Mind In Vitro Platforms: Versatile, Scalable, Robust, and Open Solutions to Interfacing with Living Neurons.

Motivated by the unexplored potential of in vitro neural systems for computing and by the corresponding need of versatile, scalable interfaces for multimodal interaction, an accurate, modular, fully customizable, and portable recording/stimulation solution that can be easily fabricated, robustly operated, and broadly disseminated is presented. This approach entails a reconfigurable platform that works across multiple industry standards and that enables a complete signal chain, from neural substrates sampled through micro-electrode arrays (MEAs) to data acquisition, downstream analysis, and cloud storage. Built-in modularity supports the seamless integration of electrical/optical stimulation and fluidic interfaces. Custom MEA fabrication leverages maskless photolithography, favoring the rapid prototyping of a variety of configurations, spatial topologies, and constitutive materials. Through a dedicated analysis and management software suite, the utility and robustness of this system are demonstrated across neural cultures and applications, including embryonic stem cell-derived and primary neurons, organotypic brain slices, 3D engineered tissue mimics, concurrent calcium imaging, and long-term recording. Overall, this technology, termed "mind in vitro" to underscore the computing inspiration, provides an end-to-end solution that can be widely deployed due to its affordable (>10× cost reduction) and open-source nature, catering to the expanding needs of both conventional and unconventional electrophysiology.

Acupuncture for gait disturbance of patients with subacute and chronic stroke: a systematic review and meta-analysis protocol.

INTRODUCTION: Hemiparetic gait is one of the most common sequelae of a stroke. Acupuncture has shown potential in correcting hemiplegic gait patterns and improving motor function recovery after stroke. However, controversial findings and a lack of supportive evidence on the effectiveness of acupuncture for post-stroke hemiplegia. The intelligent gait analysis system provides a new perspective for the study of hemiparetic gait. This systematic review aims to collect relevant studies and critically evaluate the efficacy and safety of acupuncture in alleviating gait disturbance of post-stroke hemiplegia based on quantified gait parameters. METHODS AND ANALYSIS: A comprehensive search of PubMed, Embase, Cochrane stroke group trials register, Cochrane Central Register of Controlled Trials, CINAHL, AMED, three Chinese databases (Chinese Biomedical Literatures database (CBM), National Knowledge Infrastructure (CNKI), and Wan fang Digital Periodicals), four trails registries (The WHO International Clinical Trials Registry Platform, The Chinese Clinical Trial Registry, The US National Institutes of Health Ongoing Trials Register, and The Australian New Zealand Clinical Trials Registry) will be conducted to identify randomised controlled trials of acupuncture for gait disturbance in post-stroke patients. No restrictions on language or publication status. The primary outcomes are gait temporospatial parameters (eg, step length, stride length, step width, step frequency (cadence), walking speed, etc), and gait kinematic parameters (eg, hip peak flex/extend angle, knee peak flex/extend angle, ankle peak dorsi/plantar-flexion angle, etc). We will assess bias using the approach recommended by the Cochrane Handbook for Systematic Reviews of Interventions. A meta-analysis will be conducted to synthesise the evidence for each outcome measure. The χ2 test and I2 statistic will be used for assessing heterogeneity between studies. ETHICS AND DISSEMINATION: No ethical approval is needed because no primary data is collected. Scientific conferences or peer-reviewed journals will publish the findings. PROSPERO REGISTRATION NUMBER: CRD42022384348.

Clinical efficacy of the shallow puncture and more-twirling acupuncture method in migraine treatment and its effects on serum 5-HT and ß-EP levels.

BACKGROUND: The incidence rate for migraine is 12% worldwide, and recurrence is common, which seriously affects the physical and mental health of patients. OBJECTIVE: To observe the clinical effect of Shallow Puncture and More Twirling method of acupuncture in treating migraine and its impact on serum 5-HT and ß-EP. METHODS: A total of 76 patients with migraine were randomized into a control group and acupuncture group with 38 cases in each. In the control group, patients were orally administered flunarizine hydrochloride before sleep, 2 capsules once daily for 4 weeks. In the acupuncture group, Shallow Puncture and More Twirling method was adopted for the acupoints of Sizhukong (SJ 23), Toulinqi (GB 15) Shuaigu (GB 8), Xuanlu (GB 5), Fengchi (GB 20), Waiguan (SJ 5), Zulinqi (GB 41). Patients were given acupuncture 3 times per week for 4 weeks. Then, the total VAS (Visual Analogue Scale) scores, composite score of migraine, serum level of 5-HT and ß-EP, and the clinical efficacy differences were observed before and after treatment and the side-effects were recorded among the two groups. RESULTS: The total VAS scores and composite score of migraine were significantly reduced among both groups after the treatment (P< 0.05), and the serum level of 5-HT and ß-EP was significantly improved (P< 0.05). Compared with control group, the acupuncture group reported lower results in VAS score and migraine composite score (P< 0.05), and higher results in serum 5-HT and ß-EP level (P< 0.05). The acupuncture group with shallow puncture and more twirling method showed a total effective rate of 86.5%, which is higher than the control group (78.4%). The difference is statistically significant (P< 0.05). CONCLUSION: Shallow Puncture and More Twirling method was superior to flunarizine hydrochloride in the treatment of clinical symptoms of migraine. Acupuncture also increases the serum level of 5-HT and ß-EP in migraine.

Shexiang Baoxin Pill attenuates myocardial ischemia/reperfusion injury by activating autophagy via modulating the ceRNA-Map3k8 pathway.

BACKGROUND: The pathogenesis of myocardial ischemia/reperfusion is complex, involving multiple regulatory genes and environmental factors, and requiring the simultaneous regulation of multiple targets. Meanwhile, Traditional Chinese Medicine (TCM) has certain advantages in the comprehensive treatment of multi-site, multi-target conditions and overall regulation of this condition. This study explores the effect of the well-known TCM, the Shexiang Baoxin Pill (SBP) on myocardial ischemia/reperfusion injury in mice. MATERIALS AND METHODS: In vivo, 20 mg/kg/day SBP was administered by gavage for 28 days. In vitro, cardiomyocytes were pretreated with 25 µg/ml SBP for 24 h. Evans blue/TTC double-staining was employed to determine the infarct size. Markers of myocardial injury were detected in the serum and cell supernatants. The changes of pyroptosis and autophagy proteins were detected by western blot. Immunofluorescence, immunohistochemistry and PCR were performed to further illustrate the results. RESULTS: SBP significantly reduced the myocardial infarct size, decreased the myocardial injury markers, inhibited cardiomyocyte pyroptosis and oxidative stress, and promoted autophagy in vivo. In vitro, SBP alleviated cardiomyocyte pyroptosis, inhibited oxidative stress, reduced IL-1ß and IL-18 secretion, and unblocked autophagy flux. Myocardial injury is mitigated by SBP via the rapid degradation of autophagosomes, and SBP promotes the accumulation of autophagosomes by downregulating mmu_circ_0005874, Map3k8 and upregulating mmu-miR-543-3p. CONCLUSION: We found for the first time that SBP can inhibit pyroptosis and oxidative stress, and protect from myocardial I/R injury. In addition, it inhibits pyroptosis and improves H/R injury by promoting autophagosome generation and accelerating autophagic flux. SBP interferes with autophagy through the interaction between mmu_circ_0005874/mmu-miR-543-3p/Map3k8.

A Single, Acute Astragaloside IV Therapy Protects Cardiomyocyte Through Attenuating Superoxide Anion-Mediated Accumulation of Autophagosomes in Myocardial Ischemia-Reperfusion Injury.

Myocardial ischemia-reperfusion (I/R) injury, characterized by myocardial cell death (e.g., apoptosis) and generation of reactive oxygen species (ROS) such as superoxide (O2 ·-) and hydrogen peroxide (H2O2), is a serious threat to human health and property. Saponin astragaloside IV (ASIV), extracted from Chinese herbal medicine astragalus, is effective in resolving multiple pathological issues including myocardial I/R injury. Recent studies have shown that autophagy is regulated by ROS and plays an important role in myocardial I/R injury. However, regulation of autophagy by ASIV during myocardial I/R injury and the role of specific ROS involved in the process have been rarely reported. In the present study, we found that SOD2 was downregulated and O2 ·- was upregulated in H2O2-induced H9C2 cardiac myocyte injury in vitro and myocardial I/R injury in vivo, while such alterations were reversed by ASIV. ASIV possessed the ability to alleviate myocardial I/R injury via attenuating I/R-caused autophagosome accumulation. Upregulate of O2 ·- by 2-methoxyestradiol (2-ME) reversed the effect of ASIV-mediated autophagy regulation, which suggested that O2 ·- was vital in this process. In conclusion, our results contribute to understanding the mechanism of ASIV-induced cardioprotective effect.

Metformin suppresses inflammation and apoptosis of myocardiocytes by inhibiting autophagy in a model of ischemia-reperfusion injury.

Metformin (Met) is a major widely used oral glucose lowering drug for the treatment of type 2 diabetes. It is reported that metformin could regulate autophagy in various diseases of cardiovascular system including in I/R injury, diabetic cardiomyopathy and heart failure. Autophagy plays a controversial role in ischemia/reperfusion (I/R) injury, and this research was performed to explore the cardioprotective effect of Met on I/R injury and discuss the underlying mechanism of autophagy in it. In vivo and in vitro, Met exerted cardioprotection function of decreasing myocardial inflammation and apoptosis with a decrease in the level of autophagy. Moreover, Met significantly inhibited autophagosome formation and restore the impairment of autophagosome processing, which lead to cardioprotection effect of Met. Akt was up-regulated in Met-treated I/R hearts and miransertib, a pan-AKT inhibitor, was able to reverse the alleviating autophagy effect of Met. We demonstrate that Met protects cardiomyocytes from I/R-induced apoptosis and inflammation through down regulation of autophagy mediated by Akt signaling pathway.

Risk factors associated with intestinal necrosis in children with failed non-surgical reduction for intussusception.

BACKGROUND: Intestinal necrosis is the most serious complication of intussusception. The risk factors associated with intestinal necrosis in pediatric patients with intussusception have not been well characterized. OBJECTIVE: This study aimed to investigate the risk factors associated with intestinal necrosis in pediatric patients with failed non-surgical reduction for intussusception. METHODS: Hospitalized patients who failed the air-enema reduction for intussusception in the outpatient department and subsequently underwent surgery were retrospectively reviewed. All cases were categorized into two groups: intestinal necrosis group and non-intestinal necrosis group based on the surgical findings. Demographic and clinical features including the findings from the surgery were recorded and analyzed. Factors associated with intestinal necrosis were analyzed using univariate and multivariate unconditional logistic regression analyses. RESULTS: A total of 728 cases were included. Among them, 171 had intestinal necrosis at the time of surgery. The group with intestinal necrosis had a longer duration of symptom or length of illness (P = 0.000), and younger (P = 0.000) than the non-intestinal necrosis group. Complex/compound type of intussusceptions is more likely to have intestinal necrosis. Multivariate analysis showed that the presence of grossly bloody stool (OR = 2.12; 95% CI 1.19-3.76, P = 0.010) and duration of symptom (OR = 1.07; 95% CI 1.06-1.08, P = 0.000) were independent risk factors for intestinal necrosis in patients hospitalized for surgical reduction for intussusceptions. CONCLUSION: At time of admission, the presence of bloody stools and duration of symptom are the important risk factors for developing intestinal necrosis for those patients who failed non-surgical reduction. The length of illness has the highest sensitivity and specificity to correlate with intestinal necrosis. This finding may suggest that we should take the intussusception cases that have the longer duration of symptom directly to operation room for reduction.

A systematic review and meta-analysis of acupuncture for improving learning and memory ability in animals.

BACKGROUND: Memory loss is the most prominent symptoms of brain aging, but there is currently no evidence-based treatment strategy. Acupuncture has been widely used in China and the effectiveness for improving learning and memory has been mentioned in previous studies. We conducted this systematic review and meta-analysis to evaluate the effectiveness of acupuncture for improving learning and memory in animal experiments. METHODS: We searched Pubmed, Embase, Ovid Medline(R), the China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical Database (VIP) and Wanfang data Information Site to collect studies published up to December 2015. Study quality for each included article was evaluated according to the CAMARADES 10-item checklist. Outcome measure is Morris water maze. A meta-analysis was conducted according to the Cochrane systematic review method by using RevMan 5.3 software. RESULTS: Forty-two studies involving 944 animals were included. The quality score of the studies ranged from 2 to 8, with a mean of 5.3. Meta-analysis results showed that 24 studies reported significant effect of acupuncture for decreasing escape latency (-3.00, 95 % CI: -3.78 ~ -2.23, P < 0.00001), 14 studies reported significant effect of acupuncture for increasing frequency of cross platform (2.57, 95 % CI: 1.92 ~ 3.22, P < 0.00001), and 7 studies reported significant effect of acupuncture for increasing time in target quadrant (2.00, 95 % CI: 1.10 ~ 2.91, P < 0.00001) compared with the control group. CONCLUSIONS: These findings show acupuncture has a potential role in improving learning and memory ability in animal models, suggesting it as a candidate therapy for memory loss of aged brain.

[From Biological Effects of Local Cutaneous Thermal Stimulation to Moxibustion Therapy].

Moxibustion is one of the major external therapies of traditional Chinese medicine (TCM) and exerts a definite favorable effect in the treatment of patients with different problems. In the present paper, the authors reviewed 38 papers about somatic thermal intervention therapy published in recent 15 years and analyzed its biological functions from local, distal, and whole body effects. The local effects include 1) improving cutaneous inflammatory illnesses as verruca, herpes simplex, Leishmania infection, cutaneous necrosis, wound disunion, and promoting percutaneous absorption of some medicines, swelling pain; 2) reliving sports fatigue and muscular injury, eliminating inflammation and pain reactions, probably by lowering local reactive oxygen species, superoxide dismutase,catalase, glutathione, etc. levels, and strengthening the flexibility of the knee-joint, and anterior and posterior cruciate ligaments; 3) increasing blood perfusion of the regional arteriola, micrangium to eliminate accumulated subcutaneous blood cells, inflammatory mediators and other metabolic products. The distal effects contain 1) increase of the distal cutaneous blood flow and suppression of the arterial stenosis; and 2) improvement of the visceral functions including the heart (ischemia), liver, gastrointestinal blood flow and smooth muscles, uterus smooth muscular tension, etc. The whole body effects include raising immunoability against cancer, and reducing tumor blood flow to damage the blood vessels in the tumor tissue, etc. In addition, the effects of thermal stimulation are affected by the temperature, stimulating duration and the stimulated positions. These research results may help us to comprehensively understand the effects and mechanisms of moxibustion therapy in the treatment of different clinical disorders.

AGAMOUS-LIKE13, a putative ancestor for the E functional genes, specifies male and female gametophyte morphogenesis.

Arabidopsis AGL13 is a member of the AGL6 clade of the MADS box gene family. GUS activity was specifically detected from the initiation to maturation of both pollen and ovules in AGL13:GUS Arabidopsis. The sterility of the flower with defective pollen and ovules was found in AGL13 RNAi knockdown and AGL13 + SRDX dominant-negative mutants. These results indicate that AGL13 acts as an activator in regulation of early initiation and further development of pollen and ovules. The production of similar floral organ defects in the severe AGL13 + SRDX and SEP2 + SRDX plants and the similar enhancement of AG nuclear localization efficiency by AGL13 and SEP3 proteins suggest a similar function for AGL13 and E functional SEP proteins. Additional fluorescence resonance energy transfer (FRET) analysis indicated that, similar to SEP proteins, AGL13 is able to interact with AG to form quartet-like complexes (AGL13-AG)2 and interact with AG-AP3-PI to form a higher-order heterotetrameric complex (AGL13-AG-AP3-PI). Through these complexes, AGL13 and AG could regulate the expression of similar downstream genes involved in pollen morphogenesis, anther cell layer formation and the ovule development. AGL13 also regulates AG/AP3/PI expression by positive regulatory feedback loops and suppresses its own expression through negative regulatory feedback loops by activating AGL6, which acts as a repressor of AGL13. Our data suggest that AGL13 is likely a putative ancestor for the E functional genes which specifies male and female gametophyte morphogenesis in plants during evolution.