Suppression of YAP Ameliorates Cartilage Degeneration in Ankle Osteoarthritis via Modulation of the Wnt/ß-Catenin Signaling Pathway.

Ankle osteoarthritis is a relatively understudied condition and the molecular mechanisms involved in its development are not well understood. This investigation aimed to explore the role and underlying molecular mechanisms of Yes-associated protein (YAP) in rat ankle osteoarthritis. The results demonstrated that YAP expression levels were abnormally increased in the ankle osteoarthritis cartilage model. In addition, knockdown of YAP expression was shown to hinder the imbalance in ECM metabolism induced by IL-1ß in chondrocytes, as demonstrated by the regulation of matrix metalloproteinase (MMP)-3, MMP-9, and MMP-13, a disintegrin, metalloprotease with thrombospondin motifs, aggrecan, and collagen II expression. Additional studies revealed that downregulation of YAP expression markedly inhibited the overexpression of ß-catenin stimulated by IL-1ß. Furthermore, inhibition of the Wnt/ß-catenin signaling pathway reversed the ECM metabolism imbalance caused by YAP overexpression in chondrocytes. It is important to note that the YAP-specific inhibitor verteporfin (VP) significantly delayed the progression of ankle osteoarthritis. In conclusion, the findings highlighted the crucial role of YAP as a regulator in modulating the progression of ankle osteoarthritis via the Wnt/ß-catenin signaling pathway. These findings suggest that pharmacological inhibition of YAP can be an effective and critical therapeutic target for alleviating ankle osteoarthritis.

Comparison of rehabilitation outcomes between robot-assisted and freehand screw placement in treatment of femoral neck fractures: a systematic review and meta-analysis.

PURPOSE: To compare the postoperative rehabilitation of femoral neck fractures treated with robot-assisted nailing and freehand nailing. METHODS: We systematically searched the PubMed, EMBASE, Cochrane, China National Knowledge Infrastructure(CNKI), WanFang database, China Science and Technology Journal Database (VIP) and Web of Science databases to identify potentially eligible articles. Indispensable data such as the year of publication, country, study type, robot type, age, number of patients, sex distribution, study design, and outcome indicators were extracted. The outcome indicators of interest included healing rate, length of healing time, Harris score, operation time, frequency of X-ray fluoroscopy, frequency of guide pin insertion, and intraoperative blood loss. RevMan 5.4.1 was used for the meta-analysis. RESULTS: Fourteen studies with 908 participants were included in this meta-analysis. The results showed that in terms of healing rate (SMD = 2.75, 95% CI, 1.03 to 7.32, P = 0.04) and Harris score (SMD = 2.27, 95% CI, 0.79 to 3.75, P = 0.003), robot-assisted screw placement technique scores were higher than the traditional freehand technique. Additionally, operative time (SMD = -12.72, 95% CI, -19.74 to -5.70, P = 0.0004), healing time (SMD = -13.63, 95% CI, -20.18 to -7.08, P < 0.0001), frequency of X-ray fluoroscopy (SMD = - 13.64, 95% CI, - 18.32 to - 8.95, P < 0.00001), frequency of guide pin insertion (SMD = - 7.95, 95% CI, - 10.13 to - 5.76, P < 0.00001), and intraoperative blood loss (SMD = - 17.33, 95% CI, - 23.66 to - 11.00, P < 0.00001) were lower for patients who underwent robotic-assisted screw placement than those for patients who underwent the conventional freehand technique. CONCLUSION: Compared to the freehand nailing technique, robot-assisted nailing helps improve postoperative healing rates in patients with femoral neck fractures; shortens healing times; better restores hip function; reduces the number of intraoperative fluoroscopies, guides pin placements; reduces intraoperative bleeding; and increases perioperative safety.

Alterations in the microenvironment and the effects produced of TRPV5 in osteoporosis.

The pathogenesis of osteoporosis involves multiple factors, among which alterations in the bone microenvironment play a crucial role in disrupting normal bone metabolic balance. Transient receptor potential vanilloid 5 (TRPV5), a member of the TRPV family, is an essential determinant of the bone microenvironment, acting at multiple levels to influence its properties. TRPV5 exerts a pivotal influence on bone through the regulation of calcium reabsorption and transportation while also responding to steroid hormones and agonists. Although the metabolic consequences of osteoporosis, such as loss of bone calcium, reduced mineralization capacity, and active osteoclasts, have received significant attention, this review focuses on the changes in the osteoporotic microenvironment and the specific effects of TRPV5 at various levels.

Brain structural correlates of postoperative axial pain in degenerative cervical myelopathy patients following posterior cervical decompression surgery: a voxel-based morphometry study.

OBJECTIVE: To investigate the brain structural correlates of postoperative axial pain (PAP) in degenerative cervical myelopathy (DCM) following posterior cervical decompression surgery. METHODS: Structural images with high-resolution T1 weighting were collected from 62 patients with DCM and analyzed, in addition to 42 age/gender matched subjects who were healthy. Voxel-based morphometry (VBM) was analyzed, grey matter volume (GMV) was computed. One-way ANOVA was performed to reveal the GMV differences among DCM patients with PAP, patients without PAP and healthy controls (HC). Post-hoc analyses were conducted to identify the pair-wise GMV differences among these three groups. Analyses of correlations were conducted to uncover the link between clinical measurements and GMV variations. Last, support vector machine (SVM) was conducted to test the utility of GMV for classifying PAP and nPAP DCM patients. RESULTS: Three main findings were observed: [1] Compared to healthy controls, DCM patients showed a significantly lower GMV in the precuneus preoperatively. DCM patients with PAP also exhibited a lower GMV within precuneus than those without; [2] In DCM patients with PAP, the precuneus GMV was inversely related to the postoperative pain intensity; [3] Moreover, successful classification between PAP and nPAP were observed via SVM based on precuneus GMV as features. CONCLUSION: In summary, our results indicate that precuneus GMV may be linked to PAP in DCM, and could be employed to forecast the emergence of PAP in DCM patients.

A three-dimensional measurement study of fracture displacement in Garden I femoral neck fracture: a retrospective study.

BACKGROUND: Garden I femoral neck fractures are nondisplaced femoral neck fractures. Nonoperative treatment and in situ fixation are the preferred treatments. However, the postoperative outcome is not satisfactory and the incidence of complications remains high, which raises doubts about the accuracy of the diagnosis of nondisplaced Garden I fractures. Recently, three-dimensional (3D) reconstruction has been reported as a mature technology for reconstructing the bone structure of patients. We further extended this technique in the measurement of the fracture spatial displacement to verify the accuracy of Garden I femoral neck fractures. METHODS: This was a retrospective study of patients with Garden I femoral neck fractures from January 2013 to December 2018 at our institution, who were included according to specified criteria. A bilateral proximal femur model of each patient was established based on computed tomography (CT) data. The displacement of the deepest portion of the femoral head fovea, the displacement of the center of the femoral head and the rotation of the femoral head were measured in the bilateral model. RESULTS: A total of 102 patients diagnosed with Garden I fractures were included in this study. The cohort included 32 men and 70 women, with an average age of 55.88 ± 15.32 years. In these patients, the average displacement of the deepest portion of the femoral head fovea was 16.43 ± 7.69 mm. The minimum and maximum displacement was 3.58 and 44.32 mm, respectively. The average displacement of the center of the femoral head was 10.39 ± 5.47 mm and ranged from 2.16 to 34.42 mm. The rotational angle was 23.81 ± 10.15 ° and ranged from 3.71 ° to 61.19 °. CONCLUSIONS: Garden I fractures have large spatial displacement and cannot be considered incomplete or nondisplaced fractures. Therefore, we suggest that anatomical reduction should be considered during treatment.

Computer-aided design combined with 3D-printed osteotomy guide-assisted derotational distal femoral osteotomy for treating recurrent patellar dislocation with increased femoral anteversion angle: a retrospective study.

PURPOSE: Derotational distal femoral osteotomy (DDFO) has good clinical outcomes for the treatment of the recurrent patellar dislocation combined with increased femoral anteversion angle (FAA). Currently, there is no uniform surgical technique. The purpose of this study was to evaluate the safety and efficacy of computer-aided design (CAD) combined 3D-printed osteotomy guide-assisted DDFO for treating these patients. METHODS: In a retrospective study of 36 patients with recurrent patellar dislocation (RPD) from December 2017 to December 2020, all patients had increased FAA and underwent DDFO assisted by CAD combined with a 3D-printed osteotomy guide. Patients' radiological parameters were used to assess the correction of increased femoral torsion and preoperative and postoperative subjective scores were recorded to evaluate the knee function. Complications were recorded to determine the safety of the surgery. RESULT: A total of 36 knees were included in this study, with a mean follow-up time of 32.6 ± 8.1 months. The mean age of the patients was 24.9±4.4 years and all patients experienced patellar dislocation preoperatively with a mean of 5.7±3.2 times. The patients' femoral anteversion angle decreased from 35.03±3.05° preoperatively to 14.80±0.87°, and the TT-TG distance decreased from 20.03±1.27 mm preoperatively to 19.22±1.22 mm. The hip-knee-ankle (HKA) angle and Insall-Salvatti index were not significantly different postoperatively compared to preoperatively. The knee function scores and visual analogue scale at the last follow-up were significantly improved compared to the preoperative scores. No major complications such as redislocation, nonunion, fixation or graft failure, or infection were observed in any patients. CONCLUSION: Computer-aided design combined with 3D-printed osteotomy guide-assisted derotational distal femoral osteotomy could correct the increased anterior femoral torsion and demonstrate good results. There were no patients experienced re-dislocation during follow-up period and the overall complication rate is low.

[Application of micro-bolus injection and piezoelectric sensors to improve the safety of radiopharmaceuticals bolus injection].

Radiopharmaceutical dynamic imaging typically necessitates intravenous injection via the bolus method. However, manual bolus injection carries the risk of handling errors as well as radiological injuries. Hence, there is potential for automated injection devices to replace manual injection methods. In this study, the effect of micro-bolus pulse injection technology was compared and verified by radioactive experiments using a programmable injection pump, and the overall bubble recognition experiment and rat tail vein simulation injection verification were performed using the piezoelectric sensor preloading method. The results showed that at the same injection peak speed, the effective flushing volume of micro-bolus pulse flushing (about 83 µL/pulse) was 49.65% lower than that of uniform injection and 25.77% lower than that of manual flushing. In order to avoid the dilution effect of long pipe on the volume of liquid, the use of piezoelectric sensor for sealing preloading detection could accurately predict the bubbles of more than 100 µL in the syringe. In the simulated injection experiment of rat tail vein, when the needle was placed in different tissues by preloading 100 µL normal saline, the piezoelectric sensor fed back a large difference in pressure attenuation rate within one second, which was 2.78% in muscle, 17.28% in subcutaneous and 54.71% in vein. Micro-bolus pulse injection method and piezoelectric sensor sealing preloading method have application potential in improving the safety of radiopharmaceutical automatic bolus injection.

[Application of automatic injection device based on automatic hemostasis in injection of radiopharmaceutical bolus injection].

In clinical practice, radiopharmaceutical dynamic imaging technology requires the bolus injection method to complete injection. Due to the failure rate and radiation damage of manual injection, even experienced technicians still bear a lot of psychological burden. This study combined the advantages and disadvantages of various manual injection modes to develop the radiopharmaceutical bolus injector, and explored the application of automatic injection in the field of bolus injection from four aspects: radiation protection, occlusion response, sterility of injection process and effect of bolus injection. Compared with the current mainstream manual injection method, the bolus manufactured by the radiopharmaceutical bolus injector based on the automatic hemostasis method had a narrower full width at half maximum and better repeatability. At the same time, radiopharmaceutical bolus injector had reduced the radiation dose of the technician's palm by 98.8%, and ensured more efficient vein occlusion recognition performance and sterility of the entire injection process. The radiopharmaceutical bolus injector based on automatic hemostasis has application potential in improving the effect and repeatability of bolus injection.

Identification and functional analysis of LncRNA-XIST ceRNA network in prostate cancer.

BACKGROUND: Long non-coding RNAs (lncRNAs) play a functional role in the progression of prostate cancer (PCa). However, the molecular mechanism, expression, or function of the lncRNA XIST in PCa is not well understood. Therefore, the major goal of this study was to investigate the involvement of XIST in PCa. METHODS: We used the The Cancer Genome Atlas (TCGA) database to conduct a pan-cancer bioinformatics analysis of XIST and identified that it may play an important role in prostate cancer. This finding was verified using clinical samples and in vitro assays. Finally, we constructed an XIST ceRNA network for prostate cancer. RESULTS: Our in vitro and in vivo results showed that the XIST gene expression level was higher in PCa derived cells and tissues compared to that in normal cells and tissues. XIST gene expression level was positively correlated with the invasion and proliferation of tumour cells. Furthermore, the downregulation of XIST inhibited the growth of subcutaneous 22Rv1 xenografts in nude mice. In addition, we constructed a XIST ceRNA network. Consistent with previous studies, we found that the role of XIST is mediated through via sponges, such as miRNA -96-5p, miRNA -153-3p, and miRNA-182-5p. CONCLUSION: High expression level of XIST can lead to enhanced carcinogenicity in PCa. Therefore, XIST has the potential to be used as a prognostic marker and may become a new research focus for the treatment of PCa.

Pulse Electromagnetic Field for Treating Postmenopausal Osteoporosis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Postmenopausal osteoporosis is a type of chronic disease with high morbidity and high economic burden. Due to the adverse effects of long-term drug therapy, physical therapy, such as pulsed electromagnetic fields (PEMF), is widely implemented in clinical practice. Therefore, we first conducted the meta-analysis on the efficacy and safety of PEMF in the treatment of postmenopausal osteoporosis. We searched eight databases to acquire potentially eligible studies. Outcome indicators include bone mineral density (BMD), visual analogue scale (VAS), biochemical markers of alkaline phosphatase (ALP), osteocalcin, bone-specific alkaline phosphatase (BSAP), type I collagen carboxy-terminal peptide (CTX), and adverse events. The results showed that a total of 19 studies (1303 patients) were retrieved from eight databases. Compared with conventional medications, PEMF combined with conventional medications significantly increased BMD of lumbar vertebra, femoral, Ward's triangle, bone-specific biochemical indicators of ALP, BSAP, and osteocalcin, and relieved pain. However, The incidence of adverse events was not statistically significant between PEMF combined with conventional medications and conventional medications alone. Compared with conventional medications, PEMF significantly increased the BMD of the femur and reduced the degree of pain, but there was no statistical difference in the BMD of the lumbar spine between PEMF and placebo. Except osteocalcin, BSAP, CTX, and ALP showed no significant difference. In view of its efficacy and safety, PEMF intervention can be considered as a potentially effective complementary therapy for postmenopausal women with osteoporosis. © 2022 Bioelectromagnetics Society.

Intra-articular opening wedge osteotomy for varus ankle arthritis with computer-assisted planning and patient-specific surgical guides: a retrospective case series.

BACKGROUND: Computer-assisted preoperative planning, combined with PSI has become an effective technique for treating complex limb deformities. The purpose of this study was to evaluate the efficacy and safety of the novel technique in corrective osteotomy for intra-articular varus ankle deformities associated with osteoarthritis and ankle instability. METHODS: Nineteen patients with intra-articular varus ankle arthritis were reviewed between April 2017 and June 2019, including ten men and nine women with a mean age of 58.3 ± 9.9 years (range, 38 to 76 years). All patients underwent intra-articular opening wedge osteotomy assisted by 3D virtual planning and PSI. Weight-bearing radiographs were used to assess the radiographic results, including TAS angle, TT angle, TMM angle, TC angle, TLS angle, opening-wedge angle, and wedge height. Functional outcomes were assessed by the AOFAS score, VAS score, and ROM of the ankle. RESULTS: The average follow-up time was 32.2 ± 9.0 months (range, 22 to 47 months). The average union time was 4.4 ± 0.9 months (range, 3.0 to 6.5 months). The TAS angle significantly changed from 84.1 ± 4.6° preoperatively to 87.7 ± 3.1° at the 1-year follow-up and 86.2 ± 2.6° at the latest follow-up. Similarly, the TT angle, TMM angle and TC angle changed significantly at the 1-year follow-up compared with the preoperative assessment and remained stable until the last follow-up. However, the TLS was not corrected significantly. The postoperative obtained opening-wedge angle, and wedge height showed no significant change with preoperative planning. The overall complication rate was 15.8%. The mean VAS score improved from 5.3 ± 0.6 to 2.7 ± 0.7. The mean AOFAS score improved from 56.2 ± 7.6 to 80.6 ± 4.6. However, the ROM showed no significant change. CONCLUSIONS: Accurate correction and satisfactory functional recovery were attained with computer-assisted planning and PSI in the corrective osteotomy of intra-articular varus ankle deformities.

Application of laser speckle blood perfusion imaging in the evaluation of erectile function in rats.

Intracavernosal pressure measurement is the gold standard for evaluating erectile function in experimental animals, but it has the shortcoming of being invasive. This study aimed to explore the application of laser speckle perfusion imaging in evaluating erectile function in rats. Sixty Sprague Dawley rats were randomly divided into the sham operation and model groups (n = 30 each). A rat model of neuroinjury erectile dysfunction was established by surgically damaging the bilateral cavernous nerves in the model group. Simulated surgery was performed in the sham operation group; the nerves were not damaged. Erectile function was evaluated by comparing the changes in intracavernosal pressure and blood flow fluctuations when the cavernous nerve was stimulated using the same voltage parameters. Intracavernosal pressure in the model group was significantly lower than that in the other group when using 2.5 V. No significant difference was found in cavernous blood flow fluctuation between the two groups when using 0.5 V. Cavernous blood flow fluctuation in the model group after 2.5 V, 5 V and 7.5 V stimulations was significantly lower than that in the sham operation group. Evaluating erectile function in rats is feasible by measuring the cavernous blood flow using laser speckle perfusion imaging.

[Research advances in photoactivatable CRISPR gene editing technology].

Since the emergence of CRISPR/Cas9, gene editing technologies have attracted increasing attention, in particular type II systems, in which nucleases consist of only a single protein. The effectors include type II Cas9, type V Cas12 and type VI Cas13, which allow precise genomic DNA or RNA editing. Catalytically inactive CRISPR/Cas9 can also be used as a platform to recruit effectors such as transcription factors, epigenetic factors, and/or base modification enzymes to target gene loci. On the other hand, optogenetics offers spatial, temporal, and reversible control of biological processes. CRISPR and optogenetics can enable precise gene editing in vitro and in vivo at the spatiotemporal level, which has a broad applicability in biology and medicine. This article has provided a review for the research advance in photoactivatable CRISPR systems, with details for the design and application of such tools and a discussion over the limitations of the current methods, which may shed light on this emerging field.

Administration of tauroursodeoxycholic acid attenuates dexamethasone-induced skeletal muscle atrophy.

Glucocorticoids are known to induce skeletal muscle atrophy by suppressing protein synthesis and promoting protein degradation. Tauroursodeoxycholic acid (TUDCA) has beneficial effects in several diseases, such as hepatobiliary disorders, hindlimb ischemia and glucocorticoid-induced osteoporosis. However, the effects of TUDCA on glucocorticoid -induced skeletal muscle atrophy remains unknown. Therefore, in the present research, we explored the effects of TUDCA on dexamethasone (DEX)-induced loss and the potential mechanisms involved. We found TUDCA alleviated DEX-induced muscle wasting in C2C12 myotubes, identified by improved myotube differentiation index and expression of myogenin and MHC. And it showed that TUDCA activated the Akt/mTOR/S6K signaling pathway and inhibited FoxO3a transcriptional activity to decreased expression of MuRF1 and Atrogin-1, while blocking Akt by MK2206 blocked these effects of TUDCA on myotubes. Besides, TUDCA also attenuated DEX-induced apoptosis of myotubes. Furthermore, TUDCA was administrated to the mouse model of DEX-induced skeletal muscle atrophy. The results showed that TUDCA improved DEX-induced skeletal muscle atrophy and weakness (identified by increased grip strength and prolonged running exhaustive time) in mice by suppression of apoptosis, reduction of protein degradation and promotion of protein synthesis. Taken together, our research proved for the first time that TUDCA protected against DEX-induced skeletal muscle atrophy not only by improving myogenic differentiation and protein synthesis, but also through decreasing protein degradation and apoptosis of skeletal muscle.

Prevalence and associated factors of erectile dysfunction, psychological disorders, and sexual performance in primary vs. secondary infertility men.

BACKGROUND: Many infertile couples might experience erectile dysfunction (ED) and significant changes in the quality of sexual life and psychological state though information is limited in secondary infertile men in China. To determine whether primary or secondary infertility is associated with ED, psychological disorders, and sexual performance. METHODS: This was a cross-sectional survey conducted at the Dongzhimen Hospital of Beijing University of Chinese Medicine (06/2019-01/2020). The participants completed a questionnaire including general information, sexual life, simplified International Index of Erectile Function (IIEF-5), Patient Health Questionnaire-9 (PHQ-9), and 7-item Generalized Anxiety Disorder Scale (GAD-7). Multivariable logistic regression was used to identify the factors associated with ED, depression, and anxiety. RESULTS: ED was more frequent in secondary vs. primary infertility (46.5 % vs. 26.7 %, P < 0.001). Compared with men with primary infertility, those with secondary infertility showed lower IIEF-5 scores (P < 0.001), higher occurrence of TOIF (P = 0.001), had a higher awareness of partner's ovulation when having ED (P = 0.001), lower GAD-7 scores (P = 0.016), lower libido (P = 0.005), fewer intercourses per month (P = 0.001) and a lower sexual satisfaction score (P = 0.027). In the multivariate analysis, primary infertility was found to be an independent risk factor of anxiety (OR: 1.812, 95 %CI: 1.015-3.236). Some overlap is observed in factors associated with ED, psychological disorders, and sexual performance between primary and secondary infertility, but some factors are distinct. CONCLUSIONS: The prevalence of ED in secondary infertility men was higher than that of primary infertility men, and the quality of sexual life was decreased. Primary infertility is an independent risk factor of anxiety.

Severe Guillain-Barré syndrome after surgery for multiple fractures: a rare case report with a 5-year follow-up and a brief review of the literature.

BACKGROUND: Guillain-Barré syndrome (GBS) is the most common and serious acute paralytic neuropathy and is usually caused by infection. It is thought to be the result of an aberrant response of the immune system. To our knowledge, GBS, especially severe GBS, after orthopaedic surgery has rarely been reported. CASE PRESENTATION: We herein report the case of a 58-year-old man who developed quadriplegia and respiratory failure on the 6th day after surgery for multiple fractures. The patient had no symptoms of respiratory or gastrointestinal tract infection within 4 weeks before the onset. The white blood cell count was normal, and there was no redness, swelling, heat or pain in the surgical incision. Brain, cervical and thoracic magnetic resonance imaging were normal, albuminocytological dissociation was found on cerebrospinal fluid examination, and electrophysiological examination showed that sensory and motor nerve evoked potentials could not be elicited. A diagnosis of post-traumatic GBS was made, and the patient was treated with intravenous immunoglobulin and plasma exchange, as well as supportive care and rehabilitation exercise. The length of stay was 18 months, and the in-hospital-related costs amounted to $127,171. At the last follow-up, the patient had recovered only grade 3 power in the upper limbs and grade 2 power in the lower limbs. CONCLUSIONS: Severe GBS is a rare complication after orthopaedic surgery. When progressive weakness occurs in trauma patients, the possibility of GBS should be considered, and cerebrospinal fluid and electrophysiological examinations should be performed in a timely manner. For patients with severe GBS after trauma, the treatment costs may be high, and the prognosis may be poor.

Enhanced effects of salidroside on erectile function and corpora cavernosa autophagy in a cavernous nerve injury rat model.

We explored the efficacy and mechanisms of salidroside treatment for erectile dysfunction induced by bilateral cavernous nerve injury (BCNI). Forty male rats were divided into four groups as follows: sham (cavernous nerves exposed only) (S); BCNI (M); BCNI + rapamycin (M + rapamycin); and BCNI + salidroside (M + salidroside). Erectile function in the rats was measured by intracavernosal pressure. Penile tissue was harvested for transmission electron microscopy, immunohistochemistry, immunofluorescence, Masson's trichrome staining, haematoxylin-eosin staining, TdT-mediated dUTP Nick End Labeling and western blotting. The M group exhibited a decrease in erectile responses and increased apoptosis and fibrosis compared to these in the S group. Meanwhile, nerve content and the penile atrophy index were also decreased in the M group. Treatment with salidroside and rapamycin for 3 weeks partially restored erectile function and significantly attenuated corporal apoptosis, fibrosis, nerve content and penile atrophy in the M group. Moreover, the autophagy level was further enhanced in the M + salidroside group, which was the same as that in the positive observation group (M + rapamycin). Salidroside treatment not only improved erectile function in rats with BCNI, but also inhibited apoptosis and fibrosis and ameliorated the loss of nerve content and endothelial and corpus cavernosum smooth muscle cells by promoting protective autophagy.

Human umbilical cord mesenchymal stem cell-derived exosomes act via the miR-1263/Mob1/Hippo signaling pathway to prevent apoptosis in disuse osteoporosis.

Disuse osteoporosis (DOP) is a common complication resulting from the lack of or disuse of mechanical loading and has been unsatisfactorily treated. We hypothesized that exosomes derived from human umbilical cord mesenchymal stem cells (HUCMSCs) could reduce bone marrow mesenchymal stem cell (BMSC) apoptosis in rat DOP via the miR-1263/Mob1/Hippo signaling pathway. To evaluate the function of exosomes derived from HUCMSCs (HUCMSC-Exos) in DOP, hind limb unloading (HLU)-induced DOP rat models were prepared. In vitro, the proliferation of BMSCs were evaluated using CCK-8 assays. Further, the apoptosis of BMSCs were evaluated using annexin V-FITC assay and Western blots. In vivo, the protective effects of HUCMSC-Exos were evaluated using HE staining and microCT analysis. The underlying molecular mechanism of exosome action on BMSC apoptosis through the miR-1263/Mob1/Hippo pathway was also investigated by high-throughput RNA sequencing, luciferase reporter assays, RNA-pull down assays and Western blots. The RNA-seq and q-PCR results showed that the level of miR-1263 was most abundant among differentially expressed microRNAs. Exosomal miR-1263 could bind to the 3'untranslated region (3' UTR) of Mob1 and exert its function by directly targeting Mob1 in recipient cells. The inhibition of Mob1 could activate YAP expression. Hippo inhibition reversed the in vitro HLU-induced apoptotic effect on BMSCs. The microCT and HE staining results indicated that HUCMSC-Exos ameliorated DOP in vivo. Exosomes derived from HUCMSCs are effective at inhibiting BMSC apoptosis and preventing rat DOP. This mechanism is mediated by the miR-1263/Mob1/Hippo signaling pathway.

Photoactivatable RNA N6 -Methyladenosine Editing with CRISPR-Cas13.

RNA has important and diverse biological roles, but the molecular methods to manipulate it spatiotemporally are limited. Here, an engineered photoactivatable RNA N6 -methyladenosine (m6 A) editing system with CRISPR-Cas13 is designed to direct specific m6 A editing. Light-inducible heterodimerizing proteins CIBN and CRY2PHR are fused to catalytically inactive PguCas13 (dCas13) and m6 A effectors, respectively. This system, referred to as PAMEC, enables the spatiotemporal control of m6 A editing in response to blue light. Further optimization of this system to create a highly efficient version, known as PAMECR , allows the manipulation of multiple genes robustly and simultaneously. When coupled with an upconversion nanoparticle film, the optogenetic operation window is extended from the visible range to tissue-penetrable near-infrared wavelengths, which offers an appealing avenue to remotely control RNA editing. These results show that PAMEC is a promising optogenetic platform for flexible and efficient targeting of RNA, with broad applicability for epitranscriptome engineering, imaging, and future therapeutic development.

Association between obesity-associated markers and semen quality parameters and serum reproductive hormones in Chinese infertile men.

BACKGROUND: The current evidence on the association between obesity-associated markers and semen quality, serum reproductive hormones and lipids remains inconsistent. In this study, we tested the hypothesis that, in infertile Chinese men, body mass index (BMI) negatively correlates with sperm concentration, serum total testosterone (TT), and high-density lipoprotein cholesterol (HDL-C). The relationship between other obesity-associated markers and semen quality parameters, serum reproductive hormones, lipids and leptin were also investigated. METHODS: 181 Chinese infertile men were recruited from September 2018 to September 2019. Their obesity-associated markers, semen parameters, and serum reproductive hormones, lipids and leptin were detected. Statistical analysis was performed to assess the relationship between obesity-associated markers and semen quality, serum reproductive hormones, lipids and leptin. RESULT(S): Statistically negative correlation was found between other obesity-associated markers (e.g. waist-to-hip ratio and waist-to-height ratio) and semen parameters (e.g. sperm concentration, ratio of progressive motility and ratio of non-progressive motility), while no significant correlation was found between BMI and semen quality, serum reproductive hormones, lipids and leptin. Ratio of morphologically normal sperm was negatively correlated with serum lipids including total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), leptin and seminal superoxide dismutase. Ratio of progressive sperm, sperm concentration and ratio of morphologically normal sperm exhibited significantly lower values in overweight group than normal group. Estradiol (E2) and E2/TT were significantly higher in obese group than normal group, while TT level was significantly lower in obese group than normal group. Univariate and multivariate analysis indicated that TC was significantly associated with BMI. Serum leptin concentration was positively correlated with seminal leptin concentration in overweight and obese groups. CONCLUSION(S): No significant correlation was found between BMI and sperm concentration, serum TT and HDL-C, while other obesity-associated markers were found to negatively correlate with sperm concentration, ratio of progressive motility and ratio of non-progressive motility. Statistically significant correlations between serum reproductive hormones, lipids and leptin also existed in Chinese infertile men.