Genomic analyses of wild argali, domestic sheep, and their hybrids provide insights into chromosome evolution, phenotypic variation, and germplasm innovation.

Understanding the genetic mechanisms of phenotypic variation in hybrids between domestic animals and their wild relatives may aid germplasm innovation. Here, we report the high-quality genome assemblies of a male Pamir argali (O ammon polii, 2n = 56), a female Tibetan sheep (O aries, 2n = 54), and a male hybrid of Pamir argali and domestic sheep, and the high-throughput sequencing of 425 ovine animals, including the hybrids of argali and domestic sheep. We detected genomic synteny between Chromosome 2 of sheep and two acrocentric chromosomes of argali. We revealed consistent satellite repeats around the chromosome breakpoints, which could have resulted in chromosome fusion. We observed many more hybrids with karyotype 2n = 54 than with 2n = 55, which could be explained by the selfish centromeres, the possible decreased rate of normal/balanced sperm, and the increased incidence of early pregnancy loss in the aneuploid ewes or rams. We identified genes and variants associated with important morphological and production traits (e.g., body weight, cannon circumference, hip height, and tail length) that show significant variations. We revealed a strong selective signature at the mutation (c.334C > A, p.G112W) in TBXT and confirmed its association with tail length among sheep populations of wide geographic and genetic origins. We produced an intercross population of 110 F2 offspring with varied number of vertebrae and validated the causal mutation by whole-genome association analysis. We verified its function using CRISPR-Cas9 genome editing. Our results provide insights into chromosomal speciation and phenotypic evolution and a foundation of genetic variants for the breeding of sheep and other animals.

Effectiveness of abduction brace versus simple sling rehabilitation following rotator cuff repair: systematic review and meta-analyses.

BACKGROUND: To date, no conclusions have been reached regarding the type of brace worn after arthroscopic rotator cuff repair. To this end, a systematic review and meta-analysis of randomized controlled trials (RCTs) were conducted. METHODS: According to the updated guidelines of the Preferred Reporting Items of Systematic Review and Meta-Analysis, all related literature in PubMed, Embase, and Cochrane Central Register of Controlled Trials, from their establishment to March 1, 2022, were searched systematically. Outcome measures included the Constant score, Western Ontario Rotator Cuff (WORC) index, visual analog scale (VAS) score, shoulder joint range of motion (ROM), and failure events of rotator cuff healing. The Cochrane risk of bias tool was used to evaluate the quality of RCT. RESULTS: Two independent reviewers (Chen, Wu) reviewed 275 articles, of which only five met the inclusion criteria, and four were included in the meta-analysis, with a total of 302 patients. The overall risk of bias was high in two RCTs, unclear in one, and low in two. Considering the clinical outcomes, the Constant score (P = .08 mean deviation [MD], 3.06; 95% confidence interval [CI], -0.42 to 6.53), WORC (P = .23; MD, 3.32; 95%CI, -2.15 to 8.79), VAS score (P = .09; MD -1.27; 95%CI, -2.75 to 0.21), ROM (P = .1; MD, 4.75; 95%CI, -0.98 to 10.48), and failure events of rotator cuff healing (P = .78; odds ratio [OR], 0.86; 95%CI, 0.32 to 2.37) did not significantly differ between the abduction brace and simple sling after arthroscopic rotator cuff repair. CONCLUSION: The findings of this systematic review and meta-analysis suggest that wearing abduction braces after rotator cuff repair neither improved the Constant score, VAS, and WORC scores, and ROM of the shoulder joint, nor did it reduce the risk of re-tearing. Therefore, a simple sling may be a better option in terms of cost effectiveness. It is expected that studies with larger and more homogeneous samples will help verify our results.

Incremental value of Alberta Stroke Program Early CT Score to collateral score for predicting target mismatch in stroke patients with extended time window or unknown onset time.

PURPOSE: To evaluate whether Alberta Stroke Program Early CT Score (ASPECTS) could provide incremental value to collateral score, and their integration could be an effective surrogate of CTP in predicting target mismatch. MATERIAL AND METHODS: One hundred and fifty-nine stroke patients (onset time 6-16 h or with unknown onset time) with MCA and/or ICA occlusion underwent non-contrast computed tomography (NCCT) and CT perfusion (CTP) scan for initial assessment. Simulated single-phase CT angiography (sCTA, peak arterial phase) and multiphase CTA (mCTA) were reconstructed from CTP. ASPECTS was assessed on NCCT and sCTA. Collateral score was evaluated on mCTA. Target mismatch was defined as infarct core volume < 70 mL, the mismatch ratio ≥ 1.8, and the absolute mismatch volume ≥ 15 mL. Pearson correlation analysis, Mann-Whitney U test, chi-square test, and receiver operating characteristic curve analyses were performed. RESULTS: Median CTA source image (CTA-SI) ASPECTS was significantly lower than NCCT ASPECTS (p = 0.001). NCCT ASPECTS, CTA-SI ASPECTS, and mCTA collateral score correlated significantly with infarct core volume and mismatch ratio (all p < 0.05). Mismatch group showed significantly higher NCCT ASPECTS, CTA-SI ASPECTS, and mCTA collateral score than non-mismatch group (all p < 0.001). NCCT ASPECTS and CTA-SI ASPECTS showed comparable predicting performance with mCTA collateral score (p > 0.05). Adding CTA-SI ASPECTS to mCTA collateral score improved the performance of mCTA in predicting target mismatch (area under curve, 0.905 vs. 0.804, p = 0.003). CONCLUSION: ASPECTS can provide incremental information to collateral score in predicting target mismatch. If CTP scan fails, clinical decision based on ASPECTS and collateral score might be reasonable.

Comparison of time consumption and success rate between CT angiography- and CT perfusion- based imaging assessment strategy for the patients with acute ischemic stroke.

BACKGROUND: Our study aimed to compare the time consumption and success rate between CTA- and CTP- based assessment strategy, and to clarify the risk factors associated with the CTP scan failure. METHODS: Clinical and radiological data of 437 consecutive AIS patients who underwent multiphase CTA or CTP for pre-treatment evaluation were retrospectively enrolled (CTA group, n = 302; CTP group, n = 135). Time consumption and success rate of CTA- and CTP- based assessment strategy were compared using Mann-Whitney U test and Chi-Squared Test. Univariate analysis and receiver operating curve analysis were used to clarify the risk factors, and their performance in predicting the CTP scan failure. RESULTS: Time consumption of CTP scan and reconstruction was significantly longer than that of CTA [775 s vs 263.5 s, P < 0.001]. CTP scan showed significantly higher failure rate than CTA (11% vs 1%, P < 0.001). Severe motion was the most common cause of CTP failure (n = 12, 80%). Baseline National Institute of Health Stroke Scale (NIHSS) score in CTP failure group was significantly higher than that in CTP success group [17 vs 13, P = 0.007]. Baseline NIHSS score of 11 was the optimal threshold value to predict CTP failure with an area under the curve of 0.715, a sensitivity of 86.7%, and a specificity of 45.0%. CONCLUSIONS: CTP- based strategy showed longer time consumption and higher failure rate than CTA- based strategy. High baseline NIHSS score was significantly associated with CTP scan failure in AIS patients.

Cerebral blood volume Alberta Stroke Program Early Computed Tomography Score predicts intracranial hemorrhage after thrombectomy in patients with acute ischemic stroke in an extended time window.

BACKGROUND: Higher baseline Alberta Stroke Program Early Computed Tomography Score (ASPECTS) was associated with a lower probability of hemorrhagic transformation in patients with acute ischemic stroke (AIS). PURPOSE: To investigate the predictive value of cerebral blood volume (CBV)-ASPECTS of intracranial hemorrhage (ICH) in AIS treated with thrombectomy selected by computed tomographic perfusion (CTP) in an extended time window. MATERIAL AND METHODS: A total of 91 consecutive patients with AIS with large vessel occlusion in the anterior circulation after thrombectomy in an extended time window were enrolled between January 2018 and September 2019. ICH was diagnosed according to Heidelberg Bleeding Classification. CBV-ASPECTS was assessed by evaluating each ASPECTS region for relatively low CBV value compared with the mirror region in the contralateral hemisphere. Demographic characteristics, clinical data, CBV-ASPECTS, and procedure process and results were compared between patients with ICH and those without. RESULTS: ICH occurred in 31/91 (34.1%) patients with AIS. Symptomatic ICH (sICH) was observed in 4 (4.4%) patients, while asymptomatic ICH (aICH) was seen in 27 (29.7%). In univariate analysis, both ICH and aICH were associated with high admission NIHSS score (P<0.001 and P<0.001, respectively), more passes of retriever (P = 0.007 and P = 0.019, respectively), low NCCT-ASPECTS (P = 0.013 and P = 0.034, respectively), and low CBV-ASPECTS (P < 0.001 and P < 0.001, respectively). After multivariable analysis, low CBV-ASPECTS remained an independent predictor of ICH (odds ratio [OR] 0.521, 95% confidence interval [CI] 0.371-0.732, P < 0.001) and aICH (OR 0.532, 95% CI 0.376-0.752, P < 0.001), respectively. CONCLUSION: Low CBV-ASPECTS independently predicts ICH in patients with AIS treated with thrombectomy selected by CTP in an extended time window.

Hyperperfusion on Arterial Spin Labeling MRI Predicts the 90-Day Functional Outcome After Mechanical Thrombectomy in Ischemic Stroke.

BACKGROUND: The prognostic significance of hyperperfusion after reperfusion therapy in patients with acute ischemic stroke (AIS) remains controversial. PURPOSE: To investigate the clinical factors associated with hyperperfusion, and the 90-day prognostic value of hyperperfusion after mechanical thrombectomy in AIS patients. STUDY TYPE: Retrospective. POPULATION/SUBJECTS: Fifty-four AIS patients who underwent mechanical thrombectomy. FIELD STRENGTH/SEQUENCE: Time-of-flight MR angiography, pulsed arterial spin labeling (ASL), diffusion-weighted imaging (DWI), and susceptibility-weighted imaging were performed at 3.0T within 1 week after thrombectomy. ASSESSMENT: Clinical factors including demographics, risk factors, stroke and treatment characteristics were collected and assessed. Hyperperfusion on ASL was defined as a focal increased cerebral blood flow on the affected side ≥130% of its mirror counterpart. Good clinical outcome at 90 days was defined as modified Rankin Scale score of 0-2. STATISTICAL TESTS: The interrater agreement was assessed using Cohen's kappa or the intraclass correlation coefficient. The relationship between hyperperfusion and clinical factors were analyzed by appropriate univariate statistics. Predictors of 90-day functional outcome were assessed by univariate analyses followed by multivariate logistic regression analysis and receiver-operating-characteristic curves. RESULTS: Thirty-six (66.7%) patients developed hyperperfusion on ASL after thrombectomy. Hyperperfusion was significantly correlated with successful recanalization (P < 0.05) and improvement of National Institutes of Health Stroke Scale scores at 24 hours (NIHSS24h ) (P < 0.05). A higher incidence of hemorrhage transformation was observed in patients with hyperperfusion than those without (63.9% vs. 50.0%), but no significant difference was found (P = 0.327). NIHSS24h (odds ratio [OR], 0.75, [95% confidence interval [CI] 0.62-0.91], P < 0.05), lesion volume on diffusion-weighted imaging (OR, 0.97, [95% CI 0.95-1.00], P < 0.05), and hyperperfusion on ASL (OR, 9.8, [95% CI 1.7-55.3], P < 0.05) were independent variables for predicting good functional outcomes. DATA CONCLUSION: Hyperperfusion on ASL correlated with successful recanalization and may be an independent prognostic marker for good neurological outcomes at 90 days in AIS patients after mechanical thrombectomy. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 2.

Comparison of CT angiography collaterals for predicting target perfusion profile and clinical outcome in patients with acute ischemic stroke.

OBJECTIVES: To compare collateral status on single-phase CT angiography (sCTA) and multiphase CT angiography (mCTA) and their ability to predict a target mismatch on CT perfusion (CTP) and clinical outcome in patients with acute ischemic stroke (AIS). METHODS: Seventy-three AIS patients with stroke onset between 5 and 15 h or with unclear onset time and occlusions in the M1/M2 segment of the middle cerebral artery and/or intracranial internal carotid artery underwent head non-contrast CT and CTP. Simulated sCTA and mCTA were reconstructed from CTP data and were compared for collaterals assessment. The ability to predict target mismatch on CTP (an ischemic core < 70 ml, a mismatch ratio ≥ 1.8, and an absolute difference ≥ 15 ml) and 90-day modified Rankin Scale (mRS) score of 0-2 was compared between sCTA and mCTA by using receiver operating curve analysis. RESULTS: sCTA underestimated the collateral status when compared with mCTA (p < 0.01). The ability of mCTA to predict target mismatch (AUC = 0.902, 95% confidence interval [CI] 0.809, 0.959) and clinical outcome (AUC = 0.771; 95% CI, 0.655, 0.864) was better than that of sCTA (p < 0.05 overall). A mCTA collateral score of > 3 best identified the target mismatch (sensitivity, 78.4%; specificity, 90.9%) and predicted 90-day mRS score of 0-2 (sensitivity, 84.8%; specificity, 69.4%). CONCLUSIONS: The collaterals were better estimated by mCTA compared with sCTA. A mCTA collateral score of > 3 optimized the prediction of a target mismatch on CTP and a good clinical outcome in patients with AIS. KEY POINTS: • Collateral circulation is a key determinant of ischemic core and penumbra. Better collaterals are associated with smaller ischemic core volumes and larger mismatch ratios on CT perfusion. • The collaterals can be better estimated by multiphase CTA compared with single-phase CTA. • A collateral score of > 3 on multiphase CTA best identifies patients with target mismatch on CT perfusion and predicts 90-day mRS score of 0-2.

Systematic rim cyano-functionalization of pillar[5]arene and corresponding host-guest property varieties.

Synthetic investigation of the systematic replacement of alkoxy groups in pillar[5]arene by cyano ones was carried out. 2nCN-pillar[5]arenes (n = 1, 2, 3, 4 or 5) bearing different numbers of cyano functions on their rims were successfully prepared for the first time. Single-crystal X-ray diffraction studies showed that the nCN-pillar[5]arenes had unique conformations in the solid states. Besides, host-guest property studies of those nCN-pillar[5]arenes and 1,4-dicyanobutane showed the functionization number-related host-guest interaction varieties.

Unidirectional complexation of pillar[4]arene[1]benzoquinoneoxime with alkyl alcohols.

Despite progress in the unidirectional complexation of cyclodextrins and calixarenes with nonsymmetric guests, unidirectional complexation using pillararenes as hosts remains scarcely explored. In this report, we describe the formation of unidirectional [2]pseudorotaxane-like complexes which were realized using n-alkyl alcohol guests and pillar[4]arene[1]benzoquinoneoxime made from pillar[4]arene[1]quinone in a selective monofunctionalizing manner.

Combinatorics of Contacts in Protein Contact Maps.

Contacts play a fundamental role in the study of protein structure and folding problems. The contact map of a protein can be represented by arranging its amino acids on a horizontal line and drawing an arc between two residues if they form a contact. In this paper, we are mainly concerned with the combinatorial enumeration of the arcs in m-regular linear stack, an elementary structure of the protein contact map, which was introduced by Chen et al. (J Comput Biol 21(12):915-935, 2014). We modify the generating function for m-regular linear stacks by introducing a new variable y regarding to the number of arcs and obtain an equation satisfied by the generating function for m-regular linear stacks with n vertices and k arcs. Consequently, we also derive an equation satisfied by the generating function of the overall number of arcs in m-regular linear stacks with n vertices.

Regular Simple Queues of Protein Contact Maps.

A protein fold can be viewed as a self-avoiding walk in certain lattice model, and its contact map is a graph that represents the patterns of contacts in the fold. Goldman, Istrail, and Papadimitriou showed that a contact map in the 2D square lattice can be decomposed into at most two stacks and one queue. In the terminology of combinatorics, stacks and queues are noncrossing and nonnesting partitions, respectively. In this paper, we are concerned with 2-regular and 3-regular simple queues, for which the degree of each vertex is at most one and the arc lengths are at least 2 and 3, respectively. We show that 2-regular simple queues are in one-to-one correspondence with hill-free Motzkin paths, which have been enumerated by Barcucci, Pergola, Pinzani, and Rinaldi by using the Enumerating Combinatorial Objects method. We derive a recurrence relation for the generating function of Motzkin paths with [Formula: see text] peaks at level i, which reduces to the generating function for hill-free Motzkin paths. Moreover, we show that 3-regular simple queues are in one-to-one correspondence with Motzkin paths avoiding certain patterns. Then we obtain a formula for the generating function of 3-regular simple queues. Asymptotic formulas for 2-regular and 3-regular simple queues are derived based on the generating functions.

Structural variant landscapes reveal convergent signatures of evolution in sheep and goats.

BACKGROUND: Sheep and goats have undergone domestication and improvement to produce similar phenotypes, which have been greatly impacted by structural variants (SVs). Here, we report a high-quality chromosome-level reference genome of Asiatic mouflon, and implement a comprehensive analysis of SVs in 897 genomes of worldwide wild and domestic populations of sheep and goats to reveal genetic signatures underlying convergent evolution. RESULTS: We characterize the SV landscapes in terms of genetic diversity, chromosomal distribution and their links with genes, QTLs and transposable elements, and examine their impacts on regulatory elements. We identify several novel SVs and annotate corresponding genes (e.g., BMPR1B, BMPR2, RALYL, COL21A1, and LRP1B) associated with important production traits such as fertility, meat and milk production, and wool/hair fineness. We detect signatures of selection involving the parallel evolution of orthologous SV-associated genes during domestication, local environmental adaptation, and improvement. In particular, we find that fecundity traits experienced convergent selection targeting the gene BMPR1B, with the DEL00067921 deletion explaining ~10.4% of the phenotypic variation observed in goats. CONCLUSIONS: Our results provide new insights into the convergent evolution of SVs and serve as a rich resource for the future improvement of sheep, goats, and related livestock.

[Comparison of antioxidant activity between two species of chamomiles produced in Xinjiang by TLC-bioautography].

OBJECTIVE: To compare the antioxidant active components from two species of chamomile-matricaria and Roman chamomile produced in Xinjiang. METHOD: The TLC-bioautography was used, with 1,1-Diphenyl-2-picrylhydrazyl (DPPH) radical as the experimental model. The peak areas of various antioxidant components were obtained by TLC-scanning for analyzing antioxidant active components contained in volatile oil extracts and flavone extracts from the two species of chamomiles. The total peak area was taken as the indicator for comparing the antioxidant capacities of the two types of extracts, and comparing them with the total antioxidant activity of flavone extracts of the two species of chamomiles. RESULTS: According to the result of TLC-bioautography in volatile oil extracts from the two species of chamomiles, volatile oil extracts from chamomile showed four white antioxidant spots, including en-yne-dicycloether, and volatile oil extracts from Roman chamomile showed only one white antioxidant spot. The TLC-scanning result showed that the peak area of antioxidant spots of volatile oil extracts from chamomile was significantly larger than that of volatile oil extracts from Roman chamomile. According to the test on the antioxidant activity of the two species of chamomiles with ultraviolet-visible spectrophotometry, the concentration of chamomile after scavenging 50% of DPPH radicals was 0.66 g x L(-1), whereas the figure for Roman chamomile was 0.33 g x L(-1). According to the result of TLC-bioautography in flavone extracts from the two species of chamomiles, flavone extracts from chamomile showed seven yellowish antioxidant spots, including apigenin and apigenin-7-glucoside, and flavone extracts of Roman chamomile showed eight yellowish antioxidant spots, including apigenin and apigenin-7-glucoside. The TLC-scanning results showed that the peak area of antioxidant spots of flavone extracts from Roman chamomile was significantly larger than that of flavone extracts from chamomile. CONCLUSION: Volatile oil extracts from the two species of chamomiles have significant difference in the antioxidant activity in TLC-bioautography. Specifically, the antioxidant activity of volatile oil extracts from chamomile is stronger than volatile oil extracts from Roman chamomile; the known antioxidant active components in volatile oil extracts from chamomile is en-yne-dicycloether, while all of the other three antioxidant active components as well as antioxidant active components in volatile oil extracts from Roman chamomile are unknown components and remain to be further determined. Considering the significant difference in the number of antioxidant active spots in volatile oil extracts from the two species of chamomiles, the result can be applied to distinguish the two species of chamomiles. The antioxidant activity determination result for flavone extracts from two species of chamomiles was consistent with the result of TLC-bioautography, showing that flavone extracts from chamomile and Roman chamomile are more antioxidant active, while that of Roman chamomile is stronger than chamomile. Flavone extracts from both of the two species of chamomiles contain apigenin and pigenin-7-glucoside, which are known, while all of the other five antioxidant active components contained in flavone extracts from chamomile and the other six antioxidant active components contained in flavone extracts from Roman chamomile are unknown and remain to be further identified. The method lays a foundation for further identification of antioxidant active components contained in chamomile.

Administration of necrostatin-1 ameliorates glucocorticoid-induced osteonecrosis of the femoral head in rats.

Glucocorticoid (GC)-induced osteonecrosis of the femoral head (ONFH) is a serious complication of glucocorticoid treatment and is characterized by dysfunctional bone reconstruction at necrotic sites. Our previous study confirmed the protective potential of necrostatin-1, a selective blocker of necroptosis, in glucocorticoid-induced osteoporosis. In this study, rat models of GC-induced ONFH were established to evaluate the effects of necrostatin-1 on osteonecrotic changes and repair processes. Osteonecrosis was verified by histopathological staining. An analysis of trabecular bone architecture was performed to evaluate osteogenesis in the osteonecrotic zone. Then, necroptotic signaling molecules such as RIP1 and RIP3 were examined by immunohistochemistry. Histopathological observations indicated that necrostatin-1 administration reduced the incidence of osteonecrosis and the osteogenic response in subchondral areas. Additionally, bone histomorphometry demonstrated that necrostatin-1 intervention could restore bone reconstruction in the necrotic zone. The protective mechanism of necrostatin-1 was related to the inhibition of RIP1 and RIP3. Necrostatin-1 administration alleviated GC-induced ONFH in rats by attenuating the formation of necrotic lesions, recovering the function of osteogenesis, and suppressing glucocorticoid-induced osteocytic necroptosis by inhibiting the expression of RIP1 and RIP3.

p38 mitogen-activated protein kinase and liver X receptor-α mediate the leptin effect on sterol regulatory element binding protein-1c expression in hepatic stellate cells.

Leptin, a key hormone in regulating energy homeostasis, is mainly produced by adipocytes. Cogent evidence indicates a unique role of leptin in the promotion of liver fibrosis. Hepatic stellate cell (HSC) activation is a pivotal step in the process of liver fibrosis. Sterol regulatory element binding protein (SREBP)-1c, a critical transcription factor for lipid synthesis and adipocyte differentiation, functions as a key transcription factor in inhibition of HSC activation. SREBP-1c is highly expressed in quiescent HSCs and downregulated upon HSC activation. The aim of this study is to examine the effect of leptin on SREBP-1c gene expression in HSCs in vitro and in vivo and elucidate the underlying mechanisms. The results of the present study demonstrated that leptin strongly inhibited SREBP-1c expression in HSCs in vivo and in vitro. p38 MAPK was involved in leptin regulation of SREBP-1c expression in cultured HSCs. Leptin-induced activation of p38 MAPK led to the decreases in liver X receptor (LXR)-α protein level, activity and its binding to the SREBP-1c promoter, which caused the downregulation of SREBP-1c expression. Moreover, leptin inhibition of SREBP-1c expression via p38 MAPK increased the expression of alpha1(I) collagen in HSCs. Our results might provide new insights into the mechanisms of the unique role of leptin in the development of liver fibrosis and might have potential implications for clarifying the molecular mechanisms underlying liver fibrosis in diseases in which circulating leptin levels are elevated such as nonalcoholic steatohepatitis, type 2 diabetes mellitus and alcoholic cirrhosis.

Acquired hookworm immunity in the golden hamster (Mesocricetus auratus) elicited by living Necator americanus third-stage infective larvae.

The aim of the study is to demonstrate and understand the acquired immunity in golden hamsters (Mesocricetus auratus) elicited by primary Necator americanus infective third-stage larvae (L3) infection. Hamsters infected with 150 L3 for 1, 2, 3, 6 and 10 weeks, were challenged with the same number of L3 and sacrificed 25 days post challenge. The primarily infected hamsters exhibited 99-100% protection against subsequent L3 challenge compared to un-infected naive hamsters. The acquired immunity was developed as early as 1 week post L3 infection and lasted up to 10 weeks. Similar protective immunity was obtained in hamsters infected with N. americanus L3 and then treated orally with a single of 100mg/kg albendazole, followed by challenge with N. americanus L3 4 and 8 weeks post-treatment. The infected hamsters exhibited a rise in IgG antibodies against L3 and juvenile adult worm antigens. Histological examination showed that challenging L3 were trapped in the skin of primarily infected hamsters and surrounded or infiltrated by different inflammatory cells. The trapped L3 were damaged and dead followed by the formation of granulomas encasing dead worms. The results demonstrate that hamsters primarily infected with N. americanus L3 develop acquired immunity against re-infection.

Effect and Mechanism of Solidified Microstructure on Deformation Behavior, Mechanical Properties, and Residual Stress of Cu-Ni-Si Alloy.

Cu-Ni-Si alloy is the key raw material for the lead frame of large integrated circuits. The disordered grain orientation of alloy billet, high hardening rate, residual stress, and poor surface quality of cold working strips seriously affect its processability. In order to improve the cold-working properties of Cu-Ni-Si alloy, two kinds of C70250 copper alloy strips were produced through hot mold continuous casting (HMCC) and cold mold continuous casting (CMCC) technology. The effects of solidified microstructure on the cold-working deformation behavior, mechanical properties, and residual stress of the alloy were studied. The results show that C70250 copper alloys with columnar grain and equiaxed grain were prepared through HMCC and CMCC. After a 98% reduction in cold rolling, columnar grain strip surface quality was very good, and the elongation was still as high as 3.2%, which is 2.9 times that of equiaxed grain alloy. The residual stress of equiaxed grain strips reached 363 MPa, which is 2.7 times that of columnar grain strips. During the cold rolling process, equiaxed grain strips are prone to cause intersecting plane dislocations, stacking faults, shear bands, and grain breakage during large deformation cold rolling. The columnar grain strip causes parallel plane dislocations, stacking faults, and shearbands. Furthermore, the deformation structure was found to be uniform, and, ultimately, the alloy formed a fibrous structure. Therefore, the elongation and latter distortion of columnar grain strips improved after being put through large deformation cold rolling, which greatly reduced residual stress.

Comparative investigation of a lattice Boltzmann boundary treatment of multiphase mass transport with heterogeneous chemical reactions.

Multiphase reactive transport in porous media is an important component of many natural and engineering processes. In the present study, boundary schemes for the continuum species transport-lattice Boltzmann (CST-LB) mass transport model and the multicomponent pseudopotential model are proposed to simulate heterogeneous chemical reactions in a multiphase system. For the CST-LB model, a lattice-interface-tracking scheme for the heterogeneous chemical reaction boundary is provided. Meanwhile, a local-average virtual density boundary scheme for the multicomponent pseudopotential model is formulated based on the work of Li et al. [Li, Yu, and Luo, Phys. Rev. E 100, 053313 (2019)10.1103/PhysRevE.100.053313]. With these boundary treatments, a numerical implementation is put forward that couples the multiphase fluid flow, interfacial species transport, heterogeneous chemical reactions, and porous matrix structural evolution. A series of comparison benchmark cases are investigated to evaluate the numerical performance for different pseudopotential wetting boundary treatments, and an application case of multiphase dissolution in porous media is conducted to validate the present models' ability to solve complex problems. By applying the present LB models with reasonable boundary treatments, multiphase reactive transport in various natural or engineering scenarios can be simulated accurately.

Astragalin mitigates inflammatory osteolysis by negatively modulating osteoclastogenesis via ROS and MAPK signaling pathway.

Inflammatory bone destruction has gradually attracted attention worldwide and has been observed in several kinds of pathological bone diseases, such as osteoarthritis, osteomyelitis, rheumatic arthritis, and other infectious clinical trials in the skeletal system. In this regard, excessive osteoclasts and bone resorption activity participate in osteolytic processes. Thus, negatively modulating osteoclast differentiation and bone erosion has been considered an effective therapeutic strategy to limit the poor progression of inflammatory osteolysis. Astragalin (AST) is a bioactive component of traditional Chinese drugs, such as Rosa agrestis, which presents anti-inflammatory and antioxidant effects. However, it is unclear how AST may play an essential role in regulating the dynamic balance of the bone matrix by affecting osteoclastogenesis. This study found that AST could inhibit osteoclastic formation and bone resorption activity in a dose-dependent manner without cytotoxicity. Administration of AST also inhibited the expression of cathepsin K, c-Fos, NFATc1, and TRAP at different stages of mRNA and protein levels during osteoclastogenesis. Reactive oxygen species (ROS) signalling could also be modulated by treatment with AST during RANKL-induced osteoclast differentiation through the Nrf2-HO1 signalling pathway. Additionally, AST could negatively regulate mitogen-activated protein kinase (MAPK) signalling in this process. In vivo, AST significantly reduced lipopolysaccharide (LPS)-induced bone loss in an osteolytic mouse model. AST might be a promising therapeutic candidate for treating osteolytic bone diseases in the future.

Microporous structures on mineralized collagen mediate osteogenesis by modulating the osteo-immune response of macrophages.

It is a new hot pot in tissue engineering and regenerative medicine to study the effects of physicochemical properties of implanted biomaterials on regulating macrophage polarization to promote bone regeneration. In this study, we designed and fabricated mineralized collagen (MC) with different microporous structures via in vitro biomimetic mineralization method. The microporous structures, mechanical properties, shore hardness and water contact angle measurements were tested. Live/dead cell staining, CCK-8 assay, phalloidine staining, staining of focal adhesions were used to detect cell behavior. ELISA, qRT-PCR, ALP, and alizarin red staining (ARS) were performed to appraise osteogenic differentiation and investigated macrophage response and their subsequent effects on the osteogenic differentiation. The results showed that RAW264.7 and MC3T3-E1 cells were able to survive on the MC. MC with the microporous structure of approximately 84 µm and 70%-80% porosity could promote M2 macrophage polarization and increase the expression level of TGF-ß and VEGF. Moreover, the gene expression of the osteogenic markers ALP, COL-1, and OCN increased. Therefore, MC with different microporous structures mediated osteoimmunomodulation in bone regeneration. These data will provide a new idea of biomaterials inducing bone repair and direct the optimal design of novel immune biomaterials, development, and rational usage.