Human distal airways contain a multipotent secretory cell that can regenerate alveoli.

The human lung differs substantially from its mouse counterpart, resulting in a distinct distal airway architecture affected by disease pathology in chronic obstructive pulmonary disease. In humans, the distal branches of the airway interweave with the alveolar gas-exchange niche, forming an anatomical structure known as the respiratory bronchioles. Owing to the lack of a counterpart in mouse, the cellular and molecular mechanisms that govern respiratory bronchioles in the human lung remain uncharacterized. Here we show that human respiratory bronchioles contain a unique secretory cell population that is distinct from cells in larger proximal airways. Organoid modelling reveals that these respiratory airway secretory (RAS) cells act as unidirectional progenitors for alveolar type 2 cells, which are essential for maintaining and regenerating the alveolar niche. RAS cell lineage differentiation into alveolar type 2 cells is regulated by Notch and Wnt signalling. In chronic obstructive pulmonary disease, RAS cells are altered transcriptionally, corresponding to abnormal alveolar type 2 cell states, which are associated with smoking exposure in both humans and ferrets. These data identify a distinct progenitor in a region of the human lung that is not found in mouse that has a critical role in maintaining the gas-exchange compartment and is altered in chronic lung disease.

Diagnostic Accuracy of Computerized Bowel Sound Analysis with Non-Invasive Devices for Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis.

Objective To assess the diagnostic accuracy of bowel sound analysis for irritable bowel syndrome (IBS) with a systematic review and meta-analysis. Methods We searched MEDLINE, Embase, the Cochrane Library, Web of Science, and IEEE Xplore databases until September 2023. Cross-sectional and case-control studies on diagnostic accuracy of bowel sound analysis for IBS were identified. We estimated the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio with a 95% confidence interval (CI), and plotted a summary receiver operating characteristic curve and evaluated the area under the curve. Results Four studies were included. The pooled diagnostic sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.94 (95% CI, 0.87-0.97), 0.89 (95% CI, 0.81-0.94), 8.43 (95% CI, 4.81-14.78), 0.07 (95% CI, 0.03-0.15), and 118.86 (95% CI, 44.18-319.75), respectively, with an area under the curve of 0.97 (95% CI, 0.95-0.98). Conclusions Computerized bowel sound analysis is a promising tool for IBS. However, limited high-quality data make the results' validity and applicability questionable. There is a need for more diagnostic test accuracy studies and better wearable devices for monitoring and analysis of IBS.

Multicenter Clinical Evaluation of ETEST Eravacycline for Susceptibility Testing of Enterobacteriaceae and Enterococci.

Eravacycline (ERV) (brand name Xerava [Tetraphase]) is a new tetracycline-class antibacterial that has been approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for treatment of complicated intra-abdominal infections (cIAIs). ETEST is a gradient diffusion method that represents a simple alternative to the broth microdilution (BMD) method for performing antimicrobial susceptibility testing (AST). A multicenter evaluation of the performance of the new ETEST ERV (bioMérieux) in comparison with BMD was conducted following FDA and International Standards Organization (ISO) recommendations, using FDA- and EUCAST-defined breakpoints. Clinical isolates of Enterobacteriaceae (n = 542) and Enterococcus spp. (n = 137) were included. Based on the BMD reference method, 92 Enterobacteriaceae isolates and 9 enterococcal isolates were nonsusceptible to ERV according to the FDA breakpoints, while 7 Escherichia coli isolates and 3 Enterococcus sp. isolates were classified as ERV resistant according the EUCAST breakpoints. Referring to FDA performance criteria, the ETEST ERV demonstrated 99.4% and 100.0% essential agreement (EA), 98.0% and 94.9% categorical agreement (CA), very major error (VME) rates of 5.4% and 33.33%, and major error (ME) rates of 1.3% and 3.1% with clinical and challenge isolates, respectively, of Enterobacteriaceae and Enterococcus spp. According to EUCAST breakpoints, E. coli and Enterococcus sp. isolate results also met ISO acceptance criteria for EA and CA (EA of 99.0% and 100.0%, respectively, and CA of 100.0% for both), without any VMEs or MEs. In conclusion, we report that ETEST ERV represents an accurate tool for performing ERV AST of Enterobacteriaceae and Enterococcus sp. isolates.

Specnuezhenide ameliorates ultraviolet-induced skin photoaging in mice by regulating the Sirtuin 3/8-Oxoguanine DNA glycosylase signal.

PURPOSE: Ultraviolet-induced skin photoaging was involved in DNA oxidative damage. Specnuezhenide, one of the secoiridoids extracted from Ligustri Lucidi Fructus, possesses antioxidant and anti-inflammatory effects. Whether specnuezhenide ameliorates skin photoaging remains unclear. This study aimed to investigate the effect of specnuezhenide on skin photoaging induced by ultraviolet and explore the underlying mechanism. METHODS: Mice were employed to treat with ultraviolet to induce skin photoaging, then administrated 10 and 20 mg/kg of specnuezhenide. Histological analysis, protein expression, network pharmacology, and autodock analysis were conducted. RESULTS: Specnuezhenide ameliorated ultraviolet-induced skin photoaging in mice via the increase in collagen contents, and decrease in epidermal thickness, malondialdehyde content, and ß-galactosidase expression in the skin. Specnuezhenide reduced cutaneous apoptosis and inflammation in mice with skin photoaging. In addition, network pharmacology data indicated that specnuezhenide possessed potential targets on the NOD-like receptor signaling pathway. Validation experiment found that specnuezhenide inhibited the expression of NOD-like receptor family pyrin domain-containing 3, gasdermin D-C1, and Caspase 1. Furthermore, the expression of 8-Oxoguanine DNA glycosylase (OGG1), sirtuin 3 (SIRT3), and superoxide dismutase 2 was increased in specnuezhenide-treated mice with photoaging. CONCLUSION: Specnuezhenide protected against ultraviolet-induced skin photoaging in mice via a probable activation of SIRT3/OGG1 signal.

Phylogenetic analyses of 41 Y-STRs and machine learning-based haplogroup prediction in the Qingdao Han population from Shandong province, Eastern China.

BACKGROUND: Known for its rich history and culture, Qingdao is a typical symbol of Chinese maritime culture. Its unique genetic landscape has aroused interest among geneticists and forensic scientists. However, the genetic landscape of Qingdao has never been uncovered. AIM: This investigation intends to provide light on Qingdao's paternal genetic diversity and its evolutionary connections to other Han subgroups. SUBJECTS AND METHODS: The genetic polymorphisms of 41 Y-chromosomal short tandem repeat (STR) loci in the Qingdao Han were investigated using SureID® PathFinder Plus Kit. Phylogenetic studies were performed using genotype data from 52 East Asian groups at 23 common Y-STR loci. A multidimensional scaling plot and cladogram were constructed. Linear Discriminant Analysis (LDA) was carried out for predicting categories among the Han people. The k-nearest neighbour (kNN) algorithm was utilised to designate Y-SNP haplogroups for each haplotype. RESULTS: The Qingdao Han were genetically far from the Tibeto-Burman populations and close with the Han people from northern China. LDA indicated a deep integration among the present-day Han people. By the kNN model, the predicted O2a2 and O2a1 were shown to be the predominant Y-SNP haplogroups. CONCLUSIONS: This study would be helpful for reconstructing the patrilineal history in China and establishing a more comprehensive Y-STR database.

[Mechanism of heat-clearing prescriptions in alleviating type 2 diabetes mellitus:a review].

Type 2 diabetes mellitus(T2DM), a common chronic metabolic disease, is often accompanied by internal heat syndrome. Heat-clearing prescriptions are widely used to treat different heat syndromes of T2DM from the aspects of clearing stagnant heat, excess heat, damp heat, phlegm heat, and heat toxin, demonstrating remarkable effects. The mechanism of blood sugar-lowering agents has always been a hotspot of research. Recently, the basic studies of heat-clearing prescriptions from different perspectives have been increasing year by year. To clarify the mechanisms of heat-clearing prescriptions and find specific mechanisms, we systematically reviewed the basic studies of heat-clearing prescriptions commonly used for the treatment of T2DM in the past decade, intending to provide a reference for related research.

Multicenter Clinical Evaluation of ETEST Plazomicin (PLZ) for Susceptibility Testing of Enterobacterales.

Plazomicin (PLZ), brand name ZEMDRI (Cipla Therapeutics), is a novel aminoglycoside antibiotic approved by the U.S. Food and Drug Administration (FDA) for treatment of complicated urinary tract infections including pyelonephritis. ETEST® is a gradient diffusion method that represents an alternative to the more laborious broth micro-dilution (BMD) method for performing antimicrobial susceptibility testing (AST). A multi-center evaluation of the performance of the new ETEST PLZ (bioMérieux) was conducted in comparison with BMD following FDA and International Standards Organization (ISO) recommendations using FDA-defined breakpoints. Clinical isolates of Enterobacterales (n = 598) were included. Fifty-three isolates were resistant to PLZ according to BMD. Overall, the ETEST PLZ demonstrated 99.0% essential agreement (EA), 92.8% category agreement (CA), 1.9% very major errors (VME), 0% major errors (ME), and 7.0% minor errors (mE) with both clinical and challenge isolates of Enterobacterales. The VME was found for a single Serratia marcescens strain. Individual species demonstrated EA rates ≥ 90%. In conclusion, we report that ETEST PLZ represents an accurate tool for performing PLZ AST of Enterobacterales.

Long-pulsed neodymium-doped yttrium-aluminum-garnet laser versus cryotherapy for the treatment of cutaneous warts: A randomized controlled trial.

BACKGROUND: Observational studies have shown promising therapeutic effects of long-pulsed neodymium-doped yttrium-aluminum-garnet (LP-Nd:YAG) laser on warts. OBJECTIVE: To evaluate whether LP-Nd:YAG laser was superior to cryotherapy for cutaneous warts. METHODS: In this study, 150 adult patients with warts were randomized equally to receive laser or cryotherapy every 3 to 4 weeks, for a maximum of 4 sessions. The primary outcomes were the cure rates at 16 weeks and 6 months; secondary outcomes included time to clearance of warts and treatment-related adverse effects. RESULTS: There was no difference in the cure rate for laser versus cryotherapy at 16 weeks (54.1% vs 46.7%, respectively) and 6 months (59.5% vs 57.3%, respectively). However, time to clearance of warts, up to 16 weeks and 6 months, tended to be shorter for laser versus cryotherapy (P = .04 and .08, respectively). Post hoc analyses showed a significantly higher cure rate for laser versus cryotherapy in 3 subgroups of human papillomavirus 2/27/57-induced recalcitrant warts but not in their counterpart subgroups. Laser had more mild adverse effects. LIMITATIONS: Single center. CONCLUSIONS: The overall therapeutic effects of LP-Nd:YAG laser were similar to cryotherapy, but laser may be more effective to relatively recalcitrant warts and may be associated with shorter time to clearance of warts.

Establishment and operation of glucose clamp technique in mice.

Glucose metabolism plays a central role in energy supply and metabolism regulation in various tissues and organs. Besides, insulin is the sole hormone lowering blood glucose in the body, and islet function and insulin sensitivity are the key steps modulating glucose metabolism. Since the development of glucose clamp technology, it has been recognized as the gold standard for evaluating insulin metabolism. The main categories include hyperinsulinemia-euglycemia clamp, hyperglycemia clamp, and hyperinsulinemia-hypoglycemia clamp. These can be done on either anesthetized mice or conscious and unrestricted mice. This protocol focuses on the establishment and operation of the mouse glucose clamp technique, including preparation of instrument consumables, surgical operations, clamping procedures, and precautions, serving as reference and guidance.

A study of congenital generalized lipodystrophy (CGL) caused by BSCL2 gene mutation.

Congenital generalized lipodystrophy (CGL) is an extremely rare genetic disease mainly characterized by absence of whole-body adipose tissue and metabolic dysfunctions such as insulin resistance, diabetes mellitus, hypertriglyceridemia, hepatic steatosis, and acanthosis nigricans. In this study, we reported a novel case of a young woman patient with CGL. The patient came to the hospital for early-onset lipodystrophy and diabetes. She was 19-year-old with a height of 160 cm, a weight of 46 kg, BMI of 17.9 kg/m2, and a serum leptin level of 0.14 µg/L. Genomic DNA was extracted from blood samples of the patient and her family members, including her mother, father and brother. Genetic analysis revealed compound heterozygous mutations of the BSCL2 gene (c.560A>G and c.565G>T) in the patient. Her father carried a heterozygous mutation (c.565G>T), and her mother carried a heterozygous mutation (c.560A>G) in the BSCL2 gene. The mutant p.Y187C plasmid was transfected into HEK293T cells. The protein expression of SEIPIN and its interaction with glycerol-3-phosphate acyltransferase (GPAT3) were observed to be reduced. In addition, based on primary cultured skin fibroblasts from the patient, SEIPIN protein was decreased, and lipid droplets were much smaller when fatty acid was stimulated compared with those observed from healthy subject controls. However, histone deacetylase inhibitors (HDACis) was found capable of rescuing SEIPIN protein in fibroblasts of the patient. In addition, we further summarized and discussed gene mutations of BSCL2 reported in the current literature. Collectively, these findings have expanded the clinical phenotype and pathogenic gene spectrum of CGL, which might help clinicians to achieve better management of lipodystrophy.

Diagnosis and genetic analysis of a case with glycogen storage disease type V caused by compound heterozygous mutations in the PYGM gene.

Glycogen storage disease type V is an autosomal recessive genetic disorder caused by muscle glycogen phosphorylase (PYGM) deficiency, which is characterized by exercise intolerance, second wind phenomena and high level of serum creatine kinase. In this study, we reported a Chinese young man with glycogen storage disease type V, with lower extremity weakness after exercise, increased creatine kinase, and slight fat infiltration in the posterior group of thigh muscle by magnetic resonance imaging (MRI). The proband had complex heterozygous PYGM disease-causing mutations, including c.308T>C (p.L103P) variant transmitted from the mother and c.260_261delCT (p.S87Ffs*23) from the father, of which the former was a novel PYGM mutation. This study enriched the PYGM pathogenic gene mutation spectrum, contributed to improve clinicians' understanding of glycogen storage disease type V and provided a reference for further genetic study of the disease.

Dietary SFAs and ω-6 Fatty Acids Alter Incorporation of ω-3 Fatty Acids into Milk Fat of Lactating CD-1 Mice and Tissues of Offspring.

BACKGROUND: Methods to increase the amount of omega-3 (n-3) PUFAs in milk are desirable for neonatal health. The n-3 PUFA, α-linolenic acid (18:3n-3), can be elongated to EPA (20:5n-3) and DHA (22:6n-3). n-6 PUFAs suppress tissue n-3 PUFA incorporation, but the effect of SFAs is not clear. OBJECTIVES: In this study, we compared the effects of SFAs and n-6 PUFAs on n-3 PUFA incorporation into milk and tissues of lactating mice and tissues of their offspring. METHODS: Female CD-1 mice were bred at 8 wk of age. All experimental diets included 3% flaxseed oil and were begun on day 8 of lactation: low-fat diet (LFD); high-SFA diet (SAT), with an additional 12% saturated oil; or high-linoleic-acid diet (HLA), with 12% high-linoleic-acid oil (% kcal, carbohydrates:fat:protein: LFD, 49:24:27; both SAT and HLA, 35:46:19; n = 5/treatment). After 5 d, pup stomach milk clot FA profiles, tissue FA profiles in dams and pups, and mammary and hepatic expression of lipid metabolism genes in dams were analyzed. Data were analyzed by ANOVA with treatment diet as a fixed effect. RESULTS: Dams in all groups had similar total milk fat concentrations, but both SAT and HLA decreased the concentration of n-3 PUFAs (SAT: -23%; HLA: -31%) compared with LFD, and HLA increased milk n-6 FAs by 347% compared with SAT. SAT pups had n-3 PUFA tissue concentrations similar to LFD, but HLA pups had lower n-3 PUFAs than SAT pups in multiple tissues (liver, -32%; kidney, -29%; heart, -28%; muscle, -18%). Mammary expression of lipid metabolism genes was mostly unchanged, but hepatic expression of elongases and desaturases was decreased with SAT compared with LFD [elongation of very-long-chain fatty acid (Elov)5, -42%; Elov6, -64%; fatty acid desaturase (Fads)1, -33%; Fads2, -44%]. CONCLUSIONS: HLA decreased n-3 PUFA concentrations across multiple pup tissues compared with SAT. This suggests that high dietary n-6 PUFAs suppress n-3 PUFA incorporation in neonates.

Development and validation a simple model for identify malignant ascites.

The differential diagnosis of benign ascites and malignant ascites is incredibly challenging for clinicians. This research aimed to develop a user-friendly predictive model to discriminate malignant ascites from non-malignant ascites through easy-to-obtain clinical parameters. All patients with new-onset ascites fluid were recruited from January 2014 to December 2018. The medical records of 317 patients with ascites for various reasons in Renmin Hospital of Wuhan University were collected and reviewed retrospectively. Thirty-six parameters were included and selected using univariate logistic regression, multivariate logistic regression, and receiver operating characteristic (ROC) curve analyses to establish a mathematical model for differential diagnosis, and its diagnostic performance was validated in the other groups. Age, cholesterol, hypersensitivity C-reactive protein (hs-CRP) in serum, ascitic fluid adenosine deaminase (AF ADA), ascitic fluid lactate dehydrogenase (AF LDH) involvement in a 5-marker model. With a cut-off level of 0.83, the sensitivity, specificity, accuracy, and area under the ROC of the model for identifying malignant ascites in the development dataset were 84.7%, 88.8%, 87.6%, and 0.874 (95% confidence interval [CI], 0.822-0.926), respectively, and 80.9%, 82.6%, 81.5%, and 0.863 (95% CI,0.817-0.913) in the validation dataset, respectively. The diagnostic model has a similar high diagnostic performance in both the development and validation datasets. The mathematical diagnostic model based on the five markers is a user-friendly method to differentiate malignant ascites from benign ascites with high efficiency.

Effects of corn grain endosperm type and conservation method on site of digestion, ruminal digestion kinetics, and flow of nitrogen fractions to the duodenum in lactating dairy cows.

Our objective was to evaluate the relative effects of endosperm type and conservation method of corn grain on ruminal kinetics, site of nutrient digestion, and flow of nitrogen fractions to the duodenum in lactating dairy cows. Seven ruminally and duodenally cannulated Holstein cows (73 ± 39 d in milk; mean ± SD) were used in a duplicated 4 × 4 Latin square design with 21-d periods. A 2 × 2 factorial arrangement of treatments was used, with main effects of corn grain endosperm type (floury or vitreous) and conserved as dry ground corn (DGC) or high-moisture corn (HMC). Rations were formulated to contain 27.0% starch, 26.6% neutral detergent fiber (NDF), 19.1% forage NDF, and 16.5% crude protein. Corn grain treatments supplied 86.6% of dietary starch, and alfalfa silage was the sole forage. True ruminal starch digestibility was increased by HMC compared with DGC (87.2 vs. 64.3%) and by floury compared with vitreous corn grain (83.7 vs. 67.7%). The increase for HMC compared with DGC was because of an increase in the degradation rate (33.8 vs. 23.1%/h) and a decrease in passage rate of starch (7.6 vs. 15.2%/h). The increase for floury compared with vitreous corn grain was because of an increase in the degradation rate (31.5 vs. 25.4%/h) and a decrease in rate of starch passage from the rumen (7.9 vs. 14.9%/h). Apparent total-tract starch digestibility was increased by HMC compared with DGC and by floury compared with vitreous corn, but the increase for floury corn was greater for the DGC treatment. Dry ground corn compared with HMC tended to increase nonammonia N flow to the duodenum (466 vs. 431 g/d) by increasing flow of nonammonia nonmicrobial N (211 vs. 111 g/d) despite a decrease in microbial N flow (255 vs. 320 g/d). Vitreous corn increased nonammonia nonmicrobial N flow to the duodenum (187 vs. 135 g/d) compared with floury corn, but microbial N flow to the duodenum was not affected by endosperm type. Efficiency of microbial N production was not affected by treatment. Endosperm type and conservation method of corn grain greatly affect digestion kinetics and ruminal digestibility of starch as well as flow of N fractions to the duodenum and should be considered during diet formulation for lactating cows.

Effects of corn grain endosperm type and conservation method on feed intake, feeding behavior, and productive performance of lactating dairy cows.

Our objective was to evaluate the effects of corn grain varying in endosperm type and conserved as high-moisture or dry ground corn on dry matter intake (DMI), feeding behavior, ruminal fermentation, and yields of milk and milk components of cows in early to mid-lactation. Seven ruminally and duodenally cannulated Holstein cows (73 ± 39 d in milk; mean ± SD) were used in a duplicated 4 × 4 Latin square design with 21-d periods. A 2 × 2 factorial arrangement of treatments was used with main effects of corn grain endosperm type (floury or vitreous) conserved as high-moisture corn (HMC) or dry ground corn (DGC). Rations were formulated to contain 27.0% starch, 26.6% neutral detergent fiber (NDF), 19.1% forage NDF, and 16.5% crude protein. Corn grain treatments supplied 86.6% of dietary starch and contained alfalfa silage as the sole forage. Dry matter intake was increased 1.3 kg/d by DGC compared with HMC. The increase in DMI by DGC was related to a shorter intermeal interval (104.4 vs. 118.2 min/d), and meal size was not affected by treatment. Dry ground corn decreased rumination bout length and number of chews per bout compared with HMC. No differences were detected between endosperm treatments for DMI, yields of milk, 3.5% fat-corrected milk (FCM), milk fat, protein, lactose, or solids-not-fat (SNF). Mean yield of 3.5% FCM across treatments was 47.5 kg/d. However, a tendency for an interaction was observed for feed efficiency; floury endosperm increased efficiency 0.05 kg 3.5% FCM per kg of DMI for DGC but decreased it by 0.14 kg 3.5% FCM per kg of DMI for HMC relative to vitreous endosperm. Vitreous compared with floury corn tended to increase true protein concentration in milk when conserved as DGC (2.68% vs. 2.62%) but not as HMC. Concentration of SNF was increased by DGC compared with HMC (8.45 vs. 8.37%) due, in part, to the effect of treatment on milk protein concentration. Body weight was not affected by treatment, but vitreous endosperm tended to increase loss of body condition compared with floury endosperm. Corn endosperm type and conservation method had little effect on productive performance of high-producing cows.

Effects of corn grain endosperm type and fineness of grind on site of digestion, ruminal digestion kinetics, and flow of nitrogen fractions to the duodenum in lactating dairy cows.

Our objective was to evaluate effects of corn grain endosperm type and fineness of grind on feed intake, feeding behavior, and productive performance of lactating cows. Eight ruminally and duodenally cannulated Holstein cows in mid lactation (130 ± 42 d in milk; mean ± standard deviation) were used in a duplicated 4 × 4 Latin square design with 21-d periods. A 2 × 2 factorial arrangement of treatments was used with main effects of corn grain endosperm type (floury or vitreous) and fineness of grind (fine or medium). Rations included alfalfa silage, corn treatments, protein supplement, minerals, and vitamins and were formulated to contain 29% starch, 27% neutral detergent fiber, 18.2% forage neutral detergent fiber, and 18% crude protein. Corn grain treatments supplied 86.2% of dietary starch. Endosperm was 25% vitreous for the floury treatment and 66% vitreous for the vitreous treatment. The floury treatment increased rate of starch degradation by 94% (19.2 vs. 9.9%/h) and decreased rate of starch passage by 38% (16.1 vs. 25.8%/h), increasing apparent ruminal starch digestibility by 117% (53.7 vs. 24.7%). The floury treatment increased total-tract starch digestibility by 8% (92.2 vs. 85.1%) despite 37% lower postruminal starch digestion for the floury treatment compared with vitreous corn (38.4 vs. 60.7% of starch intake). Fine grind size increased apparent ruminal starch digestibility by 52% (47.2 vs. 31.1%) compared with medium grind size by increasing the rate of starch degradation by 105% (19.5 vs. 9.5%/h) with no effect on rate of starch passage. However, total-tract starch digestibility was not affected by fineness of grind because postruminal starch digestibility was 37% greater for medium compared with fine grind size (57.2 vs. 41.9% of starch intake). Endosperm type did not affect flow of nitrogen (N) fractions to the duodenum or microbial N efficiency, whereas fine grind size increased duodenal flow of nonammonia N by increasing duodenal flow of microbial N by 22% compared with medium grind size (438 vs. 359 g/d) but did not affect apparent total-tract N digestibility. No interactions were detected for any measure of starch digestion, ruminal N metabolism, or flow of N fractions to the duodenum. Endosperm type greatly affected ruminal and total-tract starch digestibility independent of the fineness of grind of corn grain with no effects on flow of N fractions.

Effects of corn grain endosperm type and fineness of grind on feed intake, feeding behavior, and productive performance of lactating dairy cows.

Our objective was to evaluate effects of corn grain endosperm type and fineness of grind on feed intake, feeding behavior, ruminal fermentation, and productive performance of lactating cows. Eight ruminally and duodenally cannulated Holstein cows in mid lactation (130 ± 42 d in milk; mean ± standard deviation) were used in a duplicated 4 × 4 Latin square design with 21-d periods. A 2 × 2 factorial arrangement of treatments was used with main effects of corn grain endosperm type (floury or vitreous) and fineness of grind of corn grain (fine or medium). Rations were formulated to contain 29% starch, 27% neutral detergent fiber, 18.2% forage neutral detergent fiber, and 18% crude protein. Corn grain treatments supplied 86.2% of dietary starch. Endosperm was 25% vitreous for floury corn and 66% vitreous for vitreous corn. Fineness of grind did not affect dry matter intake (DMI), but floury corn tended to reduce DMI (23.8 vs. 25.1 kg/d) compared with vitreous corn. Floury corn increased meal frequency more for fine grind size (9.57 vs. 9.41 meals/d) than medium grind size (9.78 vs. 9.75 meals/d). However, there were no effects of treatment on any other measure of feeding behavior. Endosperm type did not affect yields of milk or milk components or milk composition except that vitreous corn tended to decrease milk lactose concentration compared with floury corn. Finely ground corn decreased yields of milk (31.1 vs. 33.1 kg/d), 3.5% fat-corrected milk (33.1 vs. 35.1 kg/d), milk fat (1.22 vs. 1.32 kg/d), milk lactose (1.48 vs. 1.59 kg/d), and solids not fat (2.46 vs. 2.63 kg/d) compared with medium grind size. However, fineness of grind did not affect milk composition. Treatments had no effect on change in body weight or body condition score or efficiency of milk production (kg of 3.5% fat-corrected milk/kg of DMI). Mean ruminal pH was not affected by treatment, but pH variance was decreased by vitreous compared with floury corn. Total volatile fatty acids and propionate concentrations in the rumen were increased by floury compared with vitreous corn but were not affected by fineness of grind. Effects of fineness of grind on yield of milk and milk components were greater than the effects of corn grain vitreousness.

MicroRNA-18a-5p mitigates oxygen-glucose-deprivation/reoxygenation-induced injury through suppression of TLRs/NF-κB signaling by targeting TLR8 in PC12 cells.

This work aimed to assess the role of TLR8 in cerebral I/R injury and its in-depth pathogenesis. Bioinformatics analysis indicated that TLR8 was up-regulated in patients with ischemic stroke than that in healthy control, and miR-18a-5p was the upstream regulatory of TLR8. Then, the rat pheochromocytoma PC12 cells were exposed in oxygen-glucose-deprivation/reoxygenation (OGD/R) conditions to construct a model in vitro. The functional experiments indicated that OGD/R can decline the viability and elevate the apoptosis of PC12 cells, while up-regulation of miR-18a-5p can alleviate OGD/R-induced cell injury. Notably, overexpression of TLR8 reverses the miR-18a-5p-mediated protection on OGD/R-induced cells injury. Finally, we found that up-regulation of miR-18a-5p obviously declined the protein levels of TLR4 and TLR7 as well as the phosphorylation of NF-κB, while overexpression of TLR8 canceled the decrease caused by miR-18a-5p up-regulation. In summing, our results illustrated that miR-18a-5p/TLR8 axis can mitigate OGD/R-induced cells injury through TLRs and NF-κB pathway.

Effects of graded versus ungraded individual readiness assurance scores in team-based learning: a quasi-experimental study.

Pre-class preparation is a crucial component of team-based learning (TBL). Lack of preparation hinders both individual learning and team performance during TBL. The purpose of the present study was to explore how the grading of the individual readiness assurance test (iRAT) can affect pre-class preparation, iRAT performance and performance in the end-of-year examination. Using a quasi-experimental design, Year 1 and 2 students' download frequency for their pre-class materials, performance on iRAT and examination were examined under two conditions; (1) under which the iRAT was graded and (2) under which the iRAT was ungraded. Medical students (N = 220) from three cohorts were included in the study. Differences between both conditions were tested by means of six separate ANCOVAs, using medical school entry test scores as the covariate to account for potential cohort effects. Results revealed that students were downloading more pre-class materials prior to their TBL sessions, and were performed significantly better on iRAT when their performance was graded, even after controlling for cohort effects. Analysis of covariance demonstrated that performance on iRAT also appeared to affect performance on their examination scores. The results of the study suggest that grading has a positive effect on students' iRAT scores. Implications for TBL are discussed.

Alantolactone, a sesquiterpene lactone, inhibits breast cancer growth by antiangiogenic activity via blocking VEGFR2 signaling.

Alantolactone (ALA), a sesquiterpene lactone isolated from several medicinal plants such as Inula helenium, has been identified to have attractive anticancer activity. However, its role in the inhibition of angiogenesis during tumor development remains unclear. In this study, we found ALA can inhibit the proliferation, motility, migration, and tube formation of human umbilical vein endothelial cells. ALA also restrained angiogenesis in chick embryo chorioallantoic membrane and delayed the growth of human MDA-MB-231 breast cancer xenograft in mice through angiogenesis inhibition. Furthermore, ALA suppressed the phosphorylation of vascular endothelial growth factor receptor 2 and its downstream protein kinase including PLCγ1, FAK, Src, and Akt in endothelial cells. Taken together, the antiangiogenic activity of ALA and its molecular mechanism are identified for the first time, indicating that ALA may be a potential drug candidate or lead compound for antiangiogenic cancer therapy.