Operation Procedure and Precautions of Thread-Embedding Acupuncture Therapy in Alzheimer.

Thread-embedding therapy (TEAT) is a treatment that prevents and manages diseases by inserting a biodegradable suture into an acupoint, providing long-lasting stimulation. TEAT is a simple approach that avoids the discomfort of regular acupuncture and provides sustained therapeutic effects. This article discusses the potential impact of TEAT on the learning and memory abilities of rats with Alzheimer's disease-like symptoms. Since chemically induced neuronal degeneration and cognitive impairments in rats does not entirely reflect the true pathological changes observed in Alzheimer's disease. Consequently, our research group has designated these manifestations as Alzheimer's disease-like symptoms. A protocol has been established to outline the selection of acupoints, the operation process, and necessary precautions for the head and lower back. The experiment was conducted on three groups: a control group, a model group, and a TEAT group, each containing 6 rats. To induce Alzheimer's disease-like symptoms, rats were intraperitoneally injected with D-galactose for 7 weeks (49 days). The rats in the TEAT group received acupoint catgut embedding treatment. Following the intervention period, a Morris Water Maze (MWM) was conducted to evaluate the rats' learning and memory. Subsequently, the rats were sacrificed, and their brain tissue was examined. A histological examination was performed to understand the effects of TEAT on the pathology of rats exhibiting symptoms of Alzheimer's disease. This study suggests that TEAT may improve learning and memory in rats with Alzheimer's disease-like symptoms, indicating a potentially promising new treatment approach for this neurodegenerative condition.

Dysfunctional adipocytes promote tumor progression through YAP/TAZ-dependent cancer-associated adipocyte transformation.

Obesity has emerged as a prominent risk factor for the development of malignant tumors. However, the existing literature on the role of adipocytes in the tumor microenvironment (TME) to elucidate the correlation between obesity and cancer remains insufficient. Here, we aim to investigate the formation of cancer-associated adipocytes (CAAs) and their contribution to tumor growth using mouse models harboring dysfunctional adipocytes. Specifically, we employ adipocyte-specific BECN1 KO (BaKO) mice, which exhibit lipodystrophy due to dysfunctional adipocytes. Our results reveal the activation of YAP/TAZ signaling in both CAAs and BECN1-deficient adipocytes, inducing adipocyte dedifferentiation and formation of a malignant TME. The additional deletion of YAP/TAZ from BaKO mice significantly restores the lipodystrophy and inflammatory phenotypes, leading to tumor regression. Furthermore, mice fed a high-fat diet (HFD) exhibit decreased BECN1 and increased YAP/TAZ expression in their adipose tissues. Treatment with the YAP/TAZ inhibitor, verteporfin, suppresses tumor progression in BaKO and HFD-fed mice, highlighting its efficacy against mice with metabolic dysregulation. Overall, our findings provide insights into the key mediators of CAA and their significance in developing a TME, thereby suggesting a viable approach targeting adipocyte homeostasis to suppress cancer growth.

Operation Procedure and Precautions of Lingnan Fire-Needle Therapy in Osteoporosis Model Rats.

Compared to filiform needle therapy, fire-needle therapy has both the stimulation of needles and the warming effect of heat, making it have unexpected effects on some chronic diseases and incurable diseases. Osteoporosis (OP) has a high incidence in postmenopausal women and middle-aged and elderly men, and the treatment cycle is long. According to Traditional Chinese Medicine (TCM), Lingnan fire-needle therapy has shown potential in treating osteoporosis. However, there is still a long way to go before it can be widely used. This article focuses on the application of Lingnan fire-needle therapy in the intervention of OP in rats. It covers the selection of needle tools, acupuncture point selection, positioning of rats' bodies, and fixation methods. We also outline the steps and precautions to be taken during and after needling with fire needles. The experiment was done with three groups: a normal group, a model group, and a fire-needle group, each containing 10 rats. The rats in the fire-needle group were treated with fire-needle intervention for six sessions. After the intervention period, we collected femoral specimens and performed micro-CT scans. The results suggest that fire needling can enhance bone morphology and mineral density in OP rats. This information can serve as a methodological basis for conducting basic research on fire-needle therapy.

The impact of SARS-CoV-2 spike mutation on peptide presentation is HLA allomorph-specific.

CD8+ T cells are crucial for viral elimination and recovery from viral infection. Nonetheless, the current understanding of the T cell response to SARS-CoV-2 at the antigen level remains limited. The Spike protein is an external structural protein that is prone to mutations, threatening the efficacy of current vaccines. Therefore, we have characterised the immune response towards the immunogenic Spike-derived peptide (S976-984, VLNDILSRL), restricted to the HLA-A*02:01 molecule, which is mutated in both Alpha (S982A) and Omicron BA.1 (L981F) variants of concern. We determined that the mutation in the Alpha variant (S982A) impacted both the stability and conformation of the peptide, bound to HLA-A*02:01, in comparison to the original S976-984. We identified a longer and overlapping immunogenic peptide (S975-984, SVLNDILSRL) that could be presented by HLA-A*02:01, HLA-A*11:01 and HLA-B*13:01 allomorphs. We showed that S975-specific CD8+ T cells were weakly cross-reactive to the mutant peptides despite their similar conformations when presented by HLA-A*11:01. Altogether, our results show that the impact of SARS-CoV-2 mutations on peptide presentation is HLA allomorph-specific, and that post vaccination there are T cells able to react and cross-react towards the variant of concern peptides.

Ribosomal S6 kinase 2-forkhead box protein O4 signaling pathway plays an essential role in melanogenesis.

Although previous studies have examined the signaling pathway involved in melanogenesis through which ultraviolet (UV) or α-melanocyte-stimulating hormones (α-MSH) stimuli act as key inducers to produce melanin at the stratum basal layer of the epidermis, the signaling pathway regulating melanogenesis is still controversial. This study reports that α-MSH, not UVA and UVB, acted as a major stimulus of melanogenesis in B16F10 melanoma cells. Signaling pathway analysis using gene knockdown technology and chemical inhibitors, the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK)/p90 ribosomal S6 kinase 2 (RSK2) played an important role in melanogenesis. Unexpectedly, LY294002, a PI3K inhibitor, increased melanogenesis without UV or α-MSH stimulation, suggesting that the PI3K/AKT signaling pathway may not be a major signaling pathway for melanogenesis. Chemical inhibition of the MEKs/ERKs/RSK2 signaling pathway using U0126 or BI-D1870 suppressed melanogenesis by stimulation of UVA or α-MSH stimulation, or both. In particular, the genetic depletion of RSK2 or constitutive active (CA)-RSK2 overexpression showed that RSK2 plays a key role in melanogenesis. Interestingly, forkhead box protein O4 (FOXO4) was phosphorylated by RSK2, resulting in the increase of FOXO4's transactivation activity. Notably, the FOXO4 mutant harboring serine-to-alanine replacement at the phosphorylation sites totally abrogated the transactivation activity and reduced melanin production, indicating that RSK2-mediated FOXO4 activity plays a key role in melanogenesis. Furthermore, kaempferol, a flavonoid inhibiting the RSK2 activity, suppressed melanogenesis. In addition, FOXO4-wt overexpression showed that FOXO4 enhance melanin synthesis. Overall, the RSK2-FOXO4 signaling pathway plays a key role in modulating melanogenesis.

Characterization of aroma characteristics of silver carp mince glycated with different reducing sugars.

The purpose of this study was to investigate the volatile flavor changes in silver carp mince (SCM) gel glycated with different reducing sugars (glucose, L-arabinose, and xylose) based on E-nose, GC-IMS, and sensory evaluation. These results showed that glycation reduced the fishy smell of SCM gel and increased the meaty, toasty, and burnt smell. A total of 10 volatile compounds were considered as characteristic flavor compounds and potential markers. Among them, the main contributors of fishy included hexanal, heptanal, n-nonanal, octanal, etc. Toasty and burnt were mainly related to the production of 3-methylbutanal and furfurol. These results heralded that glycation could be used to improve the volatile flavor of SCM. This research provided a theoretical basis and technical support for glycation in aquatic food flavor quality control, aquatic pre-made food development, and aquatic leisure food processing.

Emerging role of senescent microglia in brain aging-related neurodegenerative diseases.

Brain aging is a recognized risk factor for neurodegenerative diseases like Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease), but the intricate interplay between brain aging and the pathogenesis of these conditions remains inadequately understood. Cellular senescence is considered to contribute to cellular dysfunction and inflammaging. According to the threshold theory of senescent cell accumulation, the vulnerability to neurodegenerative diseases is associated with the rates of senescent cell generation and clearance within the brain. Given the role of microglia in eliminating senescent cells, the accumulation of senescent microglia may lead to the acceleration of brain aging, contributing to inflammaging and increased vulnerability to neurodegenerative diseases. In this review, we propose the idea that the senescence of microglia, which is notably vulnerable to aging, could potentially serve as a central catalyst in the progression of neurodegenerative diseases. The senescent microglia are emerging as a promising target for mitigating neurodegenerative diseases.

Experimental Verification of the Impact of the Contact Area between the Defect Site and the Scaffold on Bone Regeneration Efficacy.

In the field of bone tissue engineering, which is being developed for the ideal restoration of bone defects, researchers are exploring the improvement of the bone regeneration efficacy of scaffolds through various approaches involving osteoconductive, osteoinductive, and angiogenic factors. In the current trend of research, there is also a suggestion that the topological factors of recent scaffolds may influence the attachment, migration, proliferation, and differentiation of bone cells. Building upon experimental confirmation of the effect of scaffold conformity with the defect site on enhanced bone regeneration in previous studies, we conducted this research to experimentally investigate the relationship between contact area with the defect site and bone regeneration efficacy. The results demonstrated that as the contact area of the scaffold increased, not only did the resistance to bone tissue growth increase, more significant bone regeneration also occurred, as evidenced through histological analysis and micro-CT analysis. This research confirms that the contact area between the scaffold and the defect site is a critical variable affecting bone regeneration efficacy, emphasizing its importance when designing customized scaffolds. This finding holds promising implications for future studies and applications in the field.

A novel protein extracted from Hemerocallis citrina Borani inhibits hepatocellular carcinoma cell proliferation by regulating mitochondria-dependent apoptosis and aerobic glycolysis.

Hemerocallis citrina Borani is a commonly consumed food in Asia and possesses many biologically active ingredients. In this study, a protein named Hemerocallis citrina Borani protein (HcBP) was purified using ammonium sulfate fractionation and anion exchange chromatography. Protease assays revealed that HcBP has peroxidase activity. Meanwhile, the UV absorption spectrum showed that HcBP contains heme. Notably, HcBP showed significant inhibitory effects on human hepatoma cancer cell proliferation. Mechanism investigations indicated that HcBP treatment resulted in overproduction of reactive oxygen species (ROS) and induced mitochondria-dependent apoptosis in human hepatoma cancer cells. Furthermore, we found HcBP not only downregulated pyruvate kinase M2 (PKM2) activity but also decreased the expression and nuclear levels of PKM2. The inhibition of PKM2 led to the downregulation of GLUT1, LDHA and PDK, and thus caused the suppression of glycolysis. In summary, our results suggested that HcBP has potential anti-hepatocellular carcinoma activity.

Influence of Respiratory Frequency of Slow-Paced Breathing on Vagally-Mediated Heart Rate Variability.

Breathing techniques, particularly slow-paced breathing (SPB), have gained popularity among athletes due to their potential to enhance performance by increasing cardiac vagal activity (CVA), which in turn can help manage stress and regulate emotions. However, it is still unclear whether the frequency of SPB affects its effectiveness in increasing CVA. Therefore, this study aimed to investigate the effects of a brief SPB intervention (i.e., 5 min) on CVA using heart rate variability (HRV) measurement as an index. A total of 75 athletes (22 female; Mage = 22.32; age range = 19-31) participated in the study, attending one lab session where they performed six breathing exercises, including SPB at different frequencies (5 cycles per minute (cpm), 5.5 cpm, 6 cpm, 6.5 cpm, 7 cpm), and a control condition of spontaneous breathing. The study found that CVA was significantly higher in all SPB conditions compared to the control condition, as indexed by both root mean square of the successive differences (RMSSD) and low-frequency HRV (LF-HRVms2). Interestingly, LF-HRVms2 was more sensitive in differentiating the respiratory frequencies than RMSSD. These results suggest that SPB at a range of 5 cpm to 7 cpm can be an effective method to increase CVA and potentially improve stress management and emotion regulation in athletes. This short SPB exercise can be a simple yet useful tool for athletes to use during competitive scenarios and short breaks in competitions. Overall, these findings highlight the potential benefits of incorporating SPB into athletes' training and competition routines.

Exclusive Enteral Nutrition Alleviates Th17-Mediated Inflammation via Eliminating Mechanical Stress-Induced Th17-Polarizing Cytokines in Crohn's-like Colitis.

BACKGROUND AND AIMS: Exclusive enteral nutrition (EEN) with a liquid diet is the only established dietary treatment for Crohn's' disease (CD). However, the mechanism of action of EEN in CD is unclear. T helper 17 (Th17) immune response plays a critical role in CD. We hypothesized that EEN alleviates Th17 response by eliminating mechanical stress-induced expression of Th17-polarizing cytokines. METHODS: A rat model of Crohn's-like colitis was established by intracolonic instillation of TNBS (65 mg/kg in 250 µL of 40% ethanol). Control rats were treated with saline. We characterized immunophenotypes and molecular changes of the colon in control and colitis rats with and without EEN treatment. Th17 differentiation was determined using coculture assays. RESULTS: TNBS instillation induced transmural inflammation with stenosis in the inflammation site and a marked increase of Th17-polarizing cytokines interleukin (IL)-6 and osteopontin and the Th17 cell population in the mechanically distended preinflammation site (P-site). EEN treatment eliminated mechanical distention and the increase of IL-6, osteopontin, and Th17 response in the P-site. IL-6 and osteopontin expression was found mainly in the muscularis externa. Mechanical stretch of colonic smooth muscle cells in vitro induced a robust increase of IL-6 and osteopontin. When naïve T cells were cultured with conditioned media from the P-site tissue or stretched cells, Th17 differentiation was significantly increased. Inhibition of IL-6, but not deletion of osteopontin, blocked the increase of Th17 differentiation. CONCLUSIONS: Mechanical stress induces Th17-polarizing cytokines in the colon. EEN attenuates Th17 immune response by eliminating mechanical stress-induced IL-6 in Crohn's-like colitis.

Investigating Anisotropic Magnetoresistance in Epitaxially Strained CoFe Thin Films on a Flexible Mica.

This study investigates the crystal structure, epitaxial relation, and magnetic properties in CoFe thin films deposited on a flexible mica substrate. The epitaxial growth of CoFe thin films was successfully achieved by DC magnetron sputtering, forming three CoFe(002) domains exhibiting four-fold symmetry on the mica substrate. A notable achievement of this work was the attainment of the highest anisotropic magnetoresistance (AMR) value reported to date on a flexible substrate. Additionally, it was observed that the magnetic characteristics of the CoFe films on the flexible mica substrate display reversibility upon strain release. More importantly, the AMR effect of epitaxial CoFe films on flexible mica shows lesser dependence on the crystalline orientation and remains the same under different bending states. These findings demonstrate the potential of utilizing CoFe films on flexible substrates to develop wearable magnetoresistance sensors with diverse applications.

Tough Interfacial Adhesion Enabled Extremely Durable Flexible Supercapacitors.

The interfacial void and delamination between the hydrogel electrolyte and flexible electrode caused by the inconformal contact and weak adhesion lead to serious performance degradation of solid-state-sandwiched supercapacitors (SCs) upon repetitive deformation. Herein, we propose a hydrogel polymer electrolyte (HPE) engineering strategy for enhancing the interfacial adhesion (Γ) to achieve extremely durable SCs via the soft, tough, and self-adhesive HPE. Using a self-cross-linked poly(N-hydroxyethyl acrylamide)/H3PO4 (PHEAA/H3PO4) HPE as the model, the interfacial adhesion between HPE and polyaniline (PANI)-modified carbon cloth (CC) electrode (CC/PANI) reaches up to 556 J/m2, leading to excellent durability of electrochemical performance under long-term repetitive deformations. The as-assembled sandwiched SC retains 94.14 and 93.62% of initial capacitance after 180° bending and twisting for 100,000 cycles, respectively. Furthermore, benefiting from the addition of H3PO4, the flexible sandwiched SC displays excellent tolerance to low temperatures and delivers a capacitance retention of 98.03% after 180° bending for 10,000 cycles at -20 °C. This work highlights the importance of interfacial adhesion engineering for the design of extremely deformation-tolerable SCs.

Mechanical thrombectomy for symptomatic stent thrombosis after carotid artery stenting.

Background: As there is still no consensus on the treatment of carotid stent thrombosis (CST), we would like to describe our experience with the revascularization of CST by mechanical thrombectomy. Methods: We retrospectively studied patients who underwent mechanical thrombectomy after CST at Xuzhou Municipal First People's Hospital and Xuzhou Central Hospital between January 2020 and November 2022. The results of the procedures, complications, and clinical and imaging follow-up were recorded. Results: A total of six patients were included in this study. The stenosis grade before stent implantation was ≥85% in all patients, and the stenosis length ranged from 7 to 20 mm. Patients experienced CST within 6 days to 45 months after carotid artery stenting (CAS); the median admission on the National Institutes of Health Stroke Scale (NIHSS) at CST was 12 (range 8-25). Mechanical thrombectomy was successfully performed in all patients. There was no periprocedural death, and the modified Rankin Scale (mRS) at the 3-month follow-up was 0-2. All patients showed recovery from their neurological deficits. Conclusion: The treatment of symptomatic CST with mechanical thrombectomy resulted in satisfactory clinical outcomes. This regimen could be effective and safe, and future prospective and randomized studies are warranted.

Gut butyrate-producers confer post-infarction cardiac protection.

The gut microbiome and its metabolites are increasingly implicated in several cardiovascular diseases, but their role in human myocardial infarction (MI) injury responses have yet to be established. To address this, we examined stool samples from 77 ST-elevation MI (STEMI) patients using 16 S V3-V4 next-generation sequencing, metagenomics and machine learning. Our analysis identified an enriched population of butyrate-producing bacteria. These findings were then validated using a controlled ischemia/reperfusion model using eight nonhuman primates. To elucidate mechanisms, we inoculated gnotobiotic mice with these bacteria and found that they can produce beta-hydroxybutyrate, supporting cardiac function post-MI. This was further confirmed using HMGCS2-deficient mice which lack endogenous ketogenesis and have poor outcomes after MI. Inoculation increased plasma ketone levels and provided significant improvements in cardiac function post-MI. Together, this demonstrates a previously unknown role of gut butyrate-producers in the post-MI response.

Investigation of the Vibrational Characteristics of 6-Isocyano-1-Methyl-1H-Indole: Utilizing the Isonitrile Group as an Infrared Probe.

Indole derivatives have garnered considerable attention in the realm of biochemistry due to their multifaceted properties. In this study, we undertake a systematic investigation of the vibrational characteristics of a model indole derivative, 6-isocyano-1-methyl-1H-indole (6ICMI), by employing a combination of FTIR, IR pump-probe spectroscopy, and theoretical calculations. Our findings demonstrate a strong dependence of the isonitrile stretching frequency of 6ICMI on the polarizability of protic solvents and the density of hydrogen-bond donor groups in the solvent when the isonitrile group is bonded to aromatic groups. Both experimental and theoretical analyses unveil a significant correlation between the isonitrile stretch vibration of 6ICMI and the solvent acceptor number of alcohols. Furthermore, the polarization-controlled infrared pump-probe conducted on 6ICMI in dimethyl sulfoxide provides additional support for the potential use of the isonitrile stretching mode of 6ICMI as an effective infrared probe for local environments.

Exome sequencing in retinal dystrophy patients reveals a novel candidate gene ER membrane protein complex subunit 3.

Inherited retinal dystrophies (IRDs) are a heterogeneous group of visual disorders caused by different pathogenic mutations in genes and regulatory sequences. The endoplasmic reticulum (ER) membrane protein complex (EMC) subunit 3 (EMC3) is the core unit of the EMC insertase that integrates the transmembrane peptides into lipid bilayers, and the function of its cytoplasmic carboxyl terminus remains to be elucidated. In this study, an insertional mutation c.768insT in the C-terminal coding region of EMC3 was identified and associated with dominant IRDs in a five-generation family. This mutation caused a frameshift in the coding sequence and a gain of an additional 16 amino acid residues (p.L256F-fs-ext21) to form a helix structure in the C-terminus of the EMC3 protein. The mutation is heterozygous with an incomplete penetrance, and cosegregates in all patients examined. This finding indicates that the C-terminus of EMC3 is essential for EMC functions and that EMC3 may be a novel candidate gene for retinal degenerative diseases.

Thymoquinone Alleviates Paclitaxel-Induced Peripheral Neuropathy through Regulation of the TLR4-MyD88 Inflammatory Pathway.

Paclitaxel-induced peripheral neuropathy (PIPN) is one of the common adverse effects during the paclitaxel (PTX) treatment of cancer. In this study, we investigated the neuroprotective effects and mechanisms of thymoquinone (TQ) in the PIPN model. Through pain behavioral assays and histological assessment, we demonstrated that TQ significantly alleviated the nociceptive behavior, modulated the pathological changes in peripheral nerves, and decreased the expression of inflammatory factors TNF-α, IL-1ß, and IL-6 induced by PIPN in mice. In addition, TQ significantly reversed the reduced viability and inflammatory response of primary DRG neurons caused by PTX. Moreover, the gene expression of related pathways was detected by Western blot, qPCR, and immunofluorescence, and the results showed that TQ exerts neuroprotective effects by regulating TLR4/MyD88 and its downstream NF-κB and MAPKs inflammatory pathways in vivo and in vitro. The treatment with TLR4 antagonist TAK-242 further indicated the important role of the TLR4/MyD88 signaling pathway in PIPN. Furthermore, molecular docking and a cellular thermal shift assay were used to confirm the interaction of TQ with TLR4. In summary, our study shows that TQ can inhibit inflammatory responses against PIPN by regulating TLR4 and MyD88 and its downstream inflammatory pathways.

False-positive Aspergillus galactomannan immunoassay in the glucose component of total parenteral nutrition products.

IMPORTANCE: This manuscript describes an occurrence of false-positive GM tests in patients receiving TPN products from a manufacturer who had recently changed the supplier of the glucose component. We describe the clinical presentation of nine false-positive cases and the results of serologic and microbiological investigations of the TPN products suspected of contamination with GM. Attempts to detect GM in parenteral nutrition products were made since the detection of GM in sodium gluconate-containing solutions in 2007, but none of them identified the source of elevated GM indexes in TPN products. However, the present study demonstrated that the glucose component of the TPN products contained a high level of GM antigen, which caused false-positive GM assay results. The source of GM was glucoamylase, which was derived from A. niger in the manufacturing process. Physicians and clinical microbiology laboratories should be aware of this issue to improve interpretation and patient care.

Antifouling and Injectable Granular Hydrogel for the Prevention of Postoperative Intrauterine Adhesion.

Postoperative intrauterine adhesion (IUA), caused by endometrial basal layer injury, is one of the main causes of female infertility. The excessive deposition of fibrin as well as fibroblast is considered the root cause of IUA. However, few clinical strategies are effective in preventing extracellular matrix (ECM) deposition at endometrial wounds that include protein and cell deposits. Herein, the injectable granular poly(N-(2-hydroxyethyl) acrylamide) (PHEAA) hydrogel (granular PHEAA gel), which presents excellent antifouling properties and remarkably prevents protein and cell adhesions, is used to prevent postoperative IUA. The granular PHEAA gel with a jammed network structure exhibits outstanding injectability and superior stability. Compared with the IUA group, the granular PHEAA gel can promote regeneration of the endometrium while reducing the area of endometrial fibrosis. Immunohistochemical staining experiments indicate that the granular PHEAA gel can improve the proliferation of the endometrium, promote vascularization, and enhance anti-inflammatory effect in IUA rats. And the granular PHEAA gel can effectively slow down the fibrosis of uterine tissue. Importantly, the number of embryos is significantly increased after injecting granular PHEAA gel, inferring that there is an obvious reproductive function recovery of injured endometrium.