Efficacy and safety of penetrating canaloplasty versus ab externo canaloplasty for primary open-angle glaucoma: A randomized controlled trial.

PURPOSE: To report the 2-year efficacy and safety of penetrating canaloplasty versus ab externo canaloplasty for the treatment of primary open-angle glaucoma (POAG). SETTING: A single surgical site in China. DESIGN: This was a prospective, randomized controlled trial. POAG patients were randomly assigned to the penetrating canaloplasty or ab externo canaloplasty group. METHODS: This study enrolled POAG patients who underwent penetrating canaloplasty or ab externo canaloplasty randomly. Surgical success, intraocular pressure (IOP), number of glaucoma medications, and surgical complications were evaluated until 24 months post-operatively. Surgical success was defined as 6 mmHg ≤ IOP ≤21 mmHg with an IOP reduction ≥20%, which included qualified success (with or without medications) and complete success (without medications). RESULTS: A total of 52 eyes (45 patients) were randomly assigned to one of two groups: the penetrating canaloplasty group (PCP, n = 26) or the ab externo canaloplasty group (CP, n = 26). The probabilities of qualified success and complete success were 92.3% and 76.9%, respectively, in the PCP group and 64.1% and 52.1%, respectively, in the CP group at 24 months (p = 0.013, p = 0.042, log-rank test). The mean IOP decreased from 30.8 ± 10.7 and 28.6 ± 11.8 mmHg to 14.1 ± 3.3 mmHg in the PCP group and 22.1 ± 13.6 mmHg in the CP group at year two (p = 0.007). The PCP group also received fewer medications (0.2 ± 0.5) than did the CP group (0.7 ± 1.2) at year two (p = 0.038). Post-operative complications were similar, and the most common complications were transient IOP elevation and hyphema in the PCP group (42.3%, 46.2%) and the CP group (38.5%, 23.1%) (p > 0.05). CONCLUSIONS: Compared to ab externo canaloplasty, penetrating canaloplasty had a greater surgical success rate and better IOP reduction with a comparable rate of complications.

Effects of heat stress on the feeding preference of yellow-feathered broilers and its possible mechanism.

Heat stress is the most critical factor affecting animal feeding in summer. This experiment was conducted to investigate the effects of heat stress on the feeding preference of yellow-feathered broilers and its possible mechanism. As a result, the preference of yellow-feathered broilers for Tenebrio molitor was significantly decreased, and the fear response and serum corticosterone of broilers were significantly increased when the ambient temperatures are 35 °C (P < 0.05). In the central nervous system, consistent with the change in feeding preference, decreased dopamine in the nucleus accumbens (NAc) and increased mRNA levels of MAO-B in the ventral tegmental area (VTA) and NAc were found in yellow-feathered broilers (P < 0.05). In addition, we found significantly increased mRNA levels of corticotropin-releasing hormone receptor 1, corticotropin-releasing hormone receptor 2 and glucocorticoid receptor in the VTA and NAc of female broilers (P < 0.05). However, no similar change was found in male broilers. On the other hand, the serum levels of insulin and glucagon-like peptide-1 were increased only in male broilers (P < 0.05). Accordingly, the mRNA levels of insulin receptor and glucagon-like peptide-1 receptor in the VTA and the phosphorylation of mTOR and PI3K were increased only in male broilers (P < 0.05). In summary, the preference of yellow-feathered broilers for Tenebrio molitor feed decreased under heat stress conditions, and hedonic feeding behavior was significantly inhibited. However, the mechanism by which heat stress affects hedonic feeding behavior may contain gender differences. The insulin signaling pathway may participate in the regulation of heat stress on the male broiler reward system, while stress hormone-related receptors in the midbrain may play an important role in the effect of heat stress on the reward system of female broilers.

Effects of Tryptophan Supplementation in Diets with Different Protein Levels on the Production Performance of Broilers.

Tryptophan plays an important role in the pig industry but has the potential to improve performance in the poultry industry. The purpose of this study was to examine the effects of tryptophan supplementation in diets with different protein levels on the feed intake, average daily gain (ADG), and feed conversion ratio (F/G) of broilers. A total of 180 twenty-one-day-old broilers (half male and half female) were weighed and randomly allocated to twelve groups, with six male and six female groups. Each group consisted of 15 broilers. The broilers were fed low- (17.2%), medium- (19.2%), or high- (21.2%) protein diets with or without extra tryptophan (up to 0.25%) during the 28-day experiment. Food intake and body weight were measured weekly during the trial period. Male broilers fed a medium-protein diet containing more tryptophan showed a lower F/G. In the low-protein diet groups, additional tryptophan caused a significant reduction in the feed intake of female broilers during the first two weeks. Moreover, the serum GLP-1, cholesterol, and bile acid levels, as well as the expression of FXR mRNA in the ileum, were significantly increased. Additionally, the FXR mRNA in the hypothalamus and the GCG and GLP-1R mRNAs in the ileum tended to increase in these broilers. In summary, the tryptophan concentration in the diet can influence the feed intake and metabolism of broilers. Under a standard diet, an appropriate amount of tryptophan is beneficial to the F/G of male broilers, while under a low-protein diet, tryptophan supplementation may cause a short-term reduction in the feed intake of female broilers by increasing serum GLP-1 and bile acid signals.

MT1G induces lipid droplet accumulation through modulation of H3K14 trimethylation accelerating clear cell renal cell carcinoma progression.

BACKGROUND: Lipid droplet formation is a prominent histological feature in clear cell renal cell carcinoma (ccRCC), but the significance and mechanisms underlying lipid droplet accumulation remain unclear. METHODS: Expression and clinical significance of MT1G in ccRCC were analyzed by using TCGA data, GEO data and scRNASeq data. MT1G overexpression or knockdown ccRCC cell lines were constructed and in situ ccRCC model, lung metastasis assay, metabolomics and lipid droplets staining were performed to explore the role of MT1G on lipid droplet accumulation in ccRCC. RESULTS: Initially, we observed low MT1G expression in ccRCC tissues, whereas high MT1G expression correlated with advanced disease stage and poorer prognosis. Elevated MT1G expression promoted ccRCC growth and metastasis both in vitro and in vivo. Mechanistically, MT1G significantly suppressed acylcarnitine levels and downstream tricarboxylic acid (TCA) cycle activity, resulting in increased fatty acid and lipid accumulation without affecting cholesterol metabolism. Notably, MT1G inhibited H3K14 trimethylation (H3K14me3) modification. Under these conditions, MT1G-mediated H3K14me3 was recruited to the CPT1B promoter through direct interaction with specific promoter regions, leading to reduced CPT1B transcription and translation. CONCLUSIONS: Our study unveils a novel mechanism of lipid droplet accumulation in ccRCC, where MT1G inhibits CPT1B expression through modulation of H3K14 trimethylation, consequently enhancing lipid droplet accumulation and promoting ccRCC progression. Graphical abstract figure Schematic diagram illustrating MT1G/H3K14me3/CPT1B-mediated lipid droplet accumulation promoted ccRCC progression via FAO inhibition.

Anterior chamber proliferative membrane interception (AC-PMI)-enhanced trabeculectomy versus trabeculectomy for treating neovascular glaucoma: protocol for a randomized controlled trial.

BACKGROUND: Neovascular glaucoma (NVG) is an irreversible blinding eye disease worldwide and is classified as one of the refractory glaucoma conditions, severely impacting visual function and vision. Unfortunately, effective surgical interventions to improve the prognosis of NVG patients are currently lacking. The study aims to evaluate the efficacy and safety of anterior chamber proliferative membrane interception (AC-PMI)-enhanced trabeculectomy compared to the traditional trabeculectomy. METHODS: AC-PMI enhanced trabeculectomy versus trabeculectomy for the treatment of NVG is a single-center, prospective, double-arms, and randomized controlled trial of superior efficacy, which will involve 100 NVG inpatients. Patients will be randomly assigned into two groups using the random number table method. One group will undergo trabeculectomy using anti-vascular endothelial growth factor (Anti-VEGF) preoperatively and mitomycin C intraoperatively, while the other group will undergo AC-PMI enhanced trabeculectomy with the same medications (Anti-VEGF and mitomycin C). The patients will be followed up at the baseline and 1 day, 1 week, 1 month, 3 months, 6 months, 12 months, 18 months, and 24 months postoperatively. Meanwhile, we will collect the demographics, characteristics, and examination results and monitor any occurrences of adverse events at each follow-up time. DISCUSSION: This is an efficacy study of a novel surgical approach for treating neovascular glaucoma. Building upon conventional filtering surgeries, this approach introduces an additional step involving the interception of the proliferative membrane to effectively halt the growth of fibrovascular tissue. This study aims to explore a promising new surgical approach for managing NVG and contribute to the advancement of glaucoma treatment strategies. TRIAL REGISTRATION: ChiCTR ChiCTR2200055138. Registered on 01 January 2022. https://www.chictr.org.cn/showproj.html?proj=145255.

TLR4 in POMC neurons regulates thermogenesis in a sex-dependent manner.

The rising prevalence of obesity has become a worldwide health concern. Obesity usually occurs when there is an imbalance between energy intake and energy expenditure. However, energy expenditure consists of several components, including metabolism, physical activity, and thermogenesis. Toll-like receptor 4 (TLR4) is a transmembrane pattern recognition receptor, and it is abundantly expressed in the brain. Here, we showed that pro-opiomelanocortin (POMC)-specific deficiency of TLR4 directly modulates brown adipose tissue thermogenesis and lipid homeostasis in a sex-dependent manner. Deleting TLR4 in POMC neurons is sufficient to increase energy expenditure and thermogenesis resulting in reduced body weight in male mice. POMC neuron is a subpopulation of tyrosine hydroxylase neurons and projects into brown adipose tissue, which regulates the activity of sympathetic nervous system and contributes to thermogenesis in POMC-TLR4-KO male mice. By contrast, deleting TLR4 in POMC neurons decreases energy expenditure and increases body weight in female mice, which affects lipolysis of white adipose tissue (WAT). Mechanistically, TLR4 KO decreases the expression of the adipose triglyceride lipase and lipolytic enzyme hormone-sensitive lipase in WAT in female mice. Furthermore, the function of immune-related signaling pathway in WAT is inhibited because of obesity, which exacerbates the development of obesity reversely. Together, these results demonstrate that TLR4 in POMC neurons regulates thermogenesis and lipid balance in a sex-dependent manner.

Surgical Outcomes of Penetrating Canaloplasty in Patients with Uncontrolled Posner-Schlossman Syndrome: A Prospective Study.

PURPOSE: To evaluate the surgical outcomes in patients with Posner-Schlossman syndrome (PSS) at one year. METHODS: A prospective interventional study in PSS patients with penetrating canaloplasty. Main outcome measure was success rate (6 mmHg≤ intraocular pressure (IOP) ≤ 21 mmHg) with or without medications. RESULTS: Thirteen eyes in 13 patients with PSS underwent complete catheterization. The mean IOP and medications (Meds) were reduced to 16.1 ± 4.8 mmHg on 0.5 ± 1.0 Meds at 12 months. Complete and qualified success rates were 61.5% and 84.6% at 12 months. The postoperative recurrent rate of PSS was 69.2%, the mean peak IOP during attacks and episodes were decreased to 26.7 ± 8.3 mmHg and 1.7 ± 2.0 times respectively. Transient IOP spike (61.5%) and hyphema (38.5%) were the two most common postoperative complications. CONCLUSION: Penetrating canaloplasty achieves a high success rate in PSS without serious complications.

Diet containing stearic acid increased food intake in mice by reducing serum leptin compared with oleic acid.

In today's society, obesity is becoming increasingly serious, and controlling food intake and maintaining weight balance have become increasingly important. Here, we found that a stearic acid diet can increase food intake without causing obesity in mice compared with an oleic acid diet. Stearic acid increases food intake in mice by reducing serum leptin and increasing NPY neuronal excitability through the JAK2/STAT3 pathway. The impaired anorexic effect of leptin is probably due to repressive cholesterol-oxysterol-LXR-α/SREBP-1c-mediated leptin expression in mouse iWAT. At the same time, we found that stearic acid was not only poorly absorbed by itself in the small intestine but also reduced the entire absorption system of the small intestine. In conclusion, we have proven that a stearic acid diet can increase food intake in mice and avoid obesity, but whether a stearic acid diet could cause adverse reactions in the body remains to be studied.

TLR4 in Tph2 neurons modulates anxiety-related behaviors in a sex-dependent manner.

TLR4 belongs to the TLR receptor family and can induce a proinflammatory response to invading pathogens. Recent studies have identified that TLR4 is associated with major anxiety disorder. Tph2 is a rate-limiting enzyme for 5-HT biosynthesis that is expressed at high levels in the DRN, which includes the main 5-HT projection to the hippocampus and prefrontal cortex and regulates anxiety disorder. Here, we show that TLR4 expressed in Tph2 neurons in the DRN can modulate anxiety-like behaviors in a sex-dependent manner. Deletion of TLR4 in Tph2 neurons decreases anxiety-like behaviors in male but not in female mice. Meanwhile, a similar phenotype was found by selectively ablating TLR4 in the DRN of adult male but not female mice using AAV-Cre-GFP virus. Inhibition of TLR4 in DRN by infusion of LPS-RS via intra-Aq is sufficient to reverse anxiety-like behavior induced by chronic immobilization stress (CIS). The underlying mechanisms seem to involve alterations in the activity of Tph2 neurons and key components of 5-HT transmission, including synthesis, reuptake, and transmission. Our results suggest that TLR4 in Tph2 neurons is a key modulator in anxiety-like behaviors and the 5-HT system in the brain between different sexes.

Corticotropin-releasing factor receptor type 2 in the midbrain critically contributes to the hedonic feeding behavior of mice under heat stress.

Heat stress is an important factor that affects food intake. Previous studies have proven that heat stress can regulate feeding behavior through a homeostasis pathway and decrease appetite in animals and humans. However, the relationship between heat stress and midbrain reward regulation has not been reported. Corticotropin-releasing factor receptor type 2 (CRFR2) is the receptor of corticotropin-releasing factor (CRF), which is the key hypothalamic pituitary adrenal axis (HPA axis) regulating the stress response. In our study, the effects of heat stress on hedonic feeding behavior were investigated. The results showed that heat stress can affect hedonic feeding behavior and decrease high-fat diet (HFD) intake. Furthermore, the mRNA expression of tyrosine hydroxylase in the VTA decreased under heat stress compared with that at 25 °C. Meanwhile, intraventricular injection of a CRFR2 antagonist reversed the decrease in HFD intake and conditional place preference (CPP) caused by heat stress. In conclusion, CRFR2 in the midbrain plays an important role in the decrease in hedonic feeding behavior caused by heat stress.

Food reward depends on TLR4 activation in dopaminergic neurons.

The rising prevalence of obesity and being overweight is a worldwide health concern. Food reward dysregulation is the basic factor for the development of obesity. Dopamine (DA) neurons in the ventral tegmental area (VTA) play a vital role in food reward. Toll-like receptor 4 (TLR4) is a transmembrane pattern recognition receptor that can be activated by saturated fatty acids. Here, we show that the deletion of TLR4 specifically in DA neurons increases body weight, increases food intake, and decreases food reward. Conditional deletion of TLR4 also decreased the activity of DA neurons while suppressing the expression of tyrosine hydroxylase (TH) in the VTA, which regulates the concentration of DA in the nucleus accumbens (NAc) to affect food reward. Meanwhile, AAV-Cre-GFP mediated VTA-specific TLR4-deficient mice recapitulates food reward of DAT-TLR4-KO mice. Food reward could be rescued by re-expressing TLR4 in VTA DA neurons. Moreover, effects of intra-VTA infusion of lauric acid (a saturated fatty acid with 12 carbon) on food reward were abolished in mice lacking TLR4 in DA neurons. Our study demonstrates the critical role of TLR4 signaling in regulating the activity of VTA DA neurons and the normal function of the mesolimbic DA system that may contribute to food reward.

The influence of context condition on outcome evaluation in experimental conditions: Even vs. neutral.

Feedback-related negativity (FRN) is an event-related brain potential that is elicited during outcome evaluation. Studies have found that FRN reflects a good vs. bad classification; more importantly, FRN reflects this classification in a context-dependent manner, which means that the outcome evaluation is obviously influenced by its embedded context. In the current study, we examined how the context conditions of even (i.e., the feedback was +4 or -4) and neutral (i.e., the feedback was always 0) affect the outcome evaluation in experimental conditions (gain and loss). The experimental conditions of gain (i.e., the feedback was +4 or 0) and loss (i.e., the feedback was 0 or -4) were presented with the even condition as the context in one section and with the neutral condition as the context in another section. The ERP (event-related potential) results of the two experimental conditions showed that the unfavorable outcome evoked more negative FRN than the favorable outcome in both even and neutral sections, however, the amplitude difference between unfavorable and favorable outcomes was greater in neutral section than in even section. Furthermore, the favorable outcomes evoked more positive FRN in the neutral section than in the even section. These results indicate that the context condition modulates outcome evaluation, in neutral context, the discrimination between favorable and unfavorable outcome is better, which might due to the facilitated identification of favorable outcomes in neutral context.