WTAP promotes proliferation of esophageal squamous cell carcinoma via m6A-dependent epigenetic promoting of PTP4A1.

Esophageal squamous cell carcinoma (ESCC) represents a frequently seen malignancy with high prevalence worldwide. Although current studies have shown that Wilms' tumor 1-associated protein (WTAP), a major part in the methyltransferase complex, is involved in various tumor pathological processes, its specific role in ESCC remains unclear. Therefore, the present work focused on exploring WTAP's function and mechanism in ESCC progression using clinical ESCC specimens, ESCC cells, and mammalian models. Firstly, we proved WTAP was significantly upregulated within ESCC, and WTAP mRNA expression showed a good diagnostic performance for ESCC. Functionally, WTAP positively regulated in-vivo and in-vitro ESCC cells' malignant phenotype through the AKT-mTOR signaling pathway. Meanwhile, WTAP positively regulated the N6-methyladenosine (m6A) modification levels in ESCC cells. Protein tyrosine phase type IVA member 1 (PTP4A1) was confirmed to be the m6A target of WTAP, and WTAP positively regulated the expression of PTP4A1. Further study revealed that PTP4A1 showed high expression within ESCC. Silencing PTP4A1 inhibited the AKT-mTOR signaling pathway to suppress ESCC cells' proliferation. Rescue experiments showed that silencing PTP4A1 partially reversed the WTAP-promoting effect on ESCC cells' proliferation ability. Mechanistically, WTAP regulated PTP4A1 expression to activate the AKT-mTOR pathway, promoting the proliferation of ESCC cells. Our study demonstrated that WTAP regulates the progression of ESCC through the m6A-PTP4A1-AKT-mTOR signaling axis and that WTAP is a potential target for diagnosing and treating ESCC.

Conventional versus high-voltage, long-term pulse Radiofrequency of ganglion impar in perineal pain with advanced rectal cancer: a Randomized, double-blind controlled trial.

STUDY OBJECTIVE: Advanced rectal cancer is a common cause of perineal pain and research on the use of radiofrequency therapy for the treatment of this pain is limited. In the present study, we aimed to compare the effectiveness and safety of conventional radiofrequency (CRF) and high-voltage long-term pulsed radiofrequency (H-PRF) of radiofrequency therapy in the management of perineal pain in advanced rectal cancer. DESIGN: Randomized, Double-Blind Controlled Trial. SETTING: Sichuan Cancer Hospital & Institute and Yanjiang District People's Hospital in Sichuan, China. PARTICIPANTS: A total of 72 patients with advanced rectal cancer experiencing perineal pain who were accepted for radiofrequency treatment. INTERVENTIONS: Patients were assigned randomly (1:1) assigned to either the group CRF or H-PRF in a double-blind trial. MEASUREMENTS AND MAIN RESULTS: The primary focus was on assessing perineal pain using numeric rating scales (NRS) scores at various time points. Secondary outcomes included the duration of maintaining a sitting position, depression scores, sleep quality, consumption of Oral Morphine Equivalent and Pregabalin, and the incidence of perineal numbness. A total of 57 patients (28 patients in the group CRF and 29 patients in the group H-PRF) were investigated. At all observation time points postoperatively, both groups of patients exhibited significant reductions in pain, enhancements in depression, improvements in sleep quality, and increased duration of sitting compared to their baseline measurements (P<0.05). During the 3 months and 6 months follow-up period, the group CRF exhibited significant reduction in pain, improvement in depression, sleep quality, and increased the time of keeping a sitting position compared with the group H-PRF (P<0.05). The consumption of oral morphine equivalent and Pregabalin as well as the incidence of perineal numbness were not significantly different between groups (P > 0.05). CONCLUSION: Our results demonstrate that application of CRF and H-PRF in ganglion impar to reduce perineal pain and improve the quality of life of patients with advanced rectal cancer is safe and effective. However, the long-term effect of CRF is better compared with that of H-PRF. TRIAL REGISTRATION: https://www.chictr.org.cn/ (ChiCTR2200061800) on 02/07/2022. This study adheres to CONSORT guidelines.

A rare case of esophageal anthracosis presenting as a submucosal tumor.

A 62-year-old man with a history of heartburn and regurgitation was referred for the management of a black lesion in the middle esophagus. Our Esophagogastroduodenoscopy (EGD) showed a 13 mm, black protruding lesion located 29cm from the incisor teeth. Endoscopic ultrasonography (EUS) showed a 11.7 mm×7.2 mm hyperechoic mass in the esophageal wall arising in layer 2 and 3. Biopsy of the lesion showed a black and elastic hard appearance. Pathological examination showed chronic inflammatory with coal dust underneath the mucosal epithelium.

SIP/CacyBP promotes autophagy by regulating levels of BRUCE/Apollon, which stimulates LC3-I degradation.

BRUCE/Apollon is a membrane-associated inhibitor of apoptosis protein that is essential for viability and has ubiquitin-conjugating activity. On initiation of apoptosis, the ubiquitin ligase Nrdp1/RNF41 promotes proteasomal degradation of BRUCE. Here we demonstrate that BRUCE together with the proteasome activator PA28γ causes proteasomal degradation of LC3-I and thus inhibits autophagy. LC3-I on the phagophore membrane is conjugated to phosphatidylethanolamine to form LC3-II, which is required for the formation of autophagosomes and selective recruitment of substrates. SIP/CacyBP is a ubiquitination-related protein that is highly expressed in neurons and various tumors. Under normal conditions, SIP inhibits the ubiquitination and degradation of BRUCE, probably by blocking the binding of Nrdp1 to BRUCE. On DNA damage by topoisomerase inhibitors, Nrdp1 causes monoubiquitination of SIP and thus promotes apoptosis. However, on starvation, SIP together with Rab8 enhances the translocation of BRUCE into the recycling endosome, formation of autophagosomes, and degradation of BRUCE by optineurin-mediated autophagy. Accordingly, deletion of SIP in cultured cells reduces the autophagic degradation of damaged mitochondria and cytosolic protein aggregates. Thus, by stimulating proteasomal degradation of LC3-I, BRUCE also inhibits autophagy. Conversely, SIP promotes autophagy by blocking BRUCE-dependent degradation of LC3-I and by enhancing autophagosome formation and autophagic destruction of BRUCE. These actions of BRUCE and SIP represent mechanisms that link the regulation of autophagy and apoptosis under different conditions.

HSF1 functions as a key defender against palmitic acid-induced ferroptosis in cardiomyocytes.

Palmitic acid (PA)-induced myocardial injury is considered a critical contributor to the development of obesity and type 2 diabetes mellitus (T2DM)-related cardiomyopathy. However, the underlying mechanism has not been fully understood. Here, we demonstrated that PA induced the cell death of H9c2 cardiomyoblasts in a dose- and time-dependent manner, while different ferroptosis inhibitors significantly abrogated the cell death of H9c2 cardiomyoblasts and primary neonatal rat cardiomyocytes exposed to PA. Mechanistically, PA decreased the protein expression levels of both heat shock factor 1 (HSF1) and glutathione peroxidase 4 (GPX4) in a dose- and time-dependent manner, which were restored by different ferroptosis inhibitors. Overexpression of HSF1 not only alleviated PA-induced cell death and lipid peroxidation but also improved disturbed iron homeostasis by regulating the transcription of iron metabolism-related genes (e.g., Fth1, Tfrc, Slc40a1). Additionally, PA-blocked GPX4 protein expression was evidently restored by HSF1 overexpression. Inhibition of endoplasmic reticulum (ER) stress rather than autophagy contributed to HSF1-mediated GPX4 expression. Moreover, GPX4 overexpression protected against PA-induced ferroptosis, whereas knockdown of GPX4 reversed the anti-ferroptotic effect of HSF1. Consistent with the in vitro findings, PA-challenged Hsf1-/- mice exhibited more serious ferroptosis, increased Slc40a1 and Fth1 mRNA expression, decreased GPX4 and TFRC expression and enhanced ER stress in the heart compared with Hsf1+/+ mice. Altogether, HSF1 may function as a key defender against PA-induced ferroptosis in cardiomyocytes by maintaining cellular iron homeostasis and GPX4 expression.

The M6A methyltransferase METTL3 regulates proliferation in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the most lethal human cancers with a lower 5-year survival rate. N6-methyladenosine (m6A) methylation, an important epigenetic modification, has been reported to associate with physiological and pathological processes of cancers. However, its role in ESCC remains unclear. In this work, we found that the m6A levels were elevated in ESCC cancer tissues and ESCC cells. The PPI network demonstrated that METTL3, METTL14, WTAP, RBM15, and KIAA1429 were all significantly associated with each other. Moreover, we found a significant upregulation of METTL3 mRNA and protein amounts in ESCC tissues. The METTL3 mRNA expression level of tissues had associations with ESCC differentiation extent and sex (p < 0.05). The METTL3 mRNA expression level of tissues, sensitivity for diagnosing ESCC was 75.00%, specificity was 72.06% and area under the ROC curve was 0.8030. Depletion of METTL3 markedly diminished m6A levels in human ESCC cell lines and METTL3 overexpression restored the reduction in m6A levels. These results suggested that METTL3 is the primary enzyme that modulates m6A methylation and a critical regulatory factor in ESCC. Additionally, METTL3 knockdown significantly suppressed the ESCC cell proliferation, while METTL3 overexpression markedly promoted ESCC cell proliferation both in cell and animal models. These results demonstrated that METTL3 promotes ESCC development. Furthermore, METTL3 may modulate the cell cycle of ESCC cells through a p21-dependent pattern. METTL3-guided m6A modification may contribute to the progression of ESCC via the p21-axis. Our study is the first investigation to report that METTL3-mediated m6A methylation plays a crucial role in ESCC oncogenesis and highlights that METTL3 might be a potential biomarker and therapeutic target for ESCC patients.

Metformin protects against ischaemic myocardial injury by alleviating autophagy-ROS-NLRP3-mediated inflammatory response in macrophages.

Myocardial ischaemia is usually accompanied by inflammatory response which plays a critical role in the myocardial healing and scar formation, while persistent inflammatory response contributes greatly to the myocardial remodeling and consequent heart failure. Metformin (Met), a widely used hypoglycemic drug, has increasingly been shown to exert remarkable cardioprotective effect on ischaemic myocardial injury such as acute myocardial infarction (AMI). However, the underlying mechanisms are still far from being fully understood. In this study, a mouse model of AMI was established through ligating the left anterior descending coronary artery (LAD), 100 mg/kg Met was given immediately after operation once daily for 3 days. It was demonstrated that Met effectively improved the cardiac haemodynamics (LVSP, LVEDP, +dp/dt, -dp/dt), diminished the infarct size, alleviated the disarrangement of myocardial cells and reduced the infiltration of inflammatory cells (macrophages, neutrophils and lymphocytes) in the heart of AMI mice. Mechanistically, Met decreased the expression of NLRP3 and enhanced the accumulation of LC3 puncta in F4/80-positive macrophages in the heart of AMI mice. Single cell suspension of cardiac macrophages was prepared from AMI mice and exhibited increased NLRP3 mRNA and protein expression. In contrast, Met decreased the expression of NLRP3 and p62, whereas increased the ratio of LC3II/LC3I. Additionally, both conditioned medium from H9c2 cardiomyocytes exposed to hydrogen peroxide (H9c2-H2O2-CM) and combination of mtDNA and ATP (mtDNA-ATP) increased the expression of NLRP3 and cleaved caspase-1 (p10) as well as intracellular ROS production in RAW264.7 macrophages, which were abrogated by Met treatment. Strikingly, chloroquine (CQ), 3-methyladenine (3-MA) and knockdown of autophagy-related gene (Atg5) abrogated the inhibitory effects of Met on H9c2-H2O2-CM and mtDNA-ATP-induced NLRP3 expression, release of IL-1ß and IL-18 as well as ROS production in RAW264.7 macrophages. Collectively, these findings suggest that Met protects against ischaemic myocardial injury through alleviating autophagy-ROS-NLRP3 axis-mediated inflammatory response in macrophages.

Systematic prediction of key genes for ovarian cancer by co-expression network analysis.

Ovarian cancer (OC) is the most lethal gynaecological malignancy, characterized by high recurrence and mortality. However, the mechanisms of its pathogenesis remain largely unknown, hindering the investigation of the functional roles. This study sought to identify key hub genes that may serve as biomarkers correlated with prognosis. Here, we conduct an integrated analysis using the weighted gene co-expression network analysis (WGCNA) to explore the clinically significant gene sets and identify candidate hub genes associated with OC clinical phenotypes. The gene expression profiles were obtained from the MERAV database. Validations of candidate hub genes were performed with RNASeqV2 data and the corresponding clinical information available from The Cancer Genome Atlas (TCGA) database. In addition, we examined the candidate genes in ovarian cancer cells. Totally, 19 modules were identified and 26 hub genes were extracted from the most significant module (R2  = .53) in clinical stages. Through the validation of TCGA data, we found that five hub genes (COL1A1, DCN, LUM, POSTN and THBS2) predicted poor prognosis. Receiver operating characteristic (ROC) curves demonstrated that these five genes exhibited diagnostic efficiency for early-stage and advanced-stage cancer. The protein expression of these five genes in tumour tissues was significantly higher than that in normal tissues. Besides, the expression of COL1A1 was associated with the TAX resistance of tumours and could be affected by the autophagy level in OC cell line. In conclusion, our findings identified five genes could serve as biomarkers related to the prognosis of OC and may be helpful for revealing pathogenic mechanism and developing further research.

Quantitative viability detection for a single microalgae cell by two-level photoexcitation.

A novel method for quantitative detection of the viability of a single microalgae cell by two-level photoexcitation is proposed in this paper. This method overcomes the difficulty of traditional methods in determining the cell viability by a fixed standard under a single photoexcitation. It is experimentally confirmed that this method is not limited by the species, morphology, size and structure of microalgae cells. An evaluation criterion of universal applicability is presented for the assessment of cell viability based on the large amount of experimental data. To the best of our knowledge, this is the first time that the relative fluorescence yield ratio Fr has been used to characterize the viability of single microalgae cells during cell migration. By using the relative fluorescence yield ratio, this method does not require the intensity of the excitation light to be very low for the assessment of the fluorescence yield of a dark-adapted microalgae cell, nor to be very strong to reach the saturated light level to assess the maximum fluorescence yield. Therefore, this method greatly reduces the technical difficulties of developing a sensor device. Well balanced portability, accuracy and universal applicability make it suitable for on-site real-time detection.

VEGF-A promotes angiogenesis after acute myocardial infarction through increasing ROS production and enhancing ER stress-mediated autophagy.

Proangiogenesis is generally regarded as an effective approach for treating ischemic heart disease. Vascular endothelial growth factor (VEGF)-A is a strong and essential proangiogenic factor. Reactive oxygen species (ROS), endoplasmic reticulum (ER) stress, and autophagy are implicated in the process of angiogenesis. This study is designed to clarify the regulatory mechanisms underlying VEGF-A, ROS, ER stress, autophagy, and angiogenesis in acute myocardial infarction (AMI). A mouse model of AMI was successfully established by occluding the left anterior descending coronary artery. Compared with the sham-operated mice, the microvessel density, VEGF-A content, ROS production, expression of vascular endothelial cadherin, positive expression of 78 kDa glucose-regulated protein/binding immunoglobulin protein (GRP78/Bip), and LC3 puncta in CD31-positive endothelial cells of the ischemic myocardium were overtly elevated. Moreover, VEGF-A exposure predominantly increased the expression of beclin-1, autophagy-related gene (ATG) 4, ATG5, inositol-requiring enzyme-1 (IRE-1), GRP78/Bip, and LC3-II/LC3-I as well as ROS production in the human umbilical vein endothelial cells (HUVECs) in a dose and time-dependent manner. Both beclin-1 small interfering RNA and 3-methyladenine treatment predominantly mitigated VEGF-A-induced tube formation and migration of HUVECs, but they failed to elicit any notable effect on VEGF-A-increased expression of GRP78/Bip. Tauroursodeoxycholic acid not only obviously abolished VEGF-A-induced increase of IRE-1, GRP78/Bip, beclin-1 expression, and LC3-II/LC3-I, but also negated VEGF-A-induced tube formation and migration of HUVECs. Furthermore, N-acetyl- l-cysteine markedly abrogated VEGF-A-increased ROS production, IRE-1, GRP78/Bip, beclin-1 expression, and LC3-II/LC3-I in the HUVECs. Taken together, our data demonstrated that increased spontaneous production of VEGF-A may induce angiogenesis after AMI through initiating ROS-ER stress-autophagy axis in the vascular endothelial cells.

Heat-shock protein B1 upholds the cytoplasm reduced state to inhibit activation of the Hippo pathway in H9c2 cells.

Heat-shock protein B1 (HSPB1) is a multifunctional protein that protects against oxidative stress; however, its function in antioxidant pathways remains largely unknown. Here, we sought to determine the roles of HSPB1 in H9c2 cells subjected to oxidative stress. Using nonreducing sodium dodecyl sulfate polyacrylamide gel electrophoresis, we found that increased HSPB1 expression promoted the reduced states of glutathione reductase (GR), peroxiredoxin 1 (Prx1), and thioredoxin 1, whereas knockdown of HSPB1 attenuated these responses following oxidative stress. Increased HSPB1 expression promoted the activation of GR and thioredoxin reductase. Conversely, knockdown of HSPB1 attenuated these responses following oxidative stress. Importantly, overexpression of HSPB1 promoted the complex formation between HSPB1 and oxidized Prx1, leading to dephosphorylation of STE-mammalian STE20-like kinase 1 (MST1) in H9c2 cells exposed to H2 O 2 , whereas downregulation of HSPB1 induced the opposite results. Mechanistically, HSPB1 regulated the Hippo pathway by enhancing the dephosphorylation of MST1, resulting in reduced phosphorylation of LATS1 and Yes-associated protein (YAP). Moreover, HSPB1 regulated YAP-dependent gene expression. Thus, HSPB1 promoted the reduced state of endogenous antioxidant pathways following oxidative stress in H9c2 cells and improved the redox state of the cytoplasm via modulation of the Hippo signaling pathway.

A Microfluidic Prototype System towards Microalgae Cell Separation, Treatment and Viability Characterization.

There are a huge number, and abundant types, of microalgae in the ocean; and most of them have various values in many fields, such as food, medicine, energy, feed, etc. Therefore, how to identify and separation of microalgae cells quickly and effectively is a prerequisite for the microalgae research and utilization. Herein, we propose a microfluidic system that comprised microalgae cell separation, treatment and viability characterization. Specifically, the microfluidic separation function is based on the principle of deterministic lateral displacement (DLD), which can separate various microalgae species rapidly by their different sizes. Moreover, a concentration gradient generator is designed in this system to automatically produce gradient concentrations of chemical reagents to optimize the chemical treatment of samples. Finally, a single photon counter was used to evaluate the viability of treated microalgae based on laser-induced fluorescence from the intracellular chlorophyll of microalgae. To the best of our knowledge, this is the first laboratory prototype system combining DLD separation, concentration gradient generator and chlorophyll fluorescence detection technology for fast analysis and treatment of microalgae using marine samples. This study may inspire other novel applications of micro-analytical devices for utilization of microalgae resources, marine ecological environment protection and ship ballast water management.

Using the capnogram to assess pulmonary perfusion during a lobectomy: case studies.

Capnography is an effective and non-invasive method for monitoring patients during general anesthesia and can reflect the changes in both the respiratory function as well as the circulatory function. In this paper, we present four cases of lobectomy in which we observed a "chair-like" waveform on performing capnography after the surgery. In all the cases, the appearance of this "chair-like" waveform led to the suspicion of a blockage in the pulmonary artery perfusion, which was then confirmed to be an obstruction in the pulmonary artery on further investigation. This suggests that during lobectomy, capnography can help confirm that the pulmonary circulation is unobstructed. We believe that it is very important to observe the changes of end-tidal carbon dioxide pressure and capnogram during one-lung ventilation, particularly in cases of pulmonary artery anastomosis.

Nucleolin mediated pro-angiogenic role of Hydroxysafflor Yellow A in ischaemic cardiac dysfunction: Post-transcriptional regulation of VEGF-A and MMP-9.

Hydroxysafflor Yellow A (HSYA), a most representative ingredient of Carthamus tinctorius L., had long been used in treating ischaemic cardiovascular diseases in China and exhibited prominently anticoagulant and pro-angiogenic activities, but the underlying mechanisms remained largely unknown. This study aimed to further elucidate the pro-angiogenic effect and mechanism of HSYA on ischaemic cardiac dysfunction. A C57 mouse model of acute myocardial infarction (AMI) was firstly established, and 25 mg/kg HSYA was intraperitoneally injected immediately after operation and given once, respectively, each morning and evening for 2 weeks. It was found that HSYA significantly improved ischaemia-induced cardiac haemodynamics, enhanced the survival rate, alleviated the myocardial injury and increased the expressions of CD31, vascular endothelial growth factor-A (VEGF-A) and nucleolin in the ischaemic myocardium. In addition, HSYA promoted the migration and tube formation of human umbilical vein endothelial cells (HUVECs), enhanced the expressions of nucleolin, VEGF-A and matrix metalloproteinase-9 (MMP-9) in a dose- and time-dependent manner. However, down-regulation of nucleolin expression sharply abrogated the effect mentioned above of HSYA. Further protein-RNA coimmunoprecipitation and immunoprecipitation-RT-PCR assay showed that nucleolin binded to VEGF-A and MMP-9 mRNA and overexpression of nucleolin up-regulated the mRNA expressions of VEGF-A and MMP-9 in the HUVECs through enhancing the stability of VEGF-A and MMP-9 mRNA. Furthermore, HSYA increased the mRNA expressions of VEGF-A and MMP-9 in the extract of antinucleolin antibody-precipitated protein from the heart of AMI mice. Our data revealed that nucleolin mediated the pro-angiogenic effect of HSYA through post-transcriptional regulation of VEGF-A and MMP-9 expression, which contributed to the protective effect of HSYA on ischaemic cardiac dysfunction.

Screening of sustainable supply chain performance evaluation indicators based on the ill-conditioned index cycle method.

The establishment of an evaluation indicator system that can accurately assess the sustainability of a supply chain while further enhancing its performance is vital and relevant. Based on the connotation of sustainable supply chains and triple bottom line theory, indicators are initially proposed from economic, environmental, and social dimensions. To increase the explanatory power of the indicator system and decrease information redundancy, the coefficient of variation is applied to identify the indicators with weak interpretation intensity, the ill-conditioned index cycle method is utilized to filter out indicators with redundant information, and data on 100 Chinese listed companies from 2019 to 2021 are used as samples. A performance evaluation indicator system of sustainable supply chains with 16 indicators is ultimately established. The information interpretation strength index and cumulative information contribution rate verify the rationality of the final indicator system. The outcome demonstrates that this screening method can strengthen the representativeness of the indicator system and rapidly reduce redundancy, leading to the better discrimination of the evaluation results. The findings of this study provide an indicator system and a methodological reference for both companies and policymakers and can aid in the transformation of supply chains toward sustainability.

Nanostructured SnO2 Thin Films Based on a Convenient Chemical Deposition for Sensitive Detection of Ethanol.

A specific matrix sensor that can operate at low temperatures and has a high sensing response is crucial for monitoring flammable VOC gases. In this study, a nanostructured SnO2 thin film was successfully produced using a suitable chemical deposition method, and its sensing properties were comprehensively analyzed. The SEM images revealed that the thin film of the nanostructured SnO2 is made up of two different sizes of broccoli-like structure nanoparticles. The sensor, which is based on this unique micronano structure, demonstrated a high sensing response (44), low operating temperature (200 °C), and fast response time (6s). Additionally, the nanostructured sensor exhibited excellent resistance to humidity interference and long-term stability. Moreover, DFT is employed to evaluate the electronic properties and to systematically explain the gas sensing mechanism of the nanostructured sensor based on the SnO2 thin film.

Exercise as a promising alternative for sciatic nerve injury pain relief: a meta-analysis.

Objective: The efficacy of drug therapies in managing neuropathic pain is constrained by their limited effectiveness and potential for adverse effects. In contrast, exercise has emerged as a promising alternative for pain relief. In this study, we conducted a systematic evaluation of the therapeutic impact of exercise on neuropathic pain resulting from sciatic nerve injury in rodent models. Methods: The PubMed, Embase, and Web of Science databases were retrieved before April 2024. A series of studies regarding the effect of treadmill, swimming, wheel and other exercises on neuropathic pain induced by sciatic nerve injury in rats and mice were collected. Using predefined inclusion criteria, two researchers independently performed literature screening, data extraction, and methodological quality assessment utilizing SYRCLE's risk of bias tool for animal studies. Statistical analysis was conducted using RevMan 5.3 and STATA 12.0 analysis software. Results: A total of 12 relevant academic sources were included in the analysis of controlled animal studies, with 133 rodents in the exercise group and 135 rodents in the sedentary group. The meta-analysis revealed that exercise was associated with a significant increase in paw withdrawal mechanical threshold [Standard Mean Difference (SMD) = 0.84, 95% confidence interval (CI): 0.28-1.40, p = 0.003] and paw withdrawal thermal latency (SMD = 1.54, 95%CI: 0.93-2.15, p < 0.0001) in rats and mice with sciatic nerve injury. Subgroup analyses were conducted to evaluate the impact of exercise duration on heterogeneity. The results showed that postoperative exercise duration ≤3 weeks could significantly elevate paw withdrawal mechanical threshold (SMD = 1.04, 95% CI: 0.62-1.46, p < 0.00001). Postoperative exercise duration ≤4 weeks could significantly improve paw withdrawal thermal latency (SMD = 1.93, 95% CI:1.19-2.67, p < 0.00001). Conclusion: Exercise represents an effective method for improving mechanical and thermal hypersensitivity resulting from sciatic nerve injury in rodents. Factors such as pain models, the initiation of exercise, the type of exercise, and the species of rodent do not significantly impact the development of exercise-induced hypoalgesia. However, the duration of postoperative exercise plays a crucial role in the onset of exercise-induced hypoalgesia.

Dexterous electrical-driven soft robots with reconfigurable chiral-lattice foot design.

Dexterous locomotion, such as immediate direction change during fast movement or shape reconfiguration to perform diverse tasks, are essential animal survival strategies which have not been achieved in existing soft robots. Here, we present a kind of small-scale dexterous soft robot, consisting of an active dielectric elastomer artificial muscle and reconfigurable chiral-lattice foot, that enables immediate and reversible forward, backward and circular direction changes during fast movement under single voltage input. Our electric-driven soft robot with the structural design can be combined with smart materials to realize multimodal functions via shape reconfigurations under the external stimulus. We experimentally demonstrate that our dexterous soft robots can reach arbitrary points in a plane, form complex trajectories, or lower the height to pass through a narrow tunnel. The proposed structural design and shape reconfigurability may pave the way for next-generation autonomous soft robots with dexterous locomotion.

Effects of Fe, Mn Individual Doping and (Fe, Mn) Co-Doping on Ferromagnetic Properties of Co2Si Powders.

Magnetic materials are crucial energy materials that are widely used in day-to-day life. Therefore, the development and study of high-performance magnetic materials are of great significance. In this study, the magnetic materials Co66.6Si33.4, Co60.6X6Si33.4 (X = Fe, Mn), and Co60.6Fe3Mn3Si33.4 were prepared via the ball milling and sintering processes. Their crystal structures, electrical conductivity, and magnetic properties were investigated via the X-ray diffraction analysis and by using a resistivity tester, vibrating sample magnetometer, and vector network analyser. The X-ray diffraction analysis revealed that a single phase of Co66.6Si33.4 and its doped alloy powders were successfully obtained. The electrical conductivities of Mn6Co60.6Si33.4 and Fe3Mn3Co60.6Si33.4 were measured using a resistivity tester. The results indicate that Mn doping and Fe and Mn Co-doping enhanced the electrical conductivity of Co66.6Si33.4. The magnetic properties of Co66.6Si33.4 were determined using a vibrating sample magnetometer. We observed that the magnetic properties were enhanced after doping. Co60.6Fe3Mn3Si33.4 exhibited excellent magnetic properties. Further, its permeability was determined using a vector network analyser. At a low frequency, the u' and u" values of Co60.6Fe6Si33.4 and Co60.6Fe3Mn3Si33.4 were enhanced; whereas, at a high frequency, after doping, the u' and u" values changed only slightly. This study can be used as a basis for future studies on magnetic functional materials.

Aberrant HSF1 signaling activation underlies metformin amelioration of myocardial infarction in mice.

Myocardial infarction (MI) is a cardiovascular disease with high morbidity and mortality. Clinically, rehabilitation after massive MI often has a poor prognosis. Therefore, it is necessary to explore the therapeutic methods of myocardial protection after MI. As a first-line treatment for type 2 diabetes, metformin has been found to have a certain protective effect on myocardial tissue. However, its pharmacological mechanism remains unclear. In this study, we investigated key factors that reduced MI with metformin. Through in vivo, in vitro, and in silico analyses, we identified HSF1 as a key target for metformin. HSF1 could up-regulate the transcriptional level of AMPKα2 through transcriptional activation and stimulate the activity of the downstream AMPK/mTOR signaling pathway. Metformin stimulated cardiomyocytes to form stress granules (SGs), and knockdown of HSF1 reversed this process. Furthermore, HSF1 exhibited better in vitro affinity for metformin than AMPK, suggesting that HSF1 may be a more sensitive target for metformin.