Aldehydes alter TGF-ß signaling and induce obesity and cancer.

Obesity and fatty liver diseases-metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH)-affect over one-third of the global population and are exacerbated in individuals with reduced functional aldehyde dehydrogenase 2 (ALDH2), observed in approximately 560 million people. Current treatment to prevent disease progression to cancer remains inadequate, requiring innovative approaches. We observe that Aldh2-/- and Aldh2-/-Sptbn1+/- mice develop phenotypes of human metabolic syndrome (MetS) and MASH with accumulation of endogenous aldehydes such as 4-hydroxynonenal (4-HNE). Mechanistic studies demonstrate aberrant transforming growth factor ß (TGF-ß) signaling through 4-HNE modification of the SMAD3 adaptor SPTBN1 (ß2-spectrin) to pro-fibrotic and pro-oncogenic phenotypes, which is restored to normal SMAD3 signaling by targeting SPTBN1 with small interfering RNA (siRNA). Significantly, therapeutic inhibition of SPTBN1 blocks MASH and fibrosis in a human model and, additionally, improves glucose handling in Aldh2-/- and Aldh2-/-Sptbn1+/- mice. This study identifies SPTBN1 as a critical regulator of the functional phenotype of toxic aldehyde-induced MASH and a potential therapeutic target.

Prognostic and clinicopathological significance of fibrinogen-to-albumin ratio (FAR) in patients with breast cancer: a meta-analysis.

BACKGROUND: The fibrinogen-to-albumin ratio (FAR) has been extensively studied for its role in predicting the prognosis of breast cancer (BC) patients; however, existing findings are conflicting. Therefore, this meta-analysis was conducted to identify the significance of FAR in predicting BC prognosis. METHODS: We searched PubMed, Embase, Web of Science, Cochrane Library, and China National Knowledge Infrastructure databases until May 25, 2024. The value of FAR for predicting overall survival (OS) and disease-free survival (DFS) in BC was examined by calculating the combined hazard ratios (HRs) and 95% confidence intervals (CIs). Correlations between FAR and clinicopathological factors were analyzed using combined odds ratios (ORs) and 95% CIs. RESULTS: Eight studies involving 4094 patients were included in this work. As shown by our combined data, increased FAR significantly predicted poor OS (HR = 2.84, 95% CI = 1.83-4.39, p < 0.001) and poor DFS (HR = 2.43, 95% CI = 1.66-3.58, p < 0.001) of BC. Moreover, the combined data showed that increased FAR was significantly correlated with age ≥ 50 years (OR = 2.04, 95% CI = 1.37-3.04, p < 0.001), stage III cancer (OR = 1.53, 95% CI = 1.04-2.27, p = 0.033), and the presence of lymph node metastases (OR = 1.33, 95% CI = 1.11-1.61, p = 0.002). Nonetheless, FAR was not significantly associated with tumor size, ER/PR/HER-2 status, or lymphovascular invasion in patients with BC. CONCLUSION: In this meta-analysis, higher FAR was significantly associated with unfavorable OS and DFS in patients with BC and significantly correlated with several features predictive of cancer development in BC.

Germline BARD1 variants predispose to mesothelioma by impairing DNA repair and calcium signaling.

We report that ~1.8% of all mesothelioma patients and 4.9% of those younger than 55, carry rare germline variants of the BRCA1 associated RING domain 1 (BARD1) gene that were predicted to be damaging by computational analyses. We conducted functional assays, essential for accurate interpretation of missense variants, in primary fibroblasts that we established in tissue culture from a patient carrying the heterozygous BARD1V523A mutation. We found that these cells had genomic instability, reduced DNA repair, and impaired apoptosis. Investigating the underlying signaling pathways, we found that BARD1 forms a trimeric protein complex with p53 and SERCA2 that regulates calcium signaling and apoptosis. We validated these findings in BARD1-silenced primary human mesothelial cells exposed to asbestos. Our study elucidated mechanisms of BARD1 activity and revealed that heterozygous germline BARD1 mutations favor the development of mesothelioma and increase the susceptibility to asbestos carcinogenesis. These mesotheliomas are significantly less aggressive compared to mesotheliomas in asbestos workers.

Defects and Defect Passivation in Perovskite Solar Cells.

Perovskite solar cells have made significant strides in recent years. However, there are still challenges in terms of photoelectric conversion efficiency and long-term stability associated with perovskite solar cells. The presence of defects in perovskite materials is one of the important influencing factors leading to subpar film quality. Adopting additives to passivate defects within perovskite materials is an effective approach. Therefore, we first discuss the types of defects that occur in perovskite materials and the mechanisms of their effect on performance. Then, several types of additives used in perovskite solar cells are discussed, including ionic compounds, organic molecules, polymers, etc. This review provides guidance for the future development of more sustainable and effective additives to improve the performance of solar cells.

Role of durotomy on function outcome, tissue sparing, inflammation, and tissue stiffness after spinal cord injury in rats.

Currently, there is a lack of effective treatments for spinal cord injury (SCI), a debilitating medical condition associated with enduring paralysis and irreversible neuronal damage. Extradural decompression of osseous as well as soft tissue components has historically been the principal objective of surgical procedures. Nevertheless, this particular surgical procedure fails to tackle the intradural compressive alterations that contribute to secondary SCI. Here, we propose an early intrathecal decompression strategy and evaluate its role on function outcome, tissue sparing, inflammation, and tissue stiffness after SCI. Durotomy surgery significantly promoted recovery of hindlimb locomotor function in an open-field test. Radiological analysis suggested that lesion size and tissue edema were significantly reduced in animals that received durotomy. Relative to the group with laminectomy alone, the animals treated with a durotomy had decreased cavitation, scar formation, and inflammatory responses at 4 weeks after SCI. An examination of the mechanical properties revealed that durotomy facilitated an expeditious restoration of the injured tissue's elastic rigidity. In general, early decompressive durotomy could serve as a significant strategy to mitigate the impairments caused by secondary injury and establish a more conducive microenvironment for prospective cellular or biomaterial transplantation.

Detection of hepatocellular carcinoma methylation markers in salivary DNA.

BACKGROUND: Alterations to DNA methylation have been identified in both hepatocellular carcinoma (HCC) tumor and circulating DNA from affected individuals. These markers have potential utility in HCC screening. Adherence to HCC screening is poor and acceptable HCC screening tests are needed. METHODS: A feasibility study was performed on a subset of case patients and control subjects from a prior study of risk factors for HCC. Case patients (n=12) included adults aged 47-85 years with a first diagnosis of HCC between 2011 and 2016 and without viral hepatitis. Control subjects (n=12) were matched on age, sex, and state of residence. Participants provided saliva samples for DNA genotyping. Log fold change in salivary DNA methylation at 1359 CpG sites representing 25 candidate genes previously associated with HCC was compared across case patients and control subjects. RESULTS: The quantity of DNA ranged from 9.65 to 257.79 µg. The purity of DNA isolates was good, with mean OD260/280 ratio of 1.78 (SD: 0.14). Of 25 candidate genes, 16 had at ≥1 CpG site with detectable differences in methylation across HCC case patients and control subjects. Sites differentially methylated in HCC case patients included genes encoding tumor suppressors (PRDM2, RUNX3, p15/16, and RASSF1/5), regulators of cell cycle progression (DAPK1 and TP73), and DNA repair (MGMT and GSTP1). No associations met the significance threshold 3.7 × 10-5 required for multiple comparisons. CONCLUSIONS: Salivary DNA may be a feasible alternative to blood samples in the era of novel DNA-based screening tests for HCC. The ease of saliva-based testing supports further investigation of its potential.

Machine learning-based cluster analysis of immune cell subtypes and breast cancer survival.

Host immunity involves various immune cells working in concert to achieve balanced immune response. Host immunity interacts with tumorigenic process impacting disease outcome. Clusters of different immune cells may reveal unique host immunity in relation to breast cancer progression. CIBERSORT algorithm was used to estimate relative abundances of 22 immune cell types in 3 datasets, METABRIC, TCGA, and our study. The cell type data in METABRIC were analyzed for cluster using unsupervised hierarchical clustering (UHC). The UHC results were employed to train machine learning models. Kaplan-Meier and Cox regression survival analyses were performed to assess cell clusters in association with relapse-free and overall survival. Differentially expressed genes by clusters were interrogated with IPA for molecular signatures. UHC analysis identified two distinct immune cell clusters, clusters A (83.2%) and B (16.8%). Memory B cells, plasma cells, CD8 positive T cells, resting memory CD4 T cells, activated NK cells, monocytes, M1 macrophages, and resting mast cells were more abundant in clusters A than B, whereas regulatory T cells and M0 and M2 macrophages were more in clusters B than A. Patients in cluster A had favorable survival. Similar survival associations were also observed in other independent studies. IPA analysis showed that pathogen-induced cytokine storm signaling pathway, phagosome formation, and T cell receptor signaling were related to the cell type clusters. Our finding suggests that different immune cell clusters may indicate distinct immune responses to tumor growth, suggesting their potential for disease management.

Circular RNAs: biology and clinical significance of breast cancer.

Circular RNAs (circRNAs) are novel noncoding RNAs with covalently closed-loop structures that can regulate eukaryotic gene expression. Due to their stable structure, circRNAs are widely distributed in the cytoplasm and have important biological functions, including as microRNA sponges, RNA-binding protein conjugates, transcription regulators, and translation templates. Breast cancer is among the most common malignant cancers diagnosed in women worldwide. Despite the development of comprehensive treatments, breast cancer still has high mortality rates. Recent studies have unmasked critical roles for circRNAs in breast cancer as regulators of tumour initiation, progression, and metastasis. Further, research has revealed that some circRNAs have the potential for use as diagnostic and prognostic biomarkers in clinical practice. Herein, we review the biogenesis and biological functions of circRNAs, as well as their roles in different breast cancer subtypes. Moreover, we provide a comprehensive summary of the clinical significance of circRNAs in breast cancer. CircRNAs are believed to be a hot focus in basic and clinical research of breast cancer, and innovative future research directions of circRNAs could be used as biomarkers, therapeutic targets, or novel drugs.Abbreviations: CeRNA: Competitive endogenous RNA; ciRNA: Circular intronic RNA; circRNA: Circular RNA; EIciRNA: Exon-intron circRNA; EMT: Epithelial-mesenchymal transition; IRES: Internal ribosome entry site; lncRNA: Long non-coding RNA; miRNA: MicroRNA; MRE: MiRNA response element; ncRNA: Non-coding RNA; RBP: RNA-binding protein; RNA-seq: RNA sequencing; RT-PCR: Reverse transcription-polymerase chain reaction.

Effectiveness of various COVID-19 vaccine regimens among 10.4 million patients from the National COVID Cohort Collaborative during Pre-Delta to Omicron periods - United States, 11 December 2020 to 30 June 2022.

OBJECTIVE: This study reports the vaccine effectiveness (VE) of COVID-19 vaccine regimens in the United States, based on the National COVID Cohort Collaborative (N3C) database. METHODS: Data from 10.4 million adults, enrolled in the N3C from 11 December 2020 to 30 June 2022, were analyzed. VE against infection and death outcomes were evaluated across 13 vaccine regimens in recipient cohorts during the Pre-Delta, Delta, and Omicron periods. VE was estimated as (1-odds ratio) × 100% by multivariate logistic regression, using the unvaccinated cohort as reference. RESULTS: Natural immunity showed a highly protective effect (70.33%) against re-infection, but the mortality risk among the unvaccinated population was increased after re-infection; vaccination following infection reduced the risk of re-infection and death. mRNA-1273 full vaccination plus mRNA-1273 booster showed the highest anti-infection effectiveness (47.59%) (95% CI, 46.72-48.45) in the overall cohort. In the type 2 diabetes cohort, VE against infection was highest with BNT162b2 full vaccination plus mRNA-1273 booster (61.19%) (95% CI, 53.73-67.75). VE against death was also highest with BNT162b2 full vaccination plus mRNA-1273 booster (89.56%) (95% CI, 85.75-92.61). During the Pre-Delta period, all vaccination regimens showed an anti-infection effect; during the Delta period, only boosters, mixed vaccines, and Ad26.COV2.S vaccination exhibited an anti-infection effect; during the Omicron period, none of the vaccine regimens demonstrated an anti-infection effect. Irrespective of the variant period, even a single dose of mRNA vaccine offered protection against death, thus demonstrating survival benefit, even in the presence of infection or re-infection. Similar patterns were observed in patients with type 2 diabetes. CONCLUSIONS: Although the anti-infection effect declined as SARS-CoV-2 variants evolved, all COVID-19 mRNA vaccines had sustained effectiveness against death. Vaccination was crucial for preventing re-infection and reducing the risk of death following SARS-CoV-2 infection.

Fast Self-Healing at Room Temperature in Diels-Alder Elastomers.

Despite being primarily categorized as non-autonomous self-healing polymers, we demonstrate the ability of Diels-Alder polymers to heal macroscopic damages at room temperature, resulting in complete restoration of their mechanical properties within a few hours. Moreover, we observe immediate partial recovery, occurring mere minutes after reuniting the fractured surfaces. This fast room-temperature healing is accomplished by employing an off-stoichiometric maleimide-to-furan ratio in the polymer network. Through an extensive investigation of seven Diels-Alder polymers, the influence of crosslink density on self-healing, thermal, and (thermo-)mechanical performance was thoroughly examined. Crosslink density variations were achieved by adjusting the molecular weight of the monomers or utilizing the off-stoichiometric maleimide-to-furan ratio. Quasistatic tensile testing, dynamic mechanical analysis, dynamic rheometry, differential scanning calorimetry, and thermogravimetric analysis were employed to evaluate the individual effects of these parameters on material performance. While lowering the crosslink density in the polymer network via decreasing the off-stoichiometric ratio demonstrated the greatest acceleration of healing, it also led to a slight decrease in (dynamic) mechanical performance. On the other hand, reducing crosslink density using longer monomers resulted in faster healing, albeit to a lesser extent, while maintaining the (dynamic) mechanical performance.

Studies on the interaction mechanism between xanthine oxidase and osmundacetone: Molecular docking, multi-spectroscopy and dynamical simulation.

Xanthine oxidase (XO) is a key enzyme in uric acid production, and its molybdopterin (Mo-Pt) domain is an important catalytic center when xanthine and hypoxanthine are oxidated. It is found that the extract of Inonotus obliquus has an inhibitory effect on XO. In this study, five key chemical compounds were initially identified using liquid chromatography-mass spectrometry (LC-MS), and two compounds, osmundacetone ((3E)-4-(3,4-dihydroxyphenyl)-3-buten-2-one) and protocatechuic aldehyde (3,4-dihydroxybenzaldehyde), were screened as the XO inhibitors by ultrafiltration technology. Osmundacetone bound XO strongly and competitively inhibited XO with a half-maximal inhibitory concentration of 129.08 ± 1.71 µM, and its inhibition mechanism, was investigated. Osmundacetone and XO via static quenching and spontaneously bound with XO with high affinity, primarily via hydrophobic interactions and hydrogen bonds. Molecular docking studies showed that osmundacetone was inserted into the Mo-Pt center and interacted with hydrophobic residues of Phe911, Gly913, Phe914, Ser1008, Phe1009, Thr1010, Val1011, and Ala1079 of XO. In summary, these findings suggest that provide theoretical basis for the research and development of XO inhibitors from Inonotus obliquus.

Global scientific trends in laparoscopy and gastric cancer in the 21st century: A bibliometric and visual mapping analysis.

Aims: To use visual mapping and bibliometrics to analyze and summarize the valuable information on laparoscopic surgery for gastric cancer (GC) obtained in the last 20 years, so as to determine the research hotspots and trends in this field. Methods: We screened all literature on laparoscopic surgery for GC in the Web of Science published from 2000 to 2022 and analyzed the research hotspots and trends in this field using VOSviewer. Results: A total of 2796 reports from 61 countries and regions were selected. Japanese researchers published the most papers (n=946), followed by those from China (n=747) and South Korea (n=557). Papers from Japan also had the most citations (n=21,836). Surgical Endoscopy and Other Interventional Techniques published the most reports on laparoscopic surgery for GC (n=386) and also had the highest total number of citations (n=11,076), making this journal the most authoritative in this field. Among the institutions, researchers from Seoul National University in South Korea had the highest numbers of published papers and citations. The keywords of the articles could be divided into five categories: surgical methods for GC, short-term and long-term efficacy of laparoscopic surgery, guiding role of laparoscopy in the treatment of advanced GC, diagnosis and treatment of early gastric cancer (EGC), and lymph node dissection. Keywords such as "laparoscopic proximal gastrectomy", "surgical outcomes", and "esophagogastric junction" have emerged recently, and relevant studies on laparoscopic surgery for adenocarcinoma of esophagogastric junction(AEG)have gradually become a hot topic and trend. Conclusion: This study adopted bibliometric analysis to identify the current research hotspots and research trends in the field of laparoscopic surgery for GC. Five main research hotspots of laparoscopic surgery for GC were also identified. Laparoscopic surgery for AEG may become an important research focus in the future.

Anti-gout activity and the interaction mechanisms between Sanghuangporus vaninii active components and xanthine oxidase.

Xanthine oxidase (XO) plays a critical role in the progression of gout. We showed in a previous study that Sanghuangporus vaninii (S. vaninii), a perennial, medicinal, and edible fungus traditionally used to treat various symptoms, contains XO inhibitors. In the current study, we isolated an active component of S. vaninii using high performance countercurrent chromatography and identified it as davallialactone using mass spectrometry with 97.726 % purity. A microplate reader showed that davallialactone had mixed inhibition of XO activity with a half-inhibitory concentration value of 90.07 ± 2.12 µM. In addition, the collision between davallialactone and XO led to fluorescence quenching and conformational changes in XO, which were mainly driven by hydrophobicity and hydrogen bonding. Molecular simulations further showed that davallialactone was located at the center of the molybdopterin (Mo-Pt) of XO and interacted with amino acid residues Phe798, Arg912, Met1038, Ala1078, Ala1079, Gln1194, and Gly1260, suggesting that entering the enzyme-catalyzed reaction was unfavorable for the substrate. We also observed face-to-face π-π interactions between the aryl ring of davallialactone and Phe914. Cell biology experiments indicated that davallialactone reduced the expression of the inflammatory factors, tumor necrosis factor alpha and interleukin-1 beta (P < 0.05), can effectively alleviate cellular oxidative stress. This study showed that davallialactone significantly inhibits XO and has the potential to be developed into a novel medicine to prevent hyperuricemia and treat gout.

Dynamic changes in mechanical properties of the adult rat spinal cord after injury.

Spinal cord injury (SCI), a debilitating medical condition that can cause irreversible loss of neurons and permanent paralysis, currently has no cure. However, regenerative medicine may offer a promising treatment. Given that numerous regenerative strategies aim to deliver cells and materials in the form of tissue-engineered therapies, understanding and characterising the mechanical properties of the spinal cord tissue is very important. In this study, we have systematically characterised the spatiotemporal changes in elastic stiffness (elastic modulus, Pa) and viscosity (drop in peak force, %) of injured rat thoracic spinal cord tissues at distinct time points after crush injury using the indentation technique. Our results demonstrate that in comparison with uninjured spinal cord tissue, the injured tissues exhibited lower stiffness (median 3281 Pa versus 9632 Pa; P < 0.001) but demonstrated elevated viscosity (median 80% versus 57%; P < 0.001) at 3 days postinjury. Between 4 and 6 weeks after SCI, the overall viscoelastic properties of injured tissues returned to baseline values. At 12 weeks after SCI, in comparison with uninjured tissue, the injured spinal cord tissues displayed a significant increase in both elasticity (median 13698 Pa versus 9920 Pa; P < 0.001) and viscosity (median 64% versus 58%; P < 0.001). This work constitutes the first quantitative mapping of spatiotemporal changes in spinal cord tissue elasticity and viscosity in injured rats, providing a mechanical basis of the tissue for future studies on the development of biomaterials for SCI repair. STATEMENT OF SIGNIFICANCE: Spinal cord injury (SCI) is a devastating disease often leading to permanent paralysis. While enormous progress in understanding the molecular pathomechanisms of SCI has been made, the mechanical properties of injured spinal cord tissue have received considerably less attention. This study provides systematic characterization of the biomechanical evolution of rat spinal cord tissue after SCI using a microindentation test method. We find spinal cord tissue behaves significantly softer but more viscous immediately postinjury. As time passes, the lesion site gradually returns to baseline values and then displays pronounced increased viscoelastic properties. As host tissue mechanical properties are a crucial consideration for any biomaterial implanted into central nervous system, our results may have important implications for further studies of SCI repair.

Numerical Simulation Study on Flow and Heat Transfer of the Tungsten Crucible CVD Reactor.

In order to investigate the optimization of the performance and structure of a tungsten crucible CVD reactor, the CFD simulation method was used in this paper to simulate the internal flow of the tungsten crucible CVD reactor. The velocity distribution and temperature distribution in the reactor were obtained. The simulation results show that the axial and radial heat convection will occur between the susceptor and the outer wall surface, but the axial heat convection is more intense. Moreover, it was found that the temperature distribution in the CVD reactor was more uniform and reasonable when the upper gas inlet was applied, which was beneficial to the reduction and deposition processes of tungsten. The molar ratio of H2 to WF6 has a great influence on the deposition rate of tungsten, and excess H2 is not conducive to the deposition of tungsten. Thermal radiation has a great influence on the temperature distribution of CVD reactors. It cannot be neglected.

Antimicrobial Resistance Trends of the Most Common Causative Pathogens Associated with Community-acquired Respiratory Infections in China: 2009-2018.

Background: Emergence of antimicrobial resistance poses new challenges in the management of community acquired respiratory tract infections (CARTIs). Therefore, surveillance on the antimicrobial susceptibilities of common respiratory pathogens is valuable and guides empirical therapeutic choices in management of CARTIs. Objective: The objective of the current study is to summarize the antimicrobial resistance trends in common respiratory tract pathogens isolated from patients with CARTIs in China, over a 10-year period (2009-2018). Methods: Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis strains were collected from multicenter, and antimicrobial susceptibility testing was performed in the research central laboratory of each study period from 2009-2018. The pathogens that accounted for CARTIs in the adult population was considered and summarized. Results: From 2009-2018 a total of 3750 isolates were collected from 22 cities located across different regions of China. Among these the most common bacterial isolates include S. pneumoniae (53.7%) followed by H. influenza (32.4%), M. catarrhalis (13.9%). S. pneumoniae exhibited reduction in susceptibility and increase in resistance to penicillin, cephalosporins (cefaclor, cefuroxime, ceftriaxone) during the surveillance period. Invasive and noninvasive S. pneumoniae showed similar resistance. In the case of H. influenzae susceptibility to ß-lactam and ß-lactamase inhibitors (ampicillin, amoxicillin and AMC), SXT, clarithromycin and cephalosporins (cefuroxime, cefaclor, ceftazidime) was reduced over the past 10 years with an exception of ceftriaxone. Overall, moxifloxacin and levofloxacin have the highest susceptibility rates against S. pneumoniae (>95%) and H. influenza (>90%). M. catarrhalis exhibited susceptibility to almost all the tested antimicrobials. Conclusion: In China the 10-year trends showed a substantial increase in resistance to ß-lactam drugs and reduction in sensitivity. However, certain antimicrobial agents namely fluoroquinolones including moxifloxacin and levofloxacin maintained low resistance rates with better susceptibility. Further, with few exceptions decline in susceptibility rates to macrolides and cephalosporins was observed among the tested pathogens.

Corrigendum to "Prognostic Factors for COVID-19 Hospitalized Patients with Preexisting Type 2 Diabetes".

[This corrects the article DOI: 10.1155/2022/9322332.].

Clinical Manifestations of Pulmonary Mucormycosis in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation: A 21-Case Series Report and Literature Review.

Introduction: Mucormycosis is a rare, invasive disease caused by opportunistic pathogens related to the Mucorales order with high fatality rates in immunocompromised hosts, especially in recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Diagnosis and treatment of pulmonary mucormycosis in recipients of allo-HSCT remains challenging. Purpose: The aim of this study is to summarize and analyze the clinical features of pulmonary mucormycosis in recipients of allo-HSCT to explore further clinical research directions for this rare fungal infection in the particular populations. Methods: We retrospectively reviewed pulmonary mucormycosis in patients who received allo-HSCT in our hospital from January 2010 to December 2020. A total of 21 patients fulfilled the diagnostic criteria for pulmonary mucormycosis according to the European Organization for Research and Treatment of Cancer and Mycoses Study Group (EORTC/MSG) criteria. Demographic and clinical data, mycological and histopathological records, and treatment and prognosis data were collected. Clinical variables were compared between survivors and nonsurvivors. The survival days of patients with and without graft-versus-host disease (GVHD) and hemoptysis were compared separately. Results: Most of the recipients of allo-HSCT were male patients with a mean age of 43 years. Acute myeloid leukemia (AML) was the most common primary hematologic malignancy. Extrapulmonary involvement accounted for 28.6%, of the cases, including central nervous system (n = 5) and skin and soft tissue (n = 1). The median time to infection was 96 days after allo-HSCT. Clinical presentations were nonspecific, including fever (76.2%) and cough (85.7%), as well as dyspnea (19.0%), chest pain (38.1%), and hemoptysis (61.9%). Ground-glass infiltrates (95.0%) and nodules/masses (80%) were the most common radiographic patterns on chest CT. The most common pathogen was Rhizopus (63.2%), and breakthrough infection accounted for 90.5%. Fifteen of the patients died within one year, and the median time from diagnosis to death was 47 days. Conclusion: Mucormycosis is a fatal infection disease. Opportunistic infections in recipients of allo-HSCT are mainly breakthrough infections and may have a seasonal distribution (summer and autumn) and more cases of death in autumn. The marked reversed halo sign can be seen both in the initial stage of infection and after antifungal treatment. In our case series, patients with pulmonary mucormycosis with extrapulmonary involvement 100% died within one year. There are more patients with GVHD before infection and hemoptysis in nonsurvivors than survivors within 100 days. Patients with GVHD before infection and hemoptysis have a shorter survival time than those without.

LncRNA ZNF582-AS1 Expression and Methylation in Breast Cancer and Its Biological and Clinical Implications.

Background: Long non-coding RNAs (lncRNAs) play an important role in cellular activities and functions, but our understanding of their involvement in cancer is limited. Methods: TCGA data on RNA expression and DNA methylation were analyzed for lncRNAs' association with breast cancer survival, using the Cox proportional hazard regression model. Fresh tumor samples and clinical information from 361 breast cancer patients in our study were used to confirm the TCGA finding on ZNF582-AS1. A RT-qPCR method was developed to measure ZNF582-AS1 expression. Survival associations with ZNF582-AS1 were verified with a meta-analysis. In silico predictions of molecular targets and cellular functions of ZNF582-AS1 were performed based on its molecular signatures and nucleotide sequences. Results:ZNF582-AS1 expression was lower in breast tumors than adjacent normal tissues. Low ZNF582-AS1 was associated with high-grade or ER-negative tumors. Patients with high ZNF582-AS1 had a lower risk of relapse and death. These survival associations were confirmed in a meta-analysis and remained significant after adjustment for tumor grade, disease stage, patient age, and hormone receptor status. Correlation analysis indicated the possible suppression of ZNF582-AS1 expression by promoter methylation. Bioinformatics interrogation of molecular signatures suggested that ZNF582-AS1 could suppress tumor cell proliferation via downregulating the HER2-mediated signaling pathway. Analysis of online data also suggested that HIF-1-related transcription factors could suppress ZNF582-AS1 expression, and the lncRNA might bind to hsa-miR-940, a known oncogenic miRNA in breast cancer. Conclusions: ZNF582-AS1 may play a role in suppressing breast cancer progression. Elucidating the lncRNA's function and regulation may improve our understanding of the disease.

Effects of Plantation Type and Soil Depth on Microbial Community Structure and Nutrient Cycling Function.

Declining soil quality and microecological imbalances were evaluated in larch plantations in this study. One potential solution to this problem is the cultivation of mixed coniferous and broad-leaved plantations. However, it is unclear whether and how soil microbial community structure and nutrient cycling function would be affected by mixed plantations and soil depths. In this study, we used high-throughput sequencing technology to investigate bacterial 16S and fungal ITS regions for comparisons of soil microbial diversity among plantation types (a Larix gmelinii pure plantation, a Fraxinus mandshurica pure plantation, a Larix-Fraxinus mixed plantation within the Larix row, the Fraxinus row, and between the Larix and Fraxinus rows) and soil depths (0-10, 10-20, and 20-40 cm). These data were used to evaluate variations in microbial communities and nutrient cycling function with the determining environmental factors. Our results indicated that bacteria had a stronger spatial dependence than did fungi, while plantation types significantly affected the fungal community. The relative abundance of Gaiellaceae, as well as bacterial ligninolysis, nitrate ammonification, and nitrite ammonification functions significantly increased with increasing soil depth. Compared with other plantations, the relative abundance of Inocybaceae was significantly higher in the Larix plantation. Distance-based redundancy analysis (db-RDA) showed that Gaiellaceae and Inocybaceae abundances were positively correlated with ammonium nitrogen content, available phosphorus content, and phosphatase activity. Our findings indicate that variations in soil available phosphorus are closely related to the relative abundances of Gaiellaceae at different soil depths and Inocybaceae in different plantation types. Mixed plantations might change the availability of soil phosphorus by controlling the relative abundance of Inocybaceae. We recommend that fungal community changes be considered in the sustainable management of mixed plantations.