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Metal‐based nanoparticles (NPs) are particularly important tools in tissue engineering‐, drug carrier‐, interventional therapy‐, and biobased technologies. However, their complex and varied migration and transformation pathways, as well as their continuous accumulation in closed biological systems, cause various unpredictable toxic effects that threaten human and ecosystem health. Considerable experimental and theoretical efforts have been made toward understanding these cytotoxic effects, though more research on metal‐based NPs integrated with clinical medicine is required. This review summarizes the mechanisms and evaluation methods of cytotoxicity and provides an in‐depth analysis of the typical effects generated in the nervous, immune, reproductive, and genetic systems. In addition, the challenges and opportunities are discussed to enhance future investigations on safer metal‐based NPs for practical commercial adoption. Considerable experimental and theoretical efforts have been directed toward understanding the cytotoxicity of metal‐based nanoparticles but additional efforts are still needed before metal‐based nanoparticles can be routinely used in clinical medicine field. This review summarizes the state of toxic mechanisms and evaluation methods of cytotoxicity, and gives an in‐depth analysis of typical cytotoxic effects.

Observational studies have suggested an association between inflammatory markers and low back pain (LBP), but the causal relationship between these factors remains uncertain. We conducted a bidirectional two-sample Mendelian randomization analysis (MR) study to investigate whether there is a causal relationship between inflammatory markers and low back pain. We obtained genetic data for CRP, along with its upstream inflammatory markers IL-6, IL-8, and IL-10, as well as low back pain from publicly available genome-wide association studies (GWAS). We applied several MR methods, including inverse variance weighting, weighted median, MR-Egger, Wald Ratio, and MR-PRESSO, to test for causal relationships. Sensitivity analyses were also conducted to assess the robustness of the results. Our analyses utilizing the Inverse Variance Weighted (IVW) method, the MR-Egger method, and the weighted median method indicated that IL-6 may be associated with an increased risk of LBP (Effect Size: -0.009, 95% Confidence Interval: -0.013-0.006, p = 9.16e-08); however, in the reverse direction, there was no significant causal effect of LBP on inflammatory markers. Our study used a Mendelian randomization approach and found that elevated IL-6 levels may reduce the risk of LBP.

IntroductionChronic constipation (CC) is a highly prevalent health challenge that is particularly challenging to treat in elderly patients. Although lifestyle guidance and laxative therapy often yield positive outcomes, patients occasionally struggle with maintaining dietary control. Therefore, identifying an economical and safe alternative therapy to the existing treatment methods documented in the international literature is necessary. This systematic review and meta-analysis aims to evaluate the efficacy and safety of abdominal massage in elderly patients with CC to provide a basis for future mechanistic research.Methods and analysisElectronic searches will be conducted to identify clinical randomised controlled trials in various databases, including Web of Science, PubMed, Cumulated Index to Nursing and Allied Health Literature, Cochrane Library, Embase, Airiti Library, Chinese National Knowledge Infrastructure Databases, Chinese Science and Technology Periodical Database (VIP), Chinese Biomedical Literature Database and Wan Fang Database. Relevant data will be extracted, and a meta-analysis will be conducted using Reviewer Manager V.5.4. Quality and risk assessments of the included studies will be performed, and the outcome indicators of the trials will be observed. This review will evaluate abdominal massage as a treatment option for relieving symptoms and improving quality of life in elderly patients with CC. Moreover, it will provide additional insights for clinical treatment and mechanistic studies. The search will be performed following the publication of this protocol (estimated to occur on 30 December 2023).Ethics and disseminationAs this is a literature review, ethics approval will not be required. We will disseminate the findings of this study to publications in peer-reviewed journals as well as presentations at relevant national and international conferences.PROSPERO registration numberCRD42023408629.

Objective This study aimed to investigate whether electroacupuncture (EA) can regulate skeletal muscle glucose metabolism through the AMPK/PGC-1α/TFAM signaling pathway in a rat model of type 2 diabetes mellitus (T2DM). Methods T2DM was induced by feeding rats a high-fat, high-sugar diet followed by intraperitoneal streptozotocin (35 mg/kg). Rats were randomly assigned to five groups: model, EA, EA plus AMPK inhibitor (Compound C, 20 mg/kg, three times weekly), sham acupuncture (tail non-acupoint stimulation), and control. EA was applied at Zusanli, Sanyinjiao, and Weiwanxiashu for 20 min daily, six days per week, for four weeks. Random blood glucose (RBG) and body weight were monitored weekly. After intervention, fasting blood glucose (FBG), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), fasting insulin (FINS), and C-peptide (C-P) were measured, and HOMA-IR and ISI were calculated based on FBG and FINS. Skeletal muscle morphology was assessed by H&E staining; ATP levels were measured; and AMPK/PGC-1α/TFAM pathway related protein and gene expression were analyzed by Western blotting and RT-PCR. Results EA reduced RBG, body weight, FBG, TG, LDL-C, FINS, C-P levels, and HOMA-IR, while improving ISI. Moreover, EA enhances the expression of AMPK, PGC-1α, TFAM, and GLUT 4 at both the protein and mRNA levels, alleviates skeletal muscle cell injury, and increases ATP content in skeletal muscle. These beneficial effects are abolished by co-administration of an AMPK inhibitor. Conclusion EA improves glycolipid metabolism and alleviates insulin resistance in T2DM rats, potentially via activation of the AMPK/PGC-1α/TFAM pathway. These effects may be linked to improved skeletal muscle function and glucose utilization. EA shows promise as a therapeutic strategy for T2DM, warranting further investigation into its mechanisms and clinical relevance.

[This corrects the article DOI: 10.3389/fimmu.2023.1174656.].

Objective This study aimed to investigate whether electroacupuncture (EA) can regulate skeletal muscle glucose metabolism through the AMPK/PGC-1[alpha]/TFAM signaling pathway in a rat model of type 2 diabetes mellitus (T2DM). Methods T2DM was induced by feeding rats a high-fat, high-sugar diet followed by intraperitoneal streptozotocin (35 mg/kg). Rats were randomly assigned to five groups: model, EA, EA plus AMPK inhibitor (Compound C, 20 mg/kg, three times weekly), sham acupuncture (tail non-acupoint stimulation), and control. EA was applied at Zusanli, Sanyinjiao, and Weiwanxiashu for 20 min daily, six days per week, for four weeks. Random blood glucose (RBG) and body weight were monitored weekly. After intervention, fasting blood glucose (FBG), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), fasting insulin (FINS), and C-peptide (C-P) were measured, and HOMA-IR and ISI were calculated based on FBG and FINS. Skeletal muscle morphology was assessed by H&E staining; ATP levels were measured; and AMPK/PGC-1[alpha]/TFAM pathway related protein and gene expression were analyzed by Western blotting and RT-PCR. Results EA reduced RBG, body weight, FBG, TG, LDL-C, FINS, C-P levels, and HOMA-IR, while improving ISI. Moreover, EA enhances the expression of AMPK, PGC-1[alpha], TFAM, and GLUT 4 at both the protein and mRNA levels, alleviates skeletal muscle cell injury, and increases ATP content in skeletal muscle. These beneficial effects are abolished by co-administration of an AMPK inhibitor. Conclusion EA improves glycolipid metabolism and alleviates insulin resistance in T2DM rats, potentially via activation of the AMPK/PGC-1[alpha]/TFAM pathway. These effects may be linked to improved skeletal muscle function and glucose utilization. EA shows promise as a therapeutic strategy for T2DM, warranting further investigation into its mechanisms and clinical relevance. Keywords: Type 2 diabetes, Electroacupuncture, AMPK/PGC-1[alpha]/TFAM pathway, Skeletal muscle, Glucolipid metabolism

p53 and mouse double minute 2 homolog (MDM2) serve key regulatory roles in the apoptosis of synovial cells. The present study aimed to investigate the effects of electroacupuncture (EA) at the 'Zusanli' (ST36) and 'Xuanzhong' (GB39) acupoints on apoptosis in an adjuvant arthritis (AA) rat model. A total of 40 male Sprague-Dawley rats were randomly divided into Control, AA, AA + EA and AA + sham EA groups (n=10 rats in each group). Rats in all the groups, with the exception of the control group, were injected with Complete™ Freund's adjuvant into the bilateral hindlimb footpad to establish the AA model. Rats in the AA + EA group were treated with EA at the ST36 and GB39 acupoints. Rats in the AA + sham EA group were treated with percutaneous electrical stimulation at a position of 5 mm away from the ST36 and GB39 acupoints. The arthritis index scores and hindlimb paw volumes of the rats in each group were recorded. Subsequently, pathological changes in the synovial tissue were evaluated by hematoxylin and eosin (H&E) staining, and the apoptotic rate of the synovial cells was detected by TUNEL staining. In addition, the expression levels of the apoptosis-associated proteins, Bax, phorbol-12-myristate-13-acetate-induced protein 1 (Noxa) and p53 upregulated modulator of apoptosis (PUMA), were determined by western blot analysis. The expression of both the gene and protein of p53 and MDM2 in synovial tissue was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis, respectively. The results indicated that the arthritis index scores and hindlimb paw volumes upon EA stimulation were significantly decreased compared with those of the AA group (P<0.05). H&E staining revealed that the synovial inflammation of EA stimulation was significantly decreased compared with the AA group (P<0.05). The TUNEL assay results indicated that the apoptotic rate of synovial cells in the AA + EA group was significantly increased compared with that in the AA group (P<0.05). Furthermore, an increased expression of proapoptotic proteins was confirmed by the increased expression levels of Bax, Noxa and PUMA in the AA + EA group. The results of RT-qPCR and western blot analysis demonstrated that, compared with the AA group, EA stimulation led to a marked increase in p53 (P<0.05) and a significant decrease in MDM2 (P<0.05) gene and protein expression. Taken together, these results demonstrated that EA performed on the ST36 and GB39 acupoints led to a significant amelioration in AA injury of model rats, by regulating the p53 signaling pathway and inducing apoptosis.

Conclusion This work demonstrates a high-precision in-plane two-axis GMR angle sensor is prepared by post-annealing. The pinning direction of the GMR strips is modulated by annealing two times to achieve orthogonal sensitive directions of the two sensors. The sensitivity of a full-bridge sensor is 6.59 mV/V/mT, with the sensing direction along the Y -axis and the sensitivity of a half-bridge GMR sensor is 1.68 mV/V/mT with the sensing direction along the X -axis. A simulation of the two-axis sensor output with the field has been performed, which proves the correctness of the P2 direction measured by the angle test. The detectivity of the full-bridge sensor is 22 nT/(Hz) 0.5 at 10 Hz and it is 88 nT/(Hz) 0.5 at 10 Hz for half-bridge sensor. The orthogonality error of the two-axis sensor for the geomagnetic angle detection is lower than 0.04. The sensor in this study demonstrates higher detectivity than some commercial GMR sensors, such as YAS532 produced by Yamaha and HSCDTD008A produced by ALPS. This work proposes an efficient and simple method for producing two-axis GMR angle sensors, which can be a promising solution for mass production.

Conclusion This study demonstrates the manipulation of the pinning direction in MTJs with varying tIrMn under the zero magnetic field cooling process, which results from the competition between the exchange bias coupling and interlayer coupling through the SAF layer. Our results clarify the coupling mechanism for determining the pinning direction of MTJs under the zero magnetic field cooling treatment, which can guide the design scheme of full Wheatstone bridge-based TMR sensors.

The effect of the seed layers on the magnetic properties of the giant magnetoresistance thin films has received a lot of attention. Here, a synthetic spin valve film stack with a wedge-shaped NiFeCr seed layer is deposited and annealed following a zero-field cooling procedure. The film crystallinity and magnetic properties are studied as a function of the NiFeCr seed layer thickness. It is found that the exchange coupling field from the IrMn/CoFe interface and the antiferromagnetic coupling field in the synthetic antiferromagnet both increase as the seed layer thickness increases, indicating the perfection of film texture. In this film, the critical thickness of the NiFeCr seed layer for the formation of the ordered IrMn3 texture is about 9.3 nm. Meanwhile, a reversal of the pinning direction in the film is observed at this critical thickness of NiFeCr. This phenomenon can be explained in a free energy model by the competition effect between the exchange coupling and the interlayer coupling during the annealing process.