Multiple applications of metal-organic frameworks (MOFs) in the treatment of orthopedic diseases.

Pharmacologic treatment of orthopedic diseases is a common challenge for clinical orthopedic surgeons, and as an important step in the stepwise treatment of orthopedic diseases, it is often difficult to achieve satisfactory results with existing pharmacologic treatments. Therefore, it is increasingly important to find new ways to effectively improve the treatment pattern of orthopedic diseases as well as to enhance the therapeutic efficacy. It has been found that metal-organic frameworks (MOFs) possess the advantages of high specific surface area, high porosity, chemical stability, tunability of structure and biocompatibility. Therefore, MOFs are expected to improve the conventional traditional treatment modality for bone diseases. This manuscript reviewed the applications of MOFs in the treatment of common clinical bone diseases and look forward to its future development.

Spirulina platensis components mitigate bone density loss induced by simulated microgravity: A mechanistic insight.

In microgravity conditions, the consumption of Spirulina platensis (SP) as a renewable food source shows promise in mitigating osteoporosis due to its high nutritional content photosynthetic efficiency, environmental adaptability and positive effects on bone density, though the exact bioactive components and mechanisms remain unclear. Using a hindlimb suspension (HLS) model, this study investigated SP components: proteins (SPP), polysaccharides (SPS), lipids (SPL), and residue (SPR) on bone density and metabolism. Findings revealed that SPP and SPS significantly enhanced bone density and reduced oxidative stress. Activation of the FoxO3/Wnt/ß-catenin pathway reduced FoxO3a expression and increased Wnt signaling molecules and ß-catenin protein, boosting bone formation. Moreover, these components promoted beneficial gut bacteria like Turicibacter, reduced the Firmicutes-to-Bacteroidetes ratio, and enhanced SCFAs production, crucial for bone health. This study emphasized the potential of Spirulina nutrients in addressing space-induced osteoporosis and developing functional foods for long-term space missions.

Vaccarin alleviates septic cardiomyopathy by potentiating NLRP3 palmitoylation and inactivation.

BACKGROUND: Sepsis often leads to significant morbidity and mortality due to severe myocardial injury. As is known, the activation of NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome crucially contributes to septic cardiomyopathy (SCM) by facilitating the secretion of interleukin (IL)-1ß and IL-18. The removal of palmitoyl groups from NLRP3 is a crucial step in the activation of the NLRP3 inflammasome. Thus, the potential inhibitors that regulate the palmitoylation and inactivation of NLRP3 may significantly diminish sepsis-induced cardiac dysfunction. PURPOSE: The present study sought to explore the effects of the prospective flavonoid compounds targeting NLRP3 on SCM and to elucidate the associated underlying mechanisms. STUDY DESIGN: The palmitoylation and activation of NLRP3 were detected in H9c2 cells and C57BL/6 J mice. METHODS/RESULTS: Echocardiography, histological staining, western blotting, co-immunoprecipitation, qPCR, ELISA and network pharmacology were used to assess the impact of vaccarin (VAC) on SCM in mice subjected to lipopolysaccharide (LPS) injection. From the collection of 74 compounds, we identified that VAC had the strongest capability to suppress NLRP3 luciferase report gene activity in cardiomyocytes, and the anti-inflammatory characteristics of VAC were further ascertained by the network pharmacology. Exposure of LPS triggered apoptosis, inflammation, oxidative stress, mitochondrial disorder in cardiomyocytes. The detrimental alterations were significantly reversed upon VAC treatment in both septic mice and H9c2 cells exposed to LPS. In vivo experiments demonstrated that VAC treatment alleviated septic myocardial injury, indicated by enhanced cardiac function parameters, preserved cardiac structure, and reduced inflammation/oxidative response. Mechanistically, VAC induced NLRP3 palmitoylation to inactivate NLRP3 inflammasome by acting on zDHHC12. In support, the NLRP3 agonist ATP and the acylation inhibitor 2-bromopalmitate (2-BP) prevented the effects of VAC. CONCLUSION: Our findings suggest that VAC holds promise in protecting against SCM by mitigating cardiac oxidative stress and inflammation via priming NLRP3 palmitoylation and inactivation. These results lay the solid basis for further assessment of the therapeutic potential of VAC against SCM.

Development and Validation of a Nomogram for Prognosis Prediction in Patients with Synchronous Primary Thyroid and Breast Cancer Based on SEER Database.

This study aimed to develop prognostic prediction models for patients diagnosed with synchronous thyroid and breast cancer (TBC). Utilizing the SEER database, key predictive factors were identified, including T stage of thyroid cancer, T stage of breast cancer, M stage of breast cancer, patient age, thyroid cancer surgery type, and isotope therapy. A nomogram predicting 5-year and 10-year survival rates was constructed and validated, exhibiting strong performance (C-statistic: 0.79 in the development cohort (95% CI: 0.74-0.84), and 0.82 in the validation cohort (95% CI: 0.77-0.89)). The area under the Receiver Operator Characteristic (ROC) curve ranged from 0.798 to 0.883 for both cohorts. Calibration and decision curve analyses further affirmed the model's clinical utility. Stratifying patients into high-risk and low-risk groups using the nomogram revealed significant differences in survival rates (P < 0.0001). The successful development and validation of this nomogram for predicting 5-year and 10-year survival rates in patients with synchronous TBC hold promise for similar patient populations, contributing significantly to cancer research.

Consistency analysis of consciousness index and bispectral index in monitoring the depth of sevoflurane anesthesia in laparoscopic surgery.

Background: The Index of Consciousness (IoC) is a new monitoring index of anesthesia depth reflecting the state of consciousness of the brain independently developed by China. The research on monitoring the depth of anesthesia mainly focuses on propofol, and bispectral index (BIS) is a sensitive and accurate objective index to evaluate the state of consciousness at home and abroad. This study mainly analyzed the effect of IoC on monitoring the depth of sevoflurane anesthesia and the consistency and accuracy with BIS when monitoring sevoflurane maintenance anesthesia. Objective: To investigate the monitoring value of the Index of Consciousness (IoC) for the depth of sevoflurane anesthesia in laparoscopic surgery. Methods: The study population consisted of 108 patients who experienced elective whole-body anesthesia procedures within the timeframe of April 2020 to June 2023 at our hospital. Throughout the anesthesia process, which encompassed induction and maintenance using inhaled sevoflurane, all patients were diligently monitored for both the Bispectral Index (BIS) and the Index of Consciousness (IoC). We conducted an analysis to assess the correlation between IoC and BIS throughout the anesthesia induction process and from the maintenance phase to the regaining of consciousness. To evaluate the predictive accuracy of IoC and BIS for the onset of unconsciousness during induction and the return of consciousness during emergence, we employed receiver operating characteristic (ROC) curve analysis. Results: The mean difference between BIS and IoC, spanning from the pre-anesthesia induction phase to the completion of propofol induction, was 1.3 (95% Limits of Agreement [-53.4 to 56.0]). Similarly, during the interval from the initiation of sevoflurane inhalation to the point of consciousness restoration, the average difference between BIS and IoC was 0.3 (95% LOA [-10.8 to 11.4]). No statistically significant disparities were observed in the data acquired from the two measurement methodologies during both the anesthesia induction process and the journey from maintenance to the regaining of consciousness (P > 0.05). The outcomes of the ROC curve analysis disclosed that the areas under the curve (AUC) for prognosticating the occurrence of loss of consciousness were 0.967 (95% CI [0.935-0.999]) for BIS and 0.959 (95% CI [0.924-0.993]) for IoC, with optimal threshold values set at 81 (sensitivity: 88.10%, specificity: 92.16%) and 77 (sensitivity: 79.55%, specificity: 95.45%) correspondingly. For the prediction of recovery of consciousness, the AUCs were 0.995 (95% CI [0.987-1.000]) for BIS and 0.963 (95% CI [0.916-1.000]) for IoC, each associated with optimal cutoff values of 76 (sensitivity: 92.86%, specificity: 100.00%) and 72 (sensitivity: 86.36%, specificity: 100.00%) respectively. Conclusion: The monitoring of sevoflurane anesthesia maintenance using IoC demonstrates a level of comparability to BIS, and its alignment with BIS during the maintenance phase of sevoflurane anesthesia is robust. IoC displays promising potential for effectively monitoring the depth of anesthesia.

Oral administration of ellagic acid mitigates perioperative neurocognitive disorders, hippocampal oxidative stress, and neuroinflammation in aged mice by restoring IGF-1 signaling.

This study investigates the potential of ellagic acid (EA), a phytochemical with antioxidant and anti-inflammatory properties, in managing perioperative neurocognitive disorders (PND). PND, which represents a spectrum of cognitive impairments often faced by elderly patients, is principally linked to surgical and anesthesia procedures, and heavily impacted by oxidative stress in the hippocampus and microglia-induced neuroinflammation. Employing an aged mice model subjected to abdominal surgery, we delve into EA's ability to counteract postoperative oxidative stress and cerebral inflammation by engaging the Insulin-like growth factor-1 (IGF-1) pathway. Our findings revealed that administering EA orally notably alleviated post-surgical cognitive decline in older mice, a fact that was manifested in improved performance during maze tests. This enhancement in the behavioral performance of the EA-treated mice corresponded with the rejuvenation of IGF-1 signaling, a decrease in oxidative stress markers in the hippocampus (like MDA and carbonylated protein), and an increase in the activity of antioxidant enzymes such as SOD and CAT. Alongside these, we observed a decrease in microglia-driven neuroinflammation in the hippocampus, thus underscoring the antioxidant and anti-inflammatory roles of EA. Interestingly, when EA was given in conjunction with an IGF1R inhibitor, these benefits were annulled, accentuating the pivotal role that the IGF-1 pathway plays in the neuroprotective potential of EA. Hence, EA could serve as a potent candidate for safeguarding against PND in older patients by curbing oxidative stress and neuroinflammation through the activation of the IGF-1 pathway.

Selective optogenetic modulation of the PBN terminals in the lateral hypothalamic area and basal forebrain regulates emergence from isoflurane anesthesia in mice.

While the mechanism of general anesthesia has been extensively studied, the underlying neural circuitry has yet to be fully understood. The parabrachial nucleus (PBN) plays a crucial role in modulating wakefulness and promoting arousal from general anesthesia. However, the specific role of PBN projections in the process of general anesthesia remains unclear. In this study, we bilaterally injected AAV-associated viruses encoding excitatory or inhibitory optogenetic probes into the PBN and implanted optical fibers in the LH or BF area. After four weeks, we optogenetically activated or inhibited the PBN-LH and PBN-BF pathways under 1.5 vol% isoflurane. We calculated the time it took for anesthesia induction and emergence, simultaneously monitoring changes in the burst-suppression ratio using electroencephalogram recording. Our findings indicate that optogenetic activation of the PBN-LH and PBN-BF projections plays a significant role in promoting both cortical and behavioral emergence from isoflurane inhalation, without significantly affecting the induction time. Conversely, photoinhibition of these pathways prolonged the recovery time, with no notable difference observed during the induction phase.In summary, our results demonstrate that the PBN-LH and PBN-BF pathways are crucial for promoting arousal from isoflurane general anesthesia, but do not have a pronounced impact on the induction phase.

Cooperative effects of SIRT1 and SIRT2 on APP acetylation.

Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by amyloid-ß (Aß) deposition and neurofibrillary tangles. Although the NAD+ -dependent deacetylases SIRT1 and SIRT2 play pivotal roles in age-related diseases, their cooperative effects in AD have not yet been elucidated. Here, we report that the SIRT2:SIRT1 ratio is elevated in the brains of aging mice and in the AD mouse models. In HT22 mouse hippocampal neuronal cells, Aß challenge correlates with decreased SIRT1 expression, while SIRT2 expression is increased. Overexpression of SIRT1 prevents Aß-induced neurotoxicity. We find that SIRT1 impedes SIRT2-mediated APP deacetylation by inhibiting the binding of SIRT2 to APP. Deletion of SIRT1 reduces APP recycling back to the cell surface and promotes APP transiting toward the endosome, thus contributing to the amyloidogenic processing of APP. Our findings define a mechanism for neuroprotection by SIRT1 through suppression of SIRT2 deacetylation, and provide a promising avenue for therapeutic intervention of AD.

Effects of oral ß-caryophyllene (BCP) treatment on perioperative neurocognitive disorders: Attenuation of neuroinflammation associated with microglial activation and reinforcement of autophagy activity in aged mice.

Perioperative neurocognitive disorders (PND) are a constellation of cognitive impairments that arise following surgical procedures and anesthesia, with a higher incidence in elderly patients. PND is deeply entwined with microglia-mediated neuroinflammation and disrupted autophagy. ß-caryophyllene (BCP) is a natural terpene that occurs widely in dietary plants, and possesses robust anti-inflammatory properties by selectively activating CB2 receptors (CB2R). Accordingly, the present study endeavors to investigate the potential of BCP in ameliorating PND in aged mice, by mitigating hippocampal neuroinflammation and improving autophagy. In this study, an abdominal surgery was utilized to induce perioperative neurocognitive disorders (PND) in aged mice. BCP was administered orally at a dosage of 200 mg/kg for seven consecutive days prior to the scheduled surgery. In order to explore the relationship between BCP and CB2 receptors (CB2R), a co-administration of intraperitoneal injections of the CB2R antagonist AM630 was implemented, 30 min preceding the oral gavage of BCP. Postoperative cognitive functions were assessed using Morris water maze (MWM) tests. The extent of hippocampal inflammation was examined by measuring the microglial marker Iba-1 protein levels, Iba-1 and GFAP immunoactivity, as well as IL-1ß and IL-6 concentrations. Evaluation of autophagy activity was conducted based on the ratio of LC3B2/LC3B1 and protein levels of Beclin-1, p62, and phospho-mTOR (p-mTOR). After being orally administered BCP, the compromised behavioral performance of abdominal surgical interventions on aged mice was alleviated. This was evident by the extended escape latency, reduced time spent in the target quadrant, and fewer platform crossings observed through MWM testing. While hippocampal CB2R mRNA or protein expression remained unaffected by the abdominal surgical procedure, their levels were significantly upregulated in mice that were administered BCP. Moreover, the oral administration of BCP was able to reduce neuroinflammation in response to microglia activation, as evidenced by the decreased levels of Iba-1 protein and immunoactivity, as well as the reduction of IL-1ß and IL-6 concentrations. Additionally, BCP intensified autophagic activity, as detected by increased LC3B2/LC3B1 ratio and Beclin-1 protein levels, coupled with decreased levels of p62 and p-mTOR in the hippocampus of aged mice. Conversely, the treatment of AM630 ameliorated the suppressive effect of BCP triggered by the neuroinflammation caused by microglial activation post-surgery in aged mice (increased Iba-1 protein levels and immunoactivity, accompanied by higher IL-1ß and IL-6 concentrations). Furthermore, the pro-autophagy effect of BCP on aged mice following surgery was partially blocked by AM630, culminating in decreased LC3B2/LC3B1 ratio and Beclin-1 protein levels. However, the levels of p62 and p-mTOR remained unchanged by AM630. Our investigation unveils the remarkable therapeutic benefits of oral BCP administration for managing PND in aged mice through the attenuation of neuroinflammation associated with microglial activation and the fortification of autophagy activity. Hence, BCP holds great promise as a formidable candidate englobing various potential physiological mechanisms that would mitigate cognitive decline associated with aging.

De-ubiquitination of SAMHD1 by USP7 promotes DNA damage repair to overcome oncogenic stress and affect chemotherapy sensitivity.

Oncogenic stress induces DNA damage repair (DDR) that permits escape from mitotic catastrophe and allows early precursor lesions during the evolution of cancer. SAMHD1, a dNTPase protecting cells from viral infections, has been recently found to participate in DNA damage repair process. However, its role in tumorigenesis remains largely unknown. Here, we show that SAMHD1 is up-regulated in early-stage human carcinoma tissues and cell lines under oxidative stress or genotoxic insults. We further demonstrate that de-ubiquitinating enzyme USP7 interacts with SAMHD1 and de-ubiquitinates it at lysine 421, thus stabilizing SAMHD1 protein expression for further interaction with CtIP for DDR, which promotes tumor cell survival under genotoxic stress. Furthermore, SAMHD1 levels positively correlates with USP7 in various human carcinomas, and is associated with an unfavorable survival outcome in patients who underwent chemotherapy. Moreover, USP7 inhibitor sensitizes tumor cells to chemotherapeutic agents by decreasing SAMHD1 in vitro and in vivo. These findings suggest that de-ubiquitination of SAMHD1 by USP7 promotes DDR to overcome oncogenic stress and affect chemotherapy sensitivity.

Patient's age with papillary thyroid cancer: Is it a key factor for cervical lymph node metastasis?

BACKGROUND: Age is one of the important prognostic indicators of papillary thyroid cancer (PTC). However, the distinct metastatic patterns and prognosis of age-related lymph node metastasis (LNM) are unclear. This study aims to investigate the impact of age on LNM. METHODS: We conducted two independent cohort studies to assess age-nodal disease association using logistic regression analysis and a restricted cubic splines model. A multivariable Cox regression model was utilized to test the impact of nodal disease on cancer-specific survival (CSS) after age stratification. RESULTS: For this study, we included 7572 and 36,793 patients with PTC in Xiangya and SEER cohorts, respectively. After adjustment, advanced age was linearly associated with decreasing risk of central LNM. Patients of age ≤18 years (OR = 4.41, P < 0.001) and 19-45 years (OR = 1.97, P = 0.002) had a higher risk of developing lateral LNM than patients of age >60 years in both cohorts. Furthermore, CSS is significantly reduced in N1b disease (P < 0.001), not N1a disease, regardless of age. The incidence of high-volume LNM (HV-LNM) was significantly higher in patients of age ≤18 years and 19-45 years than in those of age >60 years (P < 0.001), in both cohorts. In addition, CSS was compromised in patients with PTC of age 46-60 years (HR = 1.61, P = 0.022) and those of age >60 (HR = 1.40, P = 0.021) after developing HV-LNM. CONCLUSIONS: Patient age is significantly associated with LNM and HV-LNM. Patients with N1b disease or patients with HV-LNM of age >45 years have significantly shorter CSS. Age can, thus, be a useful guide for determining treatment strategies in PTC.

The role of functional dynamic stretching training in dance sports / O papel do treino funcional de alongamento dinâmico na dança esportiva / El papel del entrenamiento funcional de estiramiento dinámico en el baile deportivo

ABSTRACT Introduction Dynamic stretching is a particular form of training. Currently, there is little research in academia about dynamic stretching in sports dancing. Objective Explore the role of functional dynamic stretching training in dance sports. Methods 60 sports dancers with a history of ankle injuries were randomly divided into a control and experimental group. All performed a training protocol twice a week, lasting 45 minutes, for eight weeks. A functional dynamic stretching training session was added to the control group. The effects were evaluated by the Cumberland scale, bilateral stability comparison, and balance control by the Perkin system. Data were statistically treated for analysis. Results There was no significant difference between the scores of healthy ankle joints and injured ankle joints in the two groups (P>0.05). After eight weeks of functional dynamic stretching training, there was a significant difference between the experimental and control groups on injured ankle joints (P<0.05). Conclusion Dynamic stretching training can effectively improve ankle joint stability in sports dancers. Concomitantly, this method effectively prevents injuries to the athlete's ankle joint. Evidence level II; Therapeutic Studies - Investigating the results.

RESUMO Introdução O alongamento dinâmico é uma forma especial de treinamento. Atualmente, existem poucas pesquisas no meio acadêmico sobre alongamento dinâmico na dança esportiva. Objetivo Explorar o papel do treino funcional de alongamento dinâmico na dança esportiva. Métodos 60 bailarinos esportivos com histórico de lesões no tornozelo foram divididos aleatoriamente em grupo controle e experimental. Todos realizaram um protocolo de treinamento duas vezes por semana, com duração de 45 minutos, por 8 semanas. Ao grupo controle foi adicionado um treino de alongamento dinâmico funcional. Os efeitos foram avaliados pela escala de Cumberland, comparação de estabilidade bilateral e controle de equilíbrio pelo sistema de Perkin. Os dados foram tratados estatisticamente para análise. Resultados Antes do experimento, não houve diferença significativa entre os escores das articulações do tornozelo saudáveis e das articulações do tornozelo lesionadas nos dois grupos (P>0,05). Após 8 semanas de treinamento funcional de alongamento dinâmico, houve diferença significativa entre o grupo experimental e o grupo controle nas articulações do tornozelo lesionadas (P<0,05). Conclusão O treinamento de alongamento dinâmico pode efetivamente melhorar a estabilidade da articulação do tornozelo nos bailarinos esportivos. Concomitantemente, esse método previne efetivamente a ocorrência de lesões na articulação do tornozelo do atleta. Nível de evidência II; Estudos terapêuticos - Investigação de resultados.

RESUMEN Introducción El estiramiento dinámico es una forma especial de entrenamiento. Actualmente, existen pocas investigaciones en el ámbito académico sobre los estiramientos dinámicos en el baile deportivo. Objetivo Explorar el papel del entrenamiento funcional de estiramiento dinámico en el baile deportivo. Métodos 60 bailarines deportivos con antecedentes de lesiones de tobillo fueron divididos aleatoriamente en un grupo de control y otro experimental. Todos realizaron un protocolo de entrenamiento dos veces por semana, de 45 minutos, durante 8 semanas. Al grupo de control se le añadió un entrenamiento de estiramiento dinámico funcional. Los efectos fueron evaluados por la escala Cumberland, la comparación de la estabilidad bilateral y el control del equilibrio por el sistema Perkin. Los datos fueron tratados estadísticamente para su análisis. Resultados Antes del experimento, no había diferencias significativas entre las puntuaciones de las articulaciones del tobillo sano y las articulaciones del tobillo lesionado en los dos grupos (P>0,05). Después de 8 semanas de entrenamiento funcional de estiramiento dinámico, hubo una diferencia significativa entre el grupo experimental y el grupo de control en las articulaciones del tobillo lesionadas (P<0,05). Conclusión El entrenamiento de estiramiento dinámico puede mejorar eficazmente la estabilidad de la articulación del tobillo en los bailarines deportivos. Al mismo tiempo, este método previene eficazmente la aparición de lesiones en la articulación del tobillo del deportista. Nivel de evidencia II; Estudios terapéuticos - Investigación de resultados.

A critical analysis of the current TNM classification for differentiated thyroid carcinoma in young patients: Time for a change?

Background: The current TNM classification that simply classifies differentiated thyroid carcinoma (DTC) patients younger than 55 years into stage I and stage II based on the presence or absence of distant metastases has been questioned. In this study, we reexamined the impact of T status and N status on prognosis and then developed a new prediction model to improve the predictability of cancer-specific survival (CSS) in young patients. Materials and methods: Kaplan-Meier method was applied to calculate the CSS. Multivariable Cox proportional hazards models were used to assess the impact of T status and N status on CSS after adjustment for known covariates. The area under the receiver operating characteristic curve (AUC), C-index, Bayesian information criterion (BIC), and Akaike information criterion (AIC) were calculated to compare model performance. Results: A total of 9,242 DTC patients younger than 55 years were enrolled in the study. After adjusting for gender, age at diagnosis, race, pathology subtype, N stage, and M stage, T3 disease [hazard ratio (HR): 3.78, P = 0.006] and T4 disease (HR: 7.96, P < 0.001) remain independent predictors of CSS. Similarly, the 10-year CSS rate of N1b disease (HR: 3.78, P < 0.001) was significantly higher than that of N0 disease after adjustment. Moreover, Kaplan-Meier survival analysis showed that the 10-year CSS of stage II disease in younger patients with DTC showed a sharp decrease compared with that in older patients with DTC (74.47% vs. 98.43%, P < 0.001). Furthermore, a modified TNM staging system based on significantly prognostic T stage and N stage was established, which showed better performance than the current TNM staging system (P < 0.05). The new prediction model is also applicable to papillary thyroid carcinoma patients and follicular thyroid carcinoma patients. Conclusions: This is the first study to question the rationality of the current TNM staging system for patients younger than 55 years and successfully develop a new prognostic model, which improves prognostic stratification and guides individualized management.

The downregulated drug-metabolism related ALDH6A1 serves as predictor for prognosis and therapeutic immune response in gastric cancer.

Drug metabolism-associated genes have been clarified to play a vital role in the process of cancer cell growth and migration. Nevertheless, the correlation between drug metabolism-associated genes and gastric cancer (GC) has not been fully explored and clarified. This paper has focused on the role of aldehyde dehydrogenase 6 family member A1 (ALDH6A1), a drug metabolism-associated gene, in the immune regulation and prognosis of GC patients. Using several bioinformatics platforms and immunohistochemistry (IHC) assay, we found that ALDH6A1 expression was significantly down-regulated in GC tissues. Moreover, higher expression of ALDH6A1 was related to the better prognosis of GC patients. ALDH6A1 was also found to be involved in the regulation of several immune-associated signatures, including immunoinhibitors. In conclusion, the above results have concluded that aberrant expression of ALDH6A1 might be served as the promising predictor for prognosis and clinical immunotherapy response in GC patients.

Comprehensive analysis of the potential cuproptosis-related biomarker LIAS that regulates prognosis and immunotherapy of pan-cancers.

Lipoic acid synthetase (LIAS) has been demonstrated to play a crucial role in the progression of cancer. Exploring the underlying mechanisms and biological functions of LIAS could have potential therapeutic guidance for cancer treatment. Our study has explored the expression levels and prognostic values of LIAS in pan-cancer through several bioinformatics platforms, including TIMER2.0, Gene Expression Profiling Interactive Analysis, version 2 (GEPIA2.0), and Human Protein Atlas (HPA). We found that a high LIAS expression was related to the good prognosis in patients with kidney renal clear cell carcinoma (KIRC), rectum adenocarcinoma (READ), breast cancer, and ovarian cancer. Inversely, a high LIAS expression showed unfavorable prognosis in lung cancer patients. In addition, the genetic alteration, methylation levels, and immune analysis of LIAS in pan-cancer have been evaluated. To elucidate the underlying molecular mechanism of LIAS, we conduct the single-cell sequencing to implicate that LIAS expression was related to hypoxia, angiogenesis, and DNA repair. Thus, these comprehensive pan-cancer analyses have conveyed that LIAS could be potentially significant in the progression of various cancers. Moreover, the LIAS expression could predict the efficacy of immunotherapy in cancer patients.

iPACK block (local anesthetic infiltration of the interspace between the popliteal artery and the posterior knee capsule) added to the adductor canal blocks versus the adductor canal blocks in the pain management after total knee arthroplasty: a systematic review and meta-analysis.

BACKGROUND: Several studies have suggested that the addition of iPACK block (the popliteal artery and the posterior knee capsule have been given interspace local anesthetic infiltration) might get better analgesia than adductor canal block (ACB) only after total knee arthroplasty (TKA). This paper compiles all available evidence on the effect of two analgesia regimens (ACB and iPACK + ACB) involving all sides. METHODS: We searched in eight major databases for all clinical trials discussing the effect of two analgesia regimens after TKA. Statistical analyses were conducted by Stata and RevMan Software. In addition, we performed GOSH analysis, subgroup analysis, meta-regression analysis to study the source of heterogeneity. Publication bias was checked using Egger's test. Trim-and-fill analysis was applied in terms of sensitivity analysis of the results. RESULTS: There are fourteen eligible studies for our meta-analysis. There are significant differences between the two groups in VAS score at rest and with activity, and the VAS scores were lower in the ACB + iPACK Group (VAS scores at rest: 95%CI [- 0.96, - 0.53], P < 0.00001. VAS scores with activity: 95%CI [- 0.79, - 0.43], P < 0.00001). A differential was discovered to support the ACB + iPACK Group when comparing the two groups on postoperative cumulative morphine consumption (95%CI: [- 0.52, - 0.14], P: 0.0007). The patients in the group of ACB + iPACK performed better in the postoperative range of knee movement (95%CI: [5.18, 10.21], P < 0.00001) and walking distance (95%CI: [0.15, 0.41], P < 0.00001). There were significant differences between the patients in the ACB + iPACK Group and ACB Group on the TUG test of POD1 and POD2. We found that patients' hospital stays in the ACB + iPACK Group were significantly shorter than in the ACB Group (95%CI: [- 0.78, - 0.16], P: 0.003). No difference was found between the patients in the ACB + iPACK Group and ACB Group on postoperative quadriceps muscle strength and the incidence of PONV. CONCLUSION: The addition of iPACK lowers postoperative VAS scores, cumulative morphine consumption, and hospital stays. Meanwhile, the addition of iPACK improves postoperative patients' activity performance without extra side effects. iPACK combined with ACB proves to be a suitable pain management technique after TKA.

Scutellarin alleviates cerebral ischemia/reperfusion by suppressing oxidative stress and inflammatory responses via MAPK/NF-κB pathways in rats.

Neuroinflammation contributes to the progression of cerebral ischemia/reperfusion (I/R) damage. Scutellarin (SL) is a glucuronide flavonoid that has apoptotic, anti-inflammatory, and anti-tumor properties. It is anti-oxidant and anti-inflammatory mechanism as a neuroprotective against ischemic brain injury is unknown. The purpose of the study was to examine the role and mechanism of SL in preventing I/R damage in a rat model. SL (40 and 80 mg/kg) was given to the rats for 14 days before the ischemic stroke. SL administration prevented I/R mediated brain injury, and neuronal apoptosis. Malondialdehyde, superoxide dismutase, glutathione, IL-6, and IL-1ß and nitric oxide were modulated by SL. SL suppressed the p65 and p38 expressions in particular. The findings show that SL protects rats from cerebral damage caused by I/R through the nuclear factor kappa-B p65 and p38 mitogen-activated protein kinase signaling pathway. Thus, SL protected the brain of rats from ischemic injury by inhibiting the inflammatory process.

Quantum channel measurement with local quantum Bernoulli noises.

As an important stochastic process, quantum Bernoulli noises has a very important physical background and is an important research object in the field of quantum information. In this paper, we review local quantum Bernoulli noises and local quantum mutual entropy, then introduce quantum channel measurement with local quantum Bernoulli noises. On this basis, we give the channel structure between two systems, and prove the completely positivity of this quantum channel. We also give a channel application on the local quantum mutual entropy.

Inhibition of SIRT2 promotes APP acetylation and ameliorates cognitive impairment in APP/PS1 transgenic mice.

Aging is a primary risk factor for neurodegenerative diseases, such as Alzheimer's disease (AD). SIRT2, an NAD+(nicotinamide adenine dinucleotide)-dependent deacetylase, accumulates in the aging brain. Here, we report that, in the amyloid precursor protein (APP)/PS1 transgenic mouse model of AD, genetic deletion of SIRT2 or pharmacological inhibition of SIRT2 ameliorates cognitive impairment. We find that suppression of SIRT2 enhances acetylation of APP, which promotes non-amyloidogenic processing of APP at the cell surface, leading to increased soluble APP-α (sAPPα). We discover that lysines 132 and 134 of the major pathogenic protein ß-amyloid (Aß) precursor are acetylated and that these residues are deacetylated by SIRT2. Strikingly, exogenous expression of wild-type or an acetylation-mimic APP mutant protects cultured primary neurons from Aß42 challenge. Our study identifies SIRT2-mediated deacetylation of APP on K132 and K134 as a regulated post-translational modification (PTM) and suggests inhibition of SIRT2 as a potential therapeutic strategy for AD.

Progerin modulates the IGF-1R/Akt signaling involved in aging.

Progerin, a product of LMNA mutation, leads to multiple nuclear abnormalities in patients with Hutchinson-Gilford progeria syndrome (HGPS), a devastating premature aging disorder. Progerin also accumulates during physiological aging. Here, we demonstrate that impaired insulin-like growth factor 1 receptor (IGF-1R)/Akt signaling pathway results in severe growth retardation and premature aging in Zmpste24-/- mice, a mouse model of progeria. Mechanistically, progerin mislocalizes outside of the nucleus, interacts with the IGF-1R, and down-regulates its expression, leading to inhibited mitochondrial respiration, retarded cell growth, and accelerated cellular senescence. Pharmacological treatment with the PTEN (phosphatase and tensin homolog deleted on chromosome 10) inhibitor bpV (HOpic) increases Akt activity and improves multiple abnormalities in Zmpste24-deficient mice. These findings provide previously unidentified insights into the role of progerin in regulating the IGF-1R/Akt signaling in HGPS and might be useful for treating LMNA-associated progeroid disorders.