Computational dissection of genetic variation modulating the response of multiple photosynthetic phenotypes to the light environment.

BACKGROUND: The expression of biological traits is modulated by genetics as well as the environment, and the level of influence exerted by the latter may vary across characteristics. Photosynthetic traits in plants are complex quantitative traits that are regulated by both endogenous genetic factors and external environmental factors such as light intensity and CO2 concentration. The specific processes impacted occur dynamically and continuously as the growth of plants changes. Although studies have been conducted to explore the genetic regulatory mechanisms of individual photosynthetic traits or to evaluate the effects of certain environmental variables on photosynthetic traits, the systematic impact of environmental variables on the dynamic process of integrated plant growth and development has not been fully elucidated. RESULTS: In this paper, we proposed a research framework to investigate the genetic mechanism of high-dimensional complex photosynthetic traits in response to the light environment at the genome level. We established a set of high-dimensional equations incorporating environmental regulators to integrate functional mapping and dynamic screening of gene‒environment complex systems to elucidate the process and pattern of intrinsic genetic regulatory mechanisms of three types of photosynthetic phenotypes of Populus simonii that varied with light intensity. Furthermore, a network structure was established to elucidate the crosstalk among significant QTLs that regulate photosynthetic phenotypic systems. Additionally, the detection of key QTLs governing the response of multiple phenotypes to the light environment, coupled with the intrinsic differences in genotype expression, provides valuable insights into the regulatory mechanisms that drive the transition of photosynthetic activity and photoprotection in the face of varying light intensity gradients. CONCLUSIONS: This paper offers a comprehensive approach to unraveling the genetic architecture of multidimensional variations in photosynthetic phenotypes, considering the combined impact of integrated environmental factors from multiple perspectives.

Clinical characteristics of acute myeloid leukaemia patients with a large number of azurophilic granules: A single-centre retrospective study.

Large amounts of azurophilic granules are considered to be a morphological feature of acute promyelocytic leukaemia (APL). However, a small percentage of acute myeloid leukaemia (AML) patients also have a large number of azurophilic granules. A large cohort of 3210 AML patients in our hospital was screened to identify AML patients who had a large number of azurophilic granules. The clinical parameters of these patients were collected and compared with typical AML patients (control Group 1) and APL patients (control Group 2). The incidence of AML with a large number of azurophilic granules was 1.26%. The fibrinogen and D-dimer levels of patients in the study group were more similar to those of patients in control Group 2, as was the incidence of bleeding events. Additionally, patients in the study group had higher FLT3-ITD and NPM1 mutation rates than patients in control Group 1. Finally, patients in the study group had a higher 30-day mortality rate than those in control Group 2 (24.2% vs. 9.09%) and showed a higher 30-day mortality trend than those in control Group 1. Therefore, we should pay more attention to the prevention of coagulation dysfunction and bleeding events for these patients.

Contribution of cuproptosis and Cu metabolism-associated genes to chronic obstructive pulmonary disease.

Airway epithelial cell injury plays a crucial role in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, a novel form of Cu-induced programmed cell death known as cuproptosis has not yet been thoroughly investigated in the context of COPD. Clinical reports have suggested that high copper exposure may increase the risk of COPD. In this study, we aimed to determine the expression and potential functions of cuproptosis-related genes and genes associated with copper metabolism in COPD. We initially identified 52 copper metabolism-related genes based on a review of the literature. Subsequently, we calculated the expression levels of these genes using data from four GEO datasets. To gain insights into the activated signalling pathways and underlying mechanisms in COPD patients, we conducted Gene Ontology (GO) and KEGG pathway analyses, examined protein-protein interactions, and performed weighted correlation network analysis. Our findings revealed that 18 key copper metabolism-related genes, including 5 cuproptosis-related genes, were significantly enriched in signalling pathways and biological processes associated with the development of COPD. Further analysis of clinical data and animal experiments confirmed the high expression of certain cuproptosis key regulators, such as DLD and CDKN2A, in both healthy smokers and COPD smokers. Additionally, these regulators exhibited abnormal expression in a COPD rat model. Notably, copper content was found to be elevated in the lung tissues of COPD rats, suggesting its potential involvement in cuproptosis. These findings provide an experimental foundation for further research into the role of cuproptosis in COPD. Targeting copper metabolism-related genes may represent an effective approach for the treatment of COPD.

Cytokine profiles in patients with newly diagnosed diffuse large B-cell lymphoma: IL-6 and IL-10 levels are associated with adverse clinical features and poor outcomes.

BACKGROUND: The development of diffuse large B-cell lymphoma (DLBCL), a prevalent subgroup of non-Hodgkin lymphoma (NHL), potentially involves various cytokines. We aimed to determine the correlation between deregulated serum levels of cytokines and clinical features and investigate their impact on the prognosis of patients with DLBCL. METHODS: We conducted a retrospective study of 77 patients with newly diagnosed DLBCL to explore the relationships between different cytokines, adverse clinical features, and poor outcomes. The Mann-Whitney U test was used to compare the cytokine profiles between patients with DLBCL and healthy controls. The Kaplan-Meier method was used to analyze the probability of survival, and the log-rank tests were used to evaluate the differences between survival curves. The Cox proportional hazards regression model was used to performed univariate and multivariate analyses to evaluate prognostic variables for survival analyze. RESULTS: Serum levels of interleukin-2 (IL-2), tumor necrosis factor (TNF)-α, IL-6, IL-10, and IFN-γ were significantly elevated in patients with untreated DLBCL. Serum levels of IL-6 and IL-10 were significantly higher in patients with an International Prognostic Index (IPI) of 3-5, bone marrow involvement, serum levels of LDH ≥ 250 U/L, and ß2-microglobulin (ß2-MG) levels ≥ 2.3 mg/L. Patients with B symptoms only had higher serum IL-10 levels, whereas patients with a partial response or no response to treatment had significantly elevated serum levels of IL-6 as well as IL-10. Significant positive correlations were observed between the levels of IL-6 and IL-10 with those of ß2-MG and LDH. Patients with levels of IL-6 ≥ 4.5 or IL-10 ≥ 5.0 pg/mL, as well as combined elevated IL-6 and IL-10 levels, exhibited shorter progression-free survival and overall survival. Additionally, univariate and multivariate analyses revealed that serum levels of IL-6 ≥ 4.5 pg/mL and IL-10 ≥ 5.0 pg/mL and IPI 3-5 were independent prognostic factors for relapse and survival in patients with DLBCL. CONCLUSIONS: Pre-treatment serum IL-6 and IL-10 levels in patients with newly diagnosed DLBCL might be powerful markers for determining treatment response and predicting the prognosis of DLBCL.

Robiginitalea aurantiaca sp. nov. and Algoriphagus sediminis sp. nov., isolated from coastal sediment.

Two novel rod-shaped, Gram-stain-negative, aerobic and non-motile bacterial strains, designated M39T and C2-7T, were isolated from the coastal sediment of Xiaoshi Island, Weihai, PR China. Growth of strain M39T occurred at 15-37 °C, at pH 6.0-9.0 and in the presence of 1.0-9.0 % (w/v) NaCl. Strain C2-7T grew at 15-40 °C, at pH 6.0-8.0 and in the presence of 0.5-8.0 % (w/v) NaCl. Phylogenetic analysis based 16S rRNA gene sequences revealed that strains M39T and C2-7T belong to the phylum Bacteroidota. Based on the results of 16S rRNA gene sequence analysis, the closest relative of strain M39T was Robiginitalea marina KCTC 92035T (95.4 %), and the closest relative of strain C2-7T was Algoriphagus namhaensis DPG-3T (97.0 %). The percentage of conserved protein and average nucleotide identity values between strain M39T and some species of the genus Robiginitalea were 66.9-77.6% and 69.3-71.0 %, respectively, while those between strain C2-7T and some species of the genus Algoriphagus were 68.0-70.1% and 56.1-72.6 %, respectively. The major cellular fatty acids (>10 %) of strain M39T consisted of iso-C15 : 1 F, iso-C15 : 0 and iso-C17 : 0 3-OH, while those of strain C2-7T were iso-C15 : 0 and C16 : 1 ω7c/C16 : 1 ω6c. MK-6 was the only respiratory quinone that was compatible with the genus of strain M39T. The predominant menaquinone of strain C2-7T was MK-7. The major polar lipids of strain M39T were phosphatidylethanolamine and glycolipids, and those of strain C2-7T were phosphatidylethanolamine, one unidentified aminolipid and four unidentified lipids. The DNA G+C contents of strains M39T and C2-7T were 46.9 and 40.8 mol%, respectively. Based upon the results presented in this study, strains M39T and C2-7T represent novel species of the genera Robiginitalea and Algoriphagus, respectively, for which the names Robiginitalea aurantiaca sp. nov. and Algoriphagus sediminis sp. nov. are proposed with the type strains M39T (=MCCC 1H00498T=KCTC 92014T) and C2-7T (=MCCC 1H00414T=KCTC 92027T).

Winogradskyella vincentii sp. nov. and Winogradskyella alexanderae sp. nov., two novel bacteria isolated from intertidal sediment.

Two novel Gram-stain-negative, facultative anaerobic, chemoheterotrophic, non-motile and rod-shaped strains were isolated from intertidal sediment sampled at Xiaoshi Island, Weihai, PR China. Full sequence analysis of the 16S rRNA genes showed that the two strains were closely related to members of the genus Winogradskyella and the phylogenetic similarities to their closest relative, Winogradskyella aquimaris, were 96.7 and 95.8 %, respectively. The DNA G+C contents of strains 2Y89T and D23T were 33.3 and 35.1 mol%, respectively. The respiratory quinone detected in both strains was MK-6. The major fatty acids detected in strain 2Y89T were iso-C15 : 0 and iso-C15 : 1G, and in strain D23T they were iso-C15 : 1G, iso-C15 : 0 and iso-C17 : 03-OH. The principal polar lipids of strain 2Y89T mainly included phosphatidylethanolamine, aminoglycolipids, unidentified aminolipids, unidentified glycolipids and unidentified lipids; strain D23T was the same as strain 2Y89T except that it did not contain aminoglycolipids. Based on the phenotypic, chemical taxonomic, genotypic and phylogenetic features established in this study, we suggest that the new strains represent two novel species of the genus Winogradskyella, for which the names Winogradskyella vincentii sp. nov. (type strain 2Y89T=MCCC 1H00477T=KCTC 92034T) and Winogradskyella alexanderae sp. nov. (type strain D23T=MCCC 1H00462T=KCTC 92023T) are proposed.

Brumimicrobium oceani sp. nov., isolated from coastal sediment saline lake and environmental adaptability analysis.

A novel Gram-stain-negative, aerobic, non-motile, rod-shaped and orange-colored bacterium, designated as strain C305T, was isolated from marine sediment of the coast area of Weihai, China. Strain C305T growth occurs at 4-40 °C (optimally at 30-33 °C), pH 6.0-9.0 (optimally at pH 8.0) and with 0.5-10.0% (w/v) NaCl (optimum 1.5-3.0%). No growth is observed without NaCl. The major cellular fatty acids of strain C305T were identified as iso-C15:0, iso-C15:1G and iso-C17:0 3-OH. The major respiratory quinone was found to be MK-6, and the DNA G + C content was determined to be 35.5 mol%. The predominant polar lipids were mainly phosphatidylethanolamines (PE), unidentified aminophospholipids (APL), andunidentified lipid (L2). Phylogenetic analysis based on 16S rRNA gene sequences revealed that C305T was a member of the genus Brumimicrobium and had a 16S rRNA gene sequence similarity values of 96.9-98.0% with recognized Brumimicrobium species. On the basis of the phylogenetic and phenotypic evidences, strain C305T represents a novel species of the genus Brumimicrobium, for which the name Brumimicrobium oceani sp. nov. is proposed. The type strain is C305T (= KCTC 62371 T = MCCC 1H00297T).

MiR-29b-3p Inhibits the Inflammation Injury in Human Umbilical Vein Endothelial Cells by Regulating SEC23A.

This study aims to investigate the effects of miR-29b-3p on the inflammation injury of human umbilical vein endothelial cells (HUVECs) induced by lipopolysaccharide (LPS) and explore the underlying mechanisms. The effects of different concentrations of LPS (0, 1, 5 and 10 µg/mL) on inflammation injury in HUVECs are detected by ELISA, CCK-8, EdU, flow cytometry and western blot analyses to determine the optimal stimulus concentration. After stimulating HUVECs with 10 µg/mL LPS, the expression levels of miR-29b-3p are detected, and the effects of miR-29b-3p on inflammation injury are detected by ELISA, CCK-8, EdU, flow cytometry and western blot analyses. Bioinformatic analysis, luciferase reporter assay and confirmatory experiments are applied to identify the target gene bound with miR-29b-3p. Rescue experiments have verified the roles of miR-29b-3p and the target gene in inflammation injury. We found that pro-inflammatory factor was increased, apoptosis was promoted, and cell proliferation was inhibited after the treatment of LPS in HUVECs. Overexpression of miR-29b-3p inhibited LPS-induced inflammatory response and apoptosis while promoting proliferation in HUVECs. Besides, bioinformatics analysis indicated that SEC23A was the target gene of miR-29b-3p and the confirmatory experiments showed that SEC23A was negatively correlated with miR-29b-3p and positively correlated with LPS concentration. Rescue experiments revealed that overexpression of SEC23A partially enhanced the inflammation injury effects in LPS-induced HUVECs with overexpression of miR-29b-3p. Hence, miR-29b-3p repressed inflammatory response, cell apoptosis and promoted cell proliferation in LPS-induced HUVECs by targeting SEC23A, providing a potential target for treating sepsis.

Relapsing MOG-IgG-associated diseases coexisting with anti-NMDAR encephalitis: a case report and literature review.

BACKGROUND: In recent years, an overlapping syndrome, MNOS, of MOG encephalomyelitis and NMDARE has been clinically identified. In these diseases, both MOG-Ab and NMDAR-Ab are positive. Previous studies were almost case reports and incomprehensive which focused on this kind of overlapping syndrome in adults. METHODS: We reported a rare case of MNOS. In addition, we reviewed the clinical characteristics, diagnosis, and treatment of MNOS in adults by consulting relevant literature. RESULTS: The patient initially presented with CNS demyelination symptoms followed by recurrent encephalitis, concomitant anti-MOG, and NMDAR antibodies. His symptoms improved significantly after initiating hormonal therapy. We searched previous MNOS case reports and 17 adult MNOS cases were retrieved. The previous history of all patients was unremarkable. Most of these patients (72.2%, 13/18) first developed NMDR encephalitis-related symptoms, such as cognitive behavior abnormalities, cognitive decline, and epilepsy. Some patients (16.7%, 3/18) first developed MOG-related demyelinating symptoms, such as visual deterioration, walking instability, and dizziness. The most common site of new brain lesions was the supratentorial region. In the acute phase, MNOS patients were sensitive to hormone therapy. During the follow-up, 72.2% (13/18) of the patients relapsed, with a median interval of 12.25 months. Immunotherapy was still effective after recurrence, and no deaths were reported. CONCLUSIONS: (1) The clinical manifestations of MNOS are atypical, sometimes like MOG encephalomyelitis, sometimes like NMDARE, sometimes both of the characteristic clinical manifestations are present. (2) Immunotherapy is the primary treatment of patients with MNOS. (3) MNOS are prone to recurrence, and serum MOG and tumor markers should be monitored.

Research on Trajectory Tracking Control of Inspection UAV Based on Real-Time Sensor Data.

In power inspection, uncertainties, such as wind gusts in the working environment, affect the trajectory of the inspection UAV (unmanned aerial vehicle), and a sliding mode adaptive robust control algorithm is proposed in this paper to solve this problem. For the nonlinear and under-driven characteristics of the inspection UAV system, a double closed-loop control system which includes a position loop and attitude loop is designed. Lyapunov stability analysis is used to determine whether the designed system could finally achieve asymptotic stability. Sliding-mode PID control and a backstepping control algorithm are applied to analyze the superiority of the control algorithm proposed in this paper. A PX4 based experimental platform system is built and experimental tests were carried out under outdoor environment. The effectiveness and superiority of the control algorithm are proposed in this paper. The experimental results show that the sliding mode PID control can achieve good accuracy with smaller computing costs. For nonlinear interference, the sliding mode adaptive robust control strategy can achieve higher trajectory tracking accuracy.

Risk assessment of cadmium intake via food among residents in the mining-affected areas of Nandan County, China.

This study investigated the dietary structure, Cadmium (Cd) contents in foods and exposure to Cd through diets of the residents in the mining-affected areas of Nandan County in summer 2013 (July to August) and winter 2014 (November to December). The weighing of foods and the chemical analysis of foods were applied to determine the dietary structure, and the concentration of trace element Cd in the diets, respectively, of the residents in the mining-affected areas (Chehe town, Dachang town, and Zhanglao town) and a control area (Liuzhai town), and subsequently the Cd exposure from the diets was estimated. In the mining-affected areas, the geometric mean of Cd in rice and rice products was the highest (0.29 µg/g) among all food types, and it exceeds the value of 0.2ug/g from the China Food Safety National Standard for Maximum Levels of Contaminants in Foods (GB2762-2017). The Cd contents in rice and rice products, vegetables, and beans in the mining-affected areas were significantly higher than those in the control area. The estimated daily food intakes of Cd in the mining-affected areas were higher than the intake in the control area. The THQ in the mining-affected areas of Chehe town, Dachang town, and Zhanglao town was 3.03, 2.31, and 3.27, respectively. All of which were higher than the value of 1.44 in the control area. Thus, the high level of dietary cadmium intakes of residents in this area deserves our attention.

Cytokine profiles in patients with newly diagnosed multiple myeloma: Survival is associated with IL-6 and IL-17A levels.

BACKGROUND: Identifying specific risk factors associated with multiple myeloma (MM) remains a significant issue. Different cytokines take part in the pathogenesis, progression, and prognosis of MM. Therefore, this study aimed to investigate the correlations between serum cytokine levels and clinical characteristics and determine their effects on disease progression and survival of MM patients. METHODS: We retrospectively analyzed the serum levels of 7 cytokines in 105 patients with newly diagnosed MM and in 20 healthy subjects. Interleukin (IL)-2, IL-4, IL-6, IL-10, and IL-17A, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ were quantitatively determined by cytometric bead assay techniques. The concentrations of each cytokine were compared between the MM patients and healthy subjects using the Mann-Whitney U test. The Kaplan-Meier method was used to analyze progression-free survival (PFS) and overall survival (OS). RESULTS: Serum IL-2, IL-4, IL-6, IL-10, IL-17A, TNF-α, and IFN-γ levels were higher in patients with newly diagnosed MM than in healthy controls. Positively significant correlations were found between IL-6, IL-10, IL-17A, and ß2-microglobulin. Significant correlations were also observed between IL-6 and IL-10, and lactate dehydrogenase. The overall response rate of low-IL-6 and IL-17A patients was significantly higher than that of high-IL-10 and IL-17A patients (P < 0.01). Univariate and multivariate analyses revealed that serum IL-6 levels were >3 pg/mL, serum IL-17A levels were >4 pg/mL, and treatment regimens were independent prognostic factors for PFS and OS. CONCLUSIONS: Cytokine deregulation, especially that of IL-6 and IL-17A, may be a powerful predictor of clinical prognosis for MM patients.

Alterations in the gut microbiota and metabolic profiles coincide with intestinal damage in mice with a bloodborne Candida albicans infection.

Candida albicans is an opportunistic fungus that can threaten life especially in patients with candidemia. The morbidity and mortality of candidemia originating from a central venous catheter (CVC) and illicit intravenous drug use (IVDU) are increasing. However, the mechanism underlying the bloodborne C. albicans infection remains unclear. Herein, we evaluated the gut microbiome, metabolites and intestinal mucosa by constructing the mouse models with candidemia. Model mice were injected with C. albicans via tail vein. Control mice underwent sham procedures. We observed basic life characteristics, intestinal damage-related alterations using hematoxylin and eosin (H&E) staining, intestinal tight junction protein levels, and intestinal permeability in these mice. Fecal samples were analyzed by performing 16S rRNA gene sequencing of the microbiota and LC-MS metabolomics to reveal the perturbations in intestinal flora and metabolism exacerbating intestinal damage. Weight loss, a decreased survival rate, C. albicans infection spread, and colonic epithelial damage occurred in the model group. Furthermore, the intestinal flora abundance was reduced. Several probiotics, such as Lactobacillus, and butyrate-producing bacteria, including Roseburia, Lachnospiraceae, and Clostridia, were depleted, and some pathogenic bacteria, such as Escherichia-Shigella and Proteus, belonging to the Proteobacteria phylum, and the inflammation mediators Ruminococcus and Parabacteroides were enriched in model mice. Multiple differentially altered metabolic pathways were observed and mainly related to bile acid, arachidonic acid, bile secretion, and arachidonic acid metabolism. This study illustrated the effects of a bloodborne C. albicans on the intestinal microbiota, metabolites, and intestinal barrier, which may provide new insights into tests or treatments for candidemia originating from CVC or IVDU.

Comparing the monetary value of a quality-adjusted life year from the payment card and the open-ended format.

BACKGROUND: The payment card (PC) format and the open-ended (OE) format are common methods in eliciting willingness-to-pay (WTP) of one additional quality-adjusted life year (QALY). The aim of this research is to compare these two formats in eliciting the monetary value of a QALY. METHODS: A contingent valuation survey was carried out using a pre-designed questionnaire with various hypothetical scenarios. The difference between the PC and the OE formats was evaluated by a two-sample equality test. Furthermore, generalized linear models were carried out to control observed heterogeneity and to test theoretical validity. RESULTS: In total, 461 individuals were involved, among whom 235 (51%) answered the PC question, while 226 (49%) answered the OE question. Excluding zero response, the mean WTP values of these two formats for different scenarios varied dramatically, which was from 13,278 to 280,177 RMB for the PC, 18,119 to 620,913 RMB for the OE. The OE format tended to elicit lower values for less serious condition and higher values for more serious condition. However, equality test of mean and median demonstrated insignificant difference of these two formats for all scenarios. For both OE and PC format, most variables were found to have significant effect on the value of WTP/QALY. Moreover, joint estimation indicated a statistically significant positive effect on the OE results. Further analysis demonstrated that the imbalanced zero response distribution caused the main difference of these two formats. CONCLUSIONS: This research indicated insignificantly different WTP/QALY estimates of the PC format and OE format with the grouped data whereas significantly higher estimates of the OE format from the pooled data. These two formats were found to be valid. More research about the difference and the validity of various WTP eliciting methods would be recommended for a robust estimation of WTP/QALY.

Evaluation of the metal(loid)s phytoextraction potential of wild plants grown in three antimony mines in southern China.

Wild plant species from three deserted antimony (Sb) mine areas in southern China were collected to measure eight metal(loid)s. Antimony, As (arsenic), Cd (cadmium), Cr (chromium), Cu (copper), Ni (nickel), Pb (lead), and Zn (zinc) concentrations in plants and soil were analyzed. The soils of the mining area was weakly alkaline and contained toxic levels of Sb, As, Pb, Cd, and Zn. Many plant species in the area (40 species and 19 families) have no clear signs of toxicity. The plants were divided into three categories (high, moderate, and low tendency to accumulate metals) based on their (ratio [RT], bioaccumulation factor [BCF], translocation factor [TF]) values. The plants with a high accumulation tendency exhibited the high potential to absorb Sb from contaminated soil; therefore, they can be used for the remediation or phytoremediation of Sb-contaminated soil.

A simplified reliability-based design method for multiple design variables considering different limit states.

A generalized reliability model comprising the objective, constraint, and judgment functions is established for the reliability index approach (RIA), taking parameters' properties of engineering practice and negative reliability index into consideration. Based on this, the reliability-based design (RBD) problem with multiple design variables is translated into the solution to the nonlinear equations, and a simplified method consisting of a simple variant of the Newton iteration method and the finite difference method (FDM) is proposed. Numerical examples are presented to verify the efficiency of the proposed reliability approach and to determine the incremental step size for FDM. RBD of a simply supported beam is illustrated and the variabilities of design variables are investigated considering the uncertainties in the manufacturing process and practical operations. Results reveal that the variations of the design variables should not be ignored. Moreover, analysis results show that the design value might not intuitively increase with the increase of its coefficient of variation (CoV), and it might not increase with the increasing reliability requirement for problems involving multiple variables. The reasons for this phenomenon are very complicated, and it is a systematic problem. One should be aware of this phenomenon, and specific analysis is required for specific problems.

A Population-Based and Propensity Score-Matched Investigation of the Occurrence, Management, and Prognosis of Anal Mucinous Adenocarcinoma Patients.

BACKGROUND: Anal mucinous adenocarcinoma (AMAC) is an extremely rare form of anal cancer. Our objective was to examine the incidence, management, and prognostic factors of AMAC. MATERIALS AND METHODS: We analyzed age-adjusted incidence rates (AAI) over time and compared the prognosis of AMAC with anal squamous cell carcinoma (ASCC) and adenocarcinoma (AAC) using propensity score matching (PSM) and Kaplan-Meier analysis. Patients were classified based on summary stage and treatments to determine cancer-specific survival (CSS). RESULTS: AAI of AMAC fluctuated within a narrow range (0.082-0.237 per million person-years) from 2000 to 2018. AMAC had a slight non-significant trend of worse prognosis than ASCC (p=0.348) and a better prognosis than AAC (p<0.01). Females made up a larger proportion of patients diagnosed with the distant disease (p<0.05) and unmarried (p<0.05), and somewhat less probably to need surgical removal (p<0.01) and radiotherapy (p<0.01). Elderly patients, with regional stage, distant-stage disease, no surgery tended to have lower rates of survival (all p<0.05). Localized stage was associated with better prognosis (p<0.05). Surgery was associated with a tendency towards better survival (p=0.095). CONCLUSIONS: The incidence of AMAC is consistently low. AMAC demonstrates a more favorable prognosis compared to typical AAC and a slightly worse prognosis compared to ASCC. Females with AMAC were less likely to undergo surgical removal or receive radiotherapy. AMAC exhibits a low incidence yet favorable prognosis compared to typical AAC and slightly worse compared to ASCC. Elderly age is associated with poorer prognosis, while localized stage indicates better prognosis. Surgery demonstrates a trend towards improved survival.

Tryptophan metabolites relieve intestinal Candida albicans infection by altering the gut microbiota to reduce IL-22 release from group 3 innate lymphoid cells of the colon lamina propria.

Invasive candidiasis may be caused by Candida albicans (C. albicans) colonization of the intestinal tract. Preventing intestinal damage caused by Candida albicans infection and protecting intestinal barrier function have become a critical issue. Integrated analyses of the microbiome with metabolome revealed a remarkable shift of the gut microbiota and tryptophan metabolites, kynurenic acid (KynA), and indolacrylic acid (IA) in mice infected with C. albicans. The transcriptome sequencing indicated that differentially expressed genes were significantly associated with innate immune responses and inflammatory responses. The results of this study suggest that KynA and IA (KI) can alleviate intestinal damage caused by Candida albicans infection in mice by reducing intestinal permeability, increasing intestinal firmness, alleviating intestinal inflammation, and reducing the secretion of interleukin-22 (IL-22) in the 3 groups of colon innate lymphoid cells (ILC3). We performed a fecal microbiota transplantation (FMT) experiment and found that the intestinal barrier function, inflammation, and IL-22 secretion of ILC3 in the colon lamina propria of the recipient mice subjected to C. albicans infection and KI treatment were consistent with the trends of the donor mice. Our results suggest that tryptophan metabolites may directly regulate colon lamina ILC3 to promote intestinal resistance to C. albicans invasion, or indirectly regulate the ILC3 secretion of IL-22 to play a protective role in the intestinal barrier by affecting intestinal microorganisms, which may become a potential target for alleviating intestine borne C. albicans infection.

HIF-1α regulates DcR3 to promote the development of endometriosis.

OBJECTIVE: The aim of this study was to investigate the expression and clinical significance of HIF-1α and DcR3 in endometriosis by analysing clinical case data. Tissue samples were collected for tissue chip analysis and staining, and human endometrial stromal cells were isolated and cultured for cell experiments. Additionally, experiments were conducted on collected peritoneal fluid to explore the association and role of HIF-1α and DcR3 in endometriosis. STUDY DESIGN: Patients who visited the Department of Obstetrics and Gynaecology at Central Hospital in Fengxian District, Shanghai, from January 2018 to December 2021 were recruited for this controlled study. Clinical data and tissue chip staining results were collected for multiple regression analysis on the clinical significance of HIF-1α and DcR3. Endometrial tissue, ovarian cysts, and pelvic fluid were collected, and human endometrial stromal cells were cultured. The impact of HIF-1α on DcR3 in different oxygen environments and its role in endometriosis were investigated through PCR, Western blotting, enzyme-linked immunosorbent assay, as well as adhesion and migration assays. RESULTS: In patients with endometriosis, the expression of DcR3 and HIF-1α was found to be upregulated and correlated in ectopic endometrium. The expression of DcR3 served as an indicator of the severity of endometriosis. Hypoxia induced the expression of DcR3, which was regulated by HIF-1α and promoted migration and adhesion. CONCLUSION: DcR3 can be used as a clinical indicator to assess the severity of endometriosis. The hypoxic environment in endometriosis enhances disease progression by regulating DcR3 through HIF-1α.

Targeting PUF60 prevents tumor progression by retarding mRNA decay of oxidative phosphorylation in ovarian cancer.

PURPOSE: Ovarian cancer (OC) is the leading cause of death from gynecological malignancies, and its etiology and pathogenesis are currently unclear. Recent studies have found that PUF60 overexpressed in various cancers. However, the exact function of PUF60 in global RNA processing and its role in OC has been unclear. METHODS: The expression of PUF60 and its relationship with clinical characteristics were analyzed by multiple database analysis and immunohistochemistry. Phenotypic effects of PUF60 on ovarian cancer cell proliferation and metastasis were examined by in vitro cell proliferation assay, migration assay, and in vivo xenograft models and lung metastasis models. RNA immunoprecipitation, seahorse analyses, RNA stability assay were used to study the effect of PUF60 on the stability of oxidative phosphorylation (OXPHOS)-related genes in OC. RESULTS: We report PUF60 is highly expressed in OC with frequent amplification of up to 33.9% and its upregulation predicts a poor prognosis. PUF60 promotes the proliferation and migration of OC cells both in vitro and in vivo. Mechanistically, we demonstrated that silencing of PUF60 enhanced the stability of mRNA transcripts involved in OXPHOS and decreased the formation of processing bodies (P-bodies), ultimately elevating the OXPHOS level. CONCLUSION: Our study unveils a novel function of PUF60 in OC energy metabolism. Thus, PUF60 may serve as a novel target for the treatment of patients with OC.