An anti-CTLA-4 heavy chain-only antibody with enhanced Treg depletion shows excellent preclinical efficacy and safety profile.

The value of anti-CTLA-4 antibodies in cancer therapy is well established. However, the broad application of currently available anti-CTLA-4 therapeutic antibodies is hampered by their narrow therapeutic index. It is therefore challenging and attractive to develop the next generation of anti-CTLA-4 therapeutics with improved safety and efficacy. To this end, we generated fully human heavy chain-only antibodies (HCAbs) against CTLA-4. The hIgG1 Fc domain of the top candidate, HCAb 4003-1, was further engineered to enhance its regulatory T (Treg) cell depletion effect and to decrease its half-life, resulting in HCAb 4003-2. We tested these HCAbs in in vitro and in vivo experiments in comparison with ipilimumab and other anti-CTLA4 antibodies. The results show that human HCAb 4003-2 binds human CTLA-4 with high affinity and potently blocks the binding of B7-1 (CD80) and B7-2 (CD86) to CTLA-4. The results also show efficient tumor penetration. HCAb 4003-2 exhibits enhanced antibody-dependent cellular cytotoxicity function, lower serum exposure, and more potent anti-tumor activity than ipilimumab in murine tumor models, which is partly driven by a substantial depletion of intratumoral Tregs. Importantly, the enhanced efficacy combined with the shorter serum half-life and less systemic drug exposure in vivo potentially provides an improved therapeutic window in cynomolgus monkeys and preliminary clinical applications. With its augmented efficacy via Treg depletion and improved safety profile, HCAb 4003-2 is a promising candidate for the development of next generation anti-CTLA-4 therapy.

Medical therapy has similar hemostatic efficacy with endoscopic treatment for PUB patients with adherent clot (FIIb ulcers).

BACKGROUND: Currently, there is no clear consensus on whether medical treatment or endoscopic treatment should be used for peptic ulcer bleeding patients with adherent clot. The aim of this study is to investigate the hemostatic effects of medical treatment, single endoscopic treatment, and combination endoscopic treatment for peptic ulcer bleeding (PUB) patients with adherent clot. METHODS: We retrospectively analyzed PUB patients with adherent clot who underwent endoscopic examination or treatment in our center from March 2014 to January 2023 and received intravenous administration of proton pump inhibitors. Patients were divided into medical treatment (MT) group, single endoscopic treatment (ST) group, and combined endoscopic treatment (CT) group. Subsequently, inverse probability of treatment weighting (IPTW) was performed to calculate the rebleeding rate. RESULTS: A total of 605 eligible patients were included in this study. After IPTW, the rebleeding rate in the MT group on days 3, 7, 14, and 30 were 13.3 (7.3), 14.2 (7.8), 14.5 (7.9), and 14.5 (7.9), respectively; the rebleeding rates in the ST group were 17.4 (5.1), 20.8 (6.1), 20.8 (6.1), and 20.8 (6.1), respectively; the rebleeding rates in the CT group were 0.4 (0.9), 1.7 (3.3), 2.3 (4.5), and 2.3 (4.5), respectively. Although the rebleeding rate in the medical treatment group was higher, there was no significant difference among the three groups on days 3, 7, 14, and 30 (P = 0.132, 0.442, 0.552, and 0.552). CONCLUSIONS: Medical therapy has similar hemostatic efficacy with endoscopic treatment for PUB patients with adherent clot (FIIb ulcers). However, for patients with more risk factors and access to well-equipped endoscopy centers, endoscopic treatment may be considered. The choice of treatment approach should be based on the individual conditions of the patient, as well as other factors such as medical resources available.

Boundary-Rich Carbon-Based Electrocatalysts with Manganese(II)-Coordinated Active Environment for Selective Synthesis of Hydrogen Peroxide.

Coordinated manganese (Mn) electrocatalysts owing to their electronic structure flexibility, non-toxic and earth abundant features are promising for electrocatalytic reactions. However, achieving selective hydrogen peroxide (H2 O2 ) production through two electron oxygen reduction (2e-ORR) is a challenge on Mn-centered catalysts. Targeting this goal, we report on the creation of a secondary Mn(II)-coordinated active environment with reactant enrichment effect on boundary-rich porous carbon-based electrocatalysts, which facilitates the selective and rapid synthesis of H2 O2 through 2e-ORR. The catalysts exhibit nearly 100 % Faradaic efficiency and H2 O2 productivity up to 15.1 mol gcat -1 h-1 at 0.1 V versus reversible hydrogen electrode, representing the record high activity for Mn-based electrocatalyst in H2 O2 electrosynthesis. Mechanistic studies reveal that the epoxide and hydroxyl groups surrounding Mn(II) centers improve spin state by modifying electronic properties and charge transfer, thus tailoring the adsorption strength of *OOH intermediate. Multiscale simulations reveal that the high-curvature boundaries facilitate oxygen (O2 ) adsorption and result in local O2 enrichment due to the enhanced interaction between carbon surface and O2 . These merits together ensure the efficient formation of H2 O2 with high local concentration, which can directly boost the tandem reaction of hydrolysis of benzonitrile to benzamide with nearly 100 % conversion rate and exclusive benzamide selectivity.

Prognosis and Remodeling after Endovascular Repair for Acute, Subacute, and Chronic Type B Aortic Dissection.

PURPOSE: Thoracic endovascular aortic repair (TEVAR) for type B aortic dissection (TBAD) is already well introduced, but the best time point to perform TEVAR has not been defined. This study was to report mid- to long-term outcomes and aortic remodeling of TEVAR in patients with TBAD. MATERIALS AND METHODS: In total, 318 TBAD patients from June 2001 to May 2016 were retrospectively reviewed. Patients were divided into 3 groups depending on interval between dissection onset to TEVAR: acute (0-7 days), subacute (8-30 days), and chronic (>30 days). Clinical and morphological data were collected and analyzed. RESULTS: The follow-up aorta-related mortality rates in the 3 groups were 17.6%, 2.6%, 4.2%, and the proximal stent-induced new entry rates were 11.8%, 1.6%, 2.8%, respectively. Aortic remodeling was satisfied in both the acute and subacute group, but the false lumen diameter did not decrease (p>0.05) in the chronic group. Compared with the VIRTUE classification (acute, 0-14 days; subacute, 15-92 days; chronic, >92 days), mid- to long-term outcomes of patients within the first overlapped interval between the 2 classifications (8-14 days) were similar to that of subacute patients (15-30 days), while aortic remodeling of patients in the second overlapped interval (31-92 days) was similar to that of chronic patients (>92 days). CONCLUSIONS: This study suggests that TEVAR for subacute TBAD is associated with a low long-term rate of aorta-related death. Aortic remodeling of chronic dissections is not satisfactory. Additional results suggest that the subacute phase (8-30 days) may be the optimal time to perform TEVAR for uncomplicated TBAD.

Epinephrine injection monotherapy shows similar hemostatic efficacy to epinephrine injection combined therapy in high-risk patients (Forrest Ib) with bleeding ulcers.

BACKGROUND: Whether combination therapy has higher hemostatic efficacy than epinephrine injection monotherapy in different Forrest classifications is not clear. This study aimed to compare hemostatic efficacy between epinephrine injection monotherapy (MT) and combination therapy (CT) based on different Forrest classifications. METHODS: We retrospectively analyzed peptic ulcer bleeding (PUB) patients who underwent endoscopic epinephrine injections or epinephrine injections combined with a second therapy between March 2014 and June 2022 in our center, and the patients were divided into MT group or CT group. Subsequently, a propensity score matching analysis (PSM) was performed and rebleeding rates were calculated according to Forrest classifications via a stratified analysis. RESULTS: Overall, 605 patients who met the inclusion criteria were included, and after PSM, 173 patients in each of the CT and MT groups were included. For PUB patients with nonbleeding visible vessels (FIIa), the rebleeding rates by Days 3, 7, 14, and 30 after PSM were 8.8%, 17.5%, 19.3%, and 19.3% in the MT group, respectively, and rates were 0%, 4.1%, 5.5%, and 5.5% in the CT group, respectively, with significant differences observed between the two groups by Days 3, 7, 14, and 30 (P = 0.015, P = 0.011, P = 0.014, and P = 0.014, respectively). However, for PUB patients with oozing bleeding (FIb), the rebleeding rates by Days 3, 7, 14, and 30 after PSM were 14.9%, 16.2%, 17.6%, and 17.6% in the MT group, respectively, and rates were 13.2%, 14.7%, 14.7%, and 16.2% in the CT group, respectively, with no significant differences observed between the two groups by Days 3, 7, 14, and 30 (P = 0.78, P = 0.804, P = 0.644 and P = 0.825). CONCLUSION: Combined therapy has higher hemostatic efficacy than epinephrine injection monotherapy for PUB patients with visible blood vessel (FIIa) ulcers. However, epinephrine injection monotherapy is equally as effective as combined therapy for PUB patients with oozing blood (FIb) ulcers.

Optimal fibular tunnel direction for anterior talofibular ligament reconstruction: 45 degrees outperforms 30 and 60 degrees.

PURPOSE: There is currently no consensus on the optimal drilling direction of the fibular bone tunnel for anterior talofibular ligament (ATFL) reconstruction, and few studies have investigated the potential injury to the peroneus longus and brevis tendons and the possibility of fibular fractures during the drilling process. The aim of this study was to assess the potential risk of drilling the tunnel from different directions and determine the most appropriate tunnel direction. The hypothesis was that drilling the tunnel in the 45-degree direction would be the safest and most suitable for the fibular tunnel. METHODS: Forty-eight fibular tunnels were drilled on fresh ankle specimens using a K-wire guide and a 5.0 mm hollow drill. Three tunnel orientations were created, parallel to the sagittal plane of the long axis of the fibula and angled 30°, 45°, and 60° to the coronal plane. The length of the fibular tunnel and the distances from the outlet of the K-wire to the peroneus longus and brevis tendons were measured. The occurrence of a fibula fracture was also observed. RESULTS: The lengths of the bone tunnels in the three groups were 32.9 ± 6.1 mm (30°), 27.2 ± 4.4 mm (45°) and 23.6 ± 4.0 mm (60°). The length of the tunnel drilled at 30° was the longest when compared with that of the tunnels drilled at 45° and 60° (all p values < 0.05). The distances from the outlet of the K-wire to the peroneus longus tendon were 3.0 ± 3.8 mm (30°), 3.8 ± 3.2 mm (45°) and 5.3 ± 1.8 mm (60°), and the distances to the peroneus brevis tendon were 4.2 ± 4.0 mm (30°), 6.1 ± 3.8 mm (45°), 7.9 ± 3.5 mm (60°). In terms of protecting the peroneus longus and brevis tendons, drilling in the 60° direction was better than drilling in the 30° and 45° directions (all p values < 0.05). The risk of injury to the peroneal longus and brevis tendons was 62.5% (30°), 31.3% (45°), and 0% (60°). Although no fibular fractures were observed in any of the three directions, drilling the bone tunnel in the 60° direction disrupted the lateral cortex of the fibula. CONCLUSION: This study shows that drilling the tunnel in the 45° direction is less likely to cause injury to the peroneus longus and brevis tendons, while ensuring that the tunnel has a sufficient length and avoiding fracturing the distal fibula. Drilling a fibular bone tunnel in a 45° direction is safer and recommended for ATFL reconstruction.

Machine Learning Quantified Tumor-Stroma Ratio Is an Independent Prognosticator in Muscle-Invasive Bladder Cancer.

Although the tumor-stroma ratio (TSR) has prognostic value in many cancers, the traditional semi-quantitative visual assessment method has inter-observer variability, making it impossible for clinical practice. We aimed to develop a machine learning (ML) algorithm for accurately quantifying TSR in hematoxylin-and-eosin (H&E)-stained whole slide images (WSI) and further investigate its prognostic effect in patients with muscle-invasive bladder cancer (MIBC). We used an optimal cell classifier previously built based on QuPath open-source software and ML algorithm for quantitative calculation of TSR. We retrospectively analyzed data from two independent cohorts to verify the prognostic significance of ML-based TSR in MIBC patients. WSIs from 133 MIBC patients were used as the discovery set to identify the optimal association of TSR with patient survival outcomes. Furthermore, we performed validation in an independent external cohort consisting of 261 MIBC patients. We demonstrated a significant prognostic association of ML-based TSR with survival outcomes in MIBC patients (p < 0.001 for all comparisons), with higher TSR associated with better prognosis. Uni- and multivariate Cox regression analyses showed that TSR was independently associated with overall survival (p < 0.001 for all analyses) after adjusting for clinicopathological factors including age, gender, and pathologic stage. TSR was found to be a strong prognostic factor that was not redundant with the existing staging system in different subgroup analyses (p < 0.05 for all analyses). Finally, the expression of six genes (DACH1, DEEND2A, NOTCH4, DTWD1, TAF6L, and MARCHF5) were significantly associated with TSR, revealing possible potential biological relevance. In conclusion, we developed an ML algorithm based on WSIs of MIBC patients to accurately quantify TSR and demonstrated its prognostic validity for MIBC patients in two independent cohorts. This objective quantitative method allows application in clinical practice while reducing the workload of pathologists. Thus, it might be of significant aid in promoting precise pathology services in MIBC.

CFTR Suppresses Neointimal Formation Through Attenuating Proliferation and Migration of Aortic Smooth Muscle Cells.

ABSTRACT: Cystic fibrosis transmembrane conductance regulator (CFTR) plays important roles in arterial functions and the fate of cells. To further understand its function in vascular remodeling, we examined whether CFTR directly regulates platelet-derived growth factor-BB (PDGF-BB)-stimulated vascular smooth muscle cells (VSMCs) proliferation and migration, as well as the balloon injury-induced neointimal formation. The CFTR adenoviral gene delivery was used to evaluate the effects of CFTR on neointimal formation in a rat model of carotid artery balloon injury. The roles of CFTR in PDGF-BB-stimulated VSMC proliferation and migration were detected by mitochondrial tetrazolium assay, wound healing assay, transwell chamber method, western blot, and qPCR. We found that CFTR expression was declined in injured rat carotid arteries, while adenoviral overexpression of CFTR in vivo attenuated neointimal formation in carotid arteries. CFTR overexpression inhibited PDGF-BB-induced VSMC proliferation and migration, whereas CFTR silencing caused the opposite results. Mechanistically, CFTR suppressed the phosphorylation of PDGF receptor ß, serum and glucocorticoid-inducible kinase 1, JNK, p38 and ERK induced by PDGF-BB, and the increased mRNA expression of matrix metalloproteinase-9 and MMP2 induced by PDGF-BB. In conclusion, our results indicated that CFTR may attenuate neointimal formation by suppressing PDGF-BB-induced activation of serum and glucocorticoid-inducible kinase 1 and the JNK/p38/ERK signaling pathway.

Nomogram for predicting rebleeding after initial endoscopic epinephrine injection monotherapy hemostasis in patients with peptic ulcer bleeding: a retrospective cohort study.

BACKGROUND: Although the current guidelines recommend endoscopic combination therapy, endoscopic epinephrine injection (EI) monotherapy is still a simple, common and effective modality for treating peptic ulcer bleeding (PUB). However, the rebleeding risk after EI monotherapy is still high, and identifying rebleeding patients after EI monotherapy is unclear, which is highly important in clinical practice. This study aimed to identify risk factors and constructed a predictive nomogram related to rebleeding after EI monotherapy. METHODS: We consecutively and retrospectively analyzed 360 PUB patients who underwent EI monotherapy between March 2014 and July 2021 in our center. Then we identified independent risk factors associated with rebleeding after initial endoscopic EI monotherapy by multivariate logistic regression. A predictive nomogram was developed and validated based on the above predictors. RESULTS: Among all PUB patients enrolled, 51 (14.2%) had recurrent hemorrhage within 30 days after endoscopic EI monotherapy. After multivariate logistic regression, shock [odds ratio (OR) = 12.691, 95% confidence interval (CI) 5.129-31.399, p < 0.001], Rockall score (OR = 1.877, 95% CI 1.250-2.820, p = 0.002), tachycardia (heart rate > 100 beats/min) (OR = 2.610, 95% CI 1.098-6.203, p = 0.030), prolonged prothrombin time (PT > 13 s) (OR = 2.387, 95% CI 1.019-5.588, p = 0.045) and gastric ulcer (OR = 2.258, 95% CI 1.003-5.084, p = 0.049) were associated with an increased risk of rebleeding after an initial EI monotherapy treatment. A nomogram incorporating these independent high-risk factors showed good discrimination, with an area under the receiver operating characteristic curve (AUROC) of 0.876 (95% CI 0.817-0.934) (p < 0.001). CONCLUSIONS: We developed a predictive nomogram of rebleeding after EI monotherapy, which had excellent prediction accuracy. This predictive nomogram can be conveniently used to identify low-risk rebleeding patients after EI monotherapy, allowing for decision-making in a clinical setting.

Detection and molecular characterization of Cryptosporidium spp. in pet hairless guinea pigs (Cavia Porcellus) from China.

Cryptosporidium spp. are common protozoan parasites that can infect humans and animals worldwide. Recently, the hairless guinea pigs (also called Skinny pigs) were introduced into China as pets. However, Cryptosporidium species and their prevalence in these exotic animals were not studied. In this study, fecal samples were collected from a total of 324 hairless guinea pigs from a pet market and four breeding facilities in four provinces of China. The infection rate of Cryptosporidium was 6.8% (22/324). Three Cryptosporidium species were identified, including Cryptosporidium homai (n = 16), Cryptosporidium wrairi (n = 5), and Cryptosporidium hominis plus C. homai (n = 1). Sequence analysis of the small subunit (SSU) rRNA gene showed that the C. hominis isolate was a C. hominis variant, which mostly infects equine animals. However, the identification of C. hominis was not supported by the analysis of other genetic loci. The C. hominis isolate was characterized as C. homai at both 70-kDa heat shock protein (hsp70) and actin genes, indicating a mixed infection. At the 60-kDa glycoprotein (gp60) gene, subtyping of the C. hominis isolate was not successful. Five C. wrairi isolates were identified as subtype VIIaA13T1, which was previously reported in a guinea pig in the USA. The Cryptosporidium spp. identified in this study have no or low zoonotic potential.

Comparison of dynamic mechanical properties of dentin between deciduous and permanent teeth.

Purpose: Even though differences between deciduous and permanent dentin have been widely studied, their dynamic mechanical behavior has never been compared. The objective of the present study was to quantify the differences between deciduous and permanent dentin under cyclic mechanical loading, which is similar to masticatory stress.Materials and Methods: Deciduous and permanent teeth, respectively from children (9 ~ 12 years old) and young people (18 ~ 25 years old), were wet-sectioned perpendicular to the longitudinal axis and the central specimens of coronal dentin were evaluated by nanoscopic dynamic mechanical analysis (nanoDMA).Results: The average storage, loss, and complex moduli, as well as the hardness of deciduous dentin were significantly (p < 0.05) lower than those of permanent dentin. Moreover, the tan δ value of permanent dentin was significantly (p < 0.05) lower than that of deciduous dentin across the loading frequency range, indicating that viscoelastic behavior and loss of elastic energy were significantly reduced in the stiffer permanent dentin. All the nanoDMA responses showed a significant influence of the dynamic loading frequency (p < 0.05): Both deciduous and permanent dentin showed reduced viscoelasticty with increased loading frequencies.Conclusions: Compared with deciduous dentin, permanent dentin exhibits higher stiffness with reduced energy loss during deformation, and therefore superior mechanical characteristics for the mastication process.

Hydroazulene Diterpenes from a Dictyota Brown Alga and Their Antioxidant and Neuroprotective Effects Against Cerebral Ischemia-Reperfusion Injury.

Five new diterpenes, including four new hydroazulenes, (8R,11R)-8,11-diacetoxypachydictyol A (1), (8R*,11R*)-6-O-acetyl-8-acetoxy-11-hydroxypachydictyol A (2), (8R*,11S*)-8-acetoxy-11-hydroxypachydictyol A (3), and (8R*,11S*)-6-O-acetyl-8,11-dihydroxypachydictyol A (4), and a secohydroazulene derivative, named 7Z-7,8-seco-7,11-didehydro-8- acetoxypachydictyol A (5), were isolated from a South China Sea collection of a Dictyota sp. nov. brown alga, together with five known analogues (6-10). Structure elucidation was achieved by extensive spectroscopic analysis and comparison with reported data. All compounds showed potent antioxidant effects against H2O2-induced oxidative damage in neuron-like PC12 cells at a low concentration of 2 µM. The antioxidant property of dictyol C (9) was associated with activation of the Nrf2/ARE signaling pathway; it also showed neuroprotective effects against cerebral ischemia-reperfusion injury (CIRI) in a rat model of transient middle cerebral artery occlusion. As such, hydroazulene diterpenes could serve as lead structures for the development of novel neuroprotective agents against CIRI.

Design, green synthesis, antioxidant activity screening, and evaluation of protective effect on cerebral ischemia reperfusion injury of novel monoenone monocarbonyl curcumin analogs.

Antioxidants with high efficacy and low toxicity have the potential to treat cerebral ischemia reperfusion injury (CIRI). Dienone monocarbonyl curcumin analogs (DMCA) capable of overcoming the instability and pharmacokinetic defects of curcumin possess notable antioxidant activity but are found to be significantly toxic. In this study, a novel skeleton of the monoenone monocarbonyl curcumin analogue sAc possessing reduced toxicity and improved stability was designed on the basis of the DMCA skeleton. Moreover, 32 sAc analogs were obtained by applying a green, simple, and economical synthetic method. Multiple sAc analogs with an antioxidant protective effect in PC12 cells were screened using an H2O2-induced oxidative stress damage model, and quantitative evaluation of structure-activity relationship (QSAR) model with regression coefficient of R2 = 0.918921 was built through random forest algorithm (RF). Among these compounds, the optimally active compound sAc15 elicited a potent protective effect on cell growth of PC12 cells by effectively eliminating ROS generation in response to oxidative stress injury by activating the Nrf2/HO-1 antioxidant signaling pathway. In addition, sAc15 exhibited good protection against CIRI in the mice middle cerebral artery occlusion (MCAO) model. In this paper, we provide a novel class of antioxidants and a potential compound for stroke treatment.

Red mud-metakaolin based cementitious material for remediation of arsenic pollution: Stabilization mechanism and leaching behavior of arsenic in lollingite.

The proper treatment of lollingite is of great significance due to its rapid oxidation leading to release of arsenic into the environment. Herein, a green multi-solid waste geopolymer, consisting of red mud, metakaolin, blast furnace slag, and flue gas desulfurization gypsum, was developed. The obtained red mud-metakaolin-based (RMM) geopolymer demonstrated good arsenic retention capability. The results showed that the replacement of SO42- in ettringite with AsO42- via ion exchange, formation of Ca-As and Fe-As precipitates, and physical encapsulation with aluminosilicate gel were the main mechanisms that prevented the release of arsenic. Further dissolution of ettringite in RMM was alleviated by adding a suitable amount of Ca(OH)2 and controlling the pH of the leachate. TCLP results verified that RMM materials possessed an outstanding ability to stabilize arsenic, with a leaching rate below the permitted value of 5 mg/L for safe disposal. The low leachability of the RMM geopolymers (<0.50 mg/L) is potentially related to the pH buffering capacity of the hydration products at a pH range of 2-5. RMM geopolymers showed a high compressive strength (>15 MPa) and low arsenic leaching concentration (<2.66 mg/L) after 28 days of curing. These results demonstrate the potential of RMM geopolymers to be utilized as an environmentally friendly backfilling cementitious material for sustainable remediation of arsenic pollution.

[Feeding status of 0～23-month-old infants in poor rural areas of Gansu Province from 2018 to 2019].

OBJECTIVE: To investigate the feeding status of infants and their feeder's feeding literacy in poor rural areas of Gansu Province. METHODS: From November 2018 to January 2019, a multi-stage cluster random sampling method was used to select 1200 infant and child families aged 0 to 23 months in 40 villages of Gansu Province. A standardized questionnaire from the Chinese Nutrition Society(CNS)was used to investigate the basic situation of infant and young children's families, the situation of breastfeeding and the addition of supplementary food, and parents feeding knowledge, attitude behavior(KAP). Using chi-square test, logistic regression and other method to statistically describe and infer the collected data. RESULTS: A total of 1193 infants and 1165 feeders were investigated. The exclusive breastfeeding rate of infants and young children under the age of 6 months was 39. 02%. The rate of continuous breastfeeding at 1 year old was 37. 40%, and the rate of continuous breastfeeding at 2 years old was 20. 88%, the difference between the two was significant(χ~2=13. 498, P<0. 01). The supplementary food supplement rate of infants and children over 6 months was 94. 37%, the highest supplementary supplement for cereals and potatoes(98. 01%), and the lowest percentage for beans and nuts(23. 51%), and the distribution of supplementary foods at different ages was significantly different(χ~2=52. 336, P<0. 01). The qualification rate of infants and young children's minimum dietary diversity was 64. 13%, the minimum eating frequency qualification rate was 70. 64%, the minimum acceptable dietary intake qualification rate was 42. 16%, and the qualification rates of various indicators were significantly different between different months(χ~2=85. 421, P<0. 01;χ~2=19. 66, P<0. 01; χ~2=17. 261, P<0. 01). The KAP score passing rate of infant caregivers was 37. 34%, and there was a statistical difference between the age of infants and young children, the education level and the sex of the caregiver(χ~2=9. 411, P<0. 05;χ~2=25. 901, P<0. 01;χ~2=3. 874, P<0. 05). Taking low-month-old infants and young children, low education and male caregivers as controls, infants and young children aged over 12 months, high school education and female caregivers were the protective factors of KAP scores(P<0. 05). CONCLUSION: The problems of infant breastfeeding and supplementary feeding in poor rural areas of Gansu Province were serious, and the knowledge and skills of raising people were scarce, which were related to the age of infants and young children, the education and the sex of raising people.

[Antitumor Activity of TRAIL-Mu3 Protein in vitro and in vivo and the Mechanisms].

OBJECTIVE: TRAIL-Mu3 was obtained by mutating the N-terminus of human tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) gene to an eight continuous arginine sequence. The present study was designed to explore the antitumor effect of this soluble mutant protein and the underlying mechanisms. METHODS: The inhibitory effect of TRAIL-Mu3 on the proliferation of lung cancer cell lines NCI-H460, A549, NCI-H1299 and calu-1 was tested by CCK8 assay. The apoptotic rates of A549 and NCI-H460 treated by TRAIL-Mu3 were detected by flow cytometer (FCM). The expressions of apoptosis related proteins death receptor (DR) 4, DR5, Caspase-3, Caspase-8 and X-linked inhibitor of apoptosis protein (XIAP) were detected by Western blot .Moreover, a subcutaneous xenograft tumor mouse model of NCI-H460 was established and treated with TRAIL-Mu3 daily or every other day or three times a week. The expressions of DR4, DR5, Caspase-3, Caspase-8 and XIAP were detected by immunohistochemical staining. RESULTS: The in vitro study demonstrated that as compared to the TRAIL, the TRAIL-Mu3 was more toxic and pro-apoptotic by up-regulation of the expression and activity of DR4, Caspase-3 and Caspase-8. Also, the animal study showed a similar antitumor effect between treatment with TRAIL-Mu3 every other day and three time a week, which was better than daily use. All treatments significantly suppressed the growth of xenograft tumor, increased the expression or activity of DR4 and Caspase-3, and down-regulated the expression of XIAP ( P<0.05). CONCLUSION: TRAIL-Mu3 could improve antitumor activity in vivo and in vitro through elevating DR4 expression, activating Caspase-3/-8, and inhibiting XIAP activation.

Genome Analysis Revealing the Potential Mechanisms for the Heavy Metal Resistance of Pseudomonas sp. P11, Isolated from Industrial Wastewater Sediment.

Pseudomonas sp. P11 was isolated from the industrial wastewater sediment nearby the Daye Non-ferrous Metals Company, China. This strain possesses the ability to resist various heavy metals and efficiently precipitate arsenic. We here present a summary classification and a set of features of Pseudomonas sp. P11, together with the description of the genomic sequencing and annotation. The genomic sequence is 6,644,817 bp with a G+C content of 62.20% and contains 6143 protein-coding genes, 250 pseudo genes, and 76 tRNAs/rRNAs genes. Operons and gene clusters responsible for multiple heavy metal tolerance or detoxification were identified and accounted for the observed resistance phenotypes. Phylogenetic analysis revealed that the paralogous arsenic resistant genes possess different evolutionary paths. This study provides important insights to illuminate the versatility and adaptation of this strain to the heavy metal-contaminated environment.

Dietary nitrate protects submandibular gland from hyposalivation in ovariectomized rats via suppressing cell apoptosis.

Xerostomia, a major oral symptom of menopause, is a subjective feeling of dry mouth associated with oral pain and difficulties in deglutition and speech, which significantly reduces patient's quality of life. Dietary nitrate, which can be converted to nitric oxide, has multiple physiological functions in the body, including antioxidant activity and vasodilatation; however, its protective effect against xerostomia remains poorly understood. The present study aimed to evaluate the effects of dietary nitrate on estrogen deficiency-induced xerostomia. We established an ovariectomized (OVX) rat model, which included five groups: sham-operated, OVX, OVX + 0.4 mM nitrate, OVX + 2 mM nitrate, and OVX + 4 mM nitrate (n = 6). After ovariectomy, animals in the nitrate treatment groups received appropriate amounts of sodium nitrate dissolved in distilled water for 3 months. The results showed that nitrate treatment reduced body weight and water intake, and increased serum nitrate and nitrite levels. Furthermore, nitrate uptake increased saliva secretion as evidenced by saliva flow rates and aquaporin 5 expression, and alleviated histological lesions as evidenced by reduction of the fibrotic area and cell atrophy in the salivary glands. Although protective effects of nitrate against estrogen deficiency-induced xerostomia were observed at all doses, treatment with 2 mM nitrate was more effective than that with 0.4 mM and 4 mM nitrate. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and caspase-3 expression analyses showed that nitrate also protected cells from apoptosis, possibly through upregulation of Cu-Zn superoxide dismutase (Cu-Zn SOD) known to inhibit oxidative stress-related apoptosis. Our findings indicate that nitrate could improve functional activity of the salivary glands in OVX rats by suppressing apoptosis and upregulating Cu-Zn SOD expression, suggesting that dietary nitrate may potentially prevent hyposalivation in menopausal women.

Endovascular versus Open Surgery Repair of Ruptured Abdominal Aortic Aneurysms in Hemodynamically Unstable Patients: Literature Review and Meta-Analysis.

BACKGROUND: The better outcome achieved by endovascular aortic repair (EVAR) in ruptured abdominal aortic aneurysm (rAAA) patients might derive from the fact that patients with hemodynamic instability preferentially underwent open repair. To further evaluate the effect of EVAR for rAAAs, a meta-analysis of studies in which hemodynamic instability was similar between the 2 treatment groups was conducted. METHODS: MEDLINE, EMBASE, ISI Web of Knowledge, and the Cochrane Library were searched from January 2004 to May 2014 for randomized controlled trials (RCTs) and observational studies that compared EVAR with open surgery repair in rAAA patients. RESULTS: Three RCTs and 10 observational studies covering 1,784 patients were included. Perioperative mortality occurred in 27.3% of the patients treated with EVAR and in 38.1% of the patients who underwent open repair. Subgroup analysis revealed consistent results in favor of EVAR in single-center, observational studies. Subgroup analysis and meta-regression analysis indicated that the superior effect of EVAR might be associated with more anatomically suitable patients in EVAR group. CONCLUSION: The findings from our meta-analysis support EVAR in properly selective rAAA patients.

Block copolymer-templated surface-enhanced Raman scattering-active nanofibers for hydrogen sulfide detection.

Metabolic disorders involving endogenous H2S have been linked to a variety of serious human diseases, particularly cancer. In this study, we employed nanofibers with surface-enhanced Raman scattering (SERS) activity for the detection of H2S within live cells. These nanofibers were chosen for their minimal invasiveness, high spatial resolution, and enhanced SERS sensitivity. To improve the performance of SERS, highly sensitive core-shell multibranched-Au NPs (MBAuNP)@Ag NPs were decorated on the nanofibers as SERS tags for H2S detection. A SERS probe named MBN, embedded between the Au core and Ag shell, was utilized for quantitative detection. These nanofibers exhibited excellent reproducibility (relative standard deviation (RSD) within 5.7 %) and demonstrated a strong linear relationship with sulfide concentrations ranging from 50 nM to 1 µM, with an estimated detection limit of 0.12 nM. As a proof of concept, the aforementioned nanofibers were successfully applied to detect endogenous H2S in living cells, offering a potential analytical method in the related research of detection.