes were successfully annotated in public databases, 15 193 unigenes were mapped to 265 KEGG metabolic pathways, and 18 908 unigenes were classified into 59 GO functional subclasses, 103 unigenes encoding 15 key enzymes involved in citric acid synthesis pathway were identified and analyzed. The structural model of citrate synthetase in "Langmei" showed that it was a homodimer and the secondary structure of each monomer was mainly composed of alpha helixes. Moreover, the residues in the active site of the citrate synthetase were highly conserved. This study provides a valuable resource for identifying candidate genes involved in the citric acid biosynthesis pathway, and will promote the development and sustainable utilization of genetic resources of "Langmei".

Activation of death-associated protein kinase 1 promotes neutrophil apoptosis to accelerate inflammatory resolution in acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is a uniform progression of overwhelming inflammation in lung tissue with extensive infiltration of inflammatory cells. Neutrophil apoptosis is thought to be a significant process in the control of the resolution phase of inflammation. It has been proved that 5-Aza-2'-deoxycytidine (Aza) can inhibit cancer by activating death-associated protein kinase 1 (DAPK1) to promote apoptosis. However, the effect of DAPK1 on neutrophil apoptosis is unclear, and research on the role of Aza in inflammation is lacking. Here, we investigated whether Aza can regulate DAPK1 expression to influence the fate of neutrophils in ARDS. In vitro, we stimulated neutrophil-like HL-60 (dHL-60) cells with different concentrations of Aza for different durations and used RNA interference to up- or downregulate DAPK1 expression. We observed that culturing dHL-60 cells with Aza increased apoptosis by inhibiting NF-κB activation to modulate the expression of Bcl-2 family proteins, which was closely related to the levels of DAPK1. In vivo, ARDS was evoked by intratracheal instillation of lipopolysaccharide (LPS; 3 mg/kg). One hour after LPS administration, mice were treated with Aza (1 mg/kg, i.p.). To inhibit DAPK1 expression, mice were intraperitoneally injected with a DAPK1 inhibitor. Aza treatment accelerated inflammatory resolution in LPS-induced ARDS by suppressing pulmonary edema, alleviating lung injury and decreasing the infiltration of inflammatory cells in bronchoalveolar lavage fluid (BALF). Moreover, Aza reduced the production of proinflammatory cytokines. However, administration of the DAPK1 inhibitor attenuated the protective effects of Aza. Similarly, the proapoptotic function of Aza was prevented when DAPK1 was inhibited either in vivo or in vitro. In summary, Aza promotes neutrophil apoptosis by activating DAPK1 to accelerate inflammatory resolution in LPS-induced ARDS. This study provides the first evidence that Aza prevents LPS-induced neutrophil survival by modulating DAPK1 expression.

Cardiac and vascular causes of persistent fever: A systematic review.

Fever of unknown origin refers to a prolonged fever with an unknown cause despite adequate medical evaluations. This condition often leads to unnecessary extensive laboratory work-ups and antimicrobial therapies. The atypical presentations often cause a delayed diagnosis and an improper treatment with an increased morbidity rate. In cardiac surgical patients, fever of unknown origin remains an intriguing problem during the diagnostic process of cardiac surgical diseases. Cardiac myxoma or aortic dissection are often misdiagnosed when patients present with fever of unknown origin as an onset symptom. Under such circumstances, medical examinations by echocardiography and chest computed tomography, particularly fluorodeoxyglucose-positron emission tomography/computed tomography, have been proved crucial for early diagnosis. A better understanding of the clinical features of cardiac surgical disorders presenting with fever of unknown origin would facilitate early diagnosis of fever of unknown origin. A further decision-making of prompt treatment of choices of a cardiac operation is important for improving patients' outcomes.

Thermally Reduced Nanoporous Graphene Oxide Membrane for Desalination.

Graphene-based laminar membranes open new avenues for water treatment; in particular, reduced graphene oxide (rGO) membranes with high stability in aqueous solutions are gaining increased attention for desalination. However, the low water permeability of these membranes significantly limits their applications. In this study, the water permeability of thermally reduced GO membrane was increased by a factor of 26 times by creating in-plane nanopores with an average diameter of ∼3 nm and a high density of 2.89 × 1015 m-2 via H2O2 oxidation. These in-plane nanopores provide additional transport channels and shorten the transport distance for water molecules. Meanwhile, salt rejection of this membrane is dominated by both the Donnan effect and the size exclusion of the interspaces. Besides, the water permeability and salt rejection of the thermally reduced nanoporous GO membrane can also be simply tuned by adjusting the thermal treatment time and membrane thickness. Additionally, the fabricated membrane exhibited a relatively stable rejection of Na2SO4 during the long-term testing. This work demonstrates a novel and effective strategy for fabricating high-performance laminar rGO membranes for desalination applications.