Simultaneous Determination of Transuranium Radionuclides in Urine by Tandem Quadrupole ICP-MS/MS with Mass-Shift Mode Combined with Chemical Separation.

The urine bioassay method for transuranium nuclides (237Np, 239,240,241Pu, 241Am, and 244Cm) is needed to quickly assess the potential internal contamination in emergency situations. However, in the case that the analysis of multiple radionuclides is required in the same sample, time-consuming/tedious sequential analytical procedures using multiple chromatographic separation resins would have to be employed for the separation of every single radionuclide. In this work, a rapid method for the simultaneous determination of transuranium nuclides in urine was developed by using triple quadrupole inductively coupled plasma mass spectrometry (ICP-MS/MS) combined with a single DGA resin column. The chemical behaviors of Np/Pu and Am/Cm on the DGA resin were consistent in 8-10 mol/L HNO3 and 0.005-0.02 mol/L NaNO2 when 242Pu and 243Am were selected as tracers for Np/Pu and Am/Cm yield monitoring. Based on their different reaction rates with O2, 237Np, 239,240,241Pu, 241Am, and 244Cm in the same solution were simultaneously measured by ICP-MS/MS in the same run. The elimination efficiency of 238U+ tailing (7.43 × 10-9), 238U1H16O2+/238U16O2+ (8.11 × 10-8) and cross contamination of 241Pu and 241Am (<1%) were achieved using 10.0 mL/min He-0.3 mL/min O2 even if the eluate was directly measured without any evaporation. The detection limits of transuranium nuclides were at the femtogram level, demonstrating the feasibility of ICP-MS/MS for simultaneous transuranic radionuclides urinalysis. The developed method was validated by analyzing the spiked urine samples.

Robustness of the modified multi-trench fiber design with two gaps.

We investigate the robustness of a modified multi-trench fiber (MTF) design with two gaps numerically. The excellent suppression of high-order modes is demonstrated over a wide range of the gap misalignment and the fundamental mode loss is barely affected even with the 5 dB/m scattering loss in gaps at the modified two-gap MTF for the first time. Therefore, the required fabrication accuracy decreases.

Application of hydrogel microneedles in the oral cavity.

Microneedles are a transdermal drug delivery system in which the needle punctures the epithelium to deliver the drug directly to deep tissues, thus avoiding the influence of the first-pass effect of the gastrointestinal tract and minimizing the likelihood of pain induction. Hydrogel microneedles are microneedles prepared from hydrogels that have good biocompatibility, controllable mechanical properties, and controllable drug release and can be modified to achieve environmental control of drug release in vivo. The large epithelial tissue in the oral cavity is an ideal site for drug delivery via microneedles. Hydrogel microneedles can overcome mucosal hindrances to delivering drugs to deep tissues; this prevents humidity and a highly dynamic environment in the oral cavity from influencing the efficacy of the drugs and enables them to obtain better therapeutic effects. This article analyzes the materials and advantages of common hydrogel microneedles and reviews the application of hydrogel microneedles in the oral cavity.

[Research on emotion recognition method based on IWOA-ELM algorithm for electroencephalogram].

Emotion is a crucial physiological attribute in humans, and emotion recognition technology can significantly assist individuals in self-awareness. Addressing the challenge of significant differences in electroencephalogram (EEG) signals among different subjects, we introduce a novel mechanism in the traditional whale optimization algorithm (WOA) to expedite the optimization and convergence of the algorithm. Furthermore, the improved whale optimization algorithm (IWOA) was applied to search for the optimal training solution in the extreme learning machine (ELM) model, encompassing the best feature set, training parameters, and EEG channels. By testing 24 common EEG emotion features, we concluded that optimal EEG emotion features exhibited a certain level of specificity while also demonstrating some commonality among subjects. The proposed method achieved an average recognition accuracy of 92.19% in EEG emotion recognition, significantly reducing the manual tuning workload and offering higher accuracy with shorter training times compared to the control method. It outperformed existing methods, providing a superior performance and introducing a novel perspective for decoding EEG signals, thereby contributing to the field of emotion research from EEG signal.

Photo-Enhanced Chemo-Transistor Platform for Ultrasensitive Assay of Small Molecules.

Compared with traditional assay techniques, field-effect transistors (FETs) have advantages such as fast response, high sensitivity, being label-free, and point-of-care detection, while lacking generality to detect a wide range of small molecules since most of them are electrically neutral with a weak doping effect. Here, we demonstrate a photo-enhanced chemo-transistor platform based on a synergistic photo-chemical gating effect in order to overcome the aforementioned limitation. Under light irradiation, accumulated photoelectrons generated from covalent organic frameworks offer a photo-gating modulation, amplifying the response to small molecule adsorption including methylglyoxal, p-nitroaniline, nitrobenzene, aniline, and glyoxal when measuring the photocurrent. We perform testing in buffer, artificial urine, sweat, saliva, and diabetic mouse serum. The limit of detection is down to 10-19 M methylglyoxal, about 5 orders of magnitude lower than existing assay technologies. This work develops a photo-enhanced FET platform to detect small molecules or other neutral species with enhanced sensitivity for applications in fields such as biochemical research, health monitoring, and disease diagnosis.

LRRC23 is a conserved component of the radial spoke that is necessary for sperm motility and male fertility in mice.

Cilia and flagella are ancient structures that achieve controlled motor functions through the coordinated interaction based on microtubules and some attached projections. Radial spokes (RSs) facilitate the beating motion of these organelles by mediating signal transduction between dyneins and a central pair (CP) of singlet microtubules. RS complex isolation from Chlamydomonas axonemes enabled the detection of 23 radial spoke proteins (RSP1-RSP23), although the roles of some radial spoke proteins remain unknown. Recently, RSP15 has been reported to be bound to the stalk of RS2, but its homolog in mammals has not been identified. Herein, we show that Lrrc23 is an evolutionarily conserved testis-enriched gene encoding an RSP15 homolog in mice. We found that LRRC23 localizes to the RS complex within murine sperm flagella and interacts with RSPH3A and RSPH3B. The knockout of Lrrc23 resulted in male infertility due to RS disorganization and impaired motility in murine spermatozoa, whereas the ciliary beating was not significantly affected. These data indicate that LRRC23 is a key regulator that underpins the integrity of the RS complex within the flagella of mammalian spermatozoa, whereas it is dispensable in cilia. This article has an associated First Person interview with the first author of the paper.

Head-to-head comparisons of [68Ga]Ga-PSMA-11 PET/CT, multiparametric MRI, and prostate-specific antigen for the evaluation of therapeutic responses to neoadjuvant chemohormonal therapy in high-risk non-metastatic prostate cancer patients: a prospective study.

PURPOSE: The optimal tool to evaluate the tumour therapeutic responses to neoadjuvant chemohormonal therapy (NCHT) in patients with high-risk non-metastatic prostate cancer (PCa) remains uncertain. We compared the role of [68Ga]-labeled prostate-specific membrane antigen (PSMA)-11 positron emission tomography/computerized tomography ([68Ga]Ga-PSMA-11 PET/CT), multiparametric MRI (mpMRI), and prostate-specific antigen (PSA) and assessed the practical value of the recent European Association of Urology and European Association of Nuclear Medicine (EAU/EANM) recommended criteria of PSMA PET/CT to evaluate the therapeutic responses to NCHT in patients with high-risk non-metastatic PCa. METHODS: This prospective study included 72 high-risk non-metastatic PCa patients receiving NCHT followed by radical prostatectomy from June 2021 to March 2022. PSA testing, [68Ga]Ga-PSMA-11 PET/CT, and mpMRI scanning were conducted in all patients before and after NCHT. Therapeutic responses to NCHT were evaluated with PSA, RECIST 1.1, PERCIST 1.0, and EAU/EANM recommended criteria. Postoperative pathological results were considered the reference standard. A favourable pathological response was defined as pathologic complete remission (pCR) or minimal residual disease (MRD). Diagnostic accuracy was assessed by sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), positive predictive value (PPV), negative predictive value (NPV), and Cohen's kappa index. Logistic regression analysis was used to determine the independent predictive value of [68Ga]Ga-PSMA-11 PET/CT-derived parameters. RESULTS: All cases experienced a marked decrease in PSA levels after NCHT. Twenty-four (33.33%) cases experienced a favourable pathological response, including five (6.94%) cases of pCR and 19 (26.39%) cases of MRD. According to the results of [68Ga]Ga-PSMA-11 PET/CT, EAU/EANM recommended criteria indicated that 20 (27.78%) cases had a CR, whereas PERCIST 1.0 criteria indicated that 23 (31.94%) cases had a CR. There was a strong association between EAU/EANM recommended criteria and PERCIST 1.0 criteria (Pearson's R=0.857). The sensitivity (75.00%, 79.17% vs. 58.33%, 58.33%), specificity (95.83%, 91.67% vs. 83.33%, 68.75%), PLR (18.00, 9.50 vs. 3.50, 1.87), NLR (0.26, 0.23 vs. 0.50, 0.61), PPV (90.0%, 82.6% vs. 63.6%, 48.3%), and NPV (88.5%, 89.8% vs. 80.0%, 76.7%) of [68Ga]Ga-PSMA-11 PET/CT (including EAU/EANM recommended criteria and PERCIST 1.0 criteria) to predict favourable pathological responses were all superior to those of mpMRI and nadir PSA. The kappa index to predict a favourable pathological response was 0.257 for PSA, 0.426 for RECIST 1.1, 0.716 for PERCIST 1.0, and 0.739 for EAU/EANM recommended criteria. Multivariate logistic analysis revealed that the post-NCHT maximum standardized uptake value (SUVmax) before radical prostatectomy was an independent predictor of a favourable pathological response to NCHT. CONCLUSIONS: [68Ga]Ga-PSMA-11 PET/CT had a better concordance with a favourable pathological response to NCHT compared with nadir PSA and mpMRI. EAU/EANM recommended criteria and PERCIST 1.0 criteria performed equally to identify pathological responders when [68Ga]Ga-PSMA-11 PET/CT was used as a therapeutic response assessment tool.

A Liquid-Liquid Phase Separation-Related Index Associate with Biochemical Recurrence and Tumor Immune Environment of Prostate Cancer Patients.

To identify liquid-liquid phase separation (LLPS)-related molecular clusters, and to develop and validate a novel index based on LLPS for predicting the prognosis of prostate cancer (PCa) patients. We download the clinical and transcriptome data of PCa from TCGA and GEO database. The LLPS-related genes (LRGs) were extracted from PhaSepDB. Consensus clustering analysis was used to develop LLPS-related molecular subtypes for PCa. The LASSO cox regression analysis was performed to establish a novel LLPS-related index for predicting biochemical recurrence (BCR)-free survival (BCRFS). Preliminary experimental verification was performed. We initially identified a total of 102 differentially expressed LRGs for PCa. Three LLPS related molecular subtypes were identified. Moreover, we established a novel LLPS related signature for predicting BCRFS of PCa patients. Compared to low-risk patients in the training cohort, testing cohort and validating cohort, high-risk populations meant a higher risk of BCR and significantly poorer BCRFS. The area under receiver operating characteristic curve were 0.728, 0.762, and 0.741 at 1 year in the training cohort, testing cohort and validating cohort. Additionally, the subgroup analysis indicated that this index was especially suitable for PCa patients with age ≤ 65, T stage III-IV, N0 stage or in cluster 1. The FUS, which was the potential biomarker related to PCa liquid-liquid phase separation, was preliminarily identified and verified. This study successfully developed three LLPS-related molecular subtypes and identified a novel LLPS related molecular signature, which performed well in predicting BCRFS of PCa.

Self-Expanding Molten Salt-Driven Growth of Patterned Transition-Metal Dichalcogenide Crystals.

Transition-metal dichalcogenides (TMDs) have been considered potential materials for the next generation of semiconductors. Realizing controllable growth of TMD crystals is a prerequisite for their future applications, which remains challenging. Here, we reveal a new mechanism of self-expanding molten salt-driven growth for a salt-assisted method and achieve the patterned growth of TMD single-crystal arrays with a size of hundreds of micrometers. Time-of-flight secondary ion mass spectroscopy and other spectroscopy characterizations identify the component of the molten salt solution. Microscopic characterizations reveal the existence of salt solution as an interlayer between a TMD monolayer and the silicon substrate as well as particles along the crystal edge. The edged salt solution serves as a self-expanding liquid substrate, which confines the reactive sites to the localized liquid surface, thus avoiding random nucleation. The surface reaction also assures monolayer crystal formation due to self-limiting growth. Besides, the liquid substrate affords sources and spreads itself continuously owing to the nonwetting effect on TMD crystals, thereby facilitating the continuous extension of the TMD monolayer. This work provides novel insights into the controllable synthesis of TMD monolayers and paves the way for the fabrication of TMD-based integrated functional devices.

[The effect of different types of exercise on the intestinal mechanical barrier and related regulatory factors in type 2 diabetic mice].

The aim of this study was to investigate the effects of different types of exercise on intestinal mechanical barrier and related regulatory factors in mice with type 2 diabetes mellitus (T2DM). The model was established by high-fat diet feeding and intraperitoneal injection of streptozocin (STZ). The mice were divided into control group, model group (free exercise), resistance exercise group (tail load-bearing ladder climbing, 5 times a week), aerobic exercise group (non-load-bearing platform running, 5 times a week at a speed of 10-15 m/min), and combined exercise group (aerobic exercise was performed on the first, third and fifth days of each week, and resistance exercise on the second and fourth days of each week). After 8 weeks of intervention, the serum lipid levels and inflammatory cytokines were measured by corresponding kits. The pathological changes of ileum were detected by HE and PAS staining. The mRNA and protein expression levels of tight junction-related proteins were detected by real-time qPCR and Western blot, respectively. Moreover, the protein expression levels of hypoxia inducible factor-1α (HIF-1α) and myosin light chain kinase (MLCK) were detected by Western blot. The results showed that all three types of exercise decreased blood glucose and body weight compared to the model group. Aerobic exercise and combined exercise decreased serum lipid (triglycerides and total cholesterol) levels, up-regulated the expression levels of ileal tight junction-related proteins and HIF-1α, improved the intestinal alkaline phosphatase (AKP) activity, reduced serum lipopolysaccharide (LPS), interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α) and diamine oxidase (DAO) levels, and down-regulated MLCK protein expression level. These results suggest that all three types of exercise can reduce blood glucose and body weight of T2DM mice, and aerobic exercise and combined exercise can restore the damaged intestinal mechanical barrier by a mechanism involving HIF-1α-MLCK pathway.

1,25(OH)2 D3 attenuates sleep disturbance in mouse models of Lewis lung cancer, in silico and in vivo.

Many clinical studies have reported that patients diagnosed with cancer will suffer from sleep disturbance during their clinical process, especially among lung cancer patients, and this effect will not easily subside. 1,25-dihydroxy-vitamin-D3 [1,25(OH)2 D3 ], the activated form of vitamin D, can participate in neuronal differentiation and prevent damage to the nervous system. However, little is known about the potential therapeutic effects of cancer-related psychiatric symptoms. In light of this, we hypothesized that a low circulating level of vitamin D was related to sleep quality in the presence of a tumor, 1,25(OH)2 D3 may be an effective way to ameliorate sleep disturbance and neurochemical alterations along with the cancer progress. Male C57BL/6 mice were implanted with intracranial transmitters to monitor electroencephalogram and were subcutaneously inoculated with Lewis lung cancer cells. The results demonstrated that on Days 19-20, tumor-bearing mice displayed fragmented sleep, shortened wake phase, prolonged sleep in the non-rapid eye movement phase, and the levels of vitamin D-associated genes in the brain had changed a lot compared to control mice. Importantly, 1,25(OH)2 D3 treatment really effectively saved the sleep quality of tumor-bearing mice. We further explored and confirmed that 1,25(OH)2 D3 repressed tumor-induced neuroinflammation (IL-1ß, TNF-α, IL-6, IL-10, IFN-γ, and IL-2), enhanced neurotrophic factors (brain-derived neurotrophic factor [BDNF], glialcellline-derived neurotrophic factor) and 5-HT system in the hippocampus, hypothalamus or cortex. A molecular docking approah manifested the ability of 1,25(OH)2 D3 to affect the activity of tryptophan hydroxylase 2 and BDNF. Together, our results suggested that 1,25(OH)2 D3 treatment may attenuate sleep disturbance in Lewis lung cancer-bearing mice, and become a promising strategy for treating cancer symptom clusters to ameliorate the quality of life of patients with cancer.

Granulocyte colony-stimulating factor (G-CSF) mediates bone resorption in periodontitis.

BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) is an important immune factor that mediates bone metabolism by regulating the functions of osteoclasts and osteoblasts. Bone loss is a serious and progressive result of periodontitis. However, the mechanisms underlying the effects of G-CSF on periodontal inflammation have yet not been completely elucidated. Here, we examined whether an anti-G-CSF antibody could inhibit bone resorption in a model of experimental periodontitis and investigated the local expression of G-CSF in periodontal tissues. METHODS: Experimental periodontitis was induced in mice using ligatures. The levels of G-CSF in serum and bone marrow were measured; immunofluorescence was then performed to analyze the localization and expression of G-CSF in periodontal tissues. Mice with periodontitis were administered anti-G-CSF antibody by tail vein injection to assess the inhibition of bone resorption. Three-dimensional reconstruction was performed to measure bone destruction-related parameters via micro-computed tomography analysis. Immunofluorescence staining was used to investigate the presence of osteocalcin-positive osteoblasts; tartrate-resistant acid phosphatase (TRAP) staining was used to observe osteoclast activity in alveolar bone. RESULTS: The level of G-CSF in serum was significantly elevated in mice with periodontitis. Immunofluorescence analyses showed that G-CSF was mostly expressed in the cell membrane of gingival epithelial cells; this expression was enhanced in the periodontitis group. Additionally, systemic administration of anti-G-CSF antibody significantly inhibited alveolar bone resorption, as evidenced by improvements in bone volume/total volume, bone surface area/bone volume, trabecular thickness, trabecular spacing, and trabecular pattern factor values. Immunofluorescence analysis revealed an enhanced number of osteocalcin-positive osteoblasts, while TRAP staining revealed reduction of osteoclast activity. CONCLUSIONS: G-CSF expression levels were significantly up-regulated in the serum and gingival epithelial cells. Together, anti-G-CSF antibody administration could alleviates alveolar bone resorption, suggesting that G-CSF may be one of the essential immune factors that mediate the bone loss in periodontitis.

CRISPR/Cas9-based genome editing in mice uncovers 13 testis- or epididymis-enriched genes individually dispensable for male reproduction†.

Developing a safe and effective male contraceptive remains a challenge in the field of medical science. Molecules that selectively target the male reproductive tract and whose targets are indispensable for male reproductive function serve among the best candidates for a novel non-hormonal male contraceptive method. To determine the function of these genes in vivo, mutant mice carrying disrupted testis- or epididymis-enriched genes were generated by zygote microinjection or electroporation of the CRISPR/Cas9 components. Male fecundity was determined by consecutively pairing knockout males with wild-type females and comparing the fecundity of wild-type controls. Phenotypic analyses of testis appearance and weight, testis and epididymis histology, and sperm movement were further carried out to examine any potential spermatogenic or sperm maturation defect in mutant males. In this study, we uncovered 13 testis- or epididymis-enriched evolutionarily conserved genes that are individually dispensable for male fertility in mice. Owing to their dispensable nature, it is not feasible to use these targets for the development of a male contraceptive.

A Retrospective Population Study to Develop a Predictive Model of Prediabetes and Incident Type 2 Diabetes Mellitus from a Hospital Database in Japan Between 2004 and 2015.

BACKGROUND Type 2 diabetes mellitus is a global public health problem. Prediabetes may be reversed by weight loss, diet, and lifestyle changes. However, without intervention, between 30-50% of individuals with prediabetes develop type 2 diabetes. This retrospective population study was conducted to develop a predictive model of prediabetes and incident type 2 diabetes mellitus using data from 2004 to 2015 from the DRYAD Japanese hospital database. MATERIAL AND METHODS A retrospective longitudinal population study was conducted using the DRYAD database from Murakami Memorial Hospital, Gifu, Japan, to construct a predictive model for prediabetes and incident type 2 diabetes mellitus in the population. Univariate analysis and multivariate analysis were performed to identify the variables that were associated with prediabetes. These variables were used to construct (75% samples) and verify (25% samples) the predictive model. RESULTS From 2004 to 2015, a total of 11,113 cases were identified. Multivariate logistic regression analysis included the six variables of age, waist circumference, smoking history, the presence of fatty liver, fasting blood glucose (FBG), and glycated hemoglobin (HbA1c) level. Data were used to construct (75% samples) and verify (25% samples) in a predictive model. The area under the receiver operating characteristic (ROC) curve (AUC) of the predictive model was 0.87 (0.85-0.89) in the training cohort and 0.87 (0.86-0.90) in the validation cohort. CONCLUSIONS A prognostic model based on six variables was predictive for incident type 2 diabetes mellitus and prediabetes in a healthy population in Japan.

SOFA score is superior to APACHE-II score in predicting the prognosis of critically ill patients with acute kidney injury undergoing continuous renal replacement therapy.

BACKGROUND: Acute kidney injury (AKI) is the most common cause of organ failure in multiple organ dysfunction syndrome (MODS) and is associated with increased mortality. This study aimed at determining the efficacy of sequential organ failure assessment (SOFA), and acute physiology and chronic health evaluation II (APACHE-II) scoring systems in assessing the prognosis of critically ill patients with AKI undergoing CRRT. METHODS: The predictive value of SOFA and APACHE-II scores for 28- and 90-d mortality in patients with AKI undergoing continuous renal replacement therapy (CRRT) were determined by multivariate analysis, sensitivity analysis, and curve-fitting analysis. RESULTS: A total of 836 cases were included in this study. Multivariate Cox logistic regression analysis showed that SOFA scores were associated with 28- and 90-d mortality in patients with AKI undergoing CRRT. The adjusted HR of SOFA for28-d mortality were 1.18 (1.14, 1.21), 1.24 (1.18, 1.31), and 1.19 (1.13, 1.24) in the three models, respectively, and the adjusted HR of SOFA for 90-d mortality was 1.12 (1.09, 1.16), 1.15 (1.10, 1.19), and 1.15 (1.10, 1.19), respectively. The subgroup analysis showed that the SOFA score was associated with 28-d and 90-d mortality in patients with AKI undergoing CRRT. APACHE-II score was not associated with 28- and 90-d mortality patients with AKI undergoing CRRT. Curve fitting analysis showed that SOFA scores increased had a higher prediction accuracy for 28- and 90-d than APACHE-II. CONCLUSIONS: The SOFA score showed a higher accuracy of mortality prediction in critically ill patients with AKI undergoing CRRT than the APACHE-II score.

Pump absorption, laser amplification, and effective length in double-clad ytterbium-doped fibers with small area ratio.

We use numerical simulations with the beam propagation method (BPM) and rate equations to investigate the pump absorption and amplification characteristics in double-clad ytterbium-doped fibers with small cladding-to-core area ratios, in the range 1-3. The presence of modes with low overlap with the doped region (or alternatively, skew rays) hampers the pump absorption in a circular geometry, but we find that the effect is small for area ratios of ∼2.5 or less. We derive ray-based expressions for the small-signal absorption which show similar results. However, even when the small-signal absorption scales nearly ideally with the inverse of the area ratio, the absorption in an operating amplifier is much lower, and the dependence on the area ratio much weaker, when a large fraction of the Yb-ions is excited in a small-area-ratio fiber. We derive equations which show this, and that in contrast to conventional area ratios of, e.g., 100, the fiber length depends more strongly on the required gain than on the required pump absorption. However, fibers substantially shorter than 1 m still allow for adequate pump absorption and gain. The effective length for nonlinear interactions is less affected by this, since the Yb-excitation is low where the signal power is high. Although we treat single-mode cores, the BPM amplifier simulations show there are a few percent of the signal power in cladding-guided modes with high overlap with the Yb-doped core. Nevertheless, according to our simulations, it is possible to achieve high efficiency and mode purity with a small-area-ratio circularly symmetric double-clad fiber.

Immune tolerance of vector beetle to its partner plant parasitic nematode modulated by its insect parasitic nematode.

Immune response of insect vectors to transmitted pathogens or insect hosts against parasites are well studied, whereas the mechanism of tripartite interactions remains elusive. In this study, we investigated the immune interactions of the vector beetle Monochamus alternatus ( Ma) to the devastating plant parasitic nematode Bursaphelenchus xylophilus ( Bx) and the insect parasitic nematode Howardula phyllotretae ( Hp). We report the unique immune mechanism by which the vector beetle tolerates many devastating Bx in its trachea, yet that immune tolerance is compromised by the parasitic nematode Hp. Contact with either nematode species triggers epithelial reactive oxygen species (ROS) production in Ma. Only the entry of Bx, not Hp, infection, induces increased expression of antioxidative genes, through which the ROS levels are balanced in the trachea of beetles. Furthermore, we found that up-regulation of antioxidative genes was induced by the interaction of Toll receptors. In contrast, beetles infected by Hp retain high levels of oxidative stress and melanization in trachea, and as a result, decrease Bx loading. This study highlights the role of Toll receptors in mediating the activation of antioxidative genes in immune tolerance to plant parasitic nematodes, and suggests the use of insect parasites as a biologic control.-Zhou, J., Zhao, L.-L., Yu, H.-Y., Wang, Y.-H., Zhang, W., Hu, S.-N., Zou, Z., Sun, J.-H. Immune tolerance of vector beetle to its partner plant parasitic nematode modulated by its insect parasitic nematode.

Higher body mass index is not a protective risk factor for 28-days mortality in critically ill patients with acute kidney injury undergoing continuous renal replacement therapy.

Background: Acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT) is a fatal and common clinical disorder in critically ill patients. Recent studies have shown that the relationship between BMI and the outcome of patients with AKI undergoing CRRT is conflicting. Methods: A retrospective cohort study based on data reuse. Univariate analysis, multi-factor regression analysis and subgroup analyses were used to explore the association of the BMI with the 28-days mortality risk in patients with AKI undergoing CRRT. Results: From January 2009 to September 2016, a total of 1120 cases met the inclusion criteria and were enrolled in this study. The univariate analysis showed that BMI was associated with 28-days mortality of patients with AKI undergoing CRRT, its HR value was 0.98 (0.96, 0.99). The multi-factor regression analysis showed that BMI was not associated with 28-days mortality of patients with AKI undergoing CRRT in the four models, the adjusted HR value of four models were 1.00 (0.96, 1.04), 1.01 (0.97, 1.04), 1.00 (0.96, 1.04) and 1.00 (0.96, 1.04), respectively. The subgroups analyses showed that the BMI was a risk factor of the 28-days mortality in patients with AKI undergoing CRRT when GFR ≥30 mL/min, its HR value was 1.04 (1.01, 1.09). Conclusion: Higher BMI was not a protective risk of 28-day mortality in patients with AKI undergoing CRRT. Especially, when GFR ≥30 mL/min, higher BMI increased the risk of the 28-day mortality rate in patients with AKI undergoing CRRT.

Low molecular weight chitosan-based conjugates for efficient Rhein oral delivery: synthesis, characterization, and pharmacokinetics.

OBJECTIVE: This article aims to design low molecular weight chitosan (LMWC)-based conjugates of Rhein (RH) by means of an amino acid linker (Alanine) for improved solubility and enhanced bioavailability. SIGNIFICANCE: Rhein is a potential candidate for the therapy of kidney disease. However, the poor solubility, inadequate bioavailability, and lack of proper formulation restrict its clinical applicability. LMWC-drug conjugates offer the potential to improve the water-solubility of RH, increase its oral absorption, and thereby enhance its bioavailability. METHODS: The conjugates were synthesized via a carbodiimide reaction and confirmed using UV-vis, FTIR, and 1H-NMR spectroscopy. The water-solubility and in vitro release properties were evaluated. Free RH and RH-LMWC conjugates were administered at an equivalent oral gavage dose of RH at 35 mg/kg for pharmacokinetic studies in Sprague Dawley rats. RESULTS: The conjugates with RH content of 9.65% were successfully synthesized and featured a satisfactory water-solubility of 9.73 mg/mL, which exhibited a sustained release pattern over 72 h, and the enzymes present may promote the degradation of the conjugate to increase the release of Rhein. Oral administration of RH-LMWC conjugates to rats led to seven-folds and 3.1-folds increase in the T1/2 and AUC0-∞, respectively, as compared to RH suspension. CONCLUSION: The present work demonstrated that the RH-LMWC conjugates exhibited sustained release properties with outstanding oral bioavailability enhancements compared to administration of RH itself. Potentially, RH-LMWC conjugates may serve as a promising lead for developing a new platform for RH oral delivery.

[Personality and depression: A review of theory model and behavior and neural mechanism].

The analysis of the relationship between personality and depression can facilitate the development of subclinical preventive measures and clinical treatment schemes. Moreover, the personality is associated with a variety of mental diseases, and there is substantial comorbidity between depression and some other mental diseases. So, to reveal pathological relationships between personality and depression is helpful to understand the etiology of the comorbidity between depression and multiple mental disorders. In this review, we first summarize the empirical researches on the relationship between personality and depression from the aspects of behavior and neural mechanisms, and then discuss the hypothetical model to explain the relationship between personality and depression. In a word, high neuroticism, low extroversion and conscientiousness, and other related traits (rumination, self-criticism, dependency, etc.) have a moderate to strong correlation with depression. Among them, neuroticism is the most concerned. To a certain extent, it can predict the onset of depression and affect the duration and treatment outcome of depression. Other traits, such as positive emotionality/ extroversion and effortful control/responsibility, can moderate the relationship between negative emotionality/neuroticism and depression. And after the onset of depression, the neuroticism may change, but the extroversion does not seem to change.