Bioenergetic dysfunction in the pathogenesis of intervertebral disc degeneration.

Intervertebral disc (IVD) degeneration is a frequent cause of low back pain and is the most common cause of disability. Treatments for symptomatic IVD degeneration, including conservative treatments such as analgesics, physical therapy, anti-inflammatories and surgeries, are aimed at alleviating neurological symptoms. However, there are no effective treatments to prevent or delay IVD degeneration. Previous studies have identified risk factors for IVD degeneration such as aging, inflammation, genetic factors, mechanical overload, nutrient deprivation and smoking, but metabolic dysfunction has not been highlighted. IVDs are the largest avascular structures in the human body and determine the hypoxic and glycolytic features of nucleus pulposus (NP) cells. Accumulating evidence has demonstrated that intracellular metabolic dysfunction is associated with IVD degeneration, but a comprehensive review is lacking. Here, by reviewing the physiological features of IVDs, pathological processes and metabolic changes associated with IVD degeneration and the functions of metabolic genes in IVDs, we highlight that glycolytic pathway and intact mitochondrial function are essential for IVD homeostasis. In degenerated NPs, glycolysis and mitochondrial function are downregulated. Boosting glycolysis such as HIF1α overexpression protects against IVD degeneration. Moreover, the correlations between metabolic diseases such as diabetes, obesity and IVD degeneration and their underlying molecular mechanisms are discussed. Hyperglycemia in diabetic diseases leads to cell senescence, the senescence-associated phenotype (SASP), apoptosis and catabolism of extracellualr matrix in IVDs. Correcting the global metabolic disorders such as insulin or GLP-1 receptor agonist administration is beneficial for diabetes associated IVD degeneration. Overall, we summarized the recent progress of investigations on metabolic contributions to IVD degeneration and provide a new perspective that correcting metabolic dysfunction may be beneficial for treating IVD degeneration.

Gut Clostridium sporogenes-derived indole propionic acid suppresses osteoclast formation by activating pregnane X receptor.

Bone homeostasis is maintained by osteoclast-mediated bone resorption and osteoblast-mediated bone formation. A dramatic decrease in estrogen levels in postmenopausal women leads to osteoclast overactivation, impaired bone homeostasis, and subsequent bone loss. Changes in the gut microbiome affect bone mineral density. However, the role of the gut microbiome in estrogen deficiency-induced bone loss and its underlying mechanism remain unknown. In this study, we found that the abundance of Clostridium sporogenes (C. spor.) and its derived metabolite, indole propionic acid (IPA), were decreased in ovariectomized (OVX) mice. In vitro assays suggested that IPA suppressed osteoclast differentiation and function. At the molecular level, IPA suppressed receptor activator of nuclear factor kappa-Β ligand (RANKL)-induced pregnane X receptor (PXR) ubiquitination and degradation, leading to increased binding of remaining PXR with P65. In vivo daily IPA administration or repeated C. spor. colonization protected against OVX-induced bone loss. To protect live bacteria from the harsh gastric environment and delay the emptying of orally administered C. spor. from the intestine, a C. spor.-encapsulated silk fibroin (SF) hydrogel system was developed, which achieved bone protection in OVX mice comparable to that achieved with repeated germ transplantation or daily IPA administration. Overall, we found that gut C. spor.-derived IPA was involved in estrogen deficiency-induced osteoclast overactivation by regulating the PXR/P65 complex. The C. spor.-encapsulated SF hydrogel system is a promising tool for combating postmenopausal osteoporosis without the disadvantages of repeated germ transplantation.

"Low-age, low-frequency" lung cancer screening strategies maybe adaptable to the situation in China.

BACKGROUND: The object was to compare changes in patients undergoing lung surgery before and after COVID-19 outbreak, and to explore the impact of COVID-19 on lung surgery and its coping strategies. METHOD: A retrospective review of patients undergoing thoracic surgery at a single institution was conducted. Group A included patients treated between January 23, 2019, and January 23, 2020, while Group B included patients treated between June 1, 2020, and June 1, 2021, at our center. We compared the reasons of seeking medical treatment, the general characteristics of patients, imaging features, pathological features, surgical methods and postoperative recovery. RESULT: Compared to Group A, the number of patients with pulmonary nodules screened by routine check-up increased in Group B (57.6% vs 46.9%, p < 0.05). Female patient increased (55.2%vs 44.7%). Patient without smoking history or with family history of lung cancer increased (70.7% vs 60.7%) (10.1%vs 7.8%). Early stage lung cancer increased. Lobectomy decreased (53.4% vs 64.1%). Segmental resection increased (33.3% vs 12.7%). Patients without postoperative comorbidities increased (96.1%vs 85.7%). In the case of patients with Ground Glass Opacity(GGO), their age was comparatively lower (52 ± 9.9 vs. 55 ± 10.7), the female patients increased, patient without smoking history, tumor history, family history of tumor increased, small GGO increased. Lobectomy decreased (35.2% vs 49.7%). Segmental resection increased (49.6% vs 21.2%). Patients without postoperative comorbidities increased (96.5% vs 87.4%). CONCLUSION: Since COVID-19 outbreak, more young, non-smoking, female lung cancers, more Ground Glass Opacity, none high risk patients have been detected through screening, suggesting that our current screening criteria for lung cancer may need to be revised. Higher requirements, including the selection of the timing of nodular surgery, surgical methods were put forward for thoracic surgeons' skills.

High-mobility InSnZnO Thin Film Transistors via Introducing Water Vapor Sputtering Gas.

There is always a doubt that introducing water during oxide growing has a positive or negative effect on the properties of oxide films and devices. Herein, a comparison experiment on the condition of keeping the same oxygen atom flux in the sputtering chamber is designed to examine the influences of H2O on In-Sn-Zn-O (ITZO) films and their transistors. In comparison to no-water films, numerous unstable hydrogen-related defects are induced on with-water films at the as-deposited state. Paradoxically, this induction triggers an ordered enhancement in the microstructure of the films during conventional annealing, characterized by a reduction in H-related and vacancy (Vo) defects as well as an increase in film packing density and the M-O network ordering. Ultimately, the no-water thin-film transistors (TFTs) exhibit nonswitching behavior, whereas 5 sccm-water TFT demonstrates excellent electrical performance with a remarkable saturation field-effect mobility (µFE) of 122.10 ± 5.00 cm2·V-1·s-1, a low threshold (Vth) of -2.30 ± 0.40 V, a steep sub-threshold swing (SS) of 0.18 V·dec-1, a high output current (Ion) of 1420 µA, and a small threshold voltage shift ΔVth of -0.77 V in the negative bias stability test (3600 s).

Molecular mechanism of ethylparaben on zebrafish embryo cardiotoxicity based on transcriptome analyses.

Ethylparaben (EP), one of the parabens, a ubiquitous food and cosmetic preservatives, has caused widespread concern due to its health risks. Recently, studies have found that parabens exposure during pregnancy is negatively correlated with fetal and early childhood development. However, studies about EP on embryo development are few. In this study, the cardiotoxicity effects of EP concentrations ranging from 0 to 20 mg/L on zebrafish embryo development were explored. Results showed that EP exposure induce abnormal cardiac function and morphology, mainly manifested as pericardial effusion and abnormal heart rate in early-stage development of zebrafish embryos. Through transcriptome sequencing followed by Gene Ontology enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes enrichment analysis, we further confirmed that EP exposure ultimately leads to cardiac morphologic abnormalities via the following three mechanisms: 1. Disruption of the retinoic acid signaling pathway related to original cardiac catheter development; 2. Inhibition of gene expression related to myocardial contraction; 3. Orientation development disturbance of heart tube. Moreover, O-Dianisidine staining, whole-mount in situ hybridization at 30 and 48 hours post fertilization (hpf) and hematoxylin-eosin staining results all confirmed the decreased heart's return blood volume, misoriented heart tubes toward either the right or the middle side, and heart loop defects. For the first time, we explored the mechanism by which EP exposure causes abnormal heart development in zebrafish embryos, laying the foundation for further revealing of the EP toxicity on embryonic development.