Polymorphism in F pocket affects peptide selection and stability of type 1 diabetes-associated HLA-B39 allotypes.

HLA-B*39:06, HLA-B*39:01, and HLA-B*38:01 are closely related HLA allotypes differentially associated with type 1 diabetes (T1D) risk and progression. B*39:06 is highly predisposing, while B*39:01 and B*38:01 are weakly predisposing and protective allotypes, respectively. Here, we aimed to decipher molecular mechanisms underlying the differential association of these allotypes with T1D pathogenesis. We addressed peptide binding and conformational stability of HLA-B allotypes using computational and experimental approaches. Computationally, we found that B*39:06 and B*39:01 allotypes had more rigid peptide-binding grooves and were more promiscuous in binding peptides than B*38:01. Peptidomes of B*39:06 and B*39:01 contained fewer strong binders and were of lower affinity than that of B*38:01. Experimentally, we demonstrated that B*39:06 and B*39:01 had a higher capacity to bind peptides and exit to the cell surface but lower surface levels and were degraded faster than B*38:01. In summary, we propose that promiscuous B*39:06 and B*39:01 may bind suboptimal peptides and transport them the cell surface, where such unstable complexes may contribute to the pathogenesis of T1D.

Correlation between the development of phage resistance and the original antibiotic resistance of host bacteria under the co-exposure of antibiotic and bacteriophage.

Bacteriophages (phages) are viruses capable of regulating the proliferation of antibiotic resistant bacteria (ARB). However, phages that directly cause host lethality may quickly select for phage resistant bacteria, and the co-evolutionary trade-offs under varying environmental conditions, including the presence of antibiotics, remains unclear as to their impact on phage and antibiotic resistance. Here, we report the emergence of phage resistance in three distinct E. coli strains with varying resistance to ß-lactam antibiotics, treated with different ampicillin (AMP) concentrations. Hosts exhibiting stronger antibiotic resistance demonstrated a higher propensity to develop and maintain stable phage resistance. When exposed to polyvalent phage KNT-1, the growth of AMP-sensitive E. coli K12 was nearly suppressed within 18 h, while the exponential growth of AMP-resistant E. coli TEM and super-resistant E. coli NDM-1 was delayed by 12 h and 8 h, respectively. The mutation frequency and mutated colony count of E. coli NDM-1 were almost unaffected by co-existing AMP, whereas for E. coli TEM and K12, these metrics significantly decreased with increasing AMP concentration from 8 to 50 µg/mL, becoming unquantifiable at 100 µg/mL. Furthermore, the fitness costs of phage resistance mutation and its impact on initial antibiotic resistance in bacteria were further examined, through analyzing AMP susceptibility, biofilm formation and EPS secretion of the isolated phage resistant mutants. The results indicated that acquiring phage resistance could decrease antibiotic resistance, particularly for hosts lacking strong antibiotic resistance. The ability of mutants to form biofilm contributes to antibiotic resistance, but the correlation is not entirely positive, while the secretion of extracellular polymeric substance (EPS), especially the protein content, plays a crucial role in protecting the bacteria from both antibiotic and phage exposure. This study explores phage resistance development in hosts with different antibiotic resistance and helps to understand the limitations and possible solutions of phage-based technologies.

Development and validation of a nomogram for predicting mortality in patients with acute severe traumatic brain injury: A retrospective analysis.

BACKGROUND: Recent evidence links the prognosis of traumatic brain injury (TBI) to various factors, including baseline clinical characteristics, TBI specifics, and neuroimaging outcomes. This study focuses on identifying risk factors for short-term survival in severe traumatic brain injury (sTBI) cases and developing a prognostic model. METHODS: Analyzing 430 acute sTBI patients from January 2018 to December 2023 at the 904th Hospital's Neurosurgery Department, this retrospective case-control study separated patients into survival outcomes: 288 deceased and 142 survivors. It evaluated baseline, clinical, hematological, and radiological data to identify risk and protective factors through univariate and Lasso regression. A multivariate model was then formulated to pinpoint independent prognostic factors, assessing their relationships via Spearman's correlation. The model's accuracy was gauged using the Receiver Operating Characteristic (ROC) curve, with additional statistical analyses for quantitative factors and model effectiveness. Internal validation employed ROC, calibration curves, Decision Curve Analysis (DCA), and Clinical Impact Curves (CIC) to assess model discrimination, utility, and accuracy. The International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) and Corticosteroid Randomization After Significant Head injury (CRASH) models were also compared through multivariate regression. RESULTS: Factors like unilateral and bilateral pupillary non-reactivity at admission, the derived neutrophil to lymphocyte ratio (dNLR), platelet to lymphocyte ratio (PLR), D-dimer to fibrinogen ratio (DFR), infratentorial hematoma, and Helsinki CT score were identified as independent risk factors (OR > 1), whereas serum albumin emerged as a protective factor (OR < 1). The model showed superior predictive performance with an AUC of 0.955 and surpassed both IMPACT and CRASH models in predictive accuracy. Internal validation confirmed the model's high discriminative capability, clinical relevance, and effectiveness. CONCLUSIONS: Short-term survival in sTBI is significantly influenced by factors such as pupillary response, dNLR, PLR, DFR, serum albumin levels, infratentorial hematoma occurrence, and Helsinki CT scores at admission. The developed nomogram accurately predicts sTBI outcomes, offering significant clinical utility.

Intensive Treatment of Organic Wastewater by Three-Dimensional Electrode System within Mn-Loaded Steel Slag as Catalytic Particle Electrodes.

Developing a green, low-carbon, and circular economic system is the key to achieving carbon neutrality. This study investigated the organics removal efficiency in a three-dimensional electrode reactor (3DER) constructed from repurposed industrial solid waste, i.e., Mn-loaded steel slag, as the catalytic particle electrodes (CPE). The CPE, a micron-grade material consisting primarily of transition metals, including Fe and Mn, exhibited excellent electric conductivity, catalytic ability, and recyclability. High rhodamine B (RhB) removal efficiency in the 3DER was observed through a physical modelling experiment. The optimal operating condition was determined through a single-factor experiment in which 5.0 g·L-1 CPE and 3 mM peroxymonosulfate (PMS) were added to a 200 mL solution of 10 mM RhB under a current intensity of 0.5 A and a 1.5 to 2.0 cm distance between the 2D electrodes. When the initial pH value of the simulated solution was 3 to 9, the RhB removal rate exceeded 96% after 20 min reaction. In addition, the main reactive oxidation species in the 3DER were determined. The results illustrated that HO• and SO4•- both existed, but that the contribution of SO4•- to RhB removal was much lower than that of HO• in the 3DER. In summary, this research provides information on the potential of the 3DER for removing refractory organics from water.

Reduced Adenoma Miss Rate With 9-Minute vs 6-Minute Withdrawal Times for Screening Colonoscopy: A Multicenter Randomized Tandem Trial.

INTRODUCTION: Although the 9-minute mean withdrawal time (m-WT) is often reported to be associated with the optimal adenoma detection rate (ADR), no randomized trials of screening colonoscopy have confirmed the impact of a 9-minute m-WT on adenoma miss rate (AMR) and ADR. METHODS: A multicenter tandem trial was conducted in 11 centers. Seven hundred thirty-three asymptomatic participants were randomized to receive segmental tandem screening colonoscopy with a 9-minute withdrawal, followed by a 6-minute withdrawal (9-minute-first group, 9MF, n = 366) or vice versa (6-minute-first group, 6MF, n = 367). The primary outcome was the lesion-level AMR. RESULTS: The intention-to-treat analysis revealed that 9MF significantly reduced the lesion-level (14.5% vs 36.6%, P < 0.001) and participant-level AMR (10.9% vs 25.9%, P < 0.001), advanced adenoma miss rate (AAMR, 5.3% vs 46.9%, P = 0.002), multiple adenomas miss rate (20.7% vs 56.5%, P = 0.01), and high-risk adenomas miss rate (14.6% vs 39.5%, P = 0.01) of 6MF without compromising detection efficiency ( P = 0.79). In addition, a lower false-negative rate for adenomas ( P = 0.002) and high-risk adenomas ( P < 0.05), and a lower rate of shortening surveillance schedule ( P < 0.001) were also found in 9MF, accompanying with an improved ADR in the 9-minute vs 6-minute m-WT (42.3% vs 33.5%, P = 0.02). The independent inverse association between m-WT and AMR remained significant even after adjusting ADR, and meanwhile, 9-minute m-WT was identified as an independent protector for AMR and AAMR. DISCUSSION: In addition to increasing ADR, 9-minute m-WT also significantly reduces the AMR and AAMR of screening colonoscopy without compromising detection efficiency.

HSP70 attenuates neuronal necroptosis through the HSP90α-RIPK3 pathway following neuronal trauma.

BACKGROUND: Necroptosis, a newly defined regulatable necrosis with membrane disruption, has been demonstrated to participate in trauma brain injury (TBI) related neuronal cell death. Heat shock protein 70 (HSP70) is a stress protein with neuroprotective activity, but the potential protective mechanisms are not fully understood. METHODS AND RESULTS: Here, we investigated the effects of HSP70 regulators in a cellular TBI model induced by traumatic neuronal injury (TNI) and glutamate treatment. We found that necroptosis occurred in cortical neurons after TNI and glutamate treatment. Neuronal trauma markedly upregulated HSP70 protein expression within 24 h. The results of immunostaining and lactate dehydrogenase release assay showed that necroptosis following neuronal trauma was inhibited by HSP70 activator TRC051384 (TRC), but promoted by the HSP70 inhibitor 2-phenylethyenesulfonamide (PES). In congruent, the expression and phosphorylation of receptor interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like protein (MLKL) were differently regulated by HSP70. Furthermore, the expression of HSP90α induced by neuronal trauma was further promoted by PES but decreased by TRC. The data obtained from western blot showed that the phosphorylation of RIPK3 and MLKL induced by HSP70 inhibition were reduced by RIPK3 inhibitor GSK-872 and HSP90α inhibitor geldanamycin (GA). Similarly, inhibition of HSP90α with GA could partially prevented the increased necroptosis induced by PES. CONCLUSIONS: Taken together, HSP70 activation exerted protective effects against neuronal trauma via inhibition of necroptosis. Mechanistically, the HSP90α-mediated activation of RIPK3 and MLKL is involved in these effects.

Outcomes of hospital-acquired pressure injuries and present-on-admission pressure injuries: A propensity score matching analysis.

BACKGROUND: Pressure injuries (PIs) continue to present significant challenges. In recent years, the number of patients with present-on-admission pressure injury (POA-PI) has increased, but researchers have devoted little attention to it, and little is known about its clinical outcome. AIMS: To compare the clinical outcomes of POA-PI and hospital-acquired pressure injury (HAPI) patients. METHODS: In this study, hospitalized patients with pressure injuries were divided into two groups based on whether they acquired the injury in the hospital or already present at the time of their admission. The disease prognosis, duration of stay, and healthcare costs of patients with HAPI and POA-PI were evaluated using propensity score matching analysis (PSM), t-tests, and Mann-Whitney U tests. RESULTS: The information on 1871 patients was retrieved from the electronic case system retroactively. A total of 305 pairs of patients were effectively matched between the two groups using propensity score matching (HAPI group = 305, POA-PI group = 305). There was no statistically significant difference at characteristics between the two groups (P > 0.05). The percentage of POA-PI group patients who were discharged from the hospital was greater than that of the HAPI group (P < 0.05). Conversely, the percentage of POA-PI group patients who died, ceased receiving treatment, or transferred to the hospital was lower than that of the HAPI group. Patients in the POA-PI group had shorter hospital stays than those in the HAPI group (P < 0.05). Patients in the POA-PI group had lower healthcare costs than those in the HAPI group (P < 0.05). CONCLUSIONS: Patients with POA-PI have superior clinical outcomes than patients with HAPI, but make up the overwhelming majority of hospitalized patients. It is imperative that future research focuses on the reduction of POA-PI and HAPI incidence and the identification of therapies that will enhance patient prevention for these conditions.

Transient and Prolonged Activation of Wnt Signaling Contribute Oppositely to the Pathogenesis of Asherman's Syndrome.

Asherman's Syndrome (AS) is caused by dysfunction of endometrial regenerative ability, which is controlled by adult stem cells and their niche. The Wnt signaling pathway has been demonstrated to be implicated in this process. This study aimed to clarify the relationship between the Wnt signaling pathway and the progression of AS after initial endometrial damage. Endometria with and without adhesion as well as from the intrauterine devices three months after the surgery were collected to compare the area of fibrosis. The area% of fibrosis did not vary significantly. Significantly higher expression of non-phosphorylated ß-catenin, Wnt5a and Wnt7a was identified in the endometria with adhesion. The CD140b+CD146+ endometrial stem-like cells were present in the endometria with adhesion. Both Wnt5a and Wnt7a promoted stem cell proliferation. However, only Wnt7a preserved stem cell population by stimulating self-renewal. A rat endometrial injury model was established to investigate the effect of the activated Wnt/ß-catenin signaling pathway on endometrial healing. We found that a transient activation of the Wnt/ß-catenin signaling pathway promoted angiogenesis and increased the number of glands. In conclusion, transient activation of the Wnt/ß-catenin signaling pathway during the acute endometrial damage may help the tissue regeneration, while prolonged activation may correlate to fibrosis formation.

An Experimental Study on the Preparation of Soft Rock Similar Materials Using Redispersible Latex Powder as a Modifier.

The engineering geological problems of soft rock are common in large slope engineering and underground engineering surrounding rock. In order to study the change in mechanical properties of soft rock under the action of loading, excavation and rainfall, this paper carried out experimental research on similar materials of soft rock. The similar material of soft rock is prepared by using iron fine powder, barite powder and quartz sand as aggregate, gypsum as binder and redispersible latex powder as regulator. A single-factor influence test was designed with the content of redispersible latex powder as variation parameter. Analysis the influence of redispersible latex powder from the perspectives of physical and mechanical indexes, failure forms, stress-strain states and changes after water seepage. In addition, evaluate the feasibility of this similar material in geomechanical model test. Experimental results show that the density, compressive strength and Poisson's ratio of similar materials can be improved to a certain extent by the redispersible latex powder with low dosage. However, the above indexes show a significant downward trend with the increase in dosage when the dosage exceeds 2%. The deformation modulus always shows a downward trend, and this trend becomes more significant especially when the dosage exceeds 2%. With the increase in the redispersible latex powder, the stress-strain curves of similar materials show obvious elastic and plastic stages. The failure mode gradually changes to X-shaped conjugate failure, which is common in soft rock, and the material changes from brittle failure to plastic failure. In addition, this type of similar material with gypsum as cementing agent will cause serious damage and loss of bearing capacity after seepage. These methods produce similar materials with low strength, low deformation modulus and plastic failure form, which can be used to simulate the stability of soft rock engineering caused by loading or excavation. At the same time, it also sheds lights on preparing similar materials of hard rock.

Prevalence and correlates of Mycoplasma genitalium infection among patients attending a sexually transmitted infection clinic in Guangdong, China: a cross-sectional study.

BACKGROUND: Mycoplasma genitalium (MG) causes urogenital tract infections and is associated with reproductive morbidity. Although MG has been reported across many regions and population groups, it is not yet routinely tested for in China. Our study contributes to current research by reporting the prevalence and correlates of MG infection in patients attending a sexually transmitted infection (STI) clinic in Guangdong from Jan 2017-May 2018. METHODS: Urethral (from 489 men) and endo-cervical (from 189 women) samples, blood samples, and patient histories (via questionnaires) were collected. Doctors clinically diagnosed anogenital warts (GW) during the examination (n = 678). The presence of MG was evaluated using an in-house via polymerase chain reaction protocol. We also tested all participants for herpes simplex virus-2 (HSV-2), Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT), syphilis and HIV. Univariate and multivariate logistic regression were used to evaluate factors associated with MG. RESULTS: MG was detected in 7.2% (49/678) of the patients (men, 7.4%; women, 6.9%). The MG positivity rate was 14.2% among symptomatic patients, and 5.6% for asymptomatic patients, respectively. Only 36.7% (18/49) Mg positive patients were symptomatic. Among the MG-infected patients, 10.2% were co-infected with CT, 6.1% with NG, 8.2% with HSV-2, 4.1% with syphilis and 22.4% with GW. Presentation with clinical symptoms was significantly associated with MG infection [OR = 2.52 (2.03-3.13)]. In our analysis, MG was not associated with other STIs. CONCLUSIONS: MG is a relatively common infection among individuals attending an STI clinic in Guangdong Province. Routine testing of symptomatic patients may be necessary, and more epidemiological studies are needed to provide evidence for future testing guidelines.

Negative binomial additive model for RNA-Seq data analysis.

BACKGROUND: High-throughput sequencing experiments followed by differential expression analysis is a widely used approach for detecting genomic biomarkers. A fundamental step in differential expression analysis is to model the association between gene counts and covariates of interest. Existing models assume linear effect of covariates, which is restrictive and may not be sufficient for certain phenotypes. RESULTS: We introduce NBAMSeq, a flexible statistical model based on the generalized additive model and allows for information sharing across genes in variance estimation. Specifically, we model the logarithm of mean gene counts as sums of smooth functions with the smoothing parameters and coefficients estimated simultaneously within a nested iterative method. The variance is estimated by the Bayesian shrinkage approach to fully exploit the information across all genes. CONCLUSIONS: Based on extensive simulations and case studies of RNA-Seq data, we show that NBAMSeq offers improved performance in detecting nonlinear effect and maintains equivalent performance in detecting linear effect compared to existing methods. The vignette and source code of NBAMSeq are available at http://bioconductor.org/packages/release/bioc/html/NBAMSeq.html.

methylGSA: a Bioconductor package and Shiny app for DNA methylation data length bias adjustment in gene set testing.

MOTIVATION: An important downstream analysis following differential expression from RNA sequencing (RNA-Seq) or DNA methylation analysis is the gene set testing to relate significant genes or CpGs to known biological properties. However, the traditional gene set testing approaches result in biased P-values due to the difference in gene length. Existing methods accounting for length bias were primarily developed for RNA-Seq data. For DNA methylation data profiled using the Illumina arrays, separate methods adjusting for the number of CpGs instead of gene length are necessary. RESULTS: We developed methylGSA, a Bioconductor package for gene set testing in DNA methylation data. Our accompanying Shiny app provides an interactive way of accessing functions and visualizing the results in methylGSA package. AVAILABILITY AND IMPLEMENTATION: methylGSA is available at Bioconductor repository: https://bioconductor.org/packages/methylGSA and Shiny app is available at: http://www.ams.sunysb.edu/%7epfkuan/softwares.html#methylGSA. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Circulating microRNA-21 as Stable Blood-Based Markers for Patients With ISR After PCI.

It recently has been reported that the in-stent restenosis (ISR) of expanded area after percutaneous coronary intervention (PCI) within six months can become a serious postoperative complication. A real-time quantitative PCR was used to analyze the expression of serum miR-21 in 33 ISR and 37 non-ISR patients after PCI. Expression of miR-21 was significantly higher in the ISR group compared with that in the NISR group, and a similar trend also occurred in factor- (TNF-α) level, Interleukin -6 (IL-6) level, and plaque area (PLA). However, a contrary trend occurred in the external elastic membrane area (EEM) and minimal lumen area (MLA). This study suggests that the increased expression of serum miR-21 is related to ISR after PCI, and miR-21 can be a new predictor of ISR.

Friction and Wear Mechanism Analysis of Polymer Flexible Cable Using a High Natural Frequency Piezoelectric Sensor.

The friction and wear of flexible cables are the main factors that cause electrical breakdown and insulation aging, and they greatly reduce the reliability and safety of robots. In order to enhance the reliability and safety of the robot, it is of great necessity to investigate the friction and wear mechanisms of the flexible cable. In this research, the friction and wear mechanisms have been discussed. The effects of relative speed, ambient temperature, and positive pressure on the flexible cables are considered by an orthogonal frictional movement. The cable friction force has been measured by a piezoelectric sensor with high natural frequency characteristics. The relations among friction and different factors affecting friction have also been discussed. The results show that the relative speed and the ambient temperature are the main factors affecting the friction and wear of the cable; the main form of flexible cable wear is mechanical-force chemical friction and wear. Those discoveries will greatly deepen the understanding of the friction and wear mechanisms of flexible cables, and will be beneficial to robot cable-reliability design.

Plasma miRNA-155 Levels Predict Atrial Fibrillation Recurrence after Cardioversion.

BACKGROUND: MicroRNAs (miRNAs) are widely involved in the regulation of physiological processes, such as cell proliferation, differentiation, apoptosis, angiogenesis, and lipid metabolism. They might be associated with the pathological process of atrial fibrillation (AF). The purpose of our study is to investigate whether plasma miRNA-155 levels have a relationship with AF recurrence. METHODS: A total of 110 patients with AF were studied, all with successful cardioversion. We measured the expression of plasma miRNA-155 in the recurrent group (n = 30) and in the nonrecurrent group (n = 80) by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). In addition, the serumal levels of B-type natriuretic peptide (BNP), total cholesterol (TC), and fasting blood glucose (FBG) in the groups were determined by using an automatic biochemical analyzer, and an immunoenzymatic method was applied to determine the serumal levels of tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and interleukin-6 (IL-6). The left atrial diameter (LAD) and left ventricular ejection fraction (EF) of all patients were measured by using echocardiography. RESULTS: Our RT-PCR analysis found that miRNA-155 was significantly upregulated in the recurrent group compared with the nonrecurrent group. These increases of LAD and the levels of BNP, TNF-α, CRP, and IL-6 in the recurrent group were also revealed to be relative to those in the nonrecurrent group. There were no differences in the levels of TC and FBG, as well as in EF, between the groups. Moreover, miRNA-155 expression was observed to correlate positively with these outcomes of LAD, BNP, TNF-α, CRP, IL-6, and LAD. A diagnostic significance of predicting AF recurrence for plasma miRNA-155 was elucidated via ROC curve analysis. CONCLUSIONS: Our findings revealed that plasma miRNA-155 can present an ability to calculate AF recurrence after cardioversion.

[Facilitative glucose transporters: expression, distribution and the relationship to diseases].

Facilitative glucose transporters (GLUT) are proteins that mediate glucose transmembrane transport in the form of facilitated diffusion, which play an important role in regulating cell energy metabolism. There are many breakthroughs in researches of facilitative GLUT in recent years. It has been known that there are 14 subtypes of facilitative GLUT with obvious tissue specificity in distribution and physiological function. In the present review, the tissue and cellular distribution, subcellular localization, expression regulation, physiological function and the relationship to diseases of facilitative GLUT subtypes were summarized, in order to further understand their physiological and pathophysiological significances.

Gonorrhea and chlamydia prevalence in different anatomical sites among men who have sex with men: a cross-sectional study in Guangzhou, China.

BACKGROUND: A high rectal and oropharyngeal sexually transmitted infection (STI) burden has been reported among men who have sex with men (MSM) in many regions, but little data exists on rectal and oropharyngeal STIs among MSM in China. The purpose of this study was to determine the prevalence of gonorrhea and chlamydia at different anatomic sites among MSM in Guangzhou, China. METHODS: We recruited a cross-sectional sample of MSM in one Chinese city and collected detailed information about socio-demographic characteristics and sexual behaviors. Men had urine, rectal, and pharyngeal swab samples tested for gonorrhea and chlamydia using nucleic acid amplification tests (NAAT). Univariate and multivariate logistic regressions were used to evaluate factors associated with gonorrhea and chlamydia. Among men without any STI symptoms, we also examined the prevalence of gonorrhea and chlamydia by anatomical site. RESULTS: We enrolled 463 men between January 2015 and March 2017. A total of 58/463 (12.5%) of men had gonorrhea and 84/463 (18.1%) had chlamydia. MSM with gonorrhea were more likely to have been recruited from the STI clinic (OR 3.41, 95% CI 1.94-5.99), living with HIV (OR 2.41, 95% CI 1.18-4.92), diagnosed had STI co-infection (OR 2.55, 95% CI 1.39-4.69). MSM with chlamydia were more likely to be students (OR 1.8, 95% CI 0.99-3.39). Most gonorrhea (34/58, 59%) and chlamydia (64/84, 76%) infections were not associated with STI symptoms. CONCLUSION: Asymptomatic gonorrhea and chlamydia infection were common in this sample of Chinese MSM. Further research is necessary to determine optimal STI screening programs.

[Research on relationship between occurrence of root rot and changes of fungal communities in rhizosphere of Panax quinquefolius].

The root rot disease is a common disease during the cultivation of Panax quinquefolius. In order to provide some clues for solving the root rot disease of P. quinquefolius, the relationship between rhizosphere soil fungal communities and root rot of P. quinquefolius was investigated in this study. The diversities and the changes of fungal communities structure in blank control group (group C), rhizosphere soil of healthy P. quinquefolius (group N) and occurrence of root rot in rhizosphere soil of P. quinquefolius (group R)were analyzed byusing the Illumina MiSeq high-throughput sequencing technology. A total of 505 968 high-quality sequences were obtained through high-throughput sequencing and the rare faction curves analysis showed that the sequencing depth was sufficient and the sampling was reasonable. The fungal communities structure of rhizosphere soil samples mainly belonged to 9 phylums including Ascomycota(54.9%), Basidiomycota(5.6%), etc., and the dominant specie was Ascomycota of the total fungal identified, respectively. The 115 genera of fungi were tested, including Monographella (3.9%), Archaeorhizomyces (3.9%), Mortierella, etc., and the dominant specie was Monographella. At the genus level, the abundance of Monographella and Mortierella in group R increased significantly compared with the abundance in groups C and N. Alpha diversity index of species showed that the diversity index of fungal communities reduced and the numbers of fungi reduced in group N and R, compared with group C, and reaching the minimum in group R. Beta diversity index of species showed that there was a significant difference in the fungal communities structure in each sample. In addition, the heat map analysis revealed that the dominant fungal genera were significantly different among the each sample. The proportion of Monographella and Mortierella in group R was significantly higher than that in group C and N, while the proportion of Trichoderma,Penicillium and Cadophora in group R was extremely low. The proportion of Phoma and Gibberella in group R increased significantly compared with group C. This study clarified the decline of diversity index and the imbalance of community structure in fungi may lead to the occurrence of root rot in P. quinquefolius by analysis of fungal diversity and community composition in the rhizosphere soil of P. quinquefolius in this study, which provided a theoretical basis for the prevention and treatment of occurrence of root rot in P. quinquefolius.

Tissue-specific significance of BAP1 gene mutation in prognostic prediction and molecular taxonomy among different types of cancer.

BAP1 is an emerging tumor suppressor whose inactivating mutations have been found to play critical roles in tumor development. This study was conducted to elucidate the potential value of BAP1 mutation in guiding prognostic prediction and clinical stratification. We conducted a comprehensive analysis of relevant studies from multiple databases, to determine the impact of BAP1 mutation on the overall survival and disease-free survival of patients in various cancers. A total of 2457 patients from 21 studies were included in the final analysis. Although the pooled results demonstrated that BAP1 mutation was a negative indicator of overall survival (hazard ratio = 1.73; 95% confidence interval = 1.23-2.42) and disease-free survival (hazard ratio = 2.25; 95% confidence interval = 1.47-3.45), this prognostic value was only applicable to uveal melanoma and clear cell renal cell carcinoma, but not to malignant pleural mesothelioma or cholangiocarcinoma. Consistently, BAP1 mutation was correlated with critical clinicopathological features only in uveal melanoma and clear cell renal cell carcinoma. In uveal melanoma, BAP1 mutation and SF3B1/EIF1AX mutations were negatively correlated, and BAP1-mutant tumors indicated significant worse prognosis than SF3B1/EIF1AX-mutant tumors ( p = 0.028). While in clear cell renal cell carcinoma, BAP1 mutation was mutually exclusive with PBRM1 mutations, and BAP1-mutant clear cell renal cell carcinomas also showed significantly worse prognosis than PBRM1-mutant clear cell renal cell carcinomas ( p = 0.001). Our study revealed a unique tissue-specific significance of BAP1 mutation in prognostic prediction among different types of cancer. Clinically, combining detection of BAP1 mutation and other driver mutations may further allow for a more precise molecular taxonomy to stratify patients into distinct subgroups in uveal melanoma and clear cell renal cell carcinoma.

Prophylactic somatostatin can reduce incidence of post-ERCP pancreatitis: multicenter randomized controlled trial.

BACKGROUND AND STUDY AIM: Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) remains the most common complication of ERCP. Somatostatin may inhibit pancreatic secretion and has been tested for PEP prophylaxis. However, the results of previous studies are inconsistent. The aim of the current study was to investigate whether somatostatin can reduce the incidence of PEP. PATIENTS AND METHODS: The study was a multicenter, open-label, randomized controlled trial. A total of 908 patients with normal amylase levels who were undergoing ERCP were randomized to receive somatostatin 250 µg bolus injection before ERCP and 250 µg/hour intravenous infusion for 11 hours after ERCP (somatostatin group) or no somatostatin treatments (control group). The incidences of PEP and hyperamylasemia were compared in the two groups. RESULTS: The full analysis set included 900 patients (445 in the somatostatin group, 455 in the control group). PEP developed in 34 patients (7.5 %) in the control group (95 % confidence interval [CI] 5.4 % - 10.3 %) and in 18 patients (4.0 %) in the somatostatin group (95 %CI 2.6 % - 6.3 %; P = 0.03). Hyperamylasemia occurred in 46 patients (10.1 %) in the control group (95 %CI 7.7 % - 13.2 %) and in 27 patients (6.1 %) in the somatostatin group (95 %CI 4.2 % - 8.7 %; P = 0.03). No perforation or death occurred during the study. CONCLUSIONS: This study showed that somatostatin was effective and safe for the prevention of PEP and hyperamylasemia in ERCP patients.(ClinicalTrials.gov number, NCT01431781).