DeepSS2GO: protein function prediction from secondary structure.

Predicting protein function is crucial for understanding biological life processes, preventing diseases and developing new drug targets. In recent years, methods based on sequence, structure and biological networks for protein function annotation have been extensively researched. Although obtaining a protein in three-dimensional structure through experimental or computational methods enhances the accuracy of function prediction, the sheer volume of proteins sequenced by high-throughput technologies presents a significant challenge. To address this issue, we introduce a deep neural network model DeepSS2GO (Secondary Structure to Gene Ontology). It is a predictor incorporating secondary structure features along with primary sequence and homology information. The algorithm expertly combines the speed of sequence-based information with the accuracy of structure-based features while streamlining the redundant data in primary sequences and bypassing the time-consuming challenges of tertiary structure analysis. The results show that the prediction performance surpasses state-of-the-art algorithms. It has the ability to predict key functions by effectively utilizing secondary structure information, rather than broadly predicting general Gene Ontology terms. Additionally, DeepSS2GO predicts five times faster than advanced algorithms, making it highly applicable to massive sequencing data. The source code and trained models are available at https://github.com/orca233/DeepSS2GO.

Local Management for Diabetic Foot Ulcers: A Systematic Review and Network Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: This study evaluated the efficacy of various local management strategies for diabetic foot ulcers (DFUs). BACKGROUND: Several surgical and non-surgical local interventional approaches are available for the treatment of DFUs. The comparative effectiveness of different treatments is unknown, and it remains unclear which approach is the optimal choice for DFUs treatment due to limited direct comparisons. METHODS: We did a systematic review and meta-analysis to select the optimal approach to DFUs local management. We searched Medline, Embase, Web of Science, and ClinicalTrials.gov from inception to September 1, 2023, to identify relevant randomized controlled trials (RCTs). We analysed data by pairwise meta-analyses with a random-effects model. A network meta-analysis using the surface under the cumulative ranking curve (SUCRA) was performed to evaluate the comparative efficacy of different interventional approaches in the early (within 12 wk) and late stages (over 12 wk). RESULTS: 141 RCTs involving 14076 patients and exploring 14 interventional strategies were eligible for inclusion. Most studies (102/141) had at least one risk-of-bias dimension. Good consistency was observed during the analysis. Local pairwise comparisons demonstrated obvious differences in the early-stage healing rate and early- and late-stage healing times, while no significant difference in the late-stage healing rate or adverse events were noted. SUCRAs identified the standard of care (SOC) + decellularized dressing (DD), off-loading (OL), and autogenous graft (AG) as the three most effective interventions within 12 weeks for both healing rate (97%, mean rank: 1.4; 90%, mean rank: 2.3; 80.8%, mean rank: 3.5, respectively) and healing time (96.7%, mean rank: 1.4; 83.0%, mean rank: 3.0; 76.8%, mean rank: 3.8, respectively). After 12 weeks, local drug therapy (LDT) (89.5%, mean rank: 2.4) and OL (82.4%, mean rank: 3.3) ranked the highest for healing rate, and OL (100.0%, mean rank: 1.0) for healing time. With respect to adverse events, moderate and high risks were detected in the SOC + DD (53.7%, mean rank: 7.0) and OL (24.4%, mean rank: 10.8) groups, respectively. CONCLUSION: The findings suggest that OL provided considerable benefits for DFU healing in both the early and late stages, but the high risk of adverse events warrants caution. SOC+DD may be the preferred option in the early stages, with an acceptable risk of adverse events.

Effectiveness of Wearable Activity Monitors on Metabolic Outcomes in Patients With Type 2 Diabetes: A Systematic Review and Meta-Analysis.

OBJECTIVE: Wearable activity monitors are promising tools for improving metabolic outcomes in patients with type 2 diabetes mellitus (T2DM); however, no uniform conclusive evidence is available. This study aimed to evaluate the effects of the intervention using wearable activity monitors on blood glucose, blood pressure, blood lipid, weight, waist circumference, and body mass index (BMI) in individuals with T2DM. METHODS: Two independent reviewers searched 4 online databases (PubMed, Cochrane Library, Web of Science, and Embase) to identify relevant studies published from January 2000 to October 2022. The primary outcome indicator was hemoglobin A1c (HbA1c), and the secondary outcome indicators included physical activity (steps per day), fasting blood glucose, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol, systolic blood pressure, diastolic blood pressure, BMI, waist circumference, and weight. RESULTS: A total of 25 studies were included. The HbA1c level (standardized mean difference [SMD], -0.14; 95% confidence interval [CI], -0.27 to -0.02; P = .02; I2 = 48%), BMI (SMD, -0.16; 95% CI, -0.26 to -0.05; P = .002; I2 = 0), waist circumference (SMD, -0.21; 95% CI, -0.34 to -0.09; P < .001; I2 = 0), and steps/day (SMD, 0.55; 95% CI, 0.36-0.94; P < .001; I2 = 77%) significantly improved. CONCLUSION: Wearable activity monitor-based interventions could facilitate the improvement of the HbA1c level, BMI, and waist circumference and increase in physical activity in individuals with T2DM. Wearable technology appeared to be an effective tool for the self-management of T2DM; however, there is insufficient evidence about its long-term effect.

LmFKBP24 interacts with LmEaster to inhibit the antifungal immunity of Locusta migratoria.

Locusta migratoria is one of the most destructive pests that threaten crop growth and food production security in China. Metarhizium anisopliae has been widely used to control locusts around the world. Previous laboratory studies have revealed that LmFKBP24 is significantly upregulated after M. anisopliae infection, suggesting that it may play a role in immune regulation, yet the mechanism remains largely unknown. To gain further insight, we conducted an RNA interference (RNAi) study to investigate the function of LmFKBP24 in the regulation of antifungal immunity and analyzed the expression patterns of immune-induced genes. Our research revealed that LmFKBP24 is activated and upregulated when locusts are infected by M. anisopliae, and it inhibits the expression of antimicrobial peptide (AMP) defensin in the downstream of Toll pathway by combining with LmEaster rather than LmCyPA, thus exerting an immunosuppressive effect. To further investigate this, we conducted yeast two-hybrid (Y2H) and pull down assays to identify the proteins interacting with LmFKBP24. Our results provided compelling evidence for revealing the immune mechanism of L. migratoria and uncovered an innovative target for the development of new biological pesticides. Furthermore, our research indicates that LmFKBP24 interacts with LmEaster through its intact structure, providing a strong foundation for further exploration.

Mechanical Constraint Effect on DNA Persistence Length.

Persistence length is a significant criterion to characterize the semi-flexibility of DNA molecules. The mechanical constraints applied on DNA chains in new single-molecule experiments play a complex role in measuring DNA persistence length; however, there is a difficulty in quantitatively characterizing the mechanical constraint effects due to their complex interactions with electrostatic repulsions and thermal fluctuations. In this work, the classical buckling theory of Euler beam and Manning's statistical theories of electrostatic force and thermal fluctuation force are combined for an isolated DNA fragment to formulate a quantitative model, which interprets the relationship between DNA persistence length and critical buckling length. Moreover, this relationship is further applied to identify the mechanical constraints in different DNA experiments by fitting the effective length factors of buckled fragments. Then, the mechanical constraint effects on DNA persistence lengths are explored. A good agreement among the results by theoretical models, previous experiments, and present molecular dynamics simulations demonstrates that the new superposition relationship including three constraint-dependent terms can effectively characterize changes in DNA persistence lengths with environmental conditions, and the strong constraint-environment coupling term dominates the significant changes of persistence lengths; via fitting effective length factors, the weakest mechanical constraints on DNAs in bulk experiments and stronger constraints on DNAs in single-molecule experiments are identified, respectively. Moreover, the consideration of DNA buckling provides a new perspective to examine the bendability of short-length DNA.

Immunomic Identification of Malaria Antigens Associated With Protection in Mice.

Efforts to develop vaccines against malaria represent a major research target. The observations that 1) sterile protection can be obtained when the host is exposed to live parasites and 2) the immunity against blood stage parasite is principally mediated by protective antibodies suggest that a protective vaccine is feasible. However, only a small number of proteins have been investigated so far and most of the Plasmodium proteome has yet to be explored. To date, only few immunodominant antigens have emerged for testing in clinical trials but no formulation has led to substantial protection in humans. The nature of parasite molecules associated with protection remains elusive. Here, immunomic screening of mice immune sera with different protection efficiencies against the whole parasite proteome allowed us to identify a large repertoire of antigens validated by screening a library expressing antigens. The calculation of weighted scores reflecting the likelihood of protection of each antigen using five predictive criteria derived from immunomic and proteomic data sets, highlighted a priority list of protective antigens. Altogether, the approach sheds light on conserved antigens across Plasmodium that are amenable to targeting by the host immune system upon merozoite invasion and blood stage development. Most of these antigens have preliminary protection data but have not been widely considered as candidate for vaccine trials, opening new perspectives that overcome the limited choice of immunodominant, poorly protective vaccines currently being the focus of malaria vaccine researches.

Incidental diagnosis of nonfunctional bladder paraganglioma: a case report and literature review.

BACKGROUND: Nonfunctional bladder paragangliomas is a rare urological disease. It may present clinical, radiology and pathological features similar to bladder cancer, Only scarce reports have been reported. Urologist must identify this generally benign neuroendocrine neoplasm to avoid misdiagnosis. CASE PRESENTATION: A 62-year-old female presented the outpatient department of our hospital with the symptoms of stomachache, frequent micturition, and urination pain for 20 days. Diagnosed with high blood pressure 1 year ago, administered Amlodipine besylate tablets 5 mg po qd occasionally, did not check blood pressure; denied any tumor observation in the family history. Color ultrasound of the urinary system showed a 38 mm × 34 mm hypoechoic mass on the right side of the bladder, CDFI: in the masses, blood supply was sufficient. Cystoscope showed bladder occupying lesion. Biopsy diagnosis: papillary polypoid cystitis was suspected as a malignant change (Fig. 3a). Then, the patient was admitted to our urological department. Further, computer tomography urography considered bladder cancer. Cystoscopy and biopsy failed to define the nature of the lesions in our outpatient department, which prompted a transurethral resection of the bladder tumor. histopathological and immunohistochemical results were diagnosed as bladder paragangliomas. For the reason, the tumor was removed by partial resection of the bladder. The postoperative recovery and follow-up were uneventful. CONCLUSIONS: Nonfunctional bladder paragangliomas are occasionally found on imaging studies with the symptoms of urinary tract infection or/and intermittent painless hematuria. It may present clinical, radiology and pathological features similar to bladder cancer, so knowledge of this generally benign neuroendocrine neoplasm is of great importance to avoid misdiagnosis. It should be accompanied by the clinical and pathological characteristics of the patient and image changes. Partial resection of the bladder can effectively treat this disease.

Influence of Microscopic Interactions on the Flexible Mechanical Properties of Viral DNA.

During the packaging and ejection of viral DNA, its mechanical properties play an essential role in viral infection. Some of these mechanical properties originate from different microscopic interactions of the encapsulated DNA in the capsid. Based on an updated mesoscopic model of the interaction potential by Parsegian et al., an alternative continuum elastic model of the free energy of the confined DNA in the capsid is developed in this work. With this model, we not only quantitatively identify the respective contributions from hydration repulsion, electrostatic repulsion, entropy and elastic bending but also predict the ionic effect of viral DNA's mechanical properties during the packaging and ejection. The relevant predictions are quantitively or qualitatively consistent with the existing experimental results. Furthermore, the nonmonotonous or monotonous changes in the respective contributions of microscopic interactions to the ejection force and free energy at different ejection stages are revealed systematically. Among these, the nonmonotonicity in the entropic contribution implies a transition of viral DNA structure from order to disorder during the ejection.

The pH-dependent elastic properties of nanoscale DNA films and the resultant bending signals for microcantilever biosensors.

The diverse mechanical properties of nanoscale DNA films on solid substrates have a close correlation with complex detection signals of micro-/nano-devices. This paper is devoted to formulating several multiscale models to study the effect of pH-dependent ionic inhomogeneity on the graded elastic properties of nanoscale DNA films and the resultant bending deflections of microcantilever biosensors. First, a modified inverse Debye length is introduced to improve the classical Poisson-Boltzmann equation for the electrical potential of DNA films to consider the inhomogeneous effect of hydrogen ions. Second, the graded characteristics of the particle distribution are taken into consideration for an improvement in Parsegian's mesoscopic potential for both attraction-dominated and repulsion-dominated films. Third, by the improved interchain interaction potential and the thought experiment about the compression of a macroscopic continuum DNA bar, we investigate the diversity of the elastic properties of single-stranded DNA (ssDNA) films due to pH variations. The relevant theoretical predictions quantitatively or qualitatively agree well with the relevant DNA experiments on the electrical potential, film thickness, condensation force, elastic modulus, and microcantilever deflections. The competition between attraction and repulsion among the fixed charges and the free ions endows the DNA film with mechanical properties such as a remarkable size effect and a non-monotonic behavior, and a negative elastic modulus is first revealed in the attraction-dominated ssDNA film. There exists a transition between the pH-sensitive parameter interval and the pH-insensitive one for the bending signals of microcantilevers, which is predominated by the initial stress effect in the DNA film.

Theoretical Analysis for Bending of Single-Stranded DNA Adsorption on Microcantilever Sensors.

An energy-based model is presented to establish the bending deformation of microcantilever beams induced by single-stranded DNA (ssDNA) adsorption. The total free energy of the DNA-microcantilever sensor was obtained by considering the excluded-volume energy and the polymer stretching energy of DNA chains from mean-field theory, and the mechanical energy of three non-biological layers. The radius of curvature and deflection of the cantilever were determined through the minimum principle of energy. The efficiency of the present model was confirmed through comparison with experimental data. The effects of length, grafting density, salt concentration, thickness, and elastic modulus of substrate on tip deflections are also discussed in this paper. These factors can significantly affect the deflections of the biosensor. This work demonstrates that it is useful to develop a theoretical model for the label-free nanomechanical detection technique.

Effect of surface charge state on the surface stress of a microcantilever.

The surface charge state at a liquid-solid interface is important to the variations in the physical/chemical properties of adsorbate film such as surface stress and the ensuing tip deflection of the microcantilever. The well-known Stoney's equation, derived more than 100 years ago, conceals the film electrical properties with the replacement of substrate deformation induced by adsorptions of particles. This implicit expression provides a shortcut to circumvent the difficulty in identifying some film properties, however, it limits the capacity to ascertain the relation between surface stress variation and the surface charge state. In this paper, we present an analytical expression to quantify the cantilever deflection/surface stress and the film potential difference by combining the piezoelectric theory and Poisson-Boltzmann equation for electrolyte solution. This updated version indicates that the two linear correlations between surface stress and surface charge density or the bias voltage are not contradictory, but two aspects of one thing under different conditions. Based on Parsegian's mesoscopic interaction potential, a multiscale prediction for the piezoelectric coefficient of double-stranded DNA (dsDNA) film is done, and the results show that the distinctive size effect with variations in salt concentration and nucleotide number provides us with an opportunity to obtain a more sensitive potential-actuated microcantilever sensor by careful control of packing conditions.

Laparoscopic gastrectomy versus open gastrectomy for elderly patients with gastric cancer: a systematic review and meta-analysis.

BACKGROUND: The objective of this study was to evaluate the feasibility, safety, and potential benefits of laparoscopic gastrectomy (LG) comparing with open gastrectomy (OG) in elderly population. METHODS: Studies comparing LG with OG for elderly population with gastric cancer, published between January 1994 and July 2015, were identified in the PubMed, Embase, and ISI Web of Science databases. Operative outcomes (intraoperative blood loss, operative time, and the number of lymph nodes harvested) and postoperative outcomes (time to first ambulation, time to first flatus, time to first oral intake, postoperative hospital stay, postoperative morbidity) were included and analyzed. The Newcastle-Ottawa Scale was used to assess the quality of the pooled study. A funnel plot was used to evaluate the publication bias. RESULTS: Seven studies totaling 845 patients were included in the meta-analysis. LG in comparison to OG showed less intraoperative blood loss (weighted mean difference (WMD) -127.47; 95% confidence interval (CI) -202.79 to -52.16; P < 0.01), earlier time to first ambulation (WMD -2.07; 95% CI -2.84 to -1.30; P < 0.01), first flatus (WMD -1.04; 95% CI -1.45 to -0.63; P < 0.01), and oral intake (WMD -0.94; 95% CI -1.11 to -0.77; P < 0.01), postoperative hospital stay (WMD -5.26; 95% CI -7.58 to -2.93; P < 0.01), lower overall postoperative complication rate (odd ratio (OR) 0.39; 95% CI 0.28 to 0.55; P < 0.01), less surgical complications (OR 0.47; 95% CI 0.32 to 0.69; P < 0.01), medical complication (OR 0.35; 95% CI 0.22 to 0.56; P < 0.01), incisional complication (OR 0.40; 95% CI 0.19 to 0.85; P = 0.02), and pulmonary infection (OR 0.49; 95% CI 0.26 to 0.93; P = 0.03). No significant differences were observed between LG and OG for the number of harvested lymph nodes. However, LG had longer operative times (WMD 15.73; 95% CI 6.23 to 25.23; P < 0.01). CONCLUSIONS: LG is a feasible and safe approach for elderly patients with gastric cancer. Compared with OG, LG has less blood loss, faster postoperative recovery, and reduced postoperative morbidity.

[Experience of managing substernal goiter by totally endoscopic procedure].

To summarize the experience of managing substernal goiter by totally endoscopic procedure and evaluate the curative effect, we analysed eight patients diagnosed as substernal goiter type I and treated with totally endoscopic technique via central routing approach during March 2011 to June 2013 in Beijing Shijitan Hospital retrospectively. The feasibility, safety and curative effect of this surgical technique were estimated. All the cases were successfully operated with the totally endoscopic procedure, and the pathological result showed that 6 were goiter and the other 2 were minimal papillary carcinoma. None of the patients suffered from any complication, and the median follow up time was 6 months (1-28 months). The totally endoscopic technique is a feasible, safe and cosmic one for managing substernal goiter type I.

Interrelatedness of steering and lateral position parameters: Recommendations for the assessment of driving performance.

INTRODUCTION: Loss of attention leads to less steady driving within the lane and is one of the main causes of road accidents. To improve road safety, vehicle-based parameters such as steering wheel angle and lateral position are used to objectively assess driving performance, especially in monotonous driving tasks. METHOD: The present driving simulator study investigated the extent to which eight commonly used parameters are independent indicators of driving performance. Fifteen participants undertook a monotonous highway driving task for 1 h. Four steering angle parameters were examined: average steering angle (ASA), standard deviation of steering angle (SDSA), steering angle range (SAR), and steering reversal rate (SRR); as well as four lateral position parameters: mean lateral position (MLP), standard deviation of lateral position (SDLP), lateral position range (LPR), and the out-of-lane duration. Measurements were averaged across 2-minute epochs. Repeated measures correlation analysis evaluated the similarity between each parameter, and the variance inflation factor test evaluated the multicollinearity of all the parameters. RESULTS: The results demonstrated that some parameters are highly correlated and should not be used together to assess driving performance. It is recommended that the optimal combination is ASA and SAR to assess steering angle, and SDLP and out-of-lane to assess lateral position. Out-of-lane, as a factor directly contributing to road safety, is recommended because it has the least correlation with other parameters. PRACTICAL APPLICATIONS: If implemented, these recommendations may improve the assessment of driving performance in future studies.

The predictive role of the nomogram based on clinical characteristics and thromboelastography markers for rebleeding after hypertensive intracerebral hemorrhage.

Objectives: Rebleeding after hypertensive intracerebral hemorrhage is a common and serious postoperative complication in neurosurgery, with high mortality and mental disability rates. The aim of this study was to establish a nomogram to analyze the role of thromboelastography in predicting rebleeding after hypertensive intracerebral hemorrhage. Basic methods: We selected 375 patients with hypertensive intracerebral hemorrhage who underwent surgical treatment in Yuebei People's Hospital of Shaoguan City, Guangdong Province from May 2018 to August 2022, and retrospectively analyzed the relevant data of hypertensive intracerebral hemorrhage patients (including general data and clinical thromboelastography data), and analyzed the factors and thromboelastography parameters that affect rebleeding after surgery (45 cases, defined as re-examination of head CT within 72 h after surgery showed that the hematoma in the surgical area exceeded 20 ml). Main results: Time from symptom onset to surgery, taking antiplatelet drugs, taking anticoagulant drugs, diabetes mellitus, difficulty in hemostasis during surgery, R value and EPL value in thromboelastography were risk factors for rebleeding after hypertensive intracerebral hemorrhage (P < 0.05). Logistic regression was used to determine the independent risk factors, and based on these risk factors, a nomogram was established and internally validated using a bootstrap method. ROC curve analysis showed that the nomogram model had high diagnostic value for rebleeding after hypertensive intracerebral hemorrhage, with AUC of 0.7314. The calibration curve of the nomogram showed good consistency between the predicted probabilities and the observed values. The decision curve analysis and clinical impact curve also revealed the potential clinical usefulness of the nomogram. Conclusions: The nomogram based on clinical characteristics and thromboelastography markers may be useful for predicting rebleeding after hypertensive intracerebral hemorrhage.

Molecular identification and related functional characterization of the FKBP52 gene in immunity of Locusta migratoria manilensis (Orthoptera: Oedipodidae).

Metarhizium anisopliae is an important class of entomopathogenic fungi used for the biocontrol of insects, but its virulence is affected by insect immunity. We identified a novel FK506 binding protein gene that was differentially expressed between control and Metarhizium-treated Locusta migratoria manilensis. We hypothesized that this protein played an important role in Metarhizium infection of L. migratoria and could provide new insights for developing highly efficient entomopathogenic fungi. We, therefore, cloned the specific gene and obtained its purified protein. The gene was then named FKBP52, and its dsRNA (dsFKBP52) was synthesized and used for gene interference. Bioassay results showed that the mortality of L. migratoria treated with dsFKBP52 + Metarhizium was significantly lower than that of other treatments. Furthermore, immune-related genes (MyD88, Dorsal, Cactus, and Defensin) in L. migratoria treated with dsFKBP52 + Metarhizium showed significant upregulation compared to that treated with Metarhizium only. However, the activities of peroxidase (POD), superoxide dismutase (SOD), and calcineurin (CaN) showed fluctuations. These results suggest that the FKBP52 gene may play a crucial role in the innate immunity of L. migratoria. The effect of its silencing indicated that this immunity-related protein might be a potential target for insect biocontrol.

Giant lipoma in the Retzius space resected under laparoscopy: A case report.

Lipoma is a common type of benign soft tissue tumor that can occur in the shoulders, neck and back, in addition to other body parts. The Retzius space is a small anatomical space between the pubic symphysis and the bladder located extraperitoneally and filled with loose fatty connective tissue. Giant lipomas are rare in the Retzius space. A 61-year-old Chinese male arrived at Beijing Yanhua Hospital (Beijing, China) due to frequent urination, and CT scan images of the lower abdomen observed a large pelvic mass and left inguinal hernia. Preoperative clinical manifestations and auxiliary examination suggested that the tumor originated from the urinary bladder wall. The maximum tumor diameter was ~25 cm and abdominal pressure was increased. Therefore, laparoscopic pelvic tumor resection combined with inguinal hernia repair was attempted. Intraoperatively, the tumor was found to originate from the Retzius space and the postoperative pathological diagnosis was lipoma. The present case report may serve as a reference for minimally invasive treatment of this type of rare disease in future.

Vitamin D is involved in the effects of the intestinal flora and its related metabolite TMAO on perirenal fat and kidneys in mice with DKD.

BACKGROUND: Vitamin D was shown to directly exert a protective effect on diabetic kidney disease (DKD) in our previous study. However, whether it has an effect on perirenal adipose tissue (PRAT) or the intestinal flora and its metabolites (trimethylamine N-oxide, TMAO) is unclear. METHODS: DKD mice were received different concentrations of 1,25-(OH)2D3 for 2 weeks. Serum TNF-α levels and TMAO levels were detected. 16S rRNA sequencing was used to analyze gut microbiota. qPCR was used to detect the expression of TLR4, NF-Κb, PGC1α, and UCP-1 in kidney and adipose tissue. Histological changes in kidney and perirenal adipose tissue were observed using HE, PAS, Masson and oil red staining. Immunofluorescence and immunohistochemistry were used to detect the expression of VDR, PGC1α, podocin, and UCP-1 in kidney and adipose tissue. Electron microscopy was used to observe the pathological changes in the kidney. VDR knockout mice were constructed to observe the changes in the gut and adipose tissue, and immunofluorescence and immunohistochemistry were used to detect the expression of UCP-1 and collagen IV in the kidney. RESULTS: 1,25-(OH)2D3 could improve the dysbiosis of the intestinal flora of mice with DKD, increase the abundance of beneficial bacteria, decrease the abundance of harmful bacteria, reduce the pathological changes in the kidney, reduce fat infiltration, and downregulate the expression of TLR4 and NF-κB in kidneys. The serum TMAO concentration in mice with DKD was significantly higher than that of the control group, and was significantly positively correlated with the urine ACR. In addition, vitamin D stimulated the expression of the surface markers PGC1α, UCP-1 and VDR in the PRAT in DKD mice, and TMAO downregulated the expression of PRAT and renal VDR. CONCLUSIONS: The protective effect of 1,25-(OH)2D3 in DKD mice may affect the intestinal flora and its related metabolite TMAO on perirenal fat and kidneys.

HMGA2 elicits EMT by activating the Wnt/ß-catenin pathway in gastric cancer.

BACKGROUND: The high mobility group protein A2 (HMGA2) is an architectural transcription factor that plays an important role in the development and progression of many malignant neoplasms. High expression of HMGA2 in gastric cancer correlates with invasiveness of cancer and is an independent prognostic factor. The reason for this might be HMGA2 promoting epithelial-mesenchymal transitions (EMT), which is the key process of metastasis for some underlying mechanisms. AIMS: This study was designed to test whether HMGA2 participates in the EMT and to further understand the underlying mechanisms of EMT promoted by HMGA2. METHODS: We examined the cell biology and molecular biology changes after overexpression and knockdown HMGA2 of gastric cancer cells in vitro and vivo. To further understand the underlying mechanisms of EMT promoted by HMGA2, based on our previous study, we examined the changes of target genes of HMGA2 after overexpression and knockdown HMGA2 of gastric cancer cells. RESULTS: The results indicated that overexpressing HMGA2 enabled enhancing the oncogenic properties of gastric epithelial origin cell in vitro and in vivo. Furthermore, our study showed that HMGA2 was able to elicit EMT and regulate several genes which are closely related to the Wnt/ß-catenin pathway by directly binding to their promoter thereby activating the Wnt/ß-catenin pathway. CONCLUSIONS: The Wnt/ß-catenin pathway activated by HMGA2 might be the underlying mechanism of EMT in gastric cancer cells.

Quantitative time-course profiling of parasite and host cell proteins in the human malaria parasite Plasmodium falciparum.

Studies of the Plasmodium falciparum transcriptome have shown that the tightly controlled progression of the parasite through the intra-erythrocytic developmental cycle (IDC) is accompanied by a continuous gene expression cascade in which most expressed genes exhibit a single transcriptional peak. Because the biochemical and cellular functions of most genes are mediated by the encoded proteins, understanding the relationship between mRNA and protein levels is crucial for inferring biological activity from transcriptional gene expression data. Although studies on other organisms show that <50% of protein abundance variation may be attributable to corresponding mRNA levels, the situation in Plasmodium is further complicated by the dynamic nature of the cyclic gene expression cascade. In this study, we simultaneously determined mRNA and protein abundance profiles for P. falciparum parasites during the IDC at 2-hour resolution based on oligonucleotide microarrays and two-dimensional differential gel electrophoresis protein gels. We find that most proteins are represented by more than one isoform, presumably because of post-translational modifications. Like transcripts, most proteins exhibit cyclic abundance profiles with one peak during the IDC, whereas the presence of functionally related proteins is highly correlated. In contrast, the abundance of most parasite proteins peaks significantly later (median 11 h) than the corresponding transcripts and often decreases slowly in the second half of the IDC. Computational modeling indicates that the considerable and varied incongruence between transcript and protein abundance may largely be caused by the dynamics of translation and protein degradation. Furthermore, we present cyclic abundance profiles also for parasite-associated human proteins and confirm the presence of five human proteins with a potential role in antioxidant defense within the parasites. Together, our data provide fundamental insights into transcript-protein relationships in P. falciparum that are important for the correct interpretation of transcriptional data and that may facilitate the improvement and development of malaria diagnostics and drug therapy.