Liquid Transmission Electron Microscopy for Probing Collagen Biomineralization.

Collagen biomineralization is fundamental to hard tissue assembly. While studied extensively, collagen mineralization processes are not fully understood, with the majority of theories derived from electron microscopy (EM) under static, dehydrated, or frozen conditions, unlike the liquid phase environment where mineralization occurs. Herein, novel liquid transmission EM (TEM) strategies are presented, in which collagen mineralization was explored in liquid for the first time via TEM. Custom thin-film enclosures were employed to visualize the mineralization of reconstituted collagen fibrils in a calcium phosphate and polyaspartic acid solution to promote intrafibrillar mineralization. TEM highlighted that at early time points precursor mineral particles attached to collagen and progressed to crystalline mineral platelets aligned with fibrils at later time points. This aligns with observations from other techniques and validates the liquid TEM approach. This work provides a new liquid imaging approach for exploring collagen biomineralization, advancing toward understanding disease pathogenesis and remineralization strategies for hard tissues.

Aberrant expression and functions of protocadherins in human malignant tumors.

Protocadherins (PCDHs) are a group of transmembrane proteins belonging to the cadherin superfamily and are subdivided into "clustered" and "non-clustered" groups. PCDHs vary in both structure and interaction partners and thus regulate multiple biological responses in complex and versatile patterns. Previous researches showed that PCDHs regulated the development of brain and were involved in some neuronal diseases. Recently, studies have revealed aberrant expression of PCDHs in various human malignant tumors. The down-regulation or absence of PCDHs in malignant cells has been associated with cancer progression. Further researches suggest that PCDHs may play major functions as tumor suppressor by inhibiting the proliferation and metastasis of cancer cells. In this review, we focus on the altered expression of PCDHs and their roles in the development of cancer progression. We also discuss the potential mechanisms, by which PCDHs are aberrantly expressed, and its implications in regulating cancers.

Physical Frailty and the Risk of Degenerative Valvular Heart Disease.

Background and Objectives: The relationship between physical frailty, age-related conditions, and the incidence of degenerative valvular heart disease (VHD) remains unclear. This study aimed to investigate the potential association between physical frailty and the development of degenerative VHD. Research Design and Methods: Participants from the UK Biobank who were initially free of VHD and heart failure were categorized into 3 groups based on the frailty phenotype: non-frailty, pre-frailty, and frailty. The frailty phenotype was determined by evaluating the following 5 components: weight loss, exhaustion, reduced physical activity, slow gait speed, and low grip strength. The incidence of degenerative VHD, including mitral valve regurgitation (MR), aortic valve regurgitation (AR), and aortic valve stenosis (AS), was assessed using hospital admission or death registries. Results: Among the 331 642 participants, 11 885 (3.6%) exhibited frailty and 143 379 (43.2%) were categorized as pre-frailty. During a median follow-up of 13.8 years, there were 3 684 MR, 1 205 AR, and 3 166 AS events. Compared to non-frailty participants, those with pre-frailty and frailty showed significantly increased risks for MR (hazard ratio [HR], HRpre-frailty:1.19, 95% confidence interval [CI]: 1.11-1.28; HRfrailty: 1.50, 95% CI: 1.30-1.74), AR (HRpre-frailty:1.19, 95% CI: 1.05-1.34; HRfrailty: 1.58, 95% CI: 1.22-2.04), and AS (HRpre-frailty:1.19, 95% CI: 1.11-1.29; HRfrailty: 1.74, 95% CI: 1.51-2.00). Among the 5 components, slow gait speed showed the strongest association with the risk of various types of VHD (HRMR: 1.50, 95% CI: 1.34-1.65; HRAR: 1.50, 95% CI: 1.24-1.80; HRAS: 1.46, 95% CI: 1.32-1.62), followed by exhaustion, low grip strength, and weight loss. Discussion and Implications: Pre-frailty and frailty were associated with a higher risk of all 3 types of degenerative VHD. Early detection and intervention for pre-frailty and frailty in middle-aged and older individuals may assist in preventing or delaying the onset of degenerative VHD.

Metformin ameliorates insulin resistance, thyroid nodules and thyroid function.

OBJECTIVE: To evaluate the ameliorative impact of metformin on insulin resistance (IR), as well as thyroid nodules (TNs) and function in TN patients with IR. METHODS: The clinical data of 128 TN patients with IR admitted to Yantai Laiyang Central Hospital from July 2018 to March 2020 were retrospectively analyzed and categorized into a control group (CNG, n = 64) and a study group (SG, n = 64). Patients in the CNG received standard lifestyle intervention, while those in the SG received standard lifestyle intervention in conjunction with metformin therapy for 1 year of course. Weight-related indicators, IR, thyroid function, TN diameter, and oxidative stress levels were compared between the two groups before and after treatment. Additionally, the safety of metformin was evaluated. RESULTS: Before treatment, no significant differences were observed between the two groups in fasting plasma glucose (FPG), 2-h postprandial glucose (2hPG), glycated hemoglobin (HbA1c), fasting insulin (FINS), homeostatic model assessment of insulin resistance (HOMA-IR), systolic blood pressure (SBP), diastolic blood pressure (DBP), thyroid-stimulating hormone (TSH), malondialdehyde (MDA), TN diameter, and thyroid volume (P > 0.05). After treatment, significant statistical differences were observed in the aforementioned indicators between the two groups (P < 0.05). After 1 year of treatment, the SG exhibited lower levels of FPG, 2hPG, HbA1c, FINS, HOMA-IR, SBP, DBP, TSH, MDA, TN diameter, and thyroid volume, and showed higher levels of HOMA-ß, superoxide dismutase, and glutathione peroxidase levels compared to before treatment (P < 0.05). The incidence of adverse reactions in the SG was significantly higher than that in the CNG (P < 0.05). Taking metformin and free thyroxine (FT4) were protective factors for TSH (P < 0.05). CONCLUSION: Metformin could significantly improve IR and oxidative stress levels, regulate TSH levels, and shrink TNs in TN patients with IR, with high safety. The administration of metformin and FT4 were identified as protective factors for positive prognosis.

Acupuncture treatment of glaucoma based on radar plots: A protocol for an overview of systematic reviews.

BACKGROUND: Glaucoma is the second most blinding eye disease in the world. Currently, lowering the intraocular pressure through various methods is the main treatment of glaucoma. Acupuncture has been effectively and safely used in the treatment of glaucoma. However, the evidence for the efficacy of acupuncture in the treatment of glaucoma is controversial, leading to inconsistent findings from systematic evaluations at abroad and home. Therefore, this protocol aims to provide a multivariate evaluation on the quality of evidences from current systematic reviews (SRs) and/or meta-analyzes (MAs) of acupuncture in the treatment of glaucoma, and literature quality, thus providing an intuitive and reliable evidence synthesis and basis for clinical decision making. METHODS: MAs/SRs about the acupuncture treatment of glaucoma will be searched online, including Chinese Biomedical Literature Database (CBM), China Science and Technology Journal Database (VIP), China National Knowledge Infrastructure (CNKI), WanFang Database (WF), Web of Science, Embase, PubMed, and Cochrane Library. Two investigators will independently screen literatures according to inclusion and exclusion criteria and extract data. A multivariate evaluation of the included literature will be performed by depicting radar plots in 6 aspects as follows: Year of publication, study type, SRs assessment through the Assessment of Multiple Systematic Reviews 2 (AMSTAR 2), literature quality assessment through the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA), homogeneity, and publication bias. The Grading of Recommendations Assessment, Development, and Evaluation evidence quality assessment tool will be used to grade and evaluate the quality of outcome indicators of the included literatures. RESULTS: This study will be submitted for publication in a peer-reviewed journal. CONCLUSION: We would like to provide a visual and scientific approach for clinical decision making of acupuncture treatment of glaucoma through a accessible and useful assessment of systematic reviews.