Multiple functions of HMGB1 in cancer.

High mobility group box 1 (HMGB1) is a nuclear DNA-binding protein with a dual role in cancer, acting as an oncogene and a tumor suppressor. This protein regulates nucleosomal structure, DNA damage repair, and genomic stability within the cell, while also playing a role in immune cell functions. This review comprehensively evaluates the biological and clinical significance of HMGB1 in cancer, including its involvement in cell death and survival, its potential as a therapeutic target and cancer biomarker, and as a prosurvival signal for the remaining cells after exposure to cytotoxic anticancer treatments. We highlight the need for a better understanding of the cellular markers and mechanisms involved in the involvement of HMGB1in cancer, and aim to provide a deeper understanding of its role in cancer progression.

Bioinformatics analysis and experimental verification of NLRX1 as a prognostic factor for esophageal squamous cell carcinoma.

Nucleotide binding and oligomeric domain-like receptor X1 (NLRX1), a member of the NLR family, is associated with the physiological and pathological processes of inflammation, autophagy, immunity, metabolism and mitochondrial regulation, and has been demonstrated to have pro- or antitumor effects in various tumor types. However, the biological function of NLRX1 in esophageal squamous cell carcinoma (ESCC) has remained elusive. In the present study, by using bioinformatics methods, the differential expression of NLRX1 at the mRNA level was examined. Overall survival, clinical correlation, receiver operating characteristic curve, Cox regression, co-expression, enrichment, immune infiltration and drug sensitivity analyses were carried out. A nomogram and a calibration curve were constructed. Changes in protein expression levels were investigated by immunohistochemistry and western blotting. The impact of NLRX1 on i) cell proliferation was evaluated by Cell Counting Kit-8 assays; ii) migration was examined by wound-healing assays; iii) migration and invasion were evaluated by Transwell assays; and iv) apoptosis was assessed by Annexin V/PI staining and flow cytometry. The results revealed that, compared to normal adjacent tissue, NLRX1 was lowly expressed in ESCC, and patients with low NLRX1 expression had a shorter survival time. NLRX1 was an independent prognostic factor for ESCC and was associated with tumor grading. Patients in the low-NLRX1 group showed a decrease in the infiltration of activated natural killer cells, monocytes and M0 macrophages, and these immune-cell infiltration levels were positively correlated with NLRX1 expression. Knocking down NLRX1 promoted the proliferation of KYSE450 cells, while overexpression of NLRX1 inhibited the proliferation of ECA109 cells. NLRX1 negatively regulated the PI3K/AKT signaling pathway in ESCC. These findings indicate that, through several mechanisms, NLRX1 suppresses tumor growth in ESCC, which offers new insight for investigating the causes and progression of ESCC, as well as for identifying more efficient therapeutic approaches.

The therapeutic effects of marine sulfated polysaccharides on diabetic nephropathy.

Marine sulfated polysaccharide (MSP) is a natural high molecular polysaccharide containing sulfate groups, which widely exists in various marine organisms. The sources determine structural variabilities of MSPs which have high security and wide biological activities, such as anticoagulation, antitumor, antivirus, immune regulation, regulation of glucose and lipid metabolism, antioxidant, etc. Due to the structural similarities between MSP and endogenous heparan sulfate, a majority of studies have shown that MSP can be used to treat diabetic nephropathy (DN) in vivo and in vitro. In this paper, we reviewed the anti-DN activities, the dominant mechanisms and structure-activity relationship of MSPs in order to provide the overall scene of MSPs as a modality of treating DN.

Characteristics of glucolipid metabolism and oxidative stress in breeding pigeons (Columba livia) during lactation.

Breeding pigeons is a fundamental source of profit in various enterprises but little is known on the metabolic laws governing their lactation. In this study, we analysed the metabolic profile of different sex of breeding pigeons (Columba livia, European pigeons, Mimas) during lactation. We found that male pigeons exhibited catabolism during lactation. Extension of lactation resulted in increased weight loss, then slow recovery of body weight. Conversely, the weight loss in female pigeons peaked on the seventh day of lactation. They then gradually recovered their body weight. Male pigeons showed more duration of combing, while female pigeons showed more duration of resting. In male pigeons, except for triglyceride (TG), which increased, blood lipid indexes barely changed during lactation. Conversely, in females, both TG and total cholesterol increased in middle and late lactation. The level of oxidative stress in female pigeons during lactation was higher than in males, lipid peroxide malondialdehyde, hydrogen peroxide (H2 O2 ), plasma calcium (Ca) and phosphorus (P) levels increased in late lactation. Levels of estradiol and progesterone in female pigeons increased during lactation, whereas those of luteotropic hormone (LH), follicle-stimulating hormone (FSH), prolactin (PRL) and testosterone gradually decreased. As per LC-MS spectra analysis, the differential metabolites in the plasma on the day of hatching and before laying in female pigeons in lactation were enriched in retrograde endocannabinoid signalling, α-linolenic acid, arachidonic acid, choline, glycerophospholipid metabolisms, and valine, leucine, and isoleucine degradations. Levels of fatty acids, amino acids, sphingomyelin and phosphatidylinositol related to the secretion of pigeon milk had reduced, whereas the levels of phosphatidylcholine, phosphatidylethanolamine, and TG, which are all related to egg production, had increased. In conclusion, our study systematically revealed the different metabolic characteristics of male and female breeding pigeons during lactation. This is useful for precision feeding of pigeons and applicable in nutritional interventions for improved production.

Impact of ovary-sparing treatment planning on plan quality, treatment time and gamma passing rates in intensity-modulated radiotherapy for stage I/II cervical cancer.

BACKGROUND: This study aimed to investigate the impact of ovary-sparing intensity-modulated radiotherapy (IMRT) on plan quality, treatment time, and gamma passing rates for stage I/II cervical cancer patients. METHODS: Fifteen stage I/II cervical cancer patients were retrospectively enrolled, and a pair of clinically suitable IMRT plans were designed for each patient, with (Group A) and without (Group B) ovary-sparing. Plan factors affecting plan quality, treatment time, and gamma passing rates, including the number of segments, monitor units, percentage of small-area segments (field area < 20 cm2), and percentage of small-MU segments (MU < 10), were compared and statistically analyzed. Key plan quality indicators, including ovarian dose, target dose coverage (D98%, D95%, D50%, D2%), conformity index, and homogeneity index, were evaluated and statistically assessed. Treatment time and gamma passing rates collected by IBA MatriXX were also compared. RESULTS: The median ovarian dose in Group A and Group B was 7.61 Gy (range 6.71-8.51 Gy) and 38.52 Gy (range 29.84-43.82 Gy), respectively. Except for monitor units, all other plan factors were significantly lower in Group A than in Group B (all P < .05). Correlation coefficients between plan factors, treatment time, and gamma passing rates that were statistically different were all negative. Both Groups of plans met the prescription requirement (D95% ≥ 45.00 Gy) for clinical treatment. D98% was smaller for Group A than for Group B (P < .05); D50% and D2% were larger for Group A than for Group B (P < .05, P < .05). Group A plans had worse conformity index and homogeneity index than Group B plans (P < .05, P < .05). Treatment time did not differ significantly (P > .05). Gamma passing rates in Group A were higher than in Group B with the criteria of 2%/3 mm (P < .05) and 3%/2 mm (P < .05). CONCLUSION: Despite the slightly decreased quality of the treatment plans, the ovary-sparing IMRT plans exhibited several advantages including lower ovarian dose and plan complexity, improved gamma passing rates, and a negligible impact on treatment time.

Development of self-cooperative nanochaperones with enhanced activity to facilitate protein refolding.

Regulating protein folding including assisting de novo folding, preventing misfolding and aggregation, and facilitating refolding of proteins are of significant importance for retaining protein's biological activities. Here, we report a mixed shell polymeric micelle (MSPM)-based self-cooperative nanochaperone (self-CO-nChap) with enhanced activity to facilitate protein refolding. This self-CO-nChap was fabricated by introducing Hsp40-mimetic artificial carriers into the traditional nanochaperone to cooperate with the Hsp70-mimetic confined hydrophobic microdomains. The artificial carrier facilitates transfer and immobilization of client proteins into confined hydrophobic microdomains, by which significantly improving self-CO-nChap's capability to inhibit unfolding and aggregation of client proteins, and finally facilitating refolding. Compared to traditional nanochaperones, the self-CO-nChap significantly enhances the thermal stability of horseradish peroxidase (HRP) epicyclically under harsher conditions. Moreover, the self-CO-nChap efficiently protects misfolding-prone proteins, such as immunoglobulin G (IgG) antibody from thermal denaturation, which is hardly achieved using traditional nanochaperones. In addition, a kinetic partitioning mechanism was devised to explain how self-CO-nChap facilitates refolding by regulating the cooperative effect of kinetics between the nanochaperone and client proteins. This work provides a novel strategy for the design of protein folding regulatory materials, including nanochaperones.

Effects of granular feed on reproductive metabolism of breeding pigeons, intestinal development and microbiota of squab pigeons-A double-edged sword.

Pigeons like to eat raw grains, but meat pigeon enterprises often use compound feeds instead of raw grains to feed breeding pigeons to increase economic efficiency, which may change the pigeon's dietary behavior, and consequently lead to health and welfare problems. The purpose of this study was to investigate the effect of granular feeds on the health of high-yielding breeding pigeons and squabs in lactation. The results showed that, compared with raw grain group, the provision of granular feed resulted in lower total feed intake without affecting the weight of lactating breeding pigeons. Meanwhile, reproductive metabolism was improved and no oxidative stress was observed, which indicated that granular feeds had a positive effect on breeding pigeon's health. However, granular feed adversely affected jejunum development in squabs, compare wtih raw grain group, the growth rate of squab was reduced. Sequencing of the 16 s rRNA gene revealed that granular feed induced intestinal microbiota dysbiosis in the squabs. The use of granular feed reduced the relative abundance of gut microorganisms in functional categories related to lipid and energy metabolism, resulting in a decrease in the relative abundance of beneficial bacteria such as Bifidobacterium, Ligilactobacillus, Atopobium, and an increase in that of inflammation-related Limosilactobacillus, which likely inhibited squab intestinal development and growth. Although the use of granular feed can improve breeder metabolism, it affect the composition of the microbial community and gut development of squabs. Therefore, the use of granular feed in production should be more careful to avoid causing growth obstruction of squab.

Optimal dietary energy and protein levels for breeding pigeons in the winter "2 + 3" lactation pattern.

The nutritional requirements of breeding pigeons depend on their physiological period, breeding pattern, and environmental conditions. Despite works on reduced litter size in winter production to combat high mortality and the poor welfare of squabs, there are few studies on the related nutritional requirements of these pigeons. A total of 432 pairs of European Mimas pigeons were randomly divided into 9 groups in which 3 crude protein (CP) levels (15, 16.5, and 18%) and 3 metabolizable energy (ME) levels (12.2 MJ/kg, 12.4 MJ/kg, and 12.6 MJ/kg) were tested to determine the optimal energy and protein requirements of breeding pigeons in the winter "2 + 3" breeding pattern. The results showed that ME and CP levels had little effect on the body weight, feed intake, and egg quality of breeding pigeons during the lactation period. An 18% CP diet significantly increased the laying rate and hatchability (P < 0.05), but there was no difference in the laying rate with 18% CP and 16.5% CP during the whole reproductive cycle (P > 0.05). There was a significant interaction between ME and CP levels, and the laying interval of breeding pigeons in group 9 (18% CP; 12.6 MJ/kg) was significantly shortened (P < 0.05). For squabs, the ME level had no effect on growth performance, slaughter performance, or meat quality. The body weight of 21-day-old squabs in the 18% CP group increased by 3.16% compared with that of the 15% CP group, but there was no difference between the 18% CP and 16.5% CP groups. Compared with other experimental groups, group 7 (18% CP; 12.2 MJ/kg) had the fastest growth rate in squabs (P < 0.05), and the corresponding slaughter weight was also the heaviest (P < 0.05). We further found that the height of the squab intestinal epithelium was significantly increased in both the 16.5% CP and 18% CP groups of squabs (P < 0.01), but male breeding pigeons showed a certain degree of oxidative stress with an increase in CP level. In conclusion, the effects of 15 to 18% CP levels and 12.2 to 12.6 MJ/kg ME levels on the reproductive metabolism of breeding pigeons and the growth and development of squabs in the "2 + 3" breeding pattern during winter are small. For economic efficiency, we suggest that the CP level can be reduced to 16.5% while the ME level should not be less than 12.2 MJ/kg in practical production.

Effect of different dietary energy/protein ratios on growth performance, reproductive performance of breeding pigeons and slaughter performance, meat quality of squabs in summer.

Large-scale pigeon farming in China is gradually increasing. However, studies on the basic nutritional requirements of breeding pigeons during lactation, which greatly influence the productivity and economic benefits of pigeon breeding, remain scanty. The objective of this study was to determine the optimal dietary energy/protein ratio requirements for lactating pigeons in summer. A total of 576 pairs of Mimas breeding pigeons were randomly divided into 12 groups (n = 48 per treatment), and each pair bred 4 squabs. A two-way ANOVA design with different protein levels (15%, 16%, 17%, and 18%) for factor A and different energy levels (12.6 MJ/kg, 12.8 MJ/kg, and 13.0 MJ/kg) for factor B was used to design 12 groups of experimental diets for feeding. The experiment lasted for 28 d. We found that ME level had little effect on breeding pigeons, but the CP level and dietary energy/protein ratio significantly affected the reproductive and growth performance of the pigeons. The lowest total weight loss (P < 0.01), and the highest egg production (P < 0.01) were observed in group 11 (18% CP, 12.8 MJ/kg). It had no effect on egg quality. Both ME and CP levels significantly affected the growth performance, slaughter performance and meat quality of squabs, and there was a strong interaction between CP and ME. The fastest growth rate (P < 0.01) was observed in group 11 (18% CP, 12.8 MJ/kg). The best CP and ME combination for the eviscerated weight, pectoral muscle weight, organ weight, 45 min meat color (L⁎, a⁎, b⁎), pH, and muscle fiber characteristics were also group 11. Finally, the regression model revealed that the best dietary energy/protein ratio was 17.92 to 19.02 kcal/g for squabs and 16.72 kcal/g for the breeding pigeons. There was a strong interaction between energy and protein levels in breeding pigeons during the lactation period, and the best production performance was at 18% CP 12.8 MJ/kg. And this is recommended to be applied as the energy/protein ratio dietary requirement for breeding pigeons during lactation in the summer "2 + 4" pattern.

Metabolomics analysis of the effects of different litter size on reproductive metabolism and oxidative stress in breeding pigeon (Columba livia).

The pigeon breeding industry employs a high-rearing pattern to achieve economic benefits. However, too many squabs consume more energy of the breeding pigeons causing adverse effects on their breeding performance. To determine the optimal rearing patterns and the effects of different numbers of squabs on reproductive performance, oxidative stress, and glucolipid metabolism of lactating breeding pigeons in winter, three rearing patterns consisting of "2 + 2″, "2 + 3″ and "2 + 4" (a pair of breeding pigeons feeding two, three and four squabs, respectively) were adopted using European Mimas white pigeons breed. The feed intake, bodyweight loss, feed-to-meat ratio, and squab mortality were linearly increased with the number of squabs during lactation, while the bodyweight recovery rate and squab growth performance were significantly slowed down after lactation. Similarly, the laying rate was linearly decreased on days 16, 17, and 18 of lactation, with a similar pattern on the re-laying rate on days 11, 12, and 13 after first laying. In addition, the number of non-laying pigeons in the second batch was significantly increased, implying that the number of squabs significantly affected the reproductive performance of female pigeons. The eggshell weight and thickness in the "2 + 3″ group were significantly increased. However, the number of squabs in the "2 + 3″ group had no significant effect on plasma calcium (Ca) and phosphorus (P) levels. Analysis of the glucolipid metabolism index and oxidative stress level of pigeons further revealed that the contents of triglyceride (TG), total cholesterol (T-CHO), and low-density lipoprotein cholesterol (LDL-C) in the plasma of male pigeons were significantly decreased with the increase in the number of squabs, but there was no obvious oxidative stress. On the contrary, glucose (GLU), TG, malondialdehyde (MDA) in the plasma of female pigeons were significantly increased, total antioxidant capacity (T-AOC) were significantly decreased, implying that the female pigeons suffered more oxidative stress and more dramatic changes in glucolipid metabolism. Metabolomics revealed that the differential metabolites in the plasma of female pigeons in "2 + 2″, "2 + 3″, and "2 + 4″ groups were significantly enriched in the fatty acid, phospholipid, sphingolipid metabolism, and the Krebs cycle pathways, especially under "2 + 4″ rearing pattern. Overall, in female pigeons, the available lipids were reduced; hence, their body turned to sugar dysplasia and protein utilization mode, increasing the oxidative stress level and decreasing their reproductive performance. Therefore, an increased number of squabs significantly affects the body condition and reproductive performance of breeding pigeons. The "2 + 3″ rearing pattern is the most suitable for winter breeding pigeon production under the current nutrition level.

Glucose-Responsive Nanochaperones Mediate Exendin-4 Delivery for Enhancing Therapeutic Effects.

Exendin-4 (Ex-4) is a promising therapeutic peptide for the clinical treatment of type 2 diabetes, but its instability and immunogenicity result in a short circulating half-life and low bioavailability, which severely limit its clinical application. Here, complex micelles with 4-carboxy-3-fluorophenylboronic acid (FPBA)-modified and positively charged hydrophobic domains on the surface were devised as nanochaperones to mediate the delivery of Ex-4. The nanochaperones can bind Ex-4 on the surface via the synergy of electrostatic and hydrophobic interactions, leading to efficient loading and stabilization of Ex-4. More importantly, the immunogenic site of Ex-4 was shielded by the nanochaperones, thereby effectively reducing the immune clearance and prolonging the half-life. Hyperglycemia-triggered release of Ex-4 was achieved by the hydrophobic to the hydrophilic transformation of the FPBA-modified domains and the introduced negative charge because of the binding of glucose by FPBA. The Ex-4-loaded nanochaperones exhibited an enhanced therapeutic effect on type 2 diabetic mice.

In Situ Antigen-Capturing Nanochaperone Toward Personalized Nanovaccine for Cancer Immunotherapy.

Personalized cancer vaccination using nanomaterials holds great potential for cancer immunotherapy. Here, a nanochaperone (PBA-nChap) is tailored for in situ capture of tumor-associated antigens (TAAs) to improve cancer immunotherapy. The PBA-nChap is capable of i) efficiently capturing TAAs in situ; ii) protecting TAAs from degradation; iii) transporting TAAs to antigen-presenting cells and promoting cross-presentation. Intratumor injection of PBA-nChap in combination with pretreatment with photodynamic therapy (PDT) significantly enhances immune response and exhibits excellent antitumor efficacy. Moreover, nanovaccine prepared by simply co-culturing PBA-nChap with tumor cell fragments from surgery resected primary tumor in vitro synergized with immune checkpoint blockade (ICB) therapy can effectively inhibit tumor recurrence and metastasis after an operation. This work provides a promising platform for personalized cancer vaccination.

Near-Infrared-to-Near-Infrared Optical Thermometer BaY2O4: Yb3+/Nd3+ Assembled with Photothermal Conversion Performance.

Nowadays, the construction of photothermal therapy (PTT) agents integrated with real-time thermometry for cancer treatment in deep tissues has become a research hotspot. Herein, an excellent photothermal conversion material, BaY2O4: Yb3+/Nd3+, assembled with real-time optical thermometry is developed successfully. Ultrasensitive temperature sensing is implemented through the fluorescence intensity ratio of thermally coupled Nd3+: 4Fj (j = 7/2, 5/2, and 3/2) with a maximal absolute and relative sensitivity of 68.88 and 3.29% K-1, respectively, which surpass the overwhelming majority of the same type of thermometers. Especially, a thermally enhanced Nd3+ luminescence with a factor of 180 is detected with irradiation at 980 nm, resulting from the improvement in phonon-assisted energy transfer efficiency. Meanwhile, the photothermal conversion performance of the sample is excellent enough to destroy the pathological tissues, of which the temperature can be raised to 319.3 K after 180 s of near-infrared (NIR) irradiation with an invariable power density of 13.74 mW/mm2. Besides, the NIR emission of Nd3+ can reach a depth of 7 mm in the biological tissues, as determined by an ex vivo experiment. All the results show the potential application of BaY2O4: Yb3+/Nd3+ as a deep-tissue PTT agent simultaneously equipped with photothermal conversion and temperature sensing function.

Effects of palmitic acid and eicosapentaenoic acid on angiogenesis of porcine vascular endothelial cells.

Restricted placental angiogenesis is an important cause of intrauterine growth retardation in piglets. During pregnancy, sow obesity can result in an increase in placental lipid deposition, subsequently inhibiting placental angiogenesis and fetal development. However, the effect of different types of fatty acids on placental angiogenesis is still unclear. Trophoblast cells and vascular endothelial cells constitute two important types of placental tissue. In this study, we used palmitic acid (C16:0) and eicosapentaenoic acid (C20:5, n-3), respectively, to treat porcine trophectoderm cells (pTr2) and porcine iliac artery endothelial cells (PIEC) to study the effects of saturated fatty acids and n-3 polyunsaturated fatty acids (PUFAs) on placental angiogenesis in vitro. We found that C16:0 caused significant cytotoxicity in pTr2 and PIEC (p < 0.01) and inhibited the proliferation and migration of PIEC (p < 0.01), whereas C20:5 treatment exhibited very low cytotoxicity and minimal inhibition of cellular proliferation. Meanwhile, a low concentration of C16:0 had no effect on the tube formation in PIEC, whereas C20:5 significantly promoted tube formation of PIEC (p < 0.01). These results suggested that saturated fatty acids and n-3 PUFAs had different effects on placental angiogenesis. As essential functional fatty acid, n-3 PUFA might be effective measure in alleviating the placental lipotoxicity caused by sow obesity during pregnancy.

CXCL16 may be a predisposing factor to atherosclerosis: An animal study.

Atherosclerosis (AS) is a chronic inflammatory process initiated when lipoprotein is retained in the arterial wall. Leukocyte recruitment accelerates this process. CXC chemokine ligand 16 (CXCL16) acts as a chemokine to attract immune cells and also facilitates the phagocytosis process of modified low­density lipoprotein. Whether CXCL16 promotes or inhibits the pathological process of AS remains to be elucidated. To clarify this, CXCL16 gene was introduced into C57BL/6J wild­type mice to establish a stable CXCL16 overexpression mouse model. The initial changes of AS in mice were induced by high­fat diet (HFD). To study how the interaction of HFD and CXCL16 affected fatty acid metabolism and deposition, body weight and plasma lipid profile were assessed. Soluble CXCL16, matrix metalloproteinase­9, monocyte chemoattractant protein­1 and intercellular adhesion molecule­1 were detected by immunohistochemistry and ELISA to identify how CXCL16 affects AS lesion formation. The present study suggested that overexpression of CXCL16 combined with HFD lead to atherogenesis by upregulating the aforementioned inflammatory related genes at a protein level. The present study was the first, to the best of the authors' knowledge, to build a CXCL16 homozygous transgenic mice model to study how overexpressed CXCL16 is associated with AS for intervening in the occurrence and development of AS.

Fine particulate matter inhibits phagocytosis of macrophages by disturbing autophagy.

Mounting evidence from epidemiological and clinical studies has revealed marked correlations between the air pollutant fine particulate matter (FPM) and respiratory diseases. FPM reaches distal airways and deposits in alveolar regions where it can act directly on alveolar macrophages. However, the detailed effect of FPM on the physiological function of alveolar macrophages and the underlying mechanisms remain unclear. In this study, we showed that exposing THP-1-derived macrophages to FPM led to autophagy dysfunction. FPM activated the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway, which promoted the expression of autophagy-related 2A (ATG2A) and reactive oxygen species generation. The overexpression of ATG2A enhanced the synthesis of autophagic membranes, and the excessive production of reactive oxygen species caused autophagy flux inhibition through disrupting the lysosomal activity. More importantly, FPM impaired the phagocytic ability of macrophages on Escherichia coli and apoptotic neutrophils. Finally, we showed that restoring autophagy rescued the impairment of phagocytic ability induced by FPM. In summary, these results reveal the molecular mechanism of autophagy dysfunction caused by FPM and provide a novel approach to resolve the impaired function of macrophages in respiratory diseases induced by FPM.

Evaluation of average travel delay caused by moving bottlenecks on highways.

This paper presents a modelling framework to evaluate travel delay of all vehicles influenced by moving bottlenecks on highways. During the derivation of analytical formulas, the arrival of slow vehicles was approximated by a Poisson process based on the assumption that they occupied a constant low proportion of the traffic stream. The mathematical analysis process was developed from moving bottlenecks with the same velocity to those with multiple different velocities, and the closed-form expression of expected average travel delay was obtained by utilizing kinematic-wave moving bottleneck theory, gap acceptance theory, probability theory and renewal theory. Model validation and parameters sensitive analysis were conducted by simulation relying on the open source database of US highway 10. The maximum passing rate and the macroscopic parameters of initial traffic state with maximum delay could be found by means of approximate formulas. The proposed modeling framework can be applied for evaluating impacts of slow vehicles on highway operation quantifiably, based on which traffic managements like truck prohibited period decision and speed or lane restriction could be made more scientifically.

Anterior Chamber Angle and Anterior Segment Structure of Eyes in Children With Early Stages of Retinopathy of Prematurity.

PURPOSE: To compare structural differences in the anterior chamber angle (ACA) and related optic components in children with or without retinopathy of prematurity (ROP). DESIGN: Prospective cross-sectional study. METHODS: Setting: A referred medical center in Taiwan. STUDY POPULATION: The patients included preterm children with a history of ROP who had undergone laser therapy. The controls included age-matched healthy full-term children. OBSERVATION PROCEDURE: The ACA structures were evaluated using gonioscopy. MAIN OUTCOME MEASURES: The angularity of the anterior chamber and associated anatomic changes. RESULTS: We examined 54 eyes of 29 preterm children with ROP and 134 eyes of 67 children born at term. The eyes of the ROP children exhibited a narrower ACA, steeper iris curvature, and more anteriorly inserted iris than those of the full-term children (P < .001, P = .002, and P = .08, respectively). The eyes of the ROP children also exhibited steeper corneas, shallower anterior chamber depths, thicker lenses, and higher degrees of refractive errors (all P < .001) than those of the full-term children. The axial lengths did not differ between the 2 groups (P = .15). CONCLUSIONS: The eyes of the ROP children presented a narrower ACA and a more anteriorly curved and inserted iris than those of the full-term children. A steeper cornea, shallower anterior chamber, and greater lens thickness were the main structural changes in the anterior segment components of these patients. Further research is needed to investigate the association between these structural changes and the development of certain ocular diseases, such as glaucoma, in these patients.

Addressing proteolytic efficiency in enzymatic degradation therapy for celiac disease.

Celiac disease is triggered by partially digested gluten proteins. Enzyme therapies that complete protein digestion in vivo could support a gluten-free diet, but the barrier to completeness is high. Current options require enzyme amounts on the same order as the protein meal itself. In this study, we evaluated proteolytic components of the carnivorous pitcher plant (Nepenthes spp.) for use in this context. Remarkably low doses enhance gliadin solubilization rates, and degrade gliadin slurries within the pH and temporal constraints of human gastric digestion. Potencies in excess of 1200:1 (substrate-to-enzyme) are achieved. Digestion generates small peptides through nepenthesin and neprosin, the latter a novel enzyme defining a previously-unknown class of prolyl endoprotease. The digests also exhibit reduced TG2 conversion rates in the immunogenic regions of gliadin, providing a twin mechanism for evading T-cell recognition. When sensitized and dosed with enzyme-treated gliadin, NOD/DQ8 mice did not show intestinal inflammation, when compared to mice challenged with only pepsin-treated gliadin. The low enzyme load needed for effective digestion suggests that gluten detoxification can be achieved in a meal setting, using metered dosing based on meal size. We demonstrate this by showing efficient antigen processing at total substrate-to-enzyme ratios exceeding 12,000:1.