USP8-governed GPX4 homeostasis orchestrates ferroptosis and cancer immunotherapy.

Ferroptosis is an iron-dependent type of regulated cell death resulting from extensive lipid peroxidation and plays a critical role in various physiological and pathological processes. However, the regulatory mechanisms for ferroptosis sensitivity remain incompletely understood. Here, we report that homozygous deletion of Usp8 (ubiquitin-specific protease 8) in intestinal epithelial cells (IECs) leads to architectural changes in the colonic epithelium and shortens mouse lifespan accompanied by increased IEC death and signs of lipid peroxidation. However, mice with heterozygous deletion of Usp8 in IECs display normal phenotype and become resistant to azoxymethane/dextran sodium sulfate-induced colorectal tumorigenesis. Mechanistically, USP8 interacts with and deubiquitinates glutathione peroxidase 4 (GPX4), leading to GPX4 stabilization. Thus, USP8 inhibition destabilizes GPX4 and sensitizes cancer cells to ferroptosis in vitro. Notably, USP8 inhibition in combination with ferroptosis inducers retards tumor growth and enhances CD8+ T cell infiltration, which potentiates tumor response to anti-PD-1 immunotherapy in vivo. These findings uncover that USP8 counteracts ferroptosis by stabilizing GPX4 and highlight targeting USP8 as a potential therapeutic strategy to boost ferroptosis for enhancing cancer immunotherapy.

Insulin eye drops improve corneal wound healing in STZ-induced diabetic mice by regulating corneal inflammation and neuropeptide release.

INTRODUCTION: In recent years, insulin eye drops have attracted increasing attention from researchers and ophthalmologists. The aim of this study was to investigate the efficacy and possible mechanism of action of insulin eye drops in diabetic mice with corneal wounds. METHODS: A type 1 diabetes model was induced, and a corneal epithelial injury model of 2.5 mm was established. We used corneal fluorescein staining, hematoxylin-eosin (H-E) staining and the Cochet-Bonnet esthesiometer to examine the process of wound healing. Subsequently, the expression levels of Ki-67, IL-1ß, ß3-tubulin and neuropeptides, including substance P (SP) and calcitonin gene-related peptide (CGRP), were examined at 72 h after corneal injury. RESULTS: Fluorescein staining demonstrated an acceleration of the recovery of corneal epithelial injury in diabetic mice compared with the saline treatment, which was further evidenced by the overexpression of Ki-67. Moreover, 72 h of insulin application attenuated the expression of inflammatory cytokines and neutrophil infiltration. Remarkably, the results demonstrated that topical insulin treatment enhanced the density of corneal epithelial nerves, as well as neuropeptide SP and CGRP release, in the healing cornea via immunofluorescence staining. CONCLUSIONS: Our results indicated that insulin eye drops may accelerate corneal wound healing and decrease inflammatory responses in diabetic mice by promoting nerve regeneration and increasing levels of neuropeptides SP and CGRP.

Potential mechanisms of exercise for relieving inflammatory pain: a literature review of animal studies.

Inflammatory pain (IP) is one of the most prevalent and intractable human conditions, and it leads to progressive dysfunction and reduced quality of life. Additionally, IP is incredibly challenging to treat successfully with drugs or surgery. The development of IP is complex and multifactorial, and peripheral and central sensitization may influence chronicity and treatment resistance in IP. Understanding the mechanisms underlying IP is vital for developing novel therapies. Strong evidence suggests that exercise can be a first-line relief for patients with IP during rehabilitation. However, the mechanisms through which exercise improves IP remain unclear. Here, we reviewed the current animal experimental evidence for an exercise intervention in IP and proposed biological mechanisms for the effects of synaptic plasticity in the anterior cingulate cortex, endocannabinoids, spinal dorsal horn excitability balance, immune cell polarization balance, cytokines, and glial cells. This information will contribute to basic science and strengthen the scientific basis for exercise therapy prescriptions for IP in clinical practice.

High-frequency rTMS over bilateral primary motor cortex improves freezing of gait and emotion regulation in patients with Parkinson's disease: a randomized controlled trial.

Background: Freezing of gait (FOG) is a common and disabling phenomenon in patients with Parkinson's disease (PD), but effective treatment approach remains inconclusive. Dysfunctional emotional factors play a key role in FOG. Since primary motor cortex (M1) connects with prefrontal areas via the frontal longitudinal system, where are responsible for emotional regulation, we hypothesized M1 may be a potential neuromodulation target for FOG therapy. The purpose of this study is to explore whether high-frequency rTMS over bilateral M1 could relieve FOG and emotional dysregulation in patients with PD. Methods: This study is a single-center, randomized double-blind clinical trial. Forty-eight patients with PD and FOG from the Affiliated Hospital of Xuzhou Medical University were randomly assigned to receive 10 sessions of either active (N = 24) or sham (N = 24) 10 Hz rTMS over the bilateral M1. Patients were evaluated at baseline (T0), after the last session of treatment (T1) and 30 days after the last session (T2). The primary outcomes were Freezing of Gait Questionnaire (FOGQ) scores, with Timed Up and Go Test (TUG) time, Standing-Start 180° Turn (SS-180) time, SS-180 steps, United Parkinson Disease Rating Scales (UPDRS) III, Hamilton Depression scale (HAMD)-24 and Hamilton Anxiety scale (HAMA)-14 as secondary outcomes. Results: Two patients in each group dropped out at T2 and no serious adverse events were reported by any subject. Two-way repeated ANOVAs revealed significant group × time interactions in FOGQ, TUG, SS-180 turn time, SS-180 turning steps, UPDRS III, HAMD-24 and HAMA-14. Post-hoc analyses showed that compared to T0, the active group exhibited remarkable improvements in FOGQ, TUG, SS-180 turn time, SS-180 turning steps, UPDRS III, HAMD-24 and HAMA-14 at T1 and T2. No significant improvement was found in the sham group. The Spearman correlation analysis revealed a significantly positive association between the changes in HAMD-24 and HAMA-14 scores and FOGQ scores at T1. Conclusion: High-frequency rTMS over bilateral M1 can improve FOG and reduce depression and anxiety in patients with PD.

3D bioprinting by reinforced bioink based on photocurable interpenetrating networks for cartilage tissue engineering.

Cartilage has a limited ability to repair itself, highlighting the urgent need for suitable materials for cartilage regeneration. Achieving a balance between cell survival environment and hydrogel crosslinking density is crucial for photosensitive cell-laden cartilage repair materials to achieve both high strength and good cell viability. Here, an interpenetrating hydrogel consisted of methacrylate gelatin (GelMA) and glycidyl methacrylate silk fibroin (SG) was introduced. Compared to GelMA hydrogel, GelMA/SG had desired mechanical properties, with achieving up to 5 times of compression modulus and 6 times of compression failure energy. Meanwhile, the chondrocytes inside GelMA/SG exhibited great viability which was over 90 %. GelMA/SG as a bioink had favorable printability for digital light processing (DLP) bioprinting. The mesh DLP-printed scaffolds with high precision were created and GelMA/SG had a better shape retention ability than GelMA. Moreover, GelMA/SG cell-laden scaffolds had high strength while chondrocytes proliferated significantly in vitro culture. They were implanted under the skin of nude mice to evaluate ectopic chondrogenesis in vivo. The GelMA/SG cell-laden scaffolds indicated little deformation and high expression of collagen type II and glycosaminoglycans, which was advantageous for cartilage regeneration. The scaffold and its fabrication strategy provide potential solutions for clinical cartilage repair problems in the future.

Corrigendum: Proteomic profiling reveals the potential mechanisms and regulatory targets of sirtuin 4 in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson's mouse model.

[This corrects the article DOI: 10.3389/fnins.2022.1035444.].

GLP1R rs3765467 Polymorphism Is Associated with the Risk of Early Onset Type 2 Diabetes.

Objective: To investigate the relationship between glucagon-like peptide-1 receptor gene polymorphisms and susceptibility to early onset type 2 diabetes. Methods: Samples from 316 type 2 diabetes patients with early onset type 2 diabetes (n = 137) and late-onset type 2 diabetes (n = 179) and 145 nondiabetic individuals were analyzed. Multiplex PCR combined with resequencing Hi-Reseq technology was used to detect single nucleotide polymorphisms of the glucagon-like peptide-1 receptor gene, and the allele frequency, genotype distribution, and clinical parameters were analyzed between each diabetes subgroup and the control group. Results: Sixteen single nucleotide polymorphisms were identified in the exonic region of the glucagon-like peptide-1 receptor gene according to the minor allele frequency (MAF > 0.05) in the participants. Among these, the glucagon-like peptide-1 receptor rs3765467 (G⟶A) mutation was statistically associated with early onset type 2 diabetes. Compared with that of the GG carriers, carriers of genotype AA at rs3765467 had a decreased risk of early onset type 2 diabetes after adjusting for sex and body mass index. In the dominant model, the frequencies of the rs3765467 AA + GA genotype were significantly decreased in the early onset type 2 diabetes group, and carriers of genotype AA + GA at rs3765467 had a decreased risk of early onset type 2 diabetes after adjusting for sex and body mass index. Moreover, fasting C peptide levels were significantly higher in GA + AA genotype carriers than those in GG genotype carriers. Conclusion: The glucagon-like peptide 1 receptor rs3765467 polymorphism was significantly associated with age at type 2 diabetes diagnosis and thus may be used as a marker to screen and detect individuals at risk of developing early onset type 2 diabetes.

Association between dyslipidaemia and dry eye disease: a systematic review and meta-analysis.

PURPOSE: To report a systematic review and meta-analysis of the association between dry eye disease (DED) and dyslipidaemia. METHODS: PubMed, Embase, Web of Science and Cochrane Library were systematically searched from January 2000 to December 2021. We included observational studies to assess the correlation of DED with meibomian gland dysfunction and dyslipidaemia without any language restrictions. The pooled OR with 95% CI was calculated in Stata V.15. RESULTS: Of 6727 identified studies, 18 studies (21 databases) with a total of 2 663 126 patients were analysed in our meta-analysis. The results showed that DED risk was associated with dyslipidaemia (OR=1.53, 95% CI: 1.41 to 1.66, p=0.001), especially elevated total cholesterol levels (OR=1.57, 95% CI: 1.25 to 1.99, p<0.001), elevated low-density lipoprotein cholesterol levels (OR=1.13, 95% CI: 1.06 to 1.20, p<0.001) and high-density lipoprotein cholesterol levels (OR=1.06, 95% CI: 1.01 to 1.11, p<0.001), but not with serum triglyceride levels. Moreover, having a history of lipid-lowering drug use (OR=1.41, 95% CI: 1.19 to 1.67, p<0.001) was also found to be positively associated with DED risk. CONCLUSIONS: The findings suggested that dyslipidaemia and lipid-lowering drug use might be associated with an increased risk of DED. More evidence is needed to confirm the findings by prospective studies. PROSPERO REGISTRATION NUMBER: CRD42022296664.

Tobacco roots increasing diameter and secondary lateral density in response to drought stress.

Exploring the responses of root morphology and its physiological mechanisms under drought stress is significant for further improving water and nutrient absorption in roots. Here, we simulated drought through hydroponics combined with PEG treatments in tobacco to characterize the changes in tobacco root architecture. Our results showed the total root length, first lateral root number, and first lateral root length were significantly reduced upon increasing drought severity, but the average root diameter and secondary lateral root density increased under certain drought conditions. The change of auxin content in roots under drought stress was correlated with the root diameter and second lateral root density responses. Exogenous addition of the auxin analog (NAA) and the auxin transport inhibitor (NPA), as well as DR5:GUS staining experiments further demonstrated that auxin participated in this physiological process. Meanwhile, brassinolide (BR) exhibited a similar trend. Exogenous addition of BR (EBR) and the BR synthesis inhibitor BRZ experiments demonstrated that BR may participate upstream of auxin under drought stress. PEG treatment significantly up-regulated NtBRI1 at 9-24 h, and promoted the up-regulation of NtBSK2 and NtBSK3 at 48 h and 24 h, respectively, these genes may contribute to the change in root morphology under drought stress. This study shows that auxin and BR are involved in the changes in root morphology in tobacco exposed to drought stress. The elucidation of the molecular mechanism at play thus represents a future target for breeding drought-tolerant tobacco varieties.

Dietary supplementation with honeycomb extracts positively improved egg nutritional and flavor quality, serum antioxidant and immune functions of laying ducks.

Introduction: Honeycomb is a traditional natural health medicine and has antioxidant, antibacterial, anti-inflammatory, antiviral and antitumor activities. It is currently unclear whether honeycomb extract supplementation has positive effects on the intensive farming laying duck production. This study aims to evaluate the effects of honeycomb extracts on the laying performance, egg nutritional and flavor quality, serum biochemical indexes, and antioxidant and immune status in laying ducks. Methods: A total of 672 healthy 28-week-old Shanma laying ducks with similar laying performance and body weight were randomly distributed into four dietary treatments with 6 replicates of 28 birds. The birds in each treatment were fed the basal diet supplemented with 0 (control group), 0.5, 1.0 or 1.5 g/kg honeycomb extracts, respectively. Feed and water were provided ad libitum for 45 days. Laying performance, egg quality, egg nutrition and flavor quality, serum parameters were assessed. Results: The results showed that compared with the control group, honeycomb extracts addition significantly increased the average daily feed intake but did not affect the other laying performance indexes, egg quality or serum biochemical indexes of laying ducks. Dietary supplementation with honeycomb extracts significantly increased crude protein content and decreased the contents of cholesterol and trimethylamine in eggs. Diets supplemented with 1.5 g/kg honeycomb extracts significantly improved egg total amino acids and flavor amino acids contents, monounsaturated fatty acids and polyunsaturated fatty acids composition and enhanced the serum antioxidant activity and immune functions of ducks. Discussion: Duck eggs are rich in nutrients and a valuable source of high-quality food for human, while they are rarely consumed directly by consumers because of their stronger fishy odor and lower sensory quality. Many studies have showed that the influence of dietary supplementation on egg components. This study indicated that dietary supplementation with honeycomb extracts positively reduced the contents of egg cholesterol and trimethylamine, improve egg amino acids contents and fatty acid profiles, enhanced serum antioxidant and immune status of laying ducks. The recommended supplemental level of honeycomb extracts was 1.5 g/kg in the diet of laying ducks.

The relationship between fundamental motor skills and physical fitness in preschoolers: a short-term longitudinal study.

Purpose: Physical fitness and fundamental motor skills are two important aspects for the healthy development of preschoolers. Despite the growing interest in clarifying their relationship, the scarcity of longitudinal studies prevents us from understanding causality. Method: This study employed a cross-lagged model with two time points to investigate the bidirectional relationship between these two aspects. A total of 174 preschoolers (54.0% girls) from 3 to 6 years old (M = 3.96 ± 0.47) were surveyed, they were recruited by convenience from two kindergartens in Beijing, China, and their physical fitness (via CNPFDSM-EC) and fundamental motor skills (via TGMD-3) were tracked over a period of 6 months. Results: The findings revealed a bidirectional predictive effect. The predictive strength of flexibility was found to be lower than other physical fitness aspects, while locomotor skills demonstrated a higher predictive strength than object control skills. Conclusion: This study indicates that physical fitness and fundamental motor skills mutually enhance each other in young children, and both should be emphasized in preschool sports education.

Activation of AMPK ameliorates acute severe pancreatitis by suppressing pancreatic acinar cell necroptosis in obese mice models.

Obese people with acute pancreatitis (AP) have an increased risk of developing severe acute pancreatitis (SAP), which prolongs the length of hospital stay and increases mortality. Thus, elucidation of the mechanisms through which SAP occurs in obese individuals will provide clues for possible treatment targets. Differences in early events in obese or lean patients with AP have not been conclusively reported. We selected C57BL/6 mice as lean mice models, ob/ob mice or diet induced obese (DIO) mice as obese mice models and then induced experimental AP in mice via injections of caerulein. There were suppressed p-AMPK expressions in the pancreas of obese mice, compared with same-age lean C57BL/6 mice, which were further reduced in AP mice models. Obese AP mice were treated using AICAR, a direct AMPK agonist, which prevented pancreatic damage and cell death, suppressed pancreatic enzyme levels in serum, reduced the areas of fat saponification in the peritoneal cavity, prevented injury in other organs and decreased mice mortality rate. Further assays showed that AICAR activates p-AMPK to stabilize pro-caspase-8. Pro-caspase-8 enhances RIPK3 degradation, inhibits pancreatic acinar cell necroptosis, and downregulates the release of pancreatic enzymes. Thus, activation of AMPK by AICAR alleviates pancreatic acinar cell necroptosis and converts SAP to mild acute pancreatitis in obese mice.

Effect of Influenza Vaccination on Rate of Influenza Virus Infection in Chinese Military Personnel, 2015-2016: A Cluster Randomized Trial.

Influenza is a major cause of morbidity and mortality. The protective effect of a trivalent influenza vaccine (TIV) is undetermined in military personnel. We conducted an open-label, cluster randomized trial on active-duty servicemen of Beijing, Tianjin, and Shijiazhuang, who were randomly assigned to receive either a single dose of TIV or no treatment, according to cluster randomized sampling. The subjects were then followed for a maximum of six months to assess the incidence of laboratory-confirmed influenza. A total of 5445 subjects in 114 clusters received one dose of TIV before the 2015/2016 influenza season. Laboratory-confirmed influenza was identified in 18 in the vaccine group compared with 87 in the control group (6031 subjects in 114 clusters), resulting in a vaccine effectiveness (VE) of 76.4% (95%CI: 60.7 to 85.8) against laboratory-confirmed influenza. Influenza-like illness was diagnosed in 132 in the vaccine group compared with 420 in the control group, resulting in a VE of 64.1% (95%CI: 56.2 to 70.6). The estimated VE against influenza B viruses was 80.5% (95%CI: 65.6 to 88.9) and 8.6% (95%CI: -241 to 75.5) against influenza A viruses. In conclusion, the trivalent influenza vaccine is moderately effective, highly immunogenic, and generally safe to use in healthy male military servicemen.

Targeting METTL3 reprograms the tumor microenvironment to improve cancer immunotherapy.

The tumor microenvironment (TME) is a heterogeneous ecosystem containing cancer cells, immune cells, stromal cells, cytokines, and chemokines which together govern tumor progression and response to immunotherapies. Methyltransferase-like 3 (METTL3), a core catalytic subunit for RNA N6-methyladenosine (m6A) modification, plays a crucial role in regulating various physiological and pathological processes. Whether and how METTL3 regulates the TME and anti-tumor immunity in non-small-cell lung cancer (NSCLC) remain poorly understood. Here, we report that METTL3 elevates expression of pro-tumorigenic chemokines including CXCL1, CXCL5, and CCL20, and destabilizes PD-L1 mRNA in an m6A-dependent manner, thereby shaping a non-inflamed TME. Thus, inhibiting METTL3 reprograms a more inflamed TME that renders anti-PD-1 therapy more effective in several murine lung tumor models. Clinically, NSCLC patients who exhibit low-METTL3 expression have a better prognosis when receiving anti-PD-1 therapy. Collectively, our study highlights targeting METTL3 as a promising strategy to improve immunotherapy in NSCLC patients.

A case of endobronchial metastasis of colon cancer mimics sarcoidosis, and a review of related literature.

PURPOSE: Endobronchial metastases (EBM) are defined as bronchoscopically visible lesions histopathologically identical to extrapulmonary tumors. We summarized the literature on endobronchial metastasis of colorectal cancer and give a brief review. METHOD: We present a rare case with an episode mistaken for sarcoidosis and unexpectedly identified as colon cancer by bronchoscopic biopsy. A 53-year-old man with dry cough and dyspnea had diffuse micro lung nodules and lymphadenopathy on CT and PET/CT. He was diagnosed with sarcoidosis and took steroid therapy, but the symptoms could not be alleviated. Bronchoscopy was suggested. He was finally identified with colon cancer by bronchoscopic biopsy, which was confirmed by endoscopic biopsy. We summarise the clinical manifestations, imaging, prognosis of EMB of colorectal cancer. RESULT: EBM are rare. Colorectal cancer is common in EBM and the frequency is increasing. CONCLUSION: EBM should be distinguished from primary lung cancer, sarcoidosis.

Biomimetic Hyaluronic Acid-Based Brush Polymers Modulate Chondrocyte Homeostasis via ROS/Ca2+/TRPV4.

Bionic mimics using natural cartilage matrix molecules can modulate the corresponding metabolic activity by improving the microenvironment of chondrocytes. A bionic brush polymer, HA/PX, has been found to reverse the loss of cartilage extracellular matrix (ECM) and has promising applications in the clinical treatment of osteoarthritis (OA). However, the unknown bioremediation mechanism of HA/PX severely hinders its clinical translation. In OA, the massive loss of the ECM may be attributed to a decrease in transient receptor potential vanilloid 4 (TRPV4) activity, which affects reactive oxygen species (ROS) clearance and [Ca2+]i signaling, initiating downstream catabolic pathways. In this study, we investigated the bioremediation mechanism of HA/PX in a model of interleukin 1ß (IL-1ß)-induced inflammation. Through TRPV4, HA/PX reduced ROS accumulation in chondrocytes and enhanced [Ca2+]i signaling, reflecting a short-term protection capacity for chondrocytes. In addition, HA/PX balanced the metabolic homeostasis of chondrocytes via TRPV4, including promoting the secretion of type II collagen (Col-II) and aggrecan, the major components of the ECM, and reducing the expression of matrix metal-degrading enzyme (MMP-13), exerting long-term protective effects on chondrocytes. Molecular dynamics (MD) simulations showed that HA/PX could act as a TRPV4 activator. Our results suggest that HA/PX can regulate chondrocyte homeostasis via ROS/Ca2+/TRPV4, thereby improving cartilage regeneration. Because the ECM is a prevalent feature of various cell types, HA/PX holds promising potential for improving regeneration and disease modification for not only cartilage-related healthcare but many other tissues and diseases.

Lung metastasis from thyroid cancer: A case report of unusual imaging presentation of lung metastases.

RATIONALE: Thyroid cancer (TC) is the most common malignancy of the head and neck and endocrine system. Distant metastases from TC are rare and are diagnosed in only 1% to 4% of patients, and these patients have a poor prognosis, which is the leading cause of TC-related deaths. There are few reports on metastatic TC in China and abroad, and even fewer reports on lung metastases from TC. We report a special patient with lung metastases of TC. PATIENT CONCERNS: The patient is a 31-year-old female who was found to have both lung nodules during physical examination. Chest computed tomography (CT) showed that the density of both lung nodules was the same as the vascular density, considering that the possibility of vascular origin was not excluded. DIAGNOSIS: After consultation with the whole hospital, it was considered that vascular malformations, hemangiomas, and malignant metastases were not excluded, the patient percutaneous lung biopsy had a high risk of bleeding, and thoracoscopic lobectomy could be performed in thoracic surgery to further clarify the pathology and diagnosis. OUTCOMES: The patient underwent thoracoscopic left lower lobe wedge resection on February 24, 2021. Postoperative pathology: (left lower lung mass) metastatic carcinoma, combined with morphology and immunohistochemistry, leaning toward thyroid follicular carcinoma lung metastasis. On May 27, 2021, the patient underwent "total thyroidectomy + lymph node dissection in the right cervical VI region." Pathological examination: (right lobe and isthmus of the thyroid gland) papillary TC, follicular subtype, and classic type, with interstitial fibrosis. The patient was diagnosed with lung metastasis of TC. LESSONS: This patient had the same CT value of lung metastases as the vascular CT value, which is relatively rare in our clinical practice and worthy of our study. The special CT imaging presentation of this TC patient with lung metastases further broadened our horizon. In clinical practice, when we encounter similar cases, we should combine more with other tests and examinations of patients to avoid misdiagnosis and missed diagnosis.

Effects of traditional Chinese herbal feed supplement on growth performance, immunity, antioxidant levels, and intestinal health in chickens: a study on Ningdu yellow chickens.

Traditional Chinese herbs have been widely researched as a green, safe, and effective feed additive for poultry. The purpose of this study was to investigate the effects of traditional Chinese prescription (TCP) based on various herbs in a specific ratio on the growth performance, carcass traits, immunity, antioxidant level, and intestinal health of Ningdu yellow chickens. A total of 420 female Ningdu yellow chickens were randomly divided into 5 groups, with 6 replicates of 14 each. The chickens were fed with a basal diet supplemented with 0 (CON), 0.2, 0.4, 0.6, or 0.8% TCP from d 43 to 105. Body weight, feed intake, and serum biochemical indicators were recorded at d 70 and 105, intestinal morphology and microflora of the carcass were determined at d 105. Compared to the control group, chickens fed with TCP, particularly at the level of 0.6%, showed improved average daily gain and breast muscle percentage, as well as a lower feed-to-gain ratio with statistical significance (P < 0.05). Between 43 and 70 d of age, chickens fed with TCP exhibited higher levels of serum glutathione peroxidase activity, total antioxidant capacity, and superoxide dismutase, particularly in the group fed with the 0.6% level of TCP (P < 0.05). Between 43 and 105 d of age, feeding chickens with 0.4 and 0.6% TCP resulted in a decrease in serum IL-2 concentration, and increase in the IL-4 content (P < 0.05). Chickens fed with 0.4, 0.6, and 0.8% TCP had significantly higher jejunum villous height (P < 0.05), TCP supplementation also led to a marked increase in the relative abundance of Bacteroidota compared to the control group (P < 0.05). Collectively, the study suggests that TCP supplementation can enhance immune and antioxidant functions, improve jejunum morphology, and positively impact cecum microflora in chickens. Based on these results, a level of 0.6% TCP could be considered an optimum level as a feed supplement for Ningdu yellow chickens aged 43 to 105 d.

Bioactive Phenylboronic Acid-Functionalized Hyaluronic Acid Hydrogels Induce Chondro-Aggregates and Promote Chondrocyte Phenotype.

Hydrogels are extensively investigated as biomimetic extracellular matrix (ECM) scaffolds in tissue engineering. The physiological properties of ECM affect cellular behaviors, which is an inspiration for cell-based therapies. Photocurable hyaluronic acid (HA) hydrogel (AHAMA-PBA) modified with 3-aminophenylboronic acid, sodium periodate, and methacrylic anhydride simultaneously is constructed in this study. Chondrocytes are then cultured on the surface of the hydrogels to evaluate the effect of the physicochemical properties of the hydrogels on modulating cellular behaviors. Cell viability assays demonstrate that the hydrogel is non-toxic to chondrocytes. The existence of phenylboronic acid (PBA) moieties enhances the interaction of chondrocytes and hydrogel, promoting cell adhesion and aggregation through filopodia. RT-PCR indicates that the gene expression levels of type II collagen, Aggrecan, and Sox9 are significantly up-regulated in chondrocytes cultured on hydrogels. Moreover, the mechanical properties of the hydrogels have a significant effect on the cell phenotype, with soft gels (≈2 kPa) promoting chondrocytes to exhibit a hyaline phenotype. Overall, PBA-functionalized HA hydrogel with low stiffness exhibits the best effect on promoting the chondrocyte phenotype, which is a promising biomaterial for cartilage regeneration.

Femoral offset restoration affects the early outcome of revision in patients with periprosthetic femoral fractures of Vancouver B2 - a single-center retrospective cohort study.

BACKGROUND: Femoral offset (FO) restoration plays an important role in improving the prognosis and quality of life of patients undergoing hip replacement. However, it is not given enough attention in revisions among patients with periprosthetic femoral fractures (PPFFs); instead, more attention is given to reduction, fixation of fractures and stabilizing prostheses. The primary objective of this study was to evaluate the effect of FO restoration on the function of the hip joint in revisions of patients with PPFF of Vancouver B2. Moreover, we studied whether there is a difference in FO restoration between modular and nonmodular stems. METHODS: A retrospective review of 20 patients with PPFF of Vancouver B2 revised with a tapered fluted modular titanium stem and 22 patients with PPFF of Vancouver B2 revised with a tapered fluted nonmodular titanium stem from 2016 to 2021 was conducted. Based on the difference between the FO of the affected side and that of the healthy side, 26 patients were allocated into Group A (difference ≤ 4 mm), and 16 patients were allocated into Group B (difference > 4 mm). The postoperative Harris Hip Score (HHS), range of motion of the hip joint, length of both lower limbs and dislocation were compared between Group A and Group B. The proportions of patients with FO restoration (difference ≤ 4 mm) and stem subsidence were compared between the modular and nonmodular groups. RESULTS: The mean follow-up time was 34.3 ± 17.3 months, and all cases achieved fracture healing at the last visit. Patients in Group A had a higher HHS, larger range of abduction, fewer dislocations and less limb length discrepancy (LLD). Patients in the modular group had a higher proportion of FO restoration and less subsidence. CONCLUSION: FO restoration improves postoperative hip joint function and reduces dislocation and LLD in revisions of patients with PPFF of Vancouver B2. Compared with nonmodular prostheses, modular prostheses tend to be easier for FO restoration under complex circumstances.