Compact angle-resolved metasurface spectrometer.

Light scattered or radiated from a material carries valuable information on the said material. Such information can be uncovered by measuring the light field at different angles and frequencies. However, this technique typically requires a large optical apparatus, hampering the widespread use of angle-resolved spectroscopy beyond the lab. Here we demonstrate compact angle-resolved spectral imaging by combining a tunable metasurface-based spectrometer array and a metalens. With this approach, even with a miniaturized spectrometer footprint of only 4 × 4 µm2, we demonstrate a wavelength accuracy of 0.17 nm, spectral resolution of 0.4 nm and a linear dynamic range of 149 dB. Moreover, our spectrometer has a detection limit of 1.2 fJ, and can be patterned to an array for spectral imaging. Placing such a spectrometer array directly at the back focal plane of a metalens, we achieve an angular resolution of 4.88 × 10-3 rad. Our angle-resolved spectrometers empowered by metalenses can be employed towards enhancing advanced optical imaging and spectral analysis applications.

Recommended 10-Year Follow-Up Strategy for Small Hepatocellular Carcinoma After Radiofrequency Ablation: A Cost-Effectiveness Evaluation.

INTRODUCTION: An optimal follow-up schedule for small (≤3-cm) hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA) remains unclear in clinical guidelines. We aimed to assess the cost-effectiveness of follow-up strategies in patients with small HCC after RFA. METHODS: In total, 11,243 patients were collected from global institutions to calculate recurrence rates. Subsequently, a Markov model covering a 10-year period was developed to compare 25 surveillance strategies involving different surveillance techniques (computed tomography [CT], magnetic resonance imaging or ultrasonography [US], and α-fetoprotein [AFP]) and intervals (3 or 6 months). The study endpoint was incremental cost-effectiveness ratio (ICER), which represented additional cost per incremental quality-adjusted life year. Sensitivity analysis was conducted by varying the values of input parameters to observe the ICER. RESULTS: In a base case analysis, the dominant strategy was CT every 3 months during an initial 2 years, followed by semiannual CT, and then switch to biannual the combination of US screening and AFP testing after 5 years (m3_CT-m6_CT-m6_USAFP), with an ICER of $68,570.92 compared with the "not followed" strategy. One-way sensitivity analysis showed the ICER consistently remained below the willingness-to-pay threshold of $100,000.00. In a probabilistic sensitivity analysis, m3_CT-m6_CT-m6_USAFP was the most cost-effective approach in 95.6% of simulated scenarios at a willingness-to-pay threshold. DISCUSSION: For small HCC after RFA, the recommended follow-up strategy is CT, with scans scheduled every 3 months for the first 2 years, every 6 months thereafter, and transition to biannual the combination of US screening and AFP testing after 5 years.

Hepatic arterial infusion therapy for advanced hepatocellular carcinoma after systemic treatment failure: Multicenter, real-world study.

AIM: The study was conducted to evaluate the feasibility and safety profile of hepatic arterial infusion chemotherapy with oxaliplatin, 5-fluorouracil, and leucovorin (HAIC-FOLFOX) as an alternative therapeutic choice for patients with advanced hepatocellular carcinoma (HCC) that is refractory to systemic treatment including immune checkpoint blockades or molecular targeting agents. METHODS: Two hundred and forty five consecutive patients with advanced HCC who received HAIC-FOLFOX treatment after systemic treatment failure were retrospectively reviewed in six institutions and their survival, tumor response, and tolerance were assessed. RESULTS: The median overall survival (OS) and progression-free survival of the 209 included participants were 10.5 months (95% confidence interval [CI], 8.1-12.9) and 6.0 months (95% CI, 5.1-6.9), respectively. According to Response Evaluation Criteria in Solid Tumors 1.1 criteria, the objective response rate was 21.1%, and the disease control rate was 64.6%. Multivariate analysis of risk factors of OS were albumin-bilirubin grade (2 and 3 vs. 1, hazard ratio [HR] 1.57; 95% CI, 1.05-2.34; p = 0.028), tumor number (>3 vs. 1-3, HR 2.18; 95% CI, 1.10-4.34; p = 0.026), extrahepatic spread (present vs. absent, HR 1.61, 95% CI, 1.06-2.45; p = 0.027), synchronous systemic treatment (present vs. absent, HR 0.55, 95% CI, 0.37-0.83; p = 0.004) and treatment response (responder vs. nonresponder, HR 0.30, 95% CI, 0.17-0.53; p < 0.001). Grade 3-4 adverse events (AEs) occurred in 59 (28.2%) HCC patients. All AEs were manageable, and deaths related to hepatic artery infusion chemotherapy treatment were not observed. CONCLUSIONS: Our findings support the effectiveness and safety of HAIC-FOLFOX treatment for patients with advanced HCC who have failed systemic treatment.

Low-dose thiram exposure elicits dysregulation of the gut microbial ecology in broiler chickens.

Thiram, a typical fungicide pesticide, is widely used in agricultural production. The presence of thiram residues is not only due to over-utilization, but is also primarily attributed to long-term accumulation. However, there is a paucity of information regarding the impact of prolonged utilization of thiram at low doses on the gut microbiota, particularly with respect to gut fungi. Our objective is to explore the effect of thiram on broilers from the perspective of gut microbiota, which includes both bacteria and fungi. We developed a long-term low-dose thiram model to simulate thiram residue and employed 16 S rRNA and ITS gene sequencing to investigate the diversity and profile of gut microbiota between group CC (normal diet) and TC (normal diet supplemented with 5 mg/kg thiram). The results revealed that low doses of thiram had a detrimental effect on broiler's growth performance, resulting in an approximate reduction of 669.33 g in their final body weight at day 45. Our findings indicated that low-dose thiram had a negative impact on the gut bacterial composition, leading to a notable reduction in the abundance of Merdibacter, Paenibacillus, Macrococcus, Fournierella, and Anaeroplasma (p < 0.05) compared to the CC group. Conversely, the relative level of Myroides was significantly increased (p < 0.05) in response to thiram exposure. In gut fungi, thiram significantly enhanced the diversity and richness of gut fungal populations (p < 0.05), as evidenced by the notable increase in alpha indices, i.e. ACE (CC: 346.49 ± 117.27 vs TC: 787.27 ± 379.14, p < 0.05), Chao 1 (CC: 317.63 ± 69.13 vs TC: 504.85 ± 104.50, p < 0.05), Shannon (CC: 1.28 ± 1.19 vs TC: 5.39 ± 2.66, p < 0.05), Simpson (CC: 0.21 ± 0.21 vs TC: 0.78 ± 0.34, p < 0.05). Furthermore, the abundance of Ascomycota, Kickxellomycota, and Glomeromycota were significantly increased (p < 0.05) by exposure to thiram, conversely, the level of Basidiomycota was decreased (p < 0.05) in the TC group compared to the CC group. Overall, this study demonstrated that low doses of thiram induced significant changes in the composition and abundance of gut microbiota in broilers, with more pronounced changes observed in the gut fungal community as compared to the gut bacterial community. Importantly, our findings further emphasize the potential risks associated with low dose thiram exposure and have revealed a novel discovery indicating that significant alterations in gut fungi may serve as the crucial factor contributing to the detrimental effects exerted by thiram residues.

Pesticide butachlor exposure perturbs gut microbial homeostasis.

Agricultural production relies heavily on the use of pesticides, which may accumulate in soil and water, posing a significant threat to the global ecological environment and biological health. Butachlor is a commonly used herbicide and environmental pollutant, which has been linked to liver and kidney damage, as well as neurological abnormalities. However, the potential impact of butachlor exposure on the gut microbiota remains understudied. Thus, our aim was to investigate the potential negative effects of butachlor exposure on host health and gut microbiota. Our results demonstrated that butachlor exposure significantly reduced the host antioxidant capacity, as evidenced by decreased levels of T-AOC, SOD, and GSH-Px, and increased levels of MDA. Serum biochemical analysis also revealed a significant increase in AST and ALT levels during butachlor exposure. Microbial analysis showed that butachlor exposure significantly reduced the abundance and diversity of gut microbiota. Furthermore, butachlor exposure also significantly altered the gut microbial composition. In conclusion, our findings indicate that butachlor exposure can have detrimental health effects, including dysregulation of antioxidant enzymes, abnormalities in transaminases, and hepatointestinal damage. Furthermore, it disrupts the gut microbial homeostasis by altering microbial composition and reducing diversity and abundance. In the context of the increasingly serious use of pesticides, this study will help provide impetus for standardizing the application of pesticides and reducing environmental pollution.

Miniature Two-Photon Microscopic Imaging Using Dielectric Metalens.

Miniature two-photon microscopy has emerged as a powerful technique for investigating brain activity in freely moving animals. Ongoing research objectives include reducing probe weight and minimizing animal behavior constraints caused by probe attachment. Employing dielectric metalenses, which enable the use of sizable optical components in flat device structures while maintaining imaging resolution, is a promising solution for addressing these challenges. In this study, we designed and fabricated a titanium dioxide metalens with a wavelength of 920 nm and a high aspect ratio. Furthermore, a meta-optic two-photon microscope weighing 1.36 g was developed. This meta-optic probe has a lateral resolution of 0.92 µm and an axial resolution of 18.08 µm. Experimentally, two-photon imaging of mouse brain structures in vivo was also demonstrated. The flat dielectric metalens technique holds promising opportunities for high-performance integrated miniature nonlinear microscopy and endomicroscopy platforms in the biomedical field.

The impacts of HIV infection, age, and education on functional brain networks in adults with HIV.

HIV-associated neurocognitive disorders (HAND) remain highly prevalent in people with HIV (PWH). Studies suggested that certain sociodemographic factors are associated with the risk of HAND in PWH. Here we investigated the impact of HIV infection and demographics on functional brain networks. One run of 8.5 min resting state functional MRI (fMRI) data was collected from 101 PWH (41-70 years old) and 40 demographically comparable controls. Functional connectivity (FC) was calculated using average wavelet coherence. The impact of demographic factors on FCs was investigated using canonical correlation analysis (CCA). Wavelet coherence analysis revealed a reduced within-network connectivity in the dorsal somatomotor network (dSMN), along with a reduced between-network connectivity between dSMN and medial temporal lobe (MTL) in PWH (compared to controls). Across all participants, CCA revealed that older age and HIV infection had negative impacts on network connectivity measures (mainly reduced within- and between-network FCs), whereas education had an opposite effect. In addition, being female at birth or a member of a minority ethnic/racial group was also associated with network disruptions. Our data suggested that advanced age and HIV infection are risk factors for functional brain network disruptions, whereas higher educational attainment was linked to better preserved functional network connectivity.

Characteristics of four-limb blood pressure and brachial-ankle pulse wave velocity in Chinese patients with Takayasu arteritis.

Purpose: Takayasu arteritis (TA) is a rare disease, which is frequently misdiagnosed or its diagnosis can be missed. This study aimed to analyse the characteristics of four-limb blood pressure (4LBP) and brachial-ankle pulse wave velocity (baPWV) in patients with TA, which could be useful in disease detection.Materials and Methods: We consecutively enrolled 182 patients with TA at Fuwai Hospital between January 2013 and January 2016. Pulse pressure (PP), pulsatile index (PI), inter-arm systolic blood pressure (SBP) difference (IASBPD), inter-leg SBP difference (ILSBPD), ankle-brachial index (ABI), baPWV, and inter-side baPWV difference (ΔbaPWV) were analysed and compared with those of age-, sex-, and SBP-matched participants without cardiovascular diseases.Results: In the TA group, the diastolic blood pressure was lower (67.4 ± 23.7 vs 84.1 ± 15.0 mmHg), PP was larger (69.7 ± 23.6 vs 53.7 ± 10.6 mmHg), PI was higher (1.3 ± 2.1 vs. 0.6 ± 0.1 mmHg), IASBPD was larger (18.2 ± 24.1 vs 4.2 ± 3.3 mmHg), and ILSBPD was larger (10.7 ± 15.0 vs 5.3 ± 4.1 mmHg) than those of the controls (all p < 0.01). Moreover, the proportions of PP >70 mmHg (36.8% vs 4.4%), PI > 1.0 (40.1% vs 2.2%), IASBPD >15 mmHg (34.6% vs. 0%), highest ABI >1.4 (17.6% vs. 0%), ILSBPD >15 mmHg (14.8% vs. 3.3%), lowest ABI < 0.9 (24.7% vs 2.2%), and ΔbaPWV > 185 cm/s (28.6% vs. 1.1%) were significantly greater in the TA group than in the control group (all p < 0.01). Approximately 80.8% of patients with TA (vs. 10.4% of controls) presented with at least one of these seven parameters (p = 0.000).Conclusion: The characteristics of 4LBP and baPWV in most patients with TA were abnormal, which helped us perform non-invasive primary screening and comprehensive evaluation of vascular lesions in such patients.

In daily life, many people measure the blood pressure of the arm but measuring the blood pressure of a single arm is inadequate because some hypertension and vascular diseases cannot be detected this way. Synchronous limb blood pressure measurements may be used to close this gap. Measuring synchronous limb blood pressure is very convenient and helps patients understand the value of limb blood pressure and examine many other useful parameters, such as the blood pressure differences between the two arms and two legs, as well as the ankle arm index. These values and derived parameters can also help detect many vascular diseases.Takayasu arteritis is a rare disease in young women. However, the aorta and branches of these patients are narrow or occluded. Patients often experience vague and ambiguous symptoms, such as hypertension or dizziness, so they are likely to be overlooked or misdiagnosed.Our study summarises the results of synchronous limb blood pressure measurements in patients with Takayasu arteritis and compares their results with those of a control population. Synchronous limb blood pressure measurements are easy and convenient and can detect vascular problems, which may improve the ability to diagnose Takayasu arteritis.

[Identification of Carthamus tinctorius NAC gene family and analysis of drought stress response].

The NAC(NAM/ATAF/CUC) transcription factors are members of the largest transcriptional gene family in plants and play an essential role in the response of plants to drought stress. To identify the number and function of the NAC gene family in Carthamus tinctorius, the present study adopted bioinformatics methods to identify NAC gene family members based on the whole genome data of C. tinctorius, and analyzed their physicochemical properties, chromosomal location, phylogenetic relationship, gene structure, conserved domain, and conserved motif. Meanwhile, the real-time fluorescence-based quantitative RT-PCR(qRT-PCR) was used to analyze the transcription level of four NAC genes under drought stress in different time. The results showed that C. tinctorius contained 87 NAC genes unevenly distributed on 11 chromosomes, while no NAC gene was found on chromosome 12. The encoded proteins were 103-974 amino acids and the number of CDS ranged from 3 to 9. According to the phylogenetic relationships, 87 NAC genes were clustered into17 subfamilies. The analysis of conserved domains and motifs revealed that most of the genes contained five conserved subdomains, A-E and motif2 was the most conserved among NAC genes. The expression pattern analysis showed that the transcription levels of four NAC genes related to drought resistance were all up-regulated after drought stress treatment for different time, suggesting that these four NAC genes may be related to drought resistance of C. tinctorius. This study is expected to provide a theoretical basis for further functional analysis of NAC transcription factors in C. tinctorius and references for the cultivation of drought-tolerant C. tinctorius varieties.

Depression is associated with hippocampal volume loss in adults with HIV.

Depressive symptoms are more prevalent in persons with HIV (PWH) than HIV-uninfected individuals. In HIV-uninfected individuals, depression has been associated with atrophy in the hippocampus and other brain regions. In the present study, we investigated the impact of depression on brain structure in PWH. One hundred PWH participated in a cross-sectional study (56.6 ± 6.4 yrs, range 41-70 yrs, 24 females, 63 African Americans). The Beck's Depression Inventory-II (BDI-II) was used to assess depressive symptoms. Structural MRI images were collected. Both the voxel-based morphometry (VBM) technique and a region of interest (ROI) based approach were used to examine the relationship between hippocampal gray matter volume (GMv) and depressive symptoms. The impact of HIV CD4 nadir and antidepressants was also investigated. Both VBM and ROI approaches revealed that higher BDI-II scores (implicating more severe depressive symptoms) were associated with loss of hippocampal GMv, especially in the right hippocampus and the right entorhinal cortex. Low CD4 nadir predicted additional hippocampal volume loss independent of depressive symptoms. Taking antidepressants did not have a detectable effect on hippocampal volume. In summary, having more depressive symptoms is associated with smaller hippocampal volume in PWH, and a history of severe immunosuppression (i.e., low CD4 nadir) correlates with additional hippocampal volume reduction. However, the impact of depression on hippocampal volume may be independent of HIV-disease severity such as low CD4 nadir.

Nilotinib Effects on Safety, Tolerability, and Biomarkers in Alzheimer's Disease.

OBJECTIVE: Preclinical evidence with nilotinib, a US Food and Drug Administration (FDA)-approved drug for leukemia, indicates improvement in Alzheimer's disease phenotypes. We investigated whether nilotinib is safe, and detectable in cerebrospinal fluid, and alters biomarkers and clinical decline in Alzheimer's disease. METHODS: This single-center, phase 2, randomized, double-blind, placebo-controlled study investigated the safety, tolerability, and pharmacokinetics of nilotinib, and measured biomarkers in participants with mild to moderate dementia due to Alzheimer's disease. The diagnosis was supported by cerebrospinal fluid or amyloid positron emission tomography biomarkers. Nilotinib 150 mg versus matching placebo was taken orally once daily for 26 weeks followed by nilotinib 300 mg versus placebo for another 26 weeks. RESULTS: Of the 37 individuals enrolled, 27 were women and the mean (SD) age was 70.7 (6.48) years. Nilotinib was well-tolerated, although more adverse events, particularly mood swings, were noted with the 300 mg dose. In the nilotinib group, central nervous system (CNS) amyloid burden was significantly reduced in the frontal lobe compared to the placebo group. Cerebrospinal fluid Aß40 was reduced at 6 months and Aß42 was reduced at 12 months in the nilotinib group compared to the placebo. Hippocampal volume loss was attenuated (-27%) at 12 months and phospho-tau-181 was reduced at 6 months and 12 months in the nilotinib group. INTERPRETATION: Nilotinib is safe and achieves pharmacologically relevant cerebrospinal fluid concentrations. Biomarkers of disease were altered in response to nilotinib treatment. These data support a larger, longer, multicenter study to determine the safety and efficacy of nilotinib in Alzheimer's disease. ANN NEUROL 2020 ANN NEUROL 2020;88:183-194.

Milk replacer supplementation in early life optimizes the development of intestinal microbes in goats.

Colonization and development of the gut microbiome during early life is important in establishing a host-microbial symbiotic relationship. It contributes to maintaining health and well-being throughout the life span. To date, early longitudinal development of intestinal microflora in the ileum micro-ecology of the Yimeng black goats (YBGs) is rare. The purpose of this research was to study the effect of milk replacer with age on the ileal microbiota growth and maturation in YBGs throughout the post-weaning phase. The newborn YBGs (n = 24) were divided into two groups, i.e., milk replacer (R group) and control group (B group). The microbiome of Ileum was observed on days 15, 25, 45, and 75. When compared with baseline (B group), the R group's alpha diversity was lower (day 15, 25, 45), but it gradually approached and exceeded the baseline in the later stages (day 75). On the time axis, the richness of intestinal microflora was increased with age, but there was no statistically significant difference. The relative abundances of Proteobacteria, Firmicutes, Peptoclustridium, Lachnospiraceae, and Prevotellaceae showed a continuous trend of increase initially. They then decreased except Ruminococcaceae, which reflected the gradual maturity of intestinal microbial development. Milk replacer treatment temporarily increased the abundance of Actinomycetes (day 25 and 45), while the relative proportion of several intestinal bacteria such as Parasutterella, Megasphaera, Prevotellaceae, Akkermansia, and Subdoligranulum species were significantly higher in R group than in B group. The major changes in gut microflora composition might reflect positive effect of milk replacer on the development and maturation of the intestine during the early stage, connecting with substrate availability in the gut. Our study provides an effective strategy to promote the development of the gut microbiome, which is helpful for a smooth transition during the early-weaning period in YBGs.

Clinical characteristics of concurrent primary aldosteronism and renal artery stenosis: A retrospective case-control study.

Background: Rare cases of concurrent primary aldosteronism (PA) and renal artery stenosis (RAS) have been reported. Methods: In this retrospective case-control study, we selected a cohort of 10 PA with RAS patients and a control group of 20 PA without RAS patients from January 1, 2006, to January 1, 2016.  Results: All patients presented with refractory hypertension, and a nonstatistically significant trend toward lower mean serum potassium was seen in the PA with RAS group (p =.07). PA with RAS patients had lower mean orthostatic aldosterone-to-renin ratios (38.4 ± 41.4 ng dL-1/ng mL-1 h-1 vs. 87.4.4 ± 38.4 ng dL-1/ng mL-1 h-1, respectively; p < .01) and a higher false-negative rate (50% vs. 15%, respectively; p < .05) compared with controls. All misdiagnosed patients had the diagnosis of PA confirmed when we revaluated the repeated screening and confirmative tests because of residual hypertension or hypokalemia after successful revascularization of renal artery stenosis.  Conclusions: PA is easily missed in patients with RAS because of the high false-negative rate for screening tests. RAS patients with residual hypertension after successful renal angioplasty should be monitored for coexisting PA. Reevaluation of screening and confirmatory tests is helpful in establishing the correct diagnoses.

A nomogram to predict survival of patients with intermediate-stage hepatocellular carcinoma after transarterial chemoembolization combined with microwave ablation.

OBJECTIVES: To develop a prognostic nomogram based on the albumin-bilirubin (ALBI) grade for prediction of the long-term survival of patients with intermediate-stage hepatocellular carcinoma (HCC) after transarterial chemoembolization combined with microwave ablation (TACE-MWA). METHODS: We retrospectively studied 546 consecutive patients with intermediate-stage HCC according to the Barcelona Clinic Liver Cancer guidelines who underwent TACE-MWA between January 2000 and December 2016. Overall survival (OS) and progression-free survival (PFS) were analyzed. The predictive value of the ALBI grade was investigated. The prognostic nomogram was constructed using the independent predictors assessed by the multivariate Cox proportional hazards model. RESULTS: After a median follow-up of 35.0 months (range, 4.0-221.0 months), 380 patients had died. The median OS was 35.0 months (95% confidence interval (CI), 30.84-39.16 months), and the median PFS was 6.5 months (95% CI, 6.13-6.87 months). The ALBI grade was validated as an independent predictor of OS (p < 0.001). Multivariate analyses showed that Eastern Cooperative Oncology Group performance status score more than 0, presence of liver cirrhosis, a-fetoprotein level above 400 ng/mL, tumor size greater than 5 cm, tumor number more than 3, advanced ALBI grade, and treatment sessions of TACE or MWA fewer than 3 were independently associated with overall mortality. The prognostic nomogram incorporating these eight predictors achieved good calibration and discriminatory abilities with a concordance index of 0.770 (95% CI, 0.746-0.795). CONCLUSIONS: The prognostic nomogram based on the ALBI grade resulted in reliable efficacy for prediction of individualized OS in patients with intermediate-stage HCC after TACE-MWA. KEY POINTS: • TACE-MWA was associated with a median overall survival of 35.0 months for patients with intermediate-stage HCC. • A prognostic nomogram was built to predict individualized survival of patients with intermediate-stage HCC after TACE-MWA. • The prognostic nomogram incorporating eight predictors achieved good calibration and discriminatory abilities with a concordance index of 0.770.

Puerarin enhance vascular proliferation and halt apoptosis in thiram-induced avian tibial dyschondroplasia by regulating HIF-1α, TIMP-3 and BCL-2 expressions.

Tetramethyl thiuram disulfide (thiram) is a dithiocarbamate pesticide used for crop protection and storage. But, it's widespread utilization is associated with deleterious growth plate cartilage disorder in broilers termed as avian tibial dyschondroplasia (TD). TD results in non-mineralized and less vascularized proximal tibial growth plate cartilage causing lameness and poor growth performance. This study investigated the therapeutic potential of puerarin against thiram toxicity in TD affected chickens. One-day-old broiler chickens (n = 240) were alienated into three equal groups i.e. control, TD and puerarin (n = 80) and were offered standard feed. Additionally, TD and puerarin groups were offered thiram at 50 mg/kg of feed from 4 to 7 days for TD induction followed by puerarin therapy at 120 mg/kg to puerarin group only from 8 to 18 days for TD treatment. Thiram feeding to TD and puerarin group chickens caused lameness, mortality, and increased the aspartate aminotransferase (AST), alanine aminotransferase (ALT), malondialdehyde (MDA) levels and growth plate (GP) size and upregulated HIF-1α expression. Besides, the production parameters, alkaline phosphatase (ALP), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels and the expressions of TIMP-3 and BCL-2 were decreased (p < 0.05). Puerarin alleviated lameness, enhanced angiogenesis and growth performance and serum and antioxidant enzymes, decreased apoptosis and recuperated GP width by significantly downregulating HIF-1α and upregulating the TIMP-3 and BCL-2 mRNA and protein expressions in puerarin group chickens (p < 0.05). In conclusion, the toxic effects associated with thiram can be mitigated using puerarin.

Effect of total flavonoids of Rhizoma Drynariae in thiram induced cytotoxicity of chondrocyte via BMP-2/Runx2 and IHH/PTHrP expressions.

Tibial Dyschondroplasia (TD) is a prevailing skeletal disorder that mainly affects rapidly growing avian species. It results in reduced bone strength, lameness and an increase risk of fragility fractures. Total flavonoids of Rhizoma drynariae (TFRD) have been used as an effective treatment of different bone diseases in humans. The current in vitro study was conducted to explore the therapeutic effect of TFRD on thiram-induced cytotoxicity in avian growth plate cells via bone morphogenetic protein-2/runt related transcription factor-2 (BMP-2/Runx2) and Indian hedgehog/Parathyroid hormone-related peptide (IHH/PTHrP) expressions. Chondrocytes were isolated, cultured and refined from chicken's tibial growth plates in a special medium. Then chondrocytes were treated with sublethal thiram having less concentration (2.5 µg/mL) to induce cytotoxicity of chondrocyte, and then treated with providential doses (100 µg/mL) of TFRD. Thiram caused distorted morphology of chondrocytes, nuclei appeared disintegration or lysed along with decreased expressions of BMP-2/Runx2 and IHH/PTHrP. TFRD administration not only enhanced the viability of chondrocytes by itself, but also well restored the damage caused by thiram on growth plate chondrocytes by significantly up-regulating the expressions of BMP-2/Runx2 and IHH/PTHrP. Therefore, this study provides a novel insight into the further treatment of TD and other skeletal ailments and lays the foundation for prevention and treatment.

Characterization of the microbial community structure in intestinal segments of yak (Bos grunniens).

Yak (Bos grunniens), a ruminant, has a complex gastrointestinal microbial ecosystem, which is essential for host nutrition and health. However, not much is known about gut microbial communities of yak. This study was conducted to characterize the gut microbial diversity and composition of small intestinal and cecal contents of yaks through high-throughput sequencing targeting V3-V4 hypervariable region of 16S rRNA gene. A total of 916,934 high-quality sequences were obtained and 224 core operational taxonomic units (OTUs) shared all samples. The result showed that the microbial community in the small intestine was different from cecum sample. In all samples, the majority of bacterial phyla were Firmicutes, Bacteroidetes and Proteobacteria. A large proportion of anaerobes in the families Peptostreptococcaceae, Prevotellaceae, Flavobacteriaceae, Lachnospiraceae, and Succinivibrionaceae were present in the various intestinal segments. The relative abundance of Ruminococcaceae, Bacteroidaceae and Muribaculaceae were significantly higher in cecum than in other segments of intestines. At the genus level, Bacteroides was the most predominant genus in cecum. The results indicated that yak have abundant and diverse gut microbial community. In conclusion, this study characterized the profiles of microbial communities across intestinal segments and provide better insight into microbial population structure and diversity of yak.

Different roles of frontal versus striatal atrophy in HIV-associated neurocognitive disorders.

Gray matter (GM) atrophy is frequently detected in persons living with HIV, even in the era of combination antiretroviral therapy (cART), but the specificity of regions affected remains elusive. For instance, which regions are consistently affected in HIV? In addition, atrophy at which regions is frequently associated with neurocognitive impairment in HIV? Resolving these questions can potentially help to establish the possible neural profiles of HIV-associated neurocognitive disorders (HAND) severity, which currently is solely defined by neurobehavioral assessments. Here, we addressed these questions using a novel meta-analysis technique, the colocalization-likelihood estimation (CLE) technique, to quantitatively synthesize the findings of GM atrophy in HIV+ adults. Twenty-one of 386 studies published between 1988 and November 2017 and identified in PubMed were selected, plus four identified in other resources. In the end, 25 studies (1,370 HIV+ adults, 889 HIV- controls) were included in the meta-analysis. This technique revealed that GM atrophy in HIV+ adults was dominated by two distinct but nonexclusive profiles: frontal (including anterior cingulate cortex, [ACC]) atrophy, which was associated withHIV-disease and consistently differentiated HIV+ adults from HIV- controls; and caudate/striatum atrophy, which was associated with neurocognitive impairment. The critical role of caudate/striatum atrophy in neurocognitive impairment was further supported by a separate data analysis, which examined the findings of correlation analyses between GM and neurocognitive performance. These results suggest that the frontal lobe and the striatum play critical but differential roles in HAND. A neural model of HAND severity was proposed with several testable predictions.

Neural mechanisms of vibrotactile categorization.

The grouping of sensory stimuli into categories is fundamental to cognition. Previous research in the visual and auditory systems supports a two-stage processing hierarchy that underlies perceptual categorization: (a) a "bottom-up" perceptual stage in sensory cortices where neurons show selectivity for stimulus features and (b) a "top-down" second stage in higher level cortical areas that categorizes the stimulus-selective input from the first stage. In order to test the hypothesis that the two-stage model applies to the somatosensory system, 14 human participants were trained to categorize vibrotactile stimuli presented to their right forearm. Then, during an fMRI scan, participants actively categorized the stimuli. Representational similarity analysis revealed stimulus selectivity in areas including the left precentral and postcentral gyri, the supramarginal gyrus, and the posterior middle temporal gyrus. Crucially, we identified a single category-selective region in the left ventral precentral gyrus. Furthermore, an estimation of directed functional connectivity delivered evidence for robust top-down connectivity from the second to first stage. These results support the validity of the two-stage model of perceptual categorization for the somatosensory system, suggesting common computational principles and a unified theory of perceptual categorization across the visual, auditory, and somatosensory systems.

The impact of Bacillus subtilis 18 isolated from Tibetan yaks on growth performance and gut microbial community in mice.

The purpose of this study was to evaluate the effects of Bacillus subtilis 18 (BS-18) isolated from free-ranging Tibetan yaks in high altitude regions of Tibet (3600 m) on growth performance and gut microbial community in mice. In this study, mice (15-day-old) were used as an animal model and raised under standard conditions. A total of 20 KM mice were divided equally into two groups: control group (feed and drink freely), experimental group (feed and drink freely + 1 × 109 CFU/day BS-18). The intestines (duodenum, jejunum, ileum, cecum) and organs (liver, spleen, kidney) were collected from all the mice at day 18 for high throughput sequencing and HE staining. During the whole experiment, the mice treated by BS-18 displayed no abnormal behavior or macroscopic lesions on dissection. Meanwhile, there were no pathological changes observed using HE staining compared with the control group. The results show that BS-18 isolated from Tibetan yaks was safe and could increase average daily gain (ADG) and reduce feed conversion ratio (FCR). Furthermore, supplementation with BS-18 could improve the mucosal morphology and the ratio of villi to crypt cells (P < 0.05 or P < 0.01). The high-throughput sequencing results showed that the abundance and diversity of duodenum and jejunum in the experimental group were higher than control group. Lactobacillus in experimental group had higher abundance than control group. In addition, the quantity of Candidatus arthromitu was increased after BS-18 intake, which is associated with immune system activity. Acinetobacter induced brain abscess and bronchopneumonia were reduced in the experimental group. In conclusion, this study demonstrated that BS-18 isolated from Tibetan yaks was safe, beneficial and had the potential to serve as a probiotic.