Automatic offline-capable smartphone paper-based microfluidic device for efficient biomarker detection of Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is a prevalent neurodegenerative disease with no effective treatment. Efficient and rapid detection plays a crucial role in mitigating and managing AD progression. Deep learning-assisted smartphone-based microfluidic paper analysis devices (µPADs) offer the advantages of low cost, good sensitivity, and rapid detection, providing a strategic pathway to address large-scale disease screening in resource-limited areas. However, existing smartphone-based detection platforms usually rely on large devices or cloud servers for data transfer and processing. Additionally, the implementation of automated colorimetric enzyme-linked immunoassay (c-ELISA) on µPADs can further facilitate the realization of smartphone µPADs platforms for efficient disease detection. RESULTS: This paper introduces a new deep learning-assisted offline smartphone platform for early AD screening, offering rapid disease detection in low-resource areas. The proposed platform features a simple mechanical rotating structure controlled by a smartphone, enabling fully automated c-ELISA on µPADs. Our platform successfully applied sandwich c-ELISA for detecting the ß-amyloid peptide 1-42 (Aß 1-42, a crucial AD biomarker) and demonstrated its efficacy in 38 artificial plasma samples (healthy: 19, unhealthy: 19, N = 6). Moreover, we employed the YOLOv5 deep learning model and achieved an impressive 97 % accuracy on a dataset of 1824 images, which is 10.16 % higher than the traditional method of curve-fitting results. The trained YOLOv5 model was seamlessly integrated into the smartphone using the NCNN (Tencent's Neural Network Inference Framework), enabling deep learning-assisted offline detection. A user-friendly smartphone application was developed to control the entire process, realizing a streamlined "samples in, answers out" approach. SIGNIFICANCE: This deep learning-assisted, low-cost, user-friendly, highly stable, and rapid-response automated offline smartphone-based detection platform represents a good advancement in point-of-care testing (POCT). Moreover, our platform provides a feasible approach for efficient AD detection by examining the level of Aß 1-42, particularly in areas with low resources and limited communication infrastructure.

Mechanical Characterization of Multifunctional Metal-Coated Polymer Lattice Structures.

Metal-coated lattice structures hold significant promise for customizing mechanical properties in diverse industrial applications, including the mechanical arms of unmanned aerial vehicles. However, their intricate geometries pose computational challenges, resulting in time-intensive and costly numerical evaluations. This study introduces a parameterization-based multiscale method to analyze body-centered cubic lattice structures with metal coatings. We establish the validity and precision of our proposed method with a comparative analysis of numerical results at the Representative Volume Element (RVE) scale and experimental findings, specifically addressing both elastic tensile and bending stiffness. Furthermore, we showcase the method's accuracy in interpreting the bending stiffness of coated lattice structures using a homogenized material-based solid model, underscoring its effectiveness in predicting the elastic properties of such structures. In exploring the mechanical characterization of coated lattice structures, we unveil positive correlations between elastic tensile stiffness and both coating thickness and strut diameter. Additionally, the metal coating significantly enhances the structural elastic bending stiffness multiple times over. The diverse failure patterns observed in coated lattices under tensile and bending loads primarily stem from varied loading-induced stress states rather than external factors. This work not only mitigates computational challenges but also successfully bridges the gap between mesoscale RVE mechanical properties and those at the global structural scale.

Modal Response Improvement of Periodic Lattice Materials with a Shear Modulus-Based FE Homogenized Model.

Lattice materials are widely used in industries due to their designable capabilities of specific stiffness and energy absorption. However, evaluating the mechanical response of macroscopic lattice structures can be computationally expensive. Homogenization-based multi-scale analysis offers an efficient approach to address this issue. To achieve a simpler, while precise, homogenization, the authors proposed an equidistant segmentation (ES) method for the measurement of the effective shear modulus. In this method, the periodic boundary conditions (PBCs) are approximated by constraining the lateral displacement of nodes between parallel layers of periodic cells. The validations were applied to three typical lattice topologies: body-centered cubic (BCC) lattices, gyroid-, and primitive-triply periodic minimal surface (TPMS) lattices, to predict and compare their anti-vibration capacities. The results demonstrated the rationality and the promising precision of the multi-scale-based equivalent modal analysis through the proposed method and that it eliminated the geometric limitation of lattices with diverse frameworks. Overall, a higher anti-vibration capacity of TPMS was observed. In the study, the authors examined the influence of the relative densities on the balance between the anti-vibration capacity and loading capacity (per unit mass) of the TPMS topologies. Specifically, the unit mass of the TPMS with lower relative densities was able to resist higher frequencies, and the structures were dominated by the anti-vibration capacity. In contrast, a higher relative density is better when emphasizing the loading capacity. These findings may provide notable references to the designers and inform the selection of lattice materials for various industrial applications.

Research progress on anatomy reconstruction of rat orthotopic liver transplantation.

Rat orthotopic liver transplantation (ROLT) serves as an ideal animal model and has gained popularity in addressing complications and perioperative treatments related to clinical liver transplantation. Through extensive research on ROLT model construction, the conventional "two-cuff" method has gradually become established. However, traditional methods still present challenges including limited visual field during vascular suturing, vascular torsion, biliary tract injuries, and prolonged anhepatic periods. Consequently, this paper aims to review the latest advancements and various techniques in this field, providing a valuable reference for individuals interested in constructing ROLT models.

Study on Dynamic Mechanics of Node-Enhanced Graded Lattice Structure and Application Optimization in Automobile Energy Absorbing Box.

Based on the lightweight characteristics of automotive energy absorption boxes and the requirement of good energy absorption effect, this article first applies the node-enhanced body centered cubic (NBCC) lattice structure to the inner core design of automotive energy absorption boxes. The gradient study of the NBCC lattice structure was carried out using a drop hammer impact and split Hopkinson pressure bar (SHPB). The results indicate that gradient lattice structures have advantages in energy absorption, but there are differences under different gradient strategies. When the impact is not sufficient to compact the structure, the vertical rod diameter gradient node-enhanced lattice structure (RGNBCC) can absorb more energy and improve energy absorption performance by 25%. The vertical height gradient node-enhanced lattice structure (HGNBCC) is more suitable for high-speed impact conditions. Based on the advantages of the RGNBCC in resisting low-speed impacts, it is applied to the inner core design of automotive energy absorption boxes and optimized using multi-objective optimization methods. The optimization results show that the maximum peak impact force is reduced by 45.6% and the specific energy absorption is increased by 30.4%.

INTRA-AORTIC BALLOON PUMP REDUCES 30-DAY MORTALITY IN EARLY-STAGE CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION ACCORDING TO SCAI CLASSIFICATION.

ABSTRACT: Background: Cardiogenic shock complicating acute myocardial infarction (AMICS) remains a high 30-day mortality. Mechanical circulatory support devices are increasingly used in AMICS, but their effects on mortality vary partly because of shock severity. Aims: This study aimed to evaluate the association between intra-aortic balloon pump (IABP) and 30-day mortality in patients with early-stage AMICS. Methods: We retrospectively analyzed patients with ST-segment elevation myocardial infarction (STEMI) based on a multicenter clinical trial (NCT04996901). Patients were stratified by IABP use, and shock severity was classified according to the Society for Cardiovascular Angiography and Interventions (SCAI) SHOCK stages. The primary outcome was 30-day all-cause mortality. The association between IABP and 30-day mortality was evaluated across shock stages using propensity score matching, weighting, and logistic regression. Results: Five thousand three hundred forty-three patients were included, and 299 received IABP. The SCAI SHOCK stage was associated with 30-day mortality (odds ratio [OR], 20.19; 95% confidence interval [CI], 13.60-29.97; P < 0.001). In the 580 matched patients, a significant interaction between IABP and 30-day mortality at different shock stages was observed ( P = 0.005). Intra-aortic balloon pump was associated with lower 30-day mortality among patients with shock stage A/B (5.8% vs. 1.2%; OR, 0.19; 95% CI, 0.03-0.73; P = 0.034) but not stage C/D/E (29.3% vs. 38.1%; OR, 1.49; 95% CI, 0.84-2.65; P = 0.172). These results were confirmed by sensitivity analyses of the weighted cohort. Conclusions: Intra-aortic balloon pump reduced 30-day mortality in patients with early-stage AMICS. The SCAI SHOCK stage provides risk stratification for patients with STEMI and helps identify those who may respond well to IABP.

One-Dimensional Heterobimetallic Au/Ag Coordination Polymer Showing a Selective, Reversible, and Visible Vapor-Chromic Photoluminescent Response toward Methanol.

A heterobimetallic coordination polymer [Au4(dppmt)4(AgCl)2]n (1) incorporating an in situ generated P-S ligand (dppmtH) was synthesized from the solvothermal reaction of Au(tht)Cl, AgCl, and dpppyatc in CH3CN/CH2Cl2 (dppmtH = (diphenylphosphino)methanethiol, tht = tetrahydrothiophene, dpppyatc = N,N-bis((diphenylphosphaneyl)methyl)-N-(pyridin-2-yl)-amino-thiocarbamide). The structure of 1 contains a one-dimensional helical Au-Au chain in which the unique [Au4Ag2S2] cluster units are connected by [Au2(dppmt)2] dimers. Upon excitation at 343 nm, 1 exhibited cyan (495 nm) phosphorescent emission at quantum yield (QY) = 22.3% and τ = 0.78 µs (λex = 375 nm). Coordination polymer 1 exhibited a rapid, selective, reversible, and visible vapor-chromic response on exposure to methanol (MeOH) vapor with its emission shifting to a more intense green (530 nm, λex = 388 nm) with QY = 46.8% and τ = 1.24 µs (λex = 375 nm). A polymethylmethacrylate film containing 1 served as a reversible chemical sensor for the sensitive detection of MeOH in air.

Stress-field driven conformal lattice design using circle packing algorithm.

Reliable extreme lightweight is the pursuit in many high-end manufacturing areas. Aided by additive manufacturing (AM), lattice material has become a promising candidate for lightweight optimization. Configuration of lattice units at the material level and the distribution of lattice units at the structure level are the two main research directions recently. This paper proposes a generative strategy for lattice infilling optimization using organic strut-based lattices. A sphere packing algorithm driven by von Mises stress fields determines the lattice distribution density. Two typical configurations, Voronoi polygons and Delaunay triangles, are adopted to constitute the frames, respectively. Based on finite element analysis, a simplified truss model is utilized to evaluate the lattice distribution in terms of mechanical properties. Optimization parameters, including node number, mapping gradient, and the range of varying circle size, are investigated through the genetic algorithm (GA). Multiple feasible solutions are obtained for further solidification modelling. To avoid the stress concentration, the organic strut-based lattice units are created by the iso-surface modelling method. The effectiveness of the proposed generative approach is illustrated through a classical 3-point bending beam. The stiffness of the optimized structure, verified through experimental testing, has increased 80% over the one using the traditional uniform body center cubic (BCC) lattice distribution.

Effects of initial volatile fatty acid concentrations on process characteristics, microbial communities, and metabolic pathways on solid-state anaerobic digestion.

Solid-state anaerobic digestion (SSAD) is vulnerable to excess volatile fatty acids (VFA), mainly acetate and propionate. The co-effects of VFAs and microbial dynamics under VFA accumulation were investigated in SSAD of pig manure and corn straw. Adding 2 and 4 mg/g acetate or propionate caused initial increases in total VFAs, followed by decreases after day 6, resulting in 'mild' VFA accumulation, while adding 6 mg/g caused similarly increased VFAs, but with no subsequent decrease, causing 'severe' VFA accumulation and poor methanation performance. Mild propionate accumulation promoted acetate consumption, whereas acetate accumulation inhibited propionate degradation by affecting crucial redox reactions. Under severe VFA accumulation, hydrolysis and acidification mainly conducted by acid-tolerant Clostridium sp. exacerbated VFA inhibition, causing a competition between Methanosarcina and Methanosaeta, and impairments of acetoclastic and hydrogenotrophic methanogenesis and interspecies formate transfer. This study provides new insights into mechanisms of VFA accumulation in SSAD, and its effects on methanogenesis.

Clinical efficacy and safety evaluation of camrelizumab plus lenvatinib in adjuvant therapy after hepatocellular carcinoma surgery.

Objective: To assess the efficacy and safety of camrelizumab plus different targeted drugs in adjuvant therapy after hepatocellular carcinoma (HCC) surgery. Patients and methods: This retrospective cohort study included HCC patients who, after undergoing failed postoperative adjuvant lenvatinib therapy, received intravenous camrelizumab 200 mg every 3 weeks (C group, n = 97), camrelizumab plus oral apatinib 250 mg daily (C+A group, n = 125), camrelizumab plus oral lenvatinib 12 mg daily (for bodyweight ≥60 kg)/lenvatinib 8 mg daily (for bodyweight <60 kg) (C+L group, n = 120), or camrelizumab plus oral sorafenib 400 mg bi-daily (C+S group, n = 114) between October 2020 and October 2021. The outcomes including the objective response rate (ORR) and disease control rate (DCR) were evaluated by RECIST 1.1 and iRECIST. The median progression-free survival (mPFS), median overall survival (mOS), 6-month OS rate, 12-month OS rate, and adverse events were evaluated. Results: As of 31 May 2022 with last follow-up time, the ORR was 17.2% for the C group, 44.6% for the C+A group, 47.9% for the C+L group, and 36.3% for the C+S group. The DCR was 72.0% for the C group, 81.8% for the C+A group, 85.5% for the C+L group, and 77.9% for the C+S group. The mPFS was 11.0 months (10.1-12.8) for the C group, 14.0 months (12.7-16.5) for the C+A group, 18.0 months (16.9-20.1) for the C+L group, and 12.0 months (9.7-14.4) for the C+S group. The mOS was 13.0 months (11.6-15.3) for the C group, 17.0 months (15.8-19.4) for the C+A group, 19.0 months (17.7-20.2) for the C+L group, and 15.0 months (14.1-17.3) for the C+S group. Grade 3 or 4 treatment-related adverse events occurred in 14 patients (14.4%) for the C group, 10 patients (8.0%) for the C+A group, 5 patients (4.2%) for the C+L group, and 11 patients (9.6%) for the C+S group. The most common adverse events were fatigue and transaminitis. Conclusion: Camrelizumab combined with lenvatinib as adjuvant therapy showed promising efficacy and manageable safety in HCC patients. It might be a potential adjuvant therapy or second-line treatment for these patients.

BRD4 inhibition by JQ1 protects against LPS-induced cardiac dysfunction by inhibiting activation of NLRP3 inflammasomes.

BACKGROUND: JQ1, a BRD4 inhibitor, first identified its therapeutic role in cancer, has gradually demonstrated a protective effect on the heart in recent years; however, it is unclear whether JQ1 also plays a role in LPS-induced cardiac dysfunction. METHODS AND RESULTS: A total of forty eight mice were randomly divided into control, LPS(7.5 mg/kg), and LPS + JQ1 (50 mg/kg). JQ1 was preprotected for 1 h, and LPS was stimulated for 12 h, mouse survival and cardiac function were observed, and histopathological, serum myocardial injury markers, and inflammatory indicators, and oxidative stress levels in heart tissue were examined. The experiment found that the cardiac BRD4 levels were upregulated and the heart severe damage in the LPS group compared with the control group. While compared with the LPS group, JQ1 preprotected increased survival rate and cardiac function, reducated cardiomypathological injury and CD45 infiltration, and reduced the release of LDH, CK-MB, IL-1, IL-18, reduced MDA generation, and increased SOD viability. In addition, JQ1 preprotected also upregulated SIRT1, and inhibited the expression of NLRP3, caspase-1p20, and GSDMD. Meanwhile, similar results were obtained in LPS-treated H9C2 cells, and further intervention with the SIRT1 inhibitor EX527 partially blocked the JQ1-mediated down regulation of NLRP3, caspase-1p20, and GSDMD. CONCLUSIONS: We propose that JQ1 may improve LPS-induced cardiac dysfunction by inhibiting SIRT1-dependent activation of NLRP3 inflammasomes, which may be a promising strategy for treating sepsis cardiomyopathy.

Dietary supplementation of thiamine enhances colonic integrity and modulates mucosal inflammation injury in goats challenged by lipopolysaccharide and low pH.

The current study aimed to investigate the protective effects of dietary thiamine supplementation on the regulation of colonic integrity and mucosal inflammation in goats fed a high-concentrate (HC) diet. Twenty-four Boer goats (live weight of 35·62 (sem 2·4) kg) were allocated to three groups (CON: concentrate/forage = 30:70; HC; concentrate/forage = 70:30 and HCT: concentrate/forage = 70:30 with 200 mg thiamine/kg DMI) for 12 weeks. Results showed that compared with the HC treatment, the HCT group had a significantly higher ruminal pH value from 0 to 12 h after the feeding. The haematoxylin-eosin staining showed that desquamation and severe cellular damage were observed in the colon epithelium of the HC group, whereas the HCT group exhibited more structural integrity of the epithelial cell morphology. Compared with the HC treatment, the HCT group showed a markedly increase in pyruvate dehydrogenase and α-ketoglutarate dehydrogenase enzymes activity. The mRNA expressions in the colonic epithelium of SLC19A2, SLC19A3, SLC25A19, Bcl-2, occludin, claudin-1, claudin-4 and ZO-1 in the HCT group were significantly increased in comparison with the HC diet treatment. Compared with the HC treatment, the HCT diet significantly increased the protein expression of claudin-1 and significantly decreased the protein expression of NF-κB-related proteins p65. The results show that dietary thiamine supplementation could improve the colon epithelial barrier function and alleviate mucosal inflammation injury in goats after lipopolysaccharide and low pH challenge.

Molybdenum Fertilization Improved Antioxidant Capacity of Grazing Nanjiang Brown Goat on Copper-Contaminated Pasture.

Copper (Cu) is an essential trace element, but excessive Cu intake can induce poor performance and Cu poisoning and result in various health problems. Cu and molybdenum (Mo) antagonize each other in vivo. Therefore, Mo can reduce the absorption and utilization of Cu. The aims of this study were to investigate the impacts of Mo fertilization on antioxidant capacity of grazing Nanjiang brown goat on Cu-polluted meadow and explore the control methods of Cu pollution in natural pasture. Fertilization and grazing experiments were carried out in Liangshan Yi Nationality Prefecture of the Western Sichuan Plateau, Sichuan Province, Southwest China. Cu-polluted meadows of 12 hm2 were fenced, and randomly divided into two groups (3 replications/group, 2 hm2/replication), control group and treatment group, fed with basic diets supplemented with 0 and 3 kg Mo/hm2 [ammonium molybdate tetrahydrate, (NH4)6Mo7O24·4H2O], respectively. In the current study, 36 healthy Nanjiang brown goats (1 year old, 32.8 ± 1.1 kg) were randomly divided into two groups (3 replications/group, 6 goats/replication) and assigned to the experimental pastures. The grazing experiment lasted for 60 days. The results showed that the concentration of Mo in soil in treatment group was 96.28 mg/kg, far exceeding the normal levels. At days 30 and 60, the levels of Hb, RBC, and PCV in blood in treatment group and the activities of serum SOD, GSH-Px, T-AOC, CAT, and Cp were higher than those in control group (P < 0.01). The MDA content in treatment group was lower than that in control group (P < 0.01). The contents of Cu in blood and liver in treatment goats were lower than those in control animals (P < 0.01). The contents of Zn and Mo in blood and liver in treatment goats were higher than those in control animals (P < 0.01). The Mn content in liver in treatment group was higher than that in control animals (P < 0.01). These results indicated that fertilization of (NH4)6Mo7O24 not only markedly influenced the mineral contents in blood and liver, but also extremely improved antioxidant capacity of grazing Nanjiang brown goat from fertilized pastures and relieved the damage caused by Cu pollution.

Effect of Copper-Containing Stainless Steel on Apoptosis of Coronary Artery Smooth Muscle Cells.

BACKGROUND: We aimed to investigate the effect of copper stainless steel on apoptosis of vascular smooth muscle cells in coronary artery. METHODS: The study was carried out in 2019 at Hubei University of Medicine, Xiangyang, China. The rat coronary artery smooth muscle cell was used for cell resuscitation and culture. MTT method was used to visualize cell growth curve and to detect the cell survival and growth. The incubated cells were randomly divided into copper-containing stainless-steel group, ordinary stainless-steel group, and control group. The cells were made into single cell suspension, which were intervened by experimental group and incubated in incubator with CO2 for 48 hours. TUNEL method was used to detect the apoptosis. The number of apoptotic cells in five high power fields (×200) was counted. The expression of Fas protein in three groups of cells was detected by Western blot. RESULTS: The growth curves of rat coronary artery smooth muscle cells showed that the OD value of the cells reached the plateau 7 days after inoculation, indicating that the cells grew well. TUNEL staining showed the apoptosis in all three groups. The apoptotic index in copper-containing group was significantly higher than that in common stainless-steel group (P <0.01). The results of the Fas protein expression level through Western blot showed that the level in the copper-containing group was significantly higher than that in the common stainless-steel group (P<0.01). CONCLUSION: Copper-containing stainless steel can promote apoptosis of coronary artery smooth muscle cells. The material could prevent stent restenosis.

Ruminal Microbes Exhibit a Robust Circadian Rhythm and Are Sensitive to Melatonin.

Gut hormones are not only able to regulate digestive, absorptive, and immune mechanisms of the intestine through biological rhythms, but impact the host through their interactions with intestinal microorganisms. Whether hormones in ruminal fluid have an association with the ruminal ecology is unknown. Objectives of the study were to examine relationships between the diurnal change in ruminal hormones and microbiota in lactating cows, and their associations in vivo and in vitro. For the in vivo study, six cows of similar weight (566.8 ± 19.6 kg), parity (3.0 ± 0.0), and milk performance (8,398.7 ± 1,392.9 kg/y) were used. They were adapted to natural light for 2 weeks before sampling and fed twice daily at 07:00 a.m. and 14:00 p.m. Serum, saliva, and ruminal fluid samples were collected at 02:00, 10:00, and 18:00 on the first day and 06:00, 14:00, and 22:00 on the second day of the experimental period. The concentrations of melatonin (MLT), growth hormone (GH), and prolactin (PRL) were measured via radioimmunoassay, whereas amplicon sequencing data were used to analyze relative abundance of microbiota in ruminal fluid. JTK_CYCLE analysis was performed to analyze circadian rhythms of hormone concentrations as well as the relative abundance of microbiota. For the in vitro study, exogenous MLT (9 ng) was added into ruminal fluid incubations to investigate the impacts of MLT on ruminal microbiota. The results not only showed that rumen fluid contains MLT, but the diurnal variation of MLT and the relative abundance of 9% of total rumen bacterial operational taxonomic units (OTUs) follow a circadian rhythm. Although GH and PRL were also detected in ruminal fluid, there was no obvious circadian rhythm in their concentrations. Ruminal MLT was closely associated with Muribaculaceae, Succinivibrionaceae, Veillonellaceae, and Prevotellaceae families in vivo. In vitro, these families were significantly influenced by melatonin treatment, as melatonin treatment increased the relative abundance of families Prevotellaceae, Muribaculaceae while it reduced the relative abundance of Succinivibrionaceae, Veillonellaceae. Collectively, ruminal microbes appear to maintain a circadian rhythm that is associated with the profiles of melatonin. As such, data suggest that secretion of melatonin into the rumen could play a role in host-microbe interactions in ruminants.

The combinations of sulfur and molybdenum fertilizations improved antioxidant capacity of grazing Guizhou semi-fine wool sheep under copper and cadmium stress.

Mineral development and metal smelting are the main sources of heavy metal pollution, and copper (Cu) and cadmium (Cd) are the most serious mineral elements in heavy metal pollution. Food chain is the main channel for Cu and Cd to enter human body. Excessive accumulation of Cu and Cd can lead to a variety of diseases and threaten human health. Therefore, it is urgent to repair Cu and Cd-contaminated soil. Previous several studies found that sulfur (S) and molybdenum (Mo) had the effect of alleviating the decrease of antioxidant capacity caused by heavy metal poisoning. To investigate the co-combinations of S and Mo fertilizations on antioxidant capacity of grazing Guizhou semi-fine wool sheep in Cu and Cd-contaminated meadow, and explore the control methods of co-pollutions of Cu and Cd in natural pastures, fertilizing and grazing experiments were carried out in the Wumeng Prairie in the northwest of Guizhou Province, Southwest China. 24 hm2 Cu and Cd-polluted meadows were fenced, and were randomly divided into four groups with 3 replications per group and 2 hm2 per replication. The tested groups included the control group (no fertilizer) and the three treatment groups, applied 40 kg S + 1 kg Mo, 80 kg S + 2 kg Mo, and 120 kg S + 3 kg Mo per hectare for group I, group II, and group III, respectively. 72 healthy Guizhou semi-fine wool sheep (one year old, 33.9 ± 1.2 kg) were randomly assigned to the tested pastures with 18 sheep per group. The grazing experiment lasted for 60 days. The results showed that the contents of Mn, Zn, Mo, and S in herbage in fertilized pastures were higher than that in the control group (P < 0.05). The content of Cu in herbage in fertilized pastures was lower than that in the control group (P < 0.05). The contents of Mn, Zn, Mo, and S in serum of grazing Guizhou semi-fine wool sheep were higher than that in the control group (P < 0.05). The content of Cu in serum of grazing Guizhou semi-fine wool sheep was lower than that in the control group (P < 0.05). The levels of blood Hb, RBC, and PCV, and the activities of serum SOD, GSH-Px, T-AOC, CAT, and Cp in group Ⅲ were higher than that in the control group, group Ⅰ, and group Ⅱ (P < 0.05). The MDA content of sheep in group Ⅲ was lower than that in the other treatment sheep (P < 0.05). In summary, the combinations of S and Mo fertilizers influenced the mineral contents in herbage and serum of grazing Guizhou semi-fine wool sheep. The combinations of 120 kg S + 3 kg Mo fertilizer reduced the toxicity and improved antioxidant capacity of grazing Guizhou semi-fine wool sheep in Cu and Cd-polluted grasslands.

Effectiveness of Sequential Chemoradiation vs Concurrent Chemoradiation or Radiation Alone in Adjuvant Treatment After Hysterectomy for Cervical Cancer: The STARS Phase 3 Randomized Clinical Trial.

IMPORTANCE: There is no current consensus on the role of chemotherapy in addition to radiation for postoperative adjuvant treatment of patients with early-stage cervical cancer with adverse pathological factors. OBJECTIVE: To evaluate the clinical benefits of sequential chemoradiation (SCRT) and concurrent chemoradiation (CCRT) compared with radiation alone (RT) as a postoperative adjuvant treatment in early-stage cervical cancer. DESIGN, SETTING, AND PARTICIPANTS: After radical hysterectomy at 1 of 8 participating hospitals in China, patients with FIGO (International Federation of Gynecology and Obstetrics) stage IB to IIA cervical cancer with adverse pathological factors were randomized 1:1:1 to receive adjuvant RT, CCRT, or SCRT. Data were collected from February 2008 to December 2018. INTERVENTIONS: Patients received adjuvant RT (total dose, 45-50 Gy), CCRT (weekly cisplatin, 30-40 mg/m2), or SCRT (cisplatin, 60-75 mg/m2, plus paclitaxel, 135-175 mg/m2) in a 21-day cycle, given 2 cycles before and 2 cycles after radiotherapy, respectively. MAIN OUTCOMES AND MEASURES: The primary end point was the rate of disease-free survival (DFS) at 3 years. RESULTS: A total of 1048 women (median [range] age, 48 [23-65] years) were included in the analysis (350 in the RT group, 345 in the CCRT group, and 353 in the SCRT group). Baseline demographic and disease characteristics were balanced among the treatment groups except that the rate of lymph node involvement was lowest in the RT group (18.3%). In the intention-to-treat population, SCRT was associated with a higher rate of DFS than RT (3-year rate, 90.0% vs 82.0%; hazard ratio [HR], 0.52; 95% CI, 0.35-0.76) and CCRT (90.0% vs 85.0%; HR, 0.65; 95% CI, 0.44-0.96). Treatment with SCRT also decreased cancer death risk compared with RT (5-year rate, 92.0% vs 88.0%; HR, 0.58; 95% CI, 0.35-0.95) after adjustment for lymph node involvement. However, neither DFS nor cancer death risk was different among patients treated with CCRT or RT. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, conducted in a postoperative adjuvant treatment setting, SCRT, rather than CCRT, resulted in a higher DFS and lower risk of cancer death than RT among women with early-stage cervical cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00806117.

Mechanisms and challenges of microbial fuel cells for soil heavy metal(loid)s remediation.

Bioelectrochemical approaches offer a simple, effective, and environmentally friendly solution to pollutant remediation. As a versatile technology, although many studies have shown its potential in soil heavy metal(loid) remediation, the mechanism behind this process is not simple or well-reviewed. Thus, in this review we summarized the impacts of the microbial fuel cells (MFCs) on metal (loids) movement and transformation in the soil environment in terms of changes in soil pH, electromigration, and substrate competition between anode-respiring bacteria and the soil microbial community. Furthermore, the progress of MFCs in the fixation/removal of different elements from the soil environment is described. Hence, this review provides critical insight into the use of the MFC for soil metal(loid) bioremediation.

Blocking PPARγ interaction facilitates Nur77 interdiction of fatty acid uptake and suppresses breast cancer progression.

Nuclear receptor Nur77 participates in multiple metabolic regulations and plays paradoxical roles in tumorigeneses. Herein, we demonstrated that the knockout of Nur77 stimulated mammary tumor development in two mouse models, which would be reversed by a specific reexpression of Nur77 in mammary tissues. Mechanistically, Nur77 interacted and recruited corepressors, the SWI/SNF complex, to the promoters of CD36 and FABP4 to suppress their transcriptions, which hampered the fatty acid uptake, leading to the inhibition of cell proliferation. Peroxisome proliferator-activated receptor-γ (PPARγ) played an antagonistic role in this process through binding to Nur77 to facilitate ubiquitin ligase Trim13-mediated ubiquitination and degradation of Nur77. Cocrystallographic and functional analysis revealed that Csn-B, a Nur77-targeting compound, promoted the formation of Nur77 homodimer to prevent PPARγ binding by steric hindrance, thereby strengthening the Nur77's inhibitory role in breast cancer. Therefore, our study reveals a regulatory function of Nur77 in breast cancer via impeding fatty acid uptake.