Efficacy and safety of ultrasound-guided percutaneous radiofrequency ablation for synovial hyperplasia.

PURPOSE: This study aimed to investigate the efficacy and safety of ultrasound-guided percutaneous radiofrequency ablation (RFA) for the treatment of synovial hyperplasia in the knee joints of antigen-induced arthritis (AIA) model rabbits. METHODS: Forty Japanese large-eared white rabbits were divided into AIA and control groups. After successful induction of the AIA model, the knee joints were randomly assigned to RFA and non-RFA groups. The RFA group underwent ultrasound-guided RFA to treat synovial hyperplasia in the knee joint. Dynamic observation of various detection indices was conducted to evaluate the safety and effectiveness of the RFA procedure. RESULTS: Successful synovial ablation was achieved in the RFA group, with no intraoperative or perioperative mortality. Postoperative the circumference of the knee joint reached a peak before decreasing in the third week after surgery. The incidence and diameter of postoperative skin ulcers were not significantly different compared to the non-RFA group (p > .05). Anatomical examination revealed an intact intermuscular fascia around the ablated area in the RFA group. The ablated synovial tissue initially presented as a white mass, which subsequently liquefied into a milky white viscous fluid. Gross articular cartilage was observed, along with liquefied necrosis of the synovium on pathological histology and infiltration of inflammatory cells in the surrounding soft tissue. CONCLUSION: The experimental results demonstrated that ultrasound-guided RFA of the knee in the treatment of synovial hyperplasia in AIA model animals was both effective and safe.

Predicting vulnerable carotid plaques by detecting wall shear stress based on ultrasonic vector flow imaging.

OBJECTIVE: Carotid plaque vulnerability is a significant factor in the risk of cardiocerebrovascular events, with intraplaque neovascularization (IPN) being a crucial characteristic of plaque vulnerability. This study investigates the value of ultrasound vector flow imaging (V-flow) for measuring carotid plaque wall shear stress (WSS) in predicting the extent of IPN. METHODS: We enrolled 140 patients into three groups: 53 in the plaque group (72 plaques), 23 in the stenosis group (27 plaques), and 64 in the control group. V-flow was used to measure WSS parameters, including the average WSS (WSS mean) and the maximum WSS (WSS max), across three plaque locations: mid-upstream, maximum thickness, and mid-downstream. Contrast-enhanced ultrasound examination was used in 76 patients to analyze IPN and its correlation with WSS parameters. RESULTS: WSS max in the stenosis group was significantly higher than that in the control and plaque groups at the maximum thickness part (P < .05) and WSS mean in the stenosis group was significantly lower than that in the control group at the mid-upstream and mid-downstream segments (P < .05). WSS mean in the plaque group was significantly lower than that of the control group at all three locations (P < .05). Contrast-enhanced ultrasound examination revealed that plaques with neovascularization enhancement exhibited significantly higher WSS values (P < .05), with a positive correlation between WSS parameters and IPN enhancement grades, particularly WSS max at the thickest part (r = 0.508). Receiver operating characteristic curve analysis of WSS parameters for evaluating IPN showed that the efficacy of WSS max in evaluating IPN was better than that of WSS mean (P < .05), with an area under the curve of 0.7762 and 0.6973 (95% confidence intervals, 0.725-0.822 and 0.642-0.749, respectively). The cut-offs were 4.57 Pa and 1.12 Pa, sensitivities were 74.03% and 63.64%, and specificities were 75.00% and 68.18%. CONCLUSIONS: V-flow effectively measures WSS in carotid plaques. WSS max provides a promising metric for assessing IPN, offering potential insights into plaque characteristics and showing some potential in predicting plaque vulnerability.

Anatomical study of the relationship between the lumbar intervertebral disc, nerves, and psoas major.

Cadaveric study; To describe the characteristics of the nerve and its relationship with the lumbar intervertebral disc and psoas major muscle. Nerve injury is an understudied complication of extreme lateral interbody fusion. A detailed description of the nerve anatomy would be helpful for surgeons to minimize the risk of this complication. The lumbar plexus and lumbar sympathetic nerve of 10 embalmed male cadavers were dissected, and the distribution, number, and spatial orientation of the nerves on the L1/2 to L4/5 intervertebral discs were examined. Metal wires were applied along nerve paths through the psoas major muscle. The position of the nerves was examined on CT. In zone III at L1/2 and L4/5, no nerves were found. In zone II and zone III at L2/3, no lumbar plexus was found, and only the ramus communicans passed through. At the L1-L5 level, the density of nerves in the posterior half of the psoas major muscle was greater than that in the anterior half. The lumbar plexus was found in all of zone IV. The genitofemoral nerve emerges superficially and anteriorly from the medial border of the psoas major at the L3-4 level, but at the L1/2 level, the sympathetic trunk is located in zone II. The remaining disc-level sympathetic trunks appear in zone I. No nerves were found in zone III of the L1/2 or L4/5 disc. In zones II and III of L2/3, the lumbar plexus appears safe. The genitofemoral nerve travels through zones II and III of L3/4. The distribution density of nerves in the posterior half of the psoas major muscle was greater than that in the anterior half of that muscle at the L1-L5 level.

A global meta-analysis on the drivers of salt marsh planting success and implications for ecosystem services.

Planting has been widely adopted to battle the loss of salt marshes and to establish living shorelines. However, the drivers of success in salt marsh planting and their ecological effects are poorly understood at the global scale. Here, we assemble a global database, encompassing 22,074 observations reported in 210 studies, to examine the drivers and impacts of salt marsh planting. We show that, on average, 53% of plantings survived globally, and plant survival and growth can be enhanced by careful design of sites, species selection, and novel planted technologies. Planting enhances shoreline protection, primary productivity, soil carbon storage, biodiversity conservation and fishery production (effect sizes = 0.61, 1.55, 0.21, 0.10 and 1.01, respectively), compared with degraded wetlands. However, the ecosystem services of planted marshes, except for shoreline protection, have not yet fully recovered compared with natural wetlands (effect size = -0.25, 95% CI -0.29, -0.22). Fortunately, the levels of most ecological functions related to climate change mitigation and biodiversity increase with plantation age when compared with natural wetlands, and achieve equivalence to natural wetlands after 5-25 years. Overall, our results suggest that salt marsh planting could be used as a strategy to enhance shoreline protection, biodiversity conservation and carbon sequestration.

Response spectrum-based analysis of airborne radar random vibration and multi-point control improvement.

During the flight of a UAV (unmanned aerial vehicle), the LiDAR device undergoes random vibrations due to the changing flight attitude and wind speed conditions of the UAV. It is important to control the frequency and amplitude of the vibrations within a reasonable range by means of a damping structure. As the vibrations caused by various factors during flight are random and non-linear, this paper innovates the analysis principle and damping control means for the random vibrations of airborne optoelectronic devices. The response spectrum analysis theory is used to establish the shock response spectrum, and an optimised and improved recursive digital filtering method is used to fit the frequencies of random vibration to the synthetic shock response. Considering the uncertainty of the vibration excitation signal, a virtual excitation method is used for the first time to simulate the random vibration to which the radar may be subjected in the air, and to simplify the calculation steps. The shock plate structure is designed using a multi-point control method to innovate a passive response to the random excitation. Finally, a modal analysis of the synthesised impact response was carried out. It is verified that the first six modal frequencies are controlled within 220 Hz, realising the frequency reduction. The amplitude of the three x, y, and z directions is controlled to within 0.5 mm, thus achieving vibration damping.

Anatomical Observation and Clinical Significance of the Medial Branch of the Lumbar Dorsal Rami.

STUDY DESIGN: Anatomical study. OBJECTIVE: This study aimed to elaborate on the anatomical characteristics of the medial branch of the lumbar dorsal rami and to discuss its possible clinical significance. SUMMARY OF BACKGROUND DATA: Radiofrequency ablation targeting the medial branch of the lumbar dorsal rami has been increasingly used in the clinical management of facetogenic low back pain (FLBP). Nonetheless, attention is also being given to complications such as atrophy of the lumbar soft tissues and muscles. Therefore, a more detailed understanding of the innervation pattern on the facet joint may improve the precision of nerve ablation therapy for FLBP. METHODS: An anatomical study of eight human specimens was carried out. The anatomic characteristics of the medial branch were observed and recorded. RESULTS: The medial branch originates from the lumbar dorsal rami, running close to the root of the posterolateral side of the superior articular process of the inferior cone. When passed through the mamillo-accessory ligament, it turns direction to the medial and caudal side, running in the multifidus muscle. In our study, each medial branch sent out two to five branches along the way. All the medial branches in L1-L4 gave off one to two small branches when crossing the facet joint and innervated the joint of the lower segment. Nineteen medial branches (23.75%) gave off recurrent branches to innervate the joint at the upper segment. CONCLUSION: The anatomical features of the medial branch remain similar in each lumbar segment. There are two types of joint branches, including the articular fibers that emanate from the medial branch as it runs along the medial border of the facet joint and the recurrent branch from the medial branch that innervates the upper facet joint. Moreover, an anastomotic branch was found in the medial branches between different segments.

A multilevel social-ecological network approach for reconciling coastal saltmarsh conservation and development.

In a large-scale region, governance for connectivity in an ecological system often conflicts with management boundaries, causing inefficiencies. Collaboration among management organizations in different areas can help overcome this problem. However, few studies quantified the collaborations' practical relationship with connectivity, considering that some potentially connected paths are easy to neglect by managers. In this paper, collaborations among government agencies in project application process were analyzed, and a multilevel social-ecological network analysis (SENA) approach was developed to identify the collaboration's effect on genetically connected coastal areas. The network framework and methods were shown in a case of coastal saltmarsh conservation and development in the Yellow River Delta, China. Collaboration patterns in conservation and development networks were analyzed and compared among local, subregional, and regional government agencies working in genetically connected coastal areas. Project information flow, reflecting communication frequency and decision-making chances among government agencies was quantified and correlated with ecological connectivity to inform governance effects. Results showed areas with the potential to realize social-ecological alignment, where collaborative networks were measured by network density (percentage of connected network edges). The current reveals that development has more significant potential than conservation at most levels to overcome the misalignment of the social-ecological system, also known as scale mismatch. Empirical evidence also showed a correlation between communication capacity in development networks and improved ecological conditions. The multilevel SENA advanced in this paper can be used for natural resource management when connectivity plays a major role.

Anatomic zone division and clinical significance of the lumbar sinuvertebral nerves.

BACKGROUND CONTEXT: Discogenic low-back pain (DLBP) is one of the primary causes of low back pain (LBP) and is associated with internal disc disruptions and is mainly transmitted by the sinuvertebral nerve (SVN). The lack of a universal understanding of the anatomical characteristics of the SVN has compromised surgical treatment for DLPB. PURPOSE: This study aims to elaborate on the anatomical characteristics of the SVN and to discuss their possible clinical significance. STUDY DESIGN: The SVNs were dissected and immunostained in ten human lumbar specimens. METHODS: The SVNs at the segments from L1-L2 to L5-S1 in ten human cadavers were studied, and the number, origin, course, diameter, anastomotic branches, and branching points of the SVNs were documented. Three longitudinal and five transverse zones were defined in the dorsal coronal plane of the vertebral body and disc. The vertebrae were divided longitudinally as follows: the region between the medial edges of the bilateral pedicles is divided into three equal parts, the middle third is zone I and the lateral third on both sides are zones II; the areas lateral to the medial margin of the pedicle were zones III. The transverse zones were designated as follows: (a)superior margin of the vertebral body to superior margin of the pedicle; (b) between superior and inferior margins of the pedicle; (c) inferior margin of the pedicle to inferior margin of the vertebral body; (d) superior margin of the disc to the midline of the disc; and (e) midline of the disc to the inferior margin of the disc. The distribution characteristics of SVNs in various zones were recorded, and tissue sections were immunostained with anti-NF 200 and anti-PGP 9.5. RESULTS: The SVNs are divided into main trunks and deputy branches, with 109 main trunks and 451 deputy branches identified in the 100 lumbar intervertebral foramens (IVFs). The main trunks of the SVN originate from the spinal nerve and/or the communicating branch, but the deputy branch originating from both roots was not observed. All the main trunks and deputy branches of the SVNs originate from the posterolateral disc (III d and III e). The deputy branches of the SVN primarily innervate the posterolateral aspect of the intervertebral disc (III d 46.78%, III e 36.36%) and the subpedicular vertebral body (III c 16.85%). The main trunk of the SVNs passes primarily through the subpedicular vertebral body (III c 96.33%) and divides into ascending, transverse, and descending branches in the IVF: III c (23/101, 22.77%) or spinal canal: II c (73/101, 72.28%), II d (3/101, 2.97%), II b (2/101, 1.98%). The main trunk possesses extensive innervation, and except for the most medial discs (I d and I e), it almost dominates all other zones of the spinal canal. At the segments from L1-L2 to L5-S1, 39 ipsilateral anastomoses connecting the ascending branch to the main trunk or spinal nerve at the upper level were observed, with one contralateral anastomosis observed at L5. CONCLUSION: The zone distribution characteristics of SVNs are similar across all levels. Comparatively, the proportion of double-root origin and the number of insertion points of the SVNs increased at the lower level. The three types of anastomosis offer connections between SVNs at the same level and at different levels. The posteromedial disc is innervated by corresponding and subjacent main trunks, with the posterolateral disc mainly innervated by the deputy branch. CLINICAL SIGNIFICANCE: Detailed information and zone distribution characteristics of the lumbar SVNs can help improve clinicians' understanding of DLBP and improve the effectiveness of treatments targeting the SVNs.

MEL regulates miR-21 and let-7b through the STAT3 cascade in the follicular granulosa cells of Tibetan sheep.

Under physiological and pathological conditions, melatonin (MEL) can regulate microRNA (miRNA) expression. However, the mechanisms underlying the regulatory effects of MEL on miRNAs in ovaries are not understood. Firstly, by using fluorescence in situ hybridisation, we found that in ovaries and follicular granulosa cells (FGCs), MT1 co-located with miR-21 and let-7b. Additionally, immunofluorescence revealed that MT1, STAT3, c-MYC and LIN28 proteins co-located. The mRNA and protein levels of STAT3, c-MYC and LIN28 increased under treatment with 10-7 M MEL. MEL induced an increase in miR-21 and a decrease in let-7b. The LIN28/let-7b and STAT3/miR-21 axes are related to cell differentiation, apoptosis and proliferation. We explored whether the STAT3/c-MYC/LIN28 pathway was involved in miRNA regulation by MEL to explore the putative mechanism of the above relationship. AG490, an inhibitor of the STAT3 pathway, was added before MEL treatment. AG490 inhibited the MEL-induced increases in STAT3, c-MYC, LIN28 and MT1 and changes in miRNA. Through live-cell detection, we discovered that MEL enhanced the proliferation of FGCs. However, the ki67 protein levels decreased when AG490 was added in advance. Furthermore, the dual-luciferase reporter assay verified that STAT3, LIN28 and MT1 were target genes of let-7b. Furthermore, STAT3 and SMAD7 were target genes of miR-21. In addition, the protein levels of the STAT3, c-MYC, LIN28 and MEL receptors decreased when let-7b was overexpressed in FGCs. Overall, MEL might regulate miRNA expression through the STAT3 pathway. In addition, a negative feedback loop between the STAT3 and miR-21 formed; MEL and let-7b antagonized each other in FGCs. These findings may provide a theoretical basis for improving the reproductive performance of Tibetan sheep through MEL and miRNAs.

Sinuvertebral nerve block treats discogenic low back pain: a retrospective cohort study.

Background: Discogenic low back pain (DLBP) is considered the most common type of chronic low back pain (CLBP). Sinuvertebral nerve block (SVNB) is a rapid and precise intervention performed under local anesthesia to treat DLBP induced CLBP. Thus, in this study, we aimed to explore the clinical efficacy of SVNB for DLBP. Methods: We retrospectively included 32 DLBP patients from July 2020 and April 2021. Inclusion criteria: The patients had chronic pain, diagnosed as single-segment disc degeneration induced DLBP, and suffered from one-year ineffective conservative treatment. SVNB was performed and the patients were followed up at 3 and 7 days, and at 1 and 3 months after SVNB. The basic clinical characteristics, including age and gender, were collected. The measurements of Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) were assessed. Results: The average age was 49.31±14.37 years, and females vs. males was 20 (62.50%) vs. 12 (37.50%). The preoperative VAS and ODI score were 5.75±1.41 and 32.59±21.56, respectively. The VAS score was reduced to 2.50±1.46, 2.63±1.60, 3.53±2.17, and 3.78±2.18 at 3 and 7 days, and 1 and 3 months after SVNB, respectively (P<0.05). The improvement rates in the VAS score were 56.52%, 54.34%, 38.61%, and 34.26% at 3 and 7 days, and 1 and 3 months after SVNB, respectively. 18 patients (56.25%) experienced varying degrees of pain recurrence within 3 months. The ODI score was reduced by 17.28±13.06, 16.84±13.51, 19.63±17.12, and 21.44±19.03 points at 3, 7 days and 1, 3 months after SVNB, respectively (P<0.05). At 3 day and 3 month after SVNB, the ODI scores of 22 patients (68.75%) and 20 patients (62.50%) decreased to ≤20, respectively. The ODI improvement rates were 46.98%, 48.33%, 39.80%, and 34.24% at 3, 7 days and 1, 3 months after SVNB, respectively. Conclusions: We conducted a retrospective study of the clinical efficacy of SVNB for DLBP. As a rapid and cost-effective minimally invasive treatment, SVNB provided some assistance for the short-term pain relief and physical functional improvement of DLBP. SVNB could be a good choice for the treatment of DLBP.

Gene regulation in animal miRNA biogenesis.

miRNAs are a class of noncoding RNAs of approximately 19-22 nucleotides that are widely found in animals, plants, bacteria and even viruses. Dysregulation of the expression profile of miRNAs is importantly linked to the development of diseases. Epigenetic modifications regulate gene expression and control cellular phenotypes. Although miRNAs are used as an epigenetic regulation tool, the biogenesis of miRNAs is also regulated by epigenetic events. Here the authors review the mechanisms and roles of epigenetic modification (DNA methylation, histone modifications), RNA modification and ncRNAs in the biogenesis of miRNAs, aiming to deepen the understanding of the miRNA biogenesis regulatory network.

Genes are divided into coding genes and noncoding genes, and people have always focused on coding genes because coding genes guide the synthesis of proteins and proteins are the main bearers of life activities. However, the fact that such important coding genes occupy only 2% of the large human genome shows that noncoding genes are far more complex and important than we think. Through scientific exploration, it has been found that noncoding genes are an important part of gene expression regulation. The end products of noncoding genes, such as miRNAs, also have their own expression patterns at different stages of the body's development, and an imbalance in expression patterns often causes various diseases. There are multiple levels of gene expression regulation during noncoding RNAs biogenesis, and this paper fully reviews the role and the mechanisms of gene expression regulation in miRNA biogenesis. Familiarity with gene expression regulation in miRNA biogenesis is important to understand the mechanisms of dysregulation of miRNA expression profiles in diseases and the treatments employed.

DEPTOR exacerbates bone-fat imbalance in osteoporosis by transcriptionally modulating BMSC differentiation.

Bone marrow-derived mesenchymal stem cells (BMSCs) tend to differentiate into adipocytes rather than osteoblasts in osteoporosis and other pathological conditions. Understanding the mechanisms underlying the adipo-osteogenic imbalance greatly contributes to the ability to induce specific MSC differentiation for clinical applications. This study aimed to explore whether DEP-domain containing mTOR-interacting protein (DEPTOR) regulated MSC fate and bone-fat switch, which was indicated to be a key player in bone homeostasis. We found that DEPTOR expression decreased during the osteogenesis of BMSCs but increased during adipogenesis and the shift of cell lineage commitment of BMSCs to adipocytes in mice with osteoporosis. DEPTOR facilitated adipogenic differentiation while preventing the osteogenic differentiation of BMSCs. Deptor ablation in BMSCs alleviated bone loss and reduced marrow fat accumulation in mice with osteoporosis. Mechanistically, DEPTOR binds transcriptional coactivator with a PDZ-binding motif (TAZ) and inhibits its transactivation properties, thereby repressing the transcriptional activity of RUNX2 and elevating gene transcription by peroxisome-proliferator-activated receptor-gamma. TAZ knockdown in BMSCs abolished the beneficial role of Deptor ablation in bone-fat balance in mice. Together, our data indicate that DEPTOR is a molecular rheostat that modulates BMSC differentiation and bone-fat balance, and may represent a potential therapeutic target for age-related bone loss.

mTORC1 induces plasma membrane depolarization and promotes preosteoblast senescence by regulating the sodium channel Scn1a.

Senescence impairs preosteoblast expansion and differentiation into functional osteoblasts, blunts their responses to bone formation-stimulating factors and stimulates their secretion of osteoclast-activating factors. Due to these adverse effects, preosteoblast senescence is a crucial target for the treatment of age-related bone loss; however, the underlying mechanism remains unclear. We found that mTORC1 accelerated preosteoblast senescence in vitro and in a mouse model. Mechanistically, mTORC1 induced a change in the membrane potential from polarization to depolarization, thus promoting cell senescence by increasing Ca2+ influx and activating downstream NFAT/ATF3/p53 signaling. We further identified the sodium channel Scn1a as a mediator of membrane depolarization in senescent preosteoblasts. Scn1a expression was found to be positively regulated by mTORC1 upstream of C/EBPα, whereas its permeability to Na+ was found to be gated by protein kinase A (PKA)-induced phosphorylation. Prosenescent stresses increased the permeability of Scn1a to Na+ by suppressing PKA activity and induced depolarization in preosteoblasts. Together, our findings identify a novel pathway involving mTORC1, Scn1a expression and gating, plasma membrane depolarization, increased Ca2+ influx and NFAT/ATF3/p53 signaling in the regulation of preosteoblast senescence. Pharmaceutical studies of the related pathways and agents might lead to novel potential treatments for age-related bone loss.

Anatomical study and clinical significance of rami communicantes of the lumbar spine.

BACKGROUND AND OBJECTIVES: Rami communicantes (RC) infiltration and radiofrequency lesions are new techniques for the treatment of discogenic low back pain (DLBP). Their efficacy is controversial, and the classification of RC remains unclear. We aimed to explore the differences between RC and reclassify RC according to their anatomical characteristics. METHODS: Sixteen sides of the lumbar spine from eight adult male embalmed cadavers were dissected. The presence of RC was noted. The morphology, origin, distribution, course, quantity and spatial orientation of RC on the lumbar spine were examined. The length and width of the RC were measured by a caliper. RESULTS: A total of 213 RC were found in the 8 cadavers in the lumbar region. RC were divided into three types: superficial rami (70, 32.86%), which penetrated the psoas major (PM) and ran above the aponeurosis of the PM; deep rami (125, 58.69%), which ran along the waist of the vertebral body beneath the aponeurosis of the PM; and discal rami, which ran over and adhered to the surface of the intervertebral disc. Superficial rami were divided into two subtypes: oblique rami (45, 21.13%) and parabolic rami (25, 11.74%), which crossed the vertebra and the disc in an oblique and a parabolic course, respectively. CONCLUSIONS: RC should play an important role in the innervation of the lumbar spine. Detailed knowledge of RC in the lumbar region may help surgeons improve the efficacy of infiltration and percutaneous radiofrequency as a supplementary treatment for DLBP.

An anatomical study of the origins courses and distributions of the transverse branches of lumbar arteries at the L1-L4 levels.

Pseudoaneurysms of the lumbar arteries following transforaminal lumbar interbody fusion (TLIF) are rare postoperative complications that usually occur around the transverse process. However, there are few detailed descriptions of the transverse branch and other branches of the dorsal branches at the L1-L4 disks. STUDY DESIGN: Ten adult embalmed cadavers were anatomically studied. OBJECTIVES: The purposes of the study were to describe the vascular distribution of the dorsal branches, especially the transverse branches, at the L1-L4 levels and provide information useful for TLIF. METHODS: Ten embalmed cadavers studied after their arterial systems were injected with red latex. The quantity, origin, pathway, distribution range and diameter of the branches were recorded and photographed. RESULTS: The transverse branch appeared in all 80 intervertebral foramina. The transverse branch was divided into 2 types: In type 1, the arteries divided into superior branches and inferior branches; the arteries in type 2 divided into 3 branches (superior, intermedius and inferior branches). CONCLUSIONS: The transverse branches of the dorsal arteries are common structures from L1 to L4, and 2 types of transverse branches were found. A thorough understanding of the dorsal branches, especially the transverse branches of the lumbar artery, may be very important for reducing both intraoperative bleeding during the surgery and the occurrence of pseudoaneurysms after transforaminal lumbar interbody fusion.

Skin chronological aging drives age-related bone loss via secretion of cystatin-A.

Although clinical evidence has indicated an association between skin atrophy and bone loss during aging, their causal relationship and the underlying mechanisms are unknown. Here we show that premature skin aging drives bone loss in mice. We further identify that cystatin-A (Csta), a keratinocyte-enriched secreted factor, mediates the effect of skin on bone. Keratinocyte-derived Csta binds the receptor for activated C-kinase 1 in osteoblast and osteoclast progenitors, thus promoting their proliferation but inhibiting osteoclast differentiation. Csta secretion decreases with skin aging in both mice and humans, thereby causing senile osteoporosis by differentially decreasing the numbers of osteoblasts and osteoclasts. In contrast, topical application of calcipotriol stimulates Csta production in the epidermis and alleviates osteoporosis. These results reveal a mode of endocrine regulation of bone metabolism in the skin, and identify Csta as an epidermally derived hormone linking skin aging to age-related bone loss. Enhancers of skin Csta levels could serve as a potential topical drug for treatment of senile osteoporosis.

A viroporin-like 2B protein of duck hepatitis A virus 1 that induces incomplete autophagy in DEF cells.

Duck hepatitis A virus 1 (DHAV-1) can cause high morbidity and fatal acute infectious hepatitis in ducklings, which seriously endangers animal husbandry. Viroporin is a small molecular weight hydrophobic transmembrane protein encoded by the virus, that has been suggested to induce autophagy in host cells by increasing the membrane permeability through disturbing the ion balance. In this study, we aimed to investigate whether the DHAV-1 2B protein can induce autophagy in DEF cells with a viroporin-like function. Bioinformatics analysis has indicated that the 2B protein is characterized by a viroporin domain, which is consistent with the type IA viroporin transmembrane protein. We experimentally confirmed that the 2B protein disturbed the Ca2+ balance of infected cells by elevating the intracellular Ca2+ concentration. Eukaryotic expression of the 2B protein upregulates the expression of microtubule-associated protein 1 light chain 3 II (LC3-II) and the number of autophagosomes in the cell. Interestingly, the Western Blot (WB) results showed that 2B protein expression induced less protein degradation of the autophagic substrate sequestosome 1 (SQSTM1/p62) than the positive control, while microscopy observations showed that the autophagosomes did not colocalize with the lysosomes. In summary, 2B protein expression induced autophagy in host cells, but the autophagic flow was incomplete. The results of this experiment are expected to provide reference scientific data for elucidating the infective and pathogenic mechanism of DHAV-1.