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Charcot arthropathy is a rare disease in clinic, which is easy to be misdiagnosed and delayed diagnosis. Imaging examination plays a key role in the diagnosis of Charcot arthropathy. It is important to improve the early diagnosis rate and strive for early treatment to improve the quality of life of these patients. Here we reported a rare case of charcot knee (CK) accompanied by tethered cord syndrome and lumbosacral fur sinus, who presented with joint destruction, joint deformity and multiple free bodies and received joint free bodies removal and joint replacement surgery with acceptable short and midterm follow-up results.
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Skeletal muscle aging in rats is a reduction in skeletal muscle mass caused by a decrease in the number or volume of skeletal muscle myofibers. Apoptosis has been recognized to play a key role in accelerating the process of skeletal muscle aging in rats. The thioredoxin (Trx) system is a widely expressed oxidoreductase system that controls the cellular reduction/oxidation state and has both potent anti-free radical damage and important pro-growth and apoptosis inhibitory functions. Previous studies have shown that exercise delays skeletal muscle aging. However, it is unclear whether exercise attenuates skeletal muscle aging via the Trx system. Therefore, the present study used the Trx system as an entry point to explore the effect of aerobic exercise to improve skeletal muscle aging in rats and its possible mechanisms, and to provide a theoretical basis for exercise to delay skeletal muscle aging in rats. It was shown that aerobic exercise in senescent rats resulted in increased gastrocnemius index, decreased body weight, increased endurance, decreased skeletal muscle cell apoptosis, increased activity and protein expression of the Trx system, and decreased expression of p38 and ASK1. Based on these findings, we conclude that 10 weeks of aerobic exercise may enhance the anti-apoptotic effect of Trx by up-regulating Trx and Trx reductase (TR) protein expression, which in turn increases Trx activity in rat skeletal muscle, and ultimately alleviates apoptosis in senescent skeletal muscle cells.
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Envelhecimento , Apoptose , Músculo Esquelético , Condicionamento Físico Animal , Tiorredoxinas , Animais , Músculo Esquelético/fisiologia , Músculo Esquelético/metabolismo , Masculino , Tiorredoxinas/metabolismo , Condicionamento Físico Animal/fisiologia , Envelhecimento/fisiologia , Ratos , MAP Quinase Quinase Quinase 5/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Ratos Sprague-Dawley , Tiorredoxina Dissulfeto Redutase/metabolismo , Resistência Física/fisiologiaRESUMO
The differentiation of bone marrow stromal cells (BMSCs) into Schwann-like cells (SCLCs) has the potential to promote the structural and functional restoration of injured axons. However, the optimal induction protocol and its underlying mechanisms remain unclear. This study aimed to compare the effectiveness of different induction protocols in promoting the differentiation of rat BMSCs into SCLCs and to explore their potential mechanisms. BMSCs were induced using two distinct methods: a composite factor induction approach (Protocol-1) and a conditioned culture medium induction approach (Protocol-2). The expression of Schwann cells (SCs) marker proteins and neurotrophic factors (NTFs) in the differentiated cells was assessed. Cell proliferation and apoptosis were also measured. During induction, changes in miR-21 and Sprouty RTK signaling antagonist 2 (SPRY2) mRNA were analyzed. Following the transfection of BMSCs with miR-21 agomir or miR-21 antagomir, induction was carried out using both protocols, and the expression of SPRY2, ERK1/2, and SCs marker proteins was examined. The results revealed that NTFs expression was higher in Protocol-1, whereas SCs marker proteins expression did not significantly differ between the two groups. Compared to Protocol-1, Protocol-2 exhibited enhanced cell proliferation and fewer apoptotic and necrotic cells. Both protocols showed a negative correlation between miR-21 and SPRY2 expression throughout the induction stages. After induction, the miR-21 agomir group exhibited reduced SPRY2 expression, increased ERK1/2 expression, and significantly elevated expression of SCs marker proteins. This study demonstrates that Protocol-1 yields higher NTFs expression, whereas Protocol-2 results in stronger SCLCs proliferation. Upregulating miR-21 suppresses SPRY2 expression, activates the ERK1/2 signaling pathway, and promotes BMSC differentiation into SCLCs.
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Diferenciação Celular , Células-Tronco Mesenquimais , MicroRNAs , Células de Schwann , Animais , Ratos , Apoptose/genética , Diferenciação Celular/genética , Proliferação de Células/genética , Células Cultivadas , Meios de Cultivo Condicionados/farmacologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/metabolismo , MicroRNAs/genética , Fatores de Crescimento Neural/metabolismo , Fatores de Crescimento Neural/genética , Proteínas do Tecido Nervoso , Ratos Sprague-Dawley , Células de Schwann/metabolismo , Células de Schwann/citologiaRESUMO
OBJECTIVE: The purpose of present study was to comprehensívely explore the efficacy and safety of prothrombín complex concentrate (PCC) to treat massíve bleedíng in patíents undergoing cardiac surgery. METHODS: PubMed®, Embase, and Cochrane Líbrary databases were searched for studíes ínvestigating PCC administratíon duríng cardiac surgery published before September 10, 2022. Mean dífference (MD) wíth 95% confidence interval (CI) was applíed to analyze continuous data, and dichotomous data were analyzed as risk ratio (RR) with 95% CI. RESULTS: Twelve studies were included in the meta-analysis. Compared with other non-PCC treatment regimens, PCC was not assocíated with elevated mortality (RR=1.18, 95% CI=0.86-1.60, P=0.30, I2=0%), shorter hospital stay (MD=-2.17 days; 95% CI=-5.62-1.28, P=0.22, I2=91%), reduced total thoracic drainage (MD=-67.94 ml, 95% CI=-239.52-103.65, P=0.44, I2=91%), thromboembolíc events (RR=1.10, 95% CI=0.74-1.65, P=0.63, I2=39%), increase ín atríal fibríllatíon events (RR=0.73, 95% CI=0.52-1.05, P=0.24, I2=29%), and myocardial infarction (RR=1.10, 95% CI=0.80-1.51, P=0.57, I2=81%). However, PCC use was associated with reduced intensive care unit length of stay (MD=-0.81 days, 95% CI=-1.48- -0.13, P=0.02, I2=0%), bleeding (MD=-248.67 ml, 95% CI=-465.36- -31.97, P=0.02, I2=84%), and intra-aortic balloon pump/extracorporeal membrane oxygenation (RR=0.65, 95% CI=0.42-0.996, P=0.05, I2=0%) when compared with non-PCC treatment regimens. CONCLUSION: The use of PCC in cardiac surgery did not correlate with mortality, length of hospítal stay, thoracic drainage, atríal fibríllatíon, myocardíal ínfarction, and thromboembolíc events. However, PCC sígnificantly improved postoperatíve intensíve care unít length of stay, bleedíng, and intra-aortic balloon pump/ extracorporeal membrane oxygenation outcomes ín patients undergoing cardíac surgery.
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Fatores de Coagulação Sanguínea , Procedimentos Cirúrgicos Cardíacos , Humanos , Fatores de Coagulação Sanguínea/uso terapêutico , Tempo de Internação , Hemostasia/efeitos dos fármacosRESUMO
BACKGROUND: The impact of various exercise modalities on the improvement of sleep quality in adults remains controversial. OBJECTIVE: This study aimed to perform a network meta-analysis to analyze the effects of different exercise interventions on sleep quality in adults. METHODS: The PubMed, Cochrane, Embase, Web of Science, and EBSCO databases were searched for studies published from March 18, 1993, to March 18, 2023. The Cochrane risk of bias tool was used to assess the quality of the included studies. Then, a random-effects network meta-analysis was conducted within a frequentist framework. RESULTS: A total of 2142 participants from 27 randomized controlled trials were included in the analysis. Exercise modalities such as Pilates, yoga, and traditional Chinese exercises were found to significantly improve sleep quality when compared to a no-exercise control group, with Pilates exhibiting the most potent effect at a 95.3% improvement level. CONCLUSION: This study demonstrates that exercise interventions are effective in enhancing sleep quality in adults. Adapting exercise to individual preferences and needs may maximize the sleep-related benefits of the activity. REGISTRATION: The review was registered with PROSPERO, registration number CRD42023434565.
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Exercício Físico , Metanálise em Rede , Qualidade do Sono , Humanos , Exercício Físico/fisiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto , Terapia por Exercício/métodos , YogaRESUMO
Various preclinical and a limited number of clinical studies of CAR-NK cells have shown promising results: efficient elimination of target cells without side effects similar to CAR-T therapy. However, the homing and infiltration abilities of CAR-NK cells are poor due to the inhibitory tumor microenvironment. From the perspective of clinical treatment strategies, combined with the biological and tumor microenvironment characteristics of NK cells, CAR-NK combination therapy strategies with anti-PD-1/PD-L1, radiotherapy and chemotherapy, kinase inhibitors, proteasome inhibitors, STING agonist, oncolytic virus, photothermal therapy, can greatly promote the proliferation, migration and cytotoxicity of the NK cells. In this review, we will summarize the targets selection, structure constructions and combinational therapies of CAR-NK cells for tumors to provide feasible combination strategies for overcoming the inhibitory tumor microenvironment and improving the efficacy of CAR-NK cells.
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Background: The application of chimeric antigen receptor (CAR) NK cells in solid tumors is hindered by lack of tumor-specific targets and inefficient CAR-NK cell efficacy. Claudin-6 (CLDN6) has been reported to be overexpressed in ovarian cancer and may be an attractive target for CAR-NK cells immunotherapy. However, the feasibility of using anti-CLDN6 CAR-NK cells to treat ovarian cancer remains to be explored. Methods: CLDN6 expression in primary human ovarian cancer, normal tissues and cell lines were detected by immunohistochemistry and western blot. Two types of third-generation CAR NK-92MI cells targeting CLDN6, CLDN6-CAR1 NK-92MI cells with domains containing self-activated elements (NKG2D, 2B4) and CLDN6-CAR2 NK-92MI cells with classical domains (CD28, 4-1BB) were constructed by lentivirus transfection, sorted by flow cytometry and verified by western blot and qPCR. OVCAR-3, SK-OV-3, A2780, Hey and PC-3 cells expressing the GFP and luciferase genes were transduced. Subcutaneous and intraperitoneal tumor models were established via NSG mice. The ability of CLDN6-CAR NK cells to kill CLDN6-positive ovarian cancer cells were evaluated in vitro and in vivo by live cell imaging and bioluminescence imaging. Results: Both CLDN6-CAR1 and CLDN6-CAR2 NK-92MI cells could specifically killed CLDN6-positive ovarian cancer cells (OVCAR-3, SK-OV-3, A2780 and Hey), rather than CLDN6 negative cell (PC-3), in vitro. CLDN6-CAR1 NK-92MI cells with domains containing self-activated elements (NKG2D, 2B4) exhibited stronger cytotoxicity than CLDN6-CAR2 NK-92MI cells with classical domains (CD28, 4-1BB). Furthermore, CLDN6-CAR1 NK cells could effectively eliminate ovarian cancer cells in subcutaneous and intraperitoneal tumor models. More importantly, CAR-NK cells combined with immune checkpoint inhibitors, anti-PD-L1, could synergistically enhance the antitumor efficacy of CLDN6-targeted CAR-NK cells. Conclusions: These results indicate that CLDN6-CAR NK cells possess strong antitumor activity and represent a promising immunotherapeutic modality for ovarian cancer.
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Claudinas , Neoplasias Ovarianas , Receptores de Antígenos Quiméricos , Humanos , Animais , Camundongos , Feminino , Receptores de Antígenos Quiméricos/genética , Neoplasias Ovarianas/terapia , Neoplasias Ovarianas/metabolismo , Linhagem Celular Tumoral , Apoptose , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , Antígenos CD28/metabolismo , Células Matadoras Naturais , Imunoterapia/métodos , Imunoterapia Adotiva/métodosRESUMO
BACKGROUND: Chronic diseases such as chronic obstructive pulmonary disease (COPD) have been linked to low levels of physical activity (PA) and higher frequency of leisure sedentary behavior (LSB). The main causes of COPD include respiratory and peripheral muscle dysfunction, low levels of PA, and LSB which are associated with a higher risk of developing COPD. The attribution relationship between PA or LSB and COPD risk or COPD respiratory insufficiency is unclear. To explore this further, we conducted a Mendelian randomization (MR) study using a genotype-simulated randomized trial group to systematically evaluate the causal relationships of PA/LSB on COPD risk and respiratory insufficiency. METHODS: The exposure data were obtained from large-scale genome-wide association studies (GWAS), including the PA dataset (N = 729,373) and LSB dataset (N = 1,109,337). The outcome data were derived from the Finn-Gen COPD dataset (N = 381,392). The causal effects were estimated with IVW1, MR-Egger, and WM2. Sensitivity analysis was conducted using Cochran's Q test, MR-Egger intercept test, MR-PRESSO3, leave-one-out analysis, and funnel plot to estimate the robustness of our findings. RESULTS: Genetically predicted leisure television (TV) watching significantly increased the risk of COPD (OR = 2.4895, 95 % CI: 1.85259 to 3.34536; P = 1.44 × 10-9) and COPD respiratory insufficiency (OR = 2.55, 95 % CI: 1.53 to 4.27; P = 3.54 × 10-4). No casual effect of other PA or LSB phenotypes on COPD risk or respiratory insufficiency was observed. CONCLUSION: Our study provides evidence that TV watching may increase the risk of COPD and its related respiratory insufficiency. These findings emphasized the importance of promoting regular physical exercise and reducing leisure sedentary behavior to prevent COPD.
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Doença Pulmonar Obstrutiva Crônica , Insuficiência Respiratória , Humanos , Comportamento Sedentário , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Exercício Físico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/genética , Atividades de LazerRESUMO
Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important pathogens affecting the swine industry. In this report, a novel PRRSV strain SXht2012 was isolated from Shanxi province in China. To identify genetic characteristics of SXht2012, we conducted phylogenetic and homology analyses after sequencing its complete genome. The results revealed that SXht2012 belonged to NADC30-like strain and shared 91.3% nucleotide (nt) identity with strain NADC30. Notably, sequence alignment showed that a distinctive feature in the NSP2 region, where a 131-amino acid (aa) deletion was found in the hypervariable region (HVR). Additionally, variations were also detected in the GP5 protein, specifically in the decoy peptide, T cell peptide, and a potential glycosylation site (aa 32). Furthermore, we also found that SXht2012 was likely a recombination virus originating from NADC30-like and JXA1-like strains, and three recombination breakpoints were identified in the genome at nt positions 1516, 5280 and 6851, which correspond to the NSP2, NSP3, and NSP7 regions. Overall, these findings have significant implications for understanding the genetic variation and evolutionary dynamics of PRRSV strains.
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Filogenia , Síndrome Respiratória e Reprodutiva Suína , Vírus da Síndrome Respiratória e Reprodutiva Suína , Vírus da Síndrome Respiratória e Reprodutiva Suína/genética , Animais , China , Suínos , Síndrome Respiratória e Reprodutiva Suína/virologia , Genoma Viral , Sequência de AminoácidosRESUMO
[This corrects the article DOI: 10.1371/journal.ppat.1006851.].
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BACKGROUND: To observe morphologic and functional changes in meibomian glands in pediatric patients with and without lower eyelid epiblepharon. METHODS: In this prospective observation study, 55 eyes of 55 patients( 24 males, 31 females; mean age ± SD,9.82 ± 2.59 years; range 6-14 years) and 60 eyes of 60 controls ( 32 males, 28 females; mean age ± SD,10.57 ± 2.75 years; range 6-14 years) were included. The following tests were performed: eyelid margin abnormality by slit-lamp examination, measurement of noninvasive keratographic break-up time (NIKBUT), grading of absence of meibomian gland (meibography score) assessed with noncontact meibography, morphologic changes of meibomian glands (thinning, dilatation and distortion), tear production by the Schirmer 1 test, and grading of meibum quality and meibomian gland expressibility. RESULTS: The morphologic changes in meibomian glands were more common in the epiblepharon group (56.36%) than in the control group (28.33%) (p = 0.002). The meibum quality was worse in the epiblepharon group than in the control group (p = 0.009), and the NIKBUT was significantly shorter in the epiblepharon group than in the control group (p = 0.012). There was no significant difference in the Schirmer 1 test, meibomian gland expressibility, eyelid margin abnormality score or total meibography score between the two groups. Morphologic changes in the meibomian glands in the upper eyelids (38.18%) were more common than those in the lower eyelids (20%) (p = 0.036) in the epiblepharon group, and the meibography score was higher in the upper eyelids than in the lower eyelids (p = 0.001). CONCLUSION: There are morphological and functional changes in meibomian glands in pediatric patients with lower eyelid epiblepharon. Although the inverted eyelashes were located in the lower eyelid, morphological changes in the meibomian glands were more common in the upper eyelid.
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Síndromes do Olho Seco , Doenças Palpebrais , Criança , Feminino , Humanos , Masculino , Síndromes do Olho Seco/diagnóstico , Doenças Palpebrais/diagnóstico , Glândulas Tarsais/diagnóstico por imagem , Exame Físico , Estudos Prospectivos , Microscopia com Lâmpada de Fenda , Lágrimas , AdolescenteRESUMO
This study was designed to explore the expression changes of P2Y1 receptors in the distal colonic myenteric layer of rats. An opioid induced constipation(OIC) rat model was generated by intraperitoneal (i.p) injection of loperamide. At 7 days post-treatment, the model rats were assessed by calculating the fecal water content and the gastrointestinal transit ratio. The immunofluorescence (IF)-based histochemical study was used to observe the distribution of P2Y1 receptors in the distal colonic myenteric plexus. Western blotting (WB) was performed to evaluate the expression changes of P2Y1 proteins in the myenteric layer, and the electrophysiological approaches were carried out to determine the regulatory roles of P2Y1 receptors on distal colonic motor function. IF showed that P2Y1 receptors are co-expressed MOR in the enteric nerve cells of the distal colonic myenteric plexus. Moreover, the WB revealed that the protein levels of P2Y1 were significantly decreased in the distal colonic myenteric layer of OIC rats. In vitro tension experiments exhibited that the P2Y1 receptor antagonist MRS2500 enhanced the spontaneous contraction amplitude, adding EM2 and ß-FNA did not have any effect on MRS2500. Therefore, P2Y1 receptor expression could be associated with the occurrence of OIC in this rat model and the regulation of colonic motility by MOR may be related to the release of purine neurotransmitters such as ATP in the colonic nervous system.
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Plexo Mientérico , Constipação Induzida por Opioides , Animais , Ratos , Analgésicos Opioides/efeitos adversos , Constipação Intestinal/induzido quimicamente , Western BlottingRESUMO
ABSTRACT Objective: The purpose of present study was to comprehensively explore the efficacy and safety of prothrombin complex concentrate (PCC) to treat massive bleeding in patients undergoing cardiac surgery. Methods: PubMed®, Embase, and Cochrane Library databases were searched for studies investigating PCC administration during cardiac surgery published before September 10, 2022. Mean difference (MD) with 95% confidence interval (CI) was applied to analyze continuous data, and dichotomous data were analyzed as risk ratio (RR) with 95% CI. Results: Twelve studies were included in the meta-analysis. Compared with other non-PCC treatment regimens, PCC was not associated with elevated mortality (RR=1.18, 95% CI=0.86-1.60, P=0.30, I2=0%), shorter hospital stay (MD=-2.17 days; 95% CI=-5.62-1.28, P=0.22, I2=91%), reduced total thoracic drainage (MD=-67.94 ml, 95% CI=-239.52-103.65, P=0.44, I2=91%), thromboembolic events (RR=1.10, 95% CI=0.74-1.65, P=0.63, I2=39%), increase in atrial fibrillation events (RR=0.73, 95% CI=0.52-1.05, P=0.24, I2=29%), and myocardial infarction (RR=1.10, 95% CI=0.80-1.51, P=0.57, I2=81%). However, PCC use was associated with reduced intensive care unit length of stay (MD=-0.81 days, 95% CI=-1.48- -0.13, P=0.02, I2=0%), bleeding (MD=-248.67 ml, 95% CI=-465.36- -31.97, P=0.02, I2=84%), and intra-aortic balloon pump/extracorporeal membrane oxygenation (RR=0.65, 95% CI=0.42-0.996, P=0.05, I2=0%) when compared with non-PCC treatment regimens. Conclusion: The use of PCC in cardiac surgery did not correlate with mortality, length of hospital stay, thoracic drainage, atrial fibrillation, myocardial infarction, and thromboembolic events. However, PCC significantly improved postoperative intensive care unit length of stay, bleeding, and intra-aortic balloon pump/ extracorporeal membrane oxygenation outcomes in patients undergoing cardiac surgery.
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SGLT-2 inhibitors, such as empagliflozin, have been shown to reduce the occurrence of cardiovascular events and delay the progression of atherosclerosis. However, its role in atherosclerotic calcification remains unclear. In this research, ApoE-/- mice were fed with western diet and empagliflozin was added to the drinking water for 24 weeks. Empagliflozin treatment significantly alleviated arterial calcification assessed by alizarin red and von kossa staining in aortic roots and reduced the lipid levels, while had little effect on body weight and blood glucose levels in ApoE-/- mice. In vitro studies, empagliflozin significantly inhibits calcification of primary vascular smooth muscle cells (VSMCs) and aortic rings induced by osteogenic media (OM) or inorganic phosphorus (Pi). RNA sequencing of VSMCs cultured in OM with or without empagliflozin showed that empagliflozin negatively regulated the osteogenic differentiation of VSMCs. And further studies confirmed that empagliflozin significantly inhibited osteogenic differentiation of VSMCs via qRT-PCR. Our study demonstrates that empagliflozin alleviates atherosclerotic calcification by inhibiting osteogenic differentiation of VSMCs, which addressed a critical need for the discovery of a drug-based therapeutic approach in the treatment of atherosclerotic calcification.
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Rituximab has been incorporated into the standard treatment regimen for diffuse large B-cell lymphoma (DLBCL), and induces the death of tumor cells via complement-dependent cytotoxicity (CDC). Unfortunately, the resistance of DLBCL cells to Rituximab limits its clinical usefulness. It remains unclear whether the complement system is related to Rituximab resistance in DLBCL. A Rituximab-resistant DLBCL cell line (Farage/R) was generated under the stress of Rituximab. Constituent proteins of the complement system in wild-type Farage cells (Farage/S) and Farage/R cells were analyzed by qPCR, western blotting, and immunofluorescence. In vitro and in vivo knockdown and overexpression studies confirmed that the complement 1Q subcomponent A chain (C1qA) was a regulator of Rituximab resistance. Finally, the mechanism by which C1qA is regulated by m6A methylation was explored. The reader and writer were identified by pull-down studies and RIP-qPCR. Activity of the complement system in Farage/R cells was suppressed. C1qA expression was reduced in Farage/R cells due to post-transcriptional regulation. Furthermore, in vitro and in vivo results showed that C1qA knockdown in Farage/S cells decreased their sensitivity to Rituximab, and C1qA overexpression in Farage/R cells attenuated the Rituximab resistance of those cells. Moreover, METTL3 and YTHDF2 were proven to be the reader and writer for m6A methylation of C1qA, respectively. Knockdown of METTL3 or YTHDF2 in Farage/R cells up-regulated C1qA expression and reduced their resistance to Rituximab. In summary, the aberrant downregulation of C1qA was related to Rituximab resistance in DLBCL cells, and C1qA was found to be regulated by METTL3- and YTHDF2-mediated m6A methylation. Enhancing the response of the complement system via regulation of C1qA might be an effective strategy for inhibiting Rituximab resistance in DLBCL.
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This study aimed to explore the occurrence of necroptosis in skeletal muscle after eccentric exercise and investigate the role and possible mechanisms of ZBP1 and its related pathway proteins in the process, providing a theoretical basis for the study of exercise-induced skeletal muscle injury and recovery. Forty-eight male adult Sprague-Dawley rats were randomly divided into a control group (C, n = 8) and an exercise group (E, n = 40). The exercise group was further divided into 0 h (E0), 12 h (E12), 24 h (E24), 48 h (E48), and 72 h (E72) after exercise, with 8 rats in each subgroup. At each time point, gastrocnemius muscle was collected under general anesthesia. The expression levels of ZBP1 and its related pathway proteins were assessed using Western blot analysis. The colocalization of pathway proteins was examined using immunofluorescence staining. After 48 h of eccentric exercise, the expression of necroptosis marker protein MLKL reached its peak (P < 0.01), and the protein levels of ZBP1, RIPK3, and HMGB1 also peaked (P < 0.01). At 48 h post high-load eccentric exercise, there was a significant increase in colocalization of ZBP1/RIPK3 pathway proteins, reaching a peak (P < 0.01). (1) Eccentric exercise induced necroptosis in skeletal muscle, with MLKL, p-MLKLS358, and HMGB1 significantly elevated, especially at 48 h after exercise. (2) After eccentric exercise, the ZBP1/RIPK3-related pathway proteins ZBP1, RIPK3, and p-RIPK3S232 were significantly elevated, particularly at 48 h after exercise. (3) Following high-load eccentric exercise, there was a significant increase in the colocalization of ZBP1/RIPK3 pathway proteins, with a particularly pronounced elevation observed at 48 h post-exercise.
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Proteína HMGB1 , Proteínas Quinases , Animais , Masculino , Ratos , Músculo Esquelético/metabolismo , Necroptose , Proteínas Quinases/metabolismo , Ratos Sprague-DawleyRESUMO
Introduction: There are not enough nurses around the world, and there are even fewer male nurses. It has not been easy for men to become nurses because of stereotypes about the roles of men and women in the workplace, which lead to prejudice and discrimination. This study explored how the self-esteem of male nurses and male nursing students affects their professional identity in an environment where stereotypes and social prejudice exist. This study also examined the differences of relevant variables in different sociodemographic characteristics of the research subjects in a Chinese social context. Methods: By purposive and snowball sampling, 464 male nurses and male nursing students were surveyed through questionnaires from November 2021 to January 2022. Data analysis was performed using SPSS 25.0 and PROCESS Macro 3.3. Results: Self-esteem could indirectly affect professional identity through perceived prejudice and psychological distress. Nonetheless, self-esteem still had a significant direct effect on professional identity. The total mediating effect accounted for 32.816% of the total effect, and the direct effect accounted for 67.184% of the total effect. Also of note was that 81.7% of participants reported experiencing psychological distress. Discussion: To improve the professional identity of male nurses and male nursing students, nursing educators and administrators should do the following: protect and improve their self-esteem; take steps to reduce social prejudice against them; value their mental health and alleviate their psychological distress.
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Pseudorabies virus (PRV) variants have caused substantial economic losses in the swine industry in China since 2011. To surveil the genetic variation in PRV field strains, here, two novel variant strains of PRV were isolated from Shanxi Province in central China and were designated SX1910 and SX1911. To identify the genetic characteristics of the two isolates, their complete genomes were sequenced, and phylogenetic analysis and sequence alignment revealed that field PRV variants have undergone genetic variations; notably, the protein-coding sequences UL5, UL36, US1 and IE180 exhibited extensive variation and contained one or more hypervariable regions. Furthermore, we also found that the glycoproteins gB and gD of the two isolates had some novel amino acid (aa) mutations. Importantly, most of these mutations were located on the surface of the protein molecule, according to protein structure model analysis. We constructed a mutant virus of SX1911 with deletion of the gE and gI genes via CRISPR/Cas9. When tested in mice, SX1911-ΔgE/gI-vaccinated mice were protected within a comparable range to Bartha-K61-vaccinated mice. Additionally, a higher dose of inactivated Bartha-K61 protected the mice from lethal SX1911 challenge, while a lower neutralization titer, higher viral load and more severe microscopic lesions were displayed in Bartha-K61-vaccinated mice. These findings highlight the need for continuous monitoring of PRV and novel vaccine development or vaccination program design for PRV control in China.
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Herpesvirus Suídeo 1 , Pseudorraiva , Doenças dos Suínos , Suínos , Animais , Camundongos , Pseudorraiva/prevenção & controle , Filogenia , Genômica , ChinaRESUMO
Structural variations (SVs) play an essential role in the evolution of human genomes and are associated with cancer genetics and rare disease. High-throughput chromosome capture (Hi-C) technology probed all genome-wide crosslinked chromatin to study the spatial architecture of chromosomes. Hi-C read pairs can span megabases, making the technology useful for detecting large-scale SVs. So far, the identification of SVs from Hi-C data is still in the early stages with only a few methods available. Especially, no algorithm has been developed that can detect SVs without control samples. Therefore, we developed HiSV (Hi-C for Structural Variation), a control-free method for identifying large-scale SVs from a Hi-C sample. Inspired by the single image saliency detection model, HiSV constructed a saliency map of interaction frequencies and extracted saliency segments as large-scale SVs. By evaluating both simulated and real data, HiSV not only detected all variant types, but also achieved a higher level of accuracy and sensitivity than existing methods. Moreover, our results on cancer cell lines showed that HiSV effectively detected eight complex SV events and identified two novel SVs of key factors associated with cancer development. Finally, we found that integrating the result of HiSV helped the WGS method to identify a total number of 94 novel SVs in two cancer cell lines.