Lei's formula attenuates osteoarthritis mediated by suppression of chondrocyte senescence via the mTOR axis: in vitro and in vivo experiments.

Lei's formula (LSF), a traditional Chinese herbal remedy, is recognized for its remarkable clinical effectiveness in treating osteoarthritis (OA). Despite its therapeutic potential, the exact molecular mechanisms underlying LSF's action in OA have remained enigmatic. Existing research has shed light on the role of the mTOR signaling pathway in promoting chondrocyte senescence, a central factor in OA-related cartilage degeneration. Consequently, targeting mTOR to mitigate chondrocyte senescence presents a promising avenue for OA treatment. The primary objective of this study is to establish LSF's chondroprotective potential and confirm its anti-osteoarthritic efficacy through mTOR inhibition. In vivo assessments using an OA mouse model reveal substantial articular cartilage degeneration. However, LSF serves as an effective guardian of articular cartilage, evidenced by reduced subchondral osteosclerosis, increased cartilage thickness, improved surface smoothness, decreased OARSI scores, elevated expression of cartilage anabolic markers (Col2 and Aggrecan), reduced expression of catabolic markers (Adamts5 and MMP13), increased expression of the chondrocyte hypertrophy marker (Col10), and decreased expression of chondrocyte senescence markers (P16 and P21). In vitro findings demonstrate that LSF shields chondrocytes from H2O2-induced apoptosis, inhibits senescence, enhances chondrocyte differentiation, promotes the synthesis of type II collagen and proteoglycans, and reduces cartilage degradation. Mechanistically, LSF suppresses chondrocyte senescence through the mTOR axis, orchestrating the equilibrium between chondrocyte anabolism and catabolism, ultimately leading to reduced apoptosis and decelerated OA cartilage degradation. LSF holds significant promise as a therapeutic approach for OA treatment, offering new insights into potential treatments for this prevalent age-related condition.

Dual antithrombotic therapy dose-dependently alters hemostatic plug structure and function.

BACKGROUND: Antithrombotic medications carry an inherent risk of bleeding, which may be exacerbated when anticoagulant and antiplatelet therapeutics are combined. Prior studies have shown different effects of antiplatelet vs anticoagulant drugs on the structure and function of hemostatic plugs in vivo. OBJECTIVES: We examined whether dual antithrombotic treatment consisting of combined antiplatelet and anticoagulant therapeutics alters hemostatic plug structure and function differently from treatment with either therapeutic alone. METHODS: Mice were treated with the P2Y12 antagonist clopidogrel and the factor Xa inhibitor rivaroxaban across a range of doses, either alone or in combination. The hemostatic response was assessed using a mouse jugular vein puncture injury model. Platelet accumulation and fibrin deposition were evaluated using quantitative multiphoton fluorescence microscopy, and bleeding times were recorded. RESULTS: Mice treated with clopidogrel alone exhibited a decrease in platelet accumulation at the site of injury, with prolonged bleeding times only at the highest doses of clopidogrel used. Mice treated with rivaroxaban alone instead showed a reduction in fibrin deposition with no impact on bleeding. Mice treated with both clopidogrel and rivaroxaban exhibited platelet and fibrin accumulation that was similar to that with either drug given alone; however, dual antithrombotic therapy resulted in impaired hemostasis at doses that had no impact on bleeding when given in isolation. CONCLUSION: Combined administration of antiplatelet and anticoagulant therapeutics exacerbates bleeding as compared to that with either drug alone, potentially via combined loss of both adenosine 5'-diphosphate- and thrombin-mediated platelet activation. These findings enhance our understanding of the bleeding risk associated with dual antithrombotic therapy.

The crucial role and mechanism of insulin resistance in metabolic disease.

Insulin resistance (IR) plays a crucial role in the development and progression of metabolism-related diseases such as diabetes, hypertension, tumors, and nonalcoholic fatty liver disease, and provides the basis for a common understanding of these chronic diseases. In this study, we provide a systematic review of the causes, mechanisms, and treatments of IR. The pathogenesis of IR depends on genetics, obesity, age, disease, and drug effects. Mechanistically, any factor leading to abnormalities in the insulin signaling pathway leads to the development of IR in the host, including insulin receptor abnormalities, disturbances in the internal environment (regarding inflammation, hypoxia, lipotoxicity, and immunity), metabolic function of the liver and organelles, and other abnormalities. The available therapeutic strategies for IR are mainly exercise and dietary habit improvement, and chemotherapy based on biguanides and glucagon-like peptide-1, and traditional Chinese medicine treatments (e.g., herbs and acupuncture) can also be helpful. Based on the current understanding of IR mechanisms, there are still some vacancies to follow up and consider, and there is also a need to define more precise biomarkers for different chronic diseases and lifestyle interventions, and to explore natural or synthetic drugs targeting IR treatment. This could enable the treatment of patients with multiple combined metabolic diseases, with the aim of treating the disease holistically to reduce healthcare expenditures and to improve the quality of life of patients to some extent.

Effects of Positive Psychological Nursing Combined with Free Posture on the Prognosis of Primipara with Singleton Spontaneous Delivery.

Objective: To explore the effects of positive psychological nursing combined with free posture on the prognosis of primipara with singleton spontaneous delivery. Methods: 106 cases of primipara with singleton spontaneous delivery who were admitted to the obstetrics department of our hospital from January 2017 to December 2019 were selected as the research subjects and they were divided into the observation group and control group according to the random number table method and maternal willingness, with 53 cases in each group. The control group received routine nursing, and the observation group was given positive psychological nursing combined with free posture on the basis of the control group. The stress degree during delivery (Hamilton anxiety scale (HAMA) and Hamilton depression scale (HAMD)), the time of first stage of labor, the time of second stage of labor, the time of third stage of labor, pain level during the active period of the first stage of labor, and delivery outcomes were observed and compared between the two groups. Results: The degree of anxiety and depression during childbirth in the observation group was significantly lower than that in the control group (P < 0.05). The time of first stage of labor and the time of second stage of labor in the observation group were shorter than those in the control group (P < 0.05), and there was no significant difference in the time of the third stage of labor (P > 0.05). The pain degree in the active stage of the first stage of labor in the observation group was lower than that in the control group (P < 0.05). The pain degree in the active stage of the first stage of labor in the observation group was lower than that in the control group (P < 0.05). Conclusion: Positive psychological nursing combined with free posture for primipara with singleton spontaneous delivery can shorten the stages of labor, reduce the pain, relieve psychological stress, and improve the delivery outcomes.

Flexible coding scheme for robotic arm control driven by motor imagery decoding.

Objective. Brain computer interface (BCI) technology is an innovative way of information exchange, which can effectively convert physiological signals into control instructions of machines. Due to its spontaneity and device independence, the motor imagery (MI) electroencephalography (EEG) signal is used as a common BCI signal source to achieve direct control of external devices. Several online MI EEG-based systems have shown potential for rehabilitation. However, the generalization ability of the current classification model of MI tasks is still limited and the real-time prototype is far from widespread in practice.Approach. To solve these problems, this paper proposes an optimized neural network architecture based on our previous work. Firstly, the artifact components in the MI-EEG signal are removed by using the threshold and threshold function related to the artifact removal evaluation index, and then the data is augmented by the empirical mode decomposition (EMD) algorithm. Furthermore, the ensemble learning (EL) method and fine-tuning strategy in transfer learning (TL) are used to optimize the classification model. Finally, combined with the flexible binary encoding strategy, the EEG signal recognition results are mapped to the control commands of the robotic arm, which realizes multiple degrees of freedom control of the robotic arm.Main results. The results show that EMD has an obvious data amount enhancement effect on a small dataset, and the EL and TL can improve intra-subject and inter-subject model evaluation performance, respectively. The use of a binary coding method realizes the expansion of control instructions, i.e. four kinds of MI-EEG signals are used to complete the control of 7 degrees of freedom of the robotic arm.Significance. Our work not only improves the classification accuracy of the subject and the generality of the classification model while also extending the BCI control instruction set.

Evaluation of revolving algae biofilm reactors for nutrients and metals removal from sludge thickening supernatant in a municipal wastewater treatment facility.

This work is to evaluate pilot-scale Revolving Algal Biofilm (RAB) reactors of two heights (0.9-m and 1.8-m tall) to treat supernatant from sludge sedimentation at Metropolitan Water Reclamation District of Greater Chicago (MWRD) for removing nutrients (N and P) as well as various metals. The RAB reactors demonstrated a superior performance in N and P removal as compared to control raceway ponds. Taller 1.8-m RAB reactors performed better than 0.9-m RAB reactors in terms of total nutrient removal and algal biomass productivity. At 7-day HRT, total P (TP) and Total Kjeldahl N (TKN) removal efficiency reached to 80% and 87%, respectively, while ortho-P and ammonia removal efficiency reached to 100%. Decreasing HRT led to an enhanced TP and TKN removal rate and nutrient removal capacity. At HRT of 1.3-day, the TP removal per footprint of 1.8-m tall RAB reactors was around 7-times higher than the open pond system. The RAB reactors also showed certain capabilities of removing metals from wastewater. The study demonstrated that RAB-based treatment process is an effective method to recover nutrients from municipal wastewater.

Effect of continuous ozone injection on performance and biomass accumulation of biofilters treating gaseous toluene.

Biofilters treating high-concentration gaseous volatile organic compounds (VOC) can be subject to bed clogging induced by excess biomass accumulation. In this study, O3 was continuously injected into biofilters to control biomass. Its effects on the performance of the biofilters and on biomass accumulation were investigated. Four identical biofilters designed to treat gaseous toluene were operated for 70 days, and three of them were continuously injected with O3 at different concentrations (from 80 to 320 mg/m(3)). The results showed that continuous O3 injection could effectively keep the bed pressure drop stable and had no adverse effect on toluene removal when O3 concentrations were 180-220 mg/m(3). The maximum toluene elimination capacity of the four biofilters was 140 g-toluene/m(3)/h, and the bed pressure drop of the biofilter fed with 180-220 mg/m(3) O3 remained below 3 mmH2O/m throughout the operation period. The biomass accumulation rates of the three biofilters with O3 at 80-320 mg/m(3) were lowered by 0.15-0.25 g/L/day compared with the biofilter without O3. The decreases in biomass accumulation resulted in higher void fractions of the filter beds with O3 injection. Carbon balance analysis indicated that CO2 production had increased while biomass accumulation and leachate waste production decreased in response to O3 injection. Based on the experimental results, it was concluded here that continuous O3 injection can reduce increases in bed pressure effectively, preserve VOC removal capacity, and prevent production of extra leachate waste.

Effect of continuous ozone injection on performance and biomass accumulation of biofilters treating gaseous toluene.

Biofilters treating high-concentration gaseous volatile organic compounds (VOC) can be subject to bed clogging induced by excess biomass accumulation. In this study, O3 was continuously injected into biofilters to control biomass. Its effects on the performance of the biofilters and on biomass accumulation were investigated. Four identical biofilters designed to treat gaseous toluene were operated for 70 days, and three of them were continuously injected with O3 at different concentrations (from 80 to 320 mg/m(3)). The results showed that continuous O3 injection could effectively keep the bed pressure drop stable and had no adverse effect on toluene removal when O3 concentrations were 180-220 mg/m(3). The maximum toluene elimination capacity of the four biofilters was 140 g-toluene/m(3)/h, and the bed pressure drop of the biofilter fed with 180-220 mg/m(3) O3 remained below 3 mmH2O/m throughout the operation period. The biomass accumulation rates of the three biofilters with O3 at 80-320 mg/m(3) were lowered by 0.15-0.25 g/L/day compared with the biofilter without O3. The decreases in biomass accumulation resulted in higher void fractions of the filter beds with O3 injection. Carbon balance analysis indicated that CO2 production had increased while biomass accumulation and leachate waste production decreased in response to O3 injection. Based on the experimental results, it was concluded here that continuous O3 injection can reduce increases in bed pressure effectively, preserve VOC removal capacity, and prevent production of extra leachate waste.