Longitudinal Trajectories of Biomarkers of Kidney Tubular Function in Type 1 Diabetes.

Introduction: Tubular biomarkers may shed insight into progression of kidney tubulointerstitial pathology complementary to traditional measures of glomerular function and damage. Methods: We examined trajectories of tubular biomarkers in the Diabetes Control and Complications Trial and the Epidemiology of Diabetes Interventions and Complications Study (DCCT/EDIC Study) of type 1 diabetes (T1D). Biomarkers were measured in a subset of 220 participants across 7 time points over 26 years. Measurements included the following: kidney injury molecule 1 (KIM-1), soluble tumor necrosis factor 1 (sTNFR1) in serum or plasma, epidermal growth factor (EGF), monocyte chemoattractant protein-1 (MCP1) in timed urine, and a composite tubular secretion score. We described biomarker trajectories and examined how these were affected by intensive glucose-lowering therapy and glycemia. Results: At baseline, participants had a mean age of 28 years, 45% were women, and 50% were assigned to intensive glucose-lowering therapy. The mean estimated glomerular filtration rate (eGFR) was 125 ml/min per 1.73 m2 and 90% of participants had a urinary albumin excretion rate (AER) <30 mg/24h. Mean changes in biomarkers over time (percent/decade) were: KIM-1: 27.3% (95% confidence interval [CI]: 21.4-33.5), sTNFR1: 16.9% (14.5-19.3), MCP1: 18.4% (8.9-28.8), EGF: -13.5% (-16.7 to -10.1), EGF-MCP1 ratio: -26.9% (-32.2 to -21.3), and tubular secretion score -0.9% (-1.8 to 0.0), versus -12.0% (CI: -12.9 to -11.1) for eGFR and 10.9% (2.5-20.1) for AER. Intensive versus conventional glucose-lowering therapy was associated with slower increase in sTNFR1 (relative difference in change: 0.94 [0.90-0.98]). Higher HbA1c was associated with faster increases in sTNFR1 (relative difference in change: 1.06 per 1% higher HbA1c [1.05-1.08]) and KIM-1 (1.09 [1.05-1.14]). Conclusion: Among participants with T1D and normal eGFR at baseline, kidney tubular biomarkers changed significantly over long-term follow-up. Hyperglycemia was associated with larger increases in serum or plasma sTNFR1 and KIM-1, when followed-up longitudinally.

Intensive Glycemic Management Is Associated With Reduced Retinal Structure Abnormalities on Ocular Coherence Tomography in the DCCT/EDIC Study.

OBJECTIVE: To investigate quantitative and qualitative changes in retinal structure using optical coherence tomography (OCT) and their associations with systemic or other risk factors in individuals with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: In the Epidemiology of Diabetes Interventions and Complications (EDIC) study, OCT images were obtained during study years 25-28 (2019-2022) in 937 participants; 54% and 46% were from the original intensive (INT) and conventional (CONV) glycemic management treatment groups, respectively. RESULTS: Average age for participants was 61 years old, diabetes duration 39 years, and HbA1c 7.6%. Participants originally in the CONV group were more likely to have disorganization of retinal inner layers (DRIL) (CONV 27.3% vs. INT 18.7%; P = 0.0003), intraretinal fluid (CONV 24.4% vs. INT 19.2%; P = 0.0222), and intraretinal cysts (CONV 20.8% vs. INT 16.6%; P = 0.0471). In multivariable models, sex, age, smoking, mean updated systolic blood pressure, and history of "clinically significant" macular edema (CSME) and of anti-VEGF treatment were independently associated with changes in central subfield thickness, while HbA1c, BMI, and history of CSME and of ocular surgery were associated with DRIL. Visual acuity (VA) decline was associated with significant thinning of all retinal subfields except for the central and inner nasal subfields. CONCLUSIONS: Early intensive glycemic management in T1D is associated with a decreased risk of DRIL. This important morphological abnormality was associated with a history of macular edema, a history of ocular surgery, and worse VA. This study reveals benefits of intensive glycemic management on the retina beyond features detected by fundus photographs and ophthalmoscopy.

Bacteria-derived nanovesicles enhance tumour vaccination by trained immunity.

Trained immunity enhances the responsiveness of immune cells to subsequent infections or vaccinations. Here we demonstrate that pre-vaccination with bacteria-derived outer-membrane vesicles, which contain large amounts of pathogen-associated molecular patterns, can be used to potentiate, and enhance, tumour vaccination by trained immunity. Intraperitoneal administration of these outer-membrane vesicles to mice activates inflammasome signalling pathways and induces interleukin-1ß secretion. The elevated interleukin-1ß increases the generation of antigen-presenting cell progenitors. This results in increased immune response when tumour antigens are delivered, and increases tumour-antigen-specific T-cell activation. This trained immunity increased protection from tumour challenge in two distinct cancer models.

Outer Membrane Vesicle-Based Nanohybrids Target Tumor-Associated Macrophages to Enhance Trained Immunity-Related Vaccine-Generated Antitumor Activity.

Trained immunity refers to the innate immune system building memory-like features in response to subsequent infections and vaccinations. Compared with classical tumor vaccines, trained immunity-related vaccines (TIrV) are independent of tumor-specific antigens. Bacterial outer membrane vesicles (OMVs) contain an abundance of PAMPs and have the potential to act as TIrV-inducer, but face challenges in endotoxin tolerance, systemic delivery, long-term training, and trained tumor-associated macrophage (TAM)-mediated antitumor phagocytosis. Here, an OMV-based TIrV is developed, OMV nanohybrids (OMV-SIRPα@CaP/GM-CSF) for exerting vaccine-enhanced antitumor activity. In the bone marrow, GM-CSF-assisted OMVs train bone marrow progenitor cells and monocytes, which are inherited by TAMs. In tumor tissues, SIRPα-Fc-assisted OMVs trigger TAM-mediated phagocytosis. This TIrV can be identified by metabolic and epigenetic rewiring using transposase-accessible chromatin (ATAC) and transcriptome sequencing. Furthermore, it is found that the TIrV-mediated antitumor mechanism in the MC38 tumor model (TAM-hot and T cell-cold) is trained immunity and activated T cell response, whereas in the B16-F10 tumor model (T cell-hot and TAM-cold) is primarily mediated by trained immunity. This study not only develops and identifies OMV-based TIrV, but also investigates the trained immunity signatures and therapeutic mechanisms, providing a basis for further vaccination strategies.

mRNA Delivery Platform Based on Bacterial Outer Membrane Vesicles for Tumor Vaccine.

The rapid display and delivery method for customized tumor mRNA vaccines is limited. Herein, bacteria-derived outer membrane vesicles (OMVs) are employed as an mRNA delivery platform by surface engineering of an RNA-binding protein, L7Ae. OMV-L7Ae can rapidly adsorb boxC/D sequence-labeled mRNA antigens through L7Ae-boxC/D binding and deliver them into HEK-293T and dendritic cells. This platform provides an mRNA delivery technology distinct from lipid nanoparticles (LNPs) for personalized mRNA tumor vaccination and with a Plug-and-Display strategy suitable for rapid preparation of the personalized mRNA tumor vaccine against varied tumor antigens. Key features OMVs are employed as an mRNA delivery platform through L7Ae-boxC/D binding.

Cadmium stimulated cooperation between bacterial endophytes and plant intrinsic detoxification mechanism in Lonicera japonica thunb.

Due to the intimate association between plant physiology and metabolism, the internal colonizing microbe (endophytes) community must be adjusted to support plant productivity in response to cell damage in plants under stress. However, how endophytes coordinate their activities with plant intrinsic mechanisms such as antioxidative systems and detoxification pathways during Cd accumulation remains unknown. In this hydroponic pot study, we investigated how exposure of Lonicera japonica. thunb. to different levels of Cd (0.5, 2.5, 5, 10, and 20 mg kg-1) affected plant growth, metabolic pathways, and endophyte community structure and function. Although Cd accumulation increased at 5 mg kg-1 Cd, the biomass and height of L. japonica increased in association with elevated endophyte-involved plant detoxification activities. Endophytes, such as Sphingomonas, Klenkia, and Modestobacter, expressed major antioxidative regulators (superoxide dismutase and ascorbate acid) to detoxify Cd in L. japonica. Furthermore, L. japonica and its endophytes synergistically regulated the toxic effects of Cd accumulation via multiple plant metabolic defensive pathways to increase resistance to metal-induced stress.

Site-Specific Modification of Virus-Like Particles for Exogenous Tumor Antigen Display and Minimizing Preexisting Immunity.

The widespread preexisting immunity against virus-like particles (VLPs) seriously limits the applications of VLPs as vaccine vectors. Enabling technology for exogenous antigen display should not only ensure the assembly ability of VLPs and site-specific modification, but also consider the effect of preexisting immunity on the behavior of VLPs in vivo. Here, combining genetic code expansion technique and synthetic biology strategy, a site-specific modification method for hepatitis B core (HBc) VLPs via incorporating azido-phenylalanine into the desired positions is described. Through modification position screening, it is found that HBc VLPs incorporated with azido-phenylalanine at the main immune region can effectively assemble and rapidly conjugate with the dibenzocycolctyne-modified tumor-associated antigens, mucin-1 (MUC1). The site-specific modification of HBc VLPs not only improves the immunogenicity of MUC1 antigens but also shields the immunogenicity of HBc VLPs themselves, thereby activating a strong and persistent anti-MUC1 immune response even in the presence of preexisting anti-HBc immunity, which results in the efficient tumor elimination in a lung metastatic mouse model. Together, these results demonstrate the site-specific modification strategy enabled HBc VLPs behave as a potent antitumor vaccine and this strategy to manipulate immunogenicity of VLPs may be suitable for other VLP-based vaccine vectors.

Normalizing the Immune Macroenvironment via Debulking Surgery to Strengthen Tumor Nanovaccine Efficacy and Eliminate Metastasis.

In tumor nanovaccines, nanocarriers enhance the delivery of tumor antigens to antigen-presenting cells (APCs), thereby ensuring the robust activation of tumor antigen-specific effector T-cells to kill tumor cells. Through employment of their high immunogenicity and nanosize, we have developed a "Plug-and-Display" delivery platform on the basis of bacterial outer membrane vesicles (OMVs) for tumor nanovaccines (NanoVac), which can rapidly display different tumor antigens and efficiently eliminate lung metastases of melanoma. In this study, we first upgraded the NanoVac to increase their antigen display efficiency. However, we found that the presence of a subcutaneous xenograft seriously hampered the efficiency of NanoVac to eliminate lung metastases, with the subcutaneous xenograft mimicking the primary tumor burden in clinical practice. The primary tumor secreted significant amounts of granulocyte colony-stimulating factor (G-CSF) and altered the epigenetic features of granulocyte monocyte precursor cells (GMPs) in the bone marrow, thus disrupting systemic immunity, particularly the function of APCs, and ultimately resulting in NanoVac failure to affect metastases. These changes in the systemic immune macroenvironment were plastic, and debulking surgery of primary tumor resection reversed the dysfunction of APCs and failure of NanoVac. These results demonstrate that, in addition to the formulation design of the tumor nanovaccines themselves, the systemic immune macroenvironment incapacitated by tumor development is another key factor that cannot be ignored to affect the efficiency of tumor nanovaccines, and the combination of primary tumor resection with NanoVac is a promising radical treatment for widely metastatic tumors.

Retinopathy During the First 5 Years of Type 1 Diabetes and Subsequent Risk of Advanced Retinopathy.

OBJECTIVE: To determine whether individuals with type 1 diabetes (T1D) who develop any retinopathy at any time prior to 5 years of diabetes duration have an increased subsequent risk for further progression of retinopathy or onset of proliferative diabetic retinopathy (PDR), clinically significant macular edema (CSME), diabetes-related retinal photocoagulation, or anti-vascular endothelial growth factor injections. Additionally, to determine the influence of HbA1c and other risk factors in these individuals. RESEARCH DESIGN AND METHODS: Diabetic retinopathy (DR) was assessed longitudinally using standardized stereoscopic seven-field fundus photography at time intervals of 6 months to 4 years. Early-onset DR (EDR) was defined as onset prior to 5 years of T1D duration. Cox models assessed the associations of EDR with subsequent risk of outcomes. RESULTS: In unadjusted models, individuals with EDR (n = 484) had an increased subsequent risk of PDR (hazard ratio [HR] 1.51 [95% CI 1.12, 2.02], P = 0.006), CSME (HR 1.44 [1.10, 1.88], P = 0.008), and diabetes-related retinal photocoagulation (HR 1.48 [1.12, 1.96], P = 0.006) compared with individuals without EDR (n = 369). These associations remained significant when adjusted for HbA1c, but only the association with PDR remained significant after adjustment for age, duration of T1D, HbA1c, sex, systolic/diastolic blood pressure, pulse, use of ACE inhibitors, albumin excretion rate, and estimated glomerular filtration rate (HR 1.47 [95% CI 1.04, 2.06], P = 0.028). CONCLUSIONS: These data suggest that individuals with any sign of retinopathy within the first 5 years of T1D onset may be at higher risk of long-term development of advanced DR, especially PDR. Identification of early-onset DR may influence prognosis and help guide therapeutic management to reduce the risk of future visual loss in these individuals.

Prevalence of Venous Thromboembolism in Intensive Care Units: A Meta-Analysis.

OBJECTIVE: Venous thromboembolism (VTE) is a life threating complication in intensive care units (ICUs). This study aimed to pool the prevalence of VTE and examined the risk factors of VTE in intensive care patients worldwide. METHODS: A systematic search in PubMed, EMBASE and Web of Science databases was performed. Studies reported that the data on the prevalence of VTE or relevant information were synthesized using a random-effects model. RESULTS: A total of 42 studies reporting on 27,344 patients were included. The pooled prevalence of VTE was 10.0% (95% CI: 7.0-14.0%). Subgroup and metaregression analyses found that thromboprophylaxis strategy, simplified acute physiology score (SAPS II), age, study quality, sample size, malignancy, sex, spinal cord injury and injury severity score (ISS) moderated the prevalence of VTE in intensive care patients. CONCLUSIONS: The present meta-analysis revealed a high prevalence of VTE in critically ill patients. The risk factors of VTE included thromboprophylaxis strategy, SAPS II, age, malignancy, sex, spinal cord injury and ISS. Therefore, we need to pay more attention to high-risk populations of VTE in intensive care patients.

Cymbopogon citratus (DC.) Stapf aqueous extract ameliorates loperamide-induced constipation in mice by promoting gastrointestinal motility and regulating the gut microbiota.

Slow transit constipation (STC) is the most common type of functional constipation. Drugs with good effects and few side effects are urgently needed form the treatment of STC. Cymbopogon citratus (DC.) Stapf (CC) is an important medicinal and edible spice plant. The wide range of biological activities suggested that CC may have laxative effects, but thus far, it has not been reported. In this study, the loperamide-induced STC mouse model was used to evaluate the laxative effect of the aqueous extract of CC (CCAE), and the laxative mechanism was systematically explored from the perspectives of the enteric nervous system (ENS), neurotransmitter secretion, gastrointestinal motility factors, intestinal inflammation, gut barrier and gut microbiota. The results showed that CCAE not only decreased the serum vasoactive intestinal polypeptide (VIP), induced nitric oxide synthases (iNOS), and acetylcholinesterase (AchE) in STC mice but also increased the expression of gastrointestinal motility factors in colonic interstitial cells of Cajal (ICCs) and smooth muscle cells (SMCs), thereby significantly shortening the defecation time and improving the gastrointestinal transit rate. The significantly affected gastrointestinal motility factors included stem cell factor receptor (c-Kit), stem cell factor (SCF), anoctamin 1 (Ano1), ryanodine receptor 3 (RyR3), smooth muscle myosin light chain kinase (smMLCK) and Connexin 43 (Cx43). Meanwhile, CCAE could repair loperamide-induced intestinal inflammation and intestinal barrier damage by reducing the expression of the pro-inflammatory factor IL-1ß and increasing the expression of the anti-inflammatory factor IL-10, chemical barrier (Muc-2) and mechanical barrier (Cldn4, Cldn12, Occludin, ZO-1, and ZO-2). Interestingly, CCAE could also partially restore loperamide-induced gut microbial dysbiosis in various aspects, such as microbial diversity, community structure and species composition. Importantly, we established a complex but clear network between gut microbiota and host parameters. Muribaculaceae, Lachnospiraceae and UCG-010 showed the most interesting associations with the laxative phenotypes; several other specific taxa showed significant associations with serum neurotransmitters, gastrointestinal motility factors, intestinal inflammation, and the gut barrier. These findings suggested that CCAE might promote intestinal motility by modulating the ENS-ICCs-SMCs network, intestinal inflammation, intestinal barrier and gut microbiota. CC may be an effective and safe therapeutic choice for STC.

SaMT3 in Sedum alfredii drives Cd detoxification by chelation and ROS-scavenging via Cys residues.

Metallothioneins (MTs), a group of cysteine-rich proteins, are effective chelators of cadmium (Cd) and play a key role in plant Cd detoxification. However, little is known about the role of single cysteine (Cys) residues in the MTs involved in the adaptation of plants to Cd stress, especially, in hyperaccumulators. In the present study, we functionally characterised SaMT3 in S. alfredii, a Cd/Zn hyperaccumulator native to China. Our results showed that the C- and N- terminal regions of SaMT3 had differential functional natures in S. alfredii and determined its Cd hypertolerance and detoxification. Two CXC motifs within the C-terminal region were revealed to play a crucial role in Cd sensing and binding, whereas the four Cys-residues within the N-terminal region were involved in scavenging reactive oxygen species (ROS). An S. alfredii transgenic system based on callus transformation was developed to further investigate the in-planta gene function. The SaMT3-overexpressing transgenic plant roots were more tolerant to Cd than those of wild-type plants. Knockout of SaMT3 resulted in significantly decreased Cd concentrations and increased ROS levels after exposure to Cd stress. We demonstrated the SaMT3-mediated adaptation strategy in S. alfredii, which uses metal chelation and ROS scavenging in response to Cd stress. Our results further reveal the molecular mechanisms underlying Cd detoxification in hyperaccumulating plants, as well as the relation between Cys-related motifs and the metal binding properties of MTs. This research provides valuable insights into the functions of SaMT3 in S. alfredii, and improves our understanding of Cd hyperaccumulation in plants.

Anterior cruciate ligament deficiency versus intactness for outcomes in patients after unicompartmental knee arthroplasty: a systematic review and meta-analysis.

Objective: The unicondylar knee arthroplasty (UKA) procedure is primarily indicated for osteoarthritis of the knee. Anterior cruciate ligament (ACL) defects have long been considered a contraindication to UKA. However, recent clinical studies have found that ACL defects do not affect postoperative outcomes in UKA. To elucidate whether ACL defects affect postoperative outcomes in UKA, we performed a systematic review and Meta-analysis of observational cohort studies comparing the effects of ACL defects and intactness on surgical outcomes in UKA. Methods: In this study, we used "Anterior Cruciate Ligament", "Anterior Cruciate Ligament Injuries" and "Arthroplasty, Replacement, Knee" as the subject terms according to PICOS principles. These subject terms and the corresponding free texts were used to conduct a systematic search in the three major databases PubMed, Embase and Cochrane on December 9, 2021. The main study variables included age, gender, region, definition of ACL defect and diagnosed diseases. The study used a random effect model to pool the effect of 95% CIs. To explore the sources of heterogeneity and to test the stability of the results, a sensitivity analysis was performed. Results: The systematic review found no significant differences in postoperative clinical outcomes in the elderly population when unicondylar replacement was performed in the setting of multiple factors such as injury, defects, longitudinal tear, and synovial bursa injury defined as ACL deficiency. The primary clinical outcomes included postoperative revision, Tegner activity score, and Oxford Knee Score (OKS). After statistical meta-analysis, postoperative outcomes such as postoperative revision (OR, 1.174; 95% CIs, 0.758-1.817) and Tegner activity score (OR, -0.084; 95% CIs, -0.320-0.151) were not statistically different. Conclusion: There was no difference in postoperative revision rates and functional outcomes such as Tegner activity score between the ACL-deficient group compared with the ACL-intact group. For the present results, it is not advisable to consider ACL deficiency as a contraindication of UKA.

Bacterial outer membrane vesicle-based cancer nanovaccines.

Tumor vaccines, a type of personalized tumor immunotherapy, have developed rapidly in recent decades. These vaccines evoke tumor antigen-specific T cells to achieve immune recognition and killing of tumor cells. Because the immunogenicity of tumor antigens alone is insufficient, immune adjuvants and nanocarriers are often required to enhance anti-tumor immune responses. At present, vaccine carrier development often integrates nanocarriers and immune adjuvants. Among them, outer membrane vesicles (OMVs) are receiving increasing attention as a delivery platform for tumor vaccines. OMVs are natural nanovesicles derived from Gram-negative bacteria, which have adjuvant function because they contain pathogen associated molecular patterns. Importantly, OMVs can be functionally modified by genetic engineering of bacteria, thus laying a foundation for applications as a delivery platform for tumor nanovaccines. This review summarizes 5 aspects of recent progress in, and future development of, OMV-based tumor nanovaccines: strain selection, heterogeneity, tumor antigen loading, immunogenicity and safety, and mass production of OMVs.

Engineered Bacterial Outer Membrane Vesicles as Controllable Two-Way Adaptors to Activate Macrophage Phagocytosis for Improved Tumor Immunotherapy.

The most immune cells infiltrating tumor microenvironment (TME), tumor-associated macrophages (TAMs) closely resemble immunosuppressive M2-polarized macrophages. Moreover, tumor cells exhibit high expression of CD47 "don't eat me" signal, which obstructs macrophage phagocytosis. The precise and efficient activation of TAMs is a promising approach to tumor immunotherapy; however, re-education of macrophages remains a challenge. Bacteria-derived outer membrane vesicles (OMVs) are highly immunogenic nanovesicles that can robustly stimulate macrophages. Here, an OMV-based controllable two-way adaptor is reported, in which a CD47 nanobody (CD47nb) is fused onto OMV surface (OMV-CD47nb), with the outer surface coated with a polyethylene glycol (PEG) layer containing diselenide bonds (PEG/Se) to form PEG/Se@OMV-CD47nb. The PEG/Se layer modification not only mitigates the immunogenicity of OMV-CD47nb, thereby remarkedly increasing the dose that can be administered safely through intravenous injection, but also equips the formulation with radiation-triggered controlled release of OMV-CD47nb. Application of radiation to tumors in mice injected with the nanoformulation results in remodeling of TME. As two-way adaptors, OMV-CD47nb activates TAM phagocytosis of tumor cells via multiple pathways, including induction of M1 polarization and blockade of "don't eat me" signal. Moreover, this activation of TAMs results in the stimulation of T cell-mediated antitumor immunity through effective antigen presentation.

Microglia Pyroptosis: A Candidate Target for Neurological Diseases Treatment.

In addition to its profound implications in the fight against cancer, pyroptosis have important role in the regulation of neuronal injury. Microglia are not only central members of the immune regulation of the central nervous system (CNS), but are also involved in the development and homeostatic maintenance of the nervous system. Under various pathological overstimulation, microglia pyroptosis contributes to the massive release of intracellular inflammatory mediators leading to neuroinflammation and ultimately to neuronal damages. In addition, microglia pyroptosis lead to further neurological damage by decreasing the ability to cleanse harmful substances. The pathogenic roles of microglia in a variety of CNS diseases such as neurodegenerative diseases, stroke, multiple sclerosis and depression, and many other neurological disorders have been gradually unveiled. In the context of different neurological disorders, inhibition of microglia pyroptosis by targeting NOD-like receptor family pyrin domain containing (NLRP) 3, caspase-1 and gasdermins (GSDMs) by various chemical agents as well as natural products significantly improve the symptoms or outcome in animal models. This study will provide new ideas for immunomodulatory treatment of CNS diseases.

Pre-attack and pre-episode symptoms in cluster headache: a multicenter cross-sectional study of 327 Chinese patients.

BACKGROUND: There have been a few studies regarding the pre-attack symptoms (PAS) and pre-episode symptoms (PES) of cluster headache (CH), but none have been conducted in the Chinese population. The purpose of this study was to identify the prevalence and features of PAS and PES in Chinese patients, as well as to investigate their relationships with pertinent factors. METHODS: The study included patients who visited a tertiary headache center and nine other headache clinics between January 2019 and September 2021. A questionnaire was used to collect general data and information about PAS and PES. RESULTS: Among the 327 patients who met the CH criteria (International Classification of Headache Disorders, 3rd edition), 269 (82.3%) patients experienced at least one PAS. The most common PAS were head and facial discomfort (74.4%). Multivariable logistic regression analysis depicted that the number of triggers (OR = 1.798, p = 0.001), and smoking history (OR = 2.067, p = 0.026) were correlated with increased odds of PAS. In total, 68 (20.8%) patients had PES. The most common symptoms were head and facial discomfort (23, 33.8%). Multivariable logistic regression analysis showed that the number of triggers were associated with increased odds of PES (OR = 1.372, p = 0.005). CONCLUSIONS: PAS are quite common in CH patients, demonstrating that CH attacks are not comprised of a pain phase alone; investigations of PAS and PES could help researchers better understand the pathophysiology of CH.

Sarcopenia in Patients With Spinal Metastasis: A Systematic Review and Meta-Analysis of Retrospective Cohort Studies.

Background: As a metastasis cancer that happens up to 70% of the cancer patients, spinal metastasis is drawing attention for its significant impairment to health. There exist several predictive models designed to estimate mortality in spinal metastasis patients but they are reported with limited accuracy. In recent years, some retrospective cohort studies have been carried out to associate sarcopenia with mortality in spinal metastasis. Introduction: As a risk factor leading to adverse events in many diseases, sarcopenia was considered to significantly impact on patients with spinal metastasis in mortality by some scientists. We aimed to look through the current evidence and use statistic measures to value the role of sarcopenia in spinal metastasis. In this study, we are going to perform a systematic review and meta-analysis of available retrospective cohort studies where sarcopenia is assessed for outcomes in spinal metastasis patients. Methods: On October 7, 2021, we performed a search in PubMed, Embase, and the Cochrane Library. We set no restrictions on language, date or areas. Results were expressed as hazard ratio (HR) or odds ratio (OR) with 95% CI by random effects model. Sensitivity analyses were performed to explore sources of heterogeneity and stability of results. Results: Of the 4,196 papers screened, 10 retrospective cohort studies were included, with a total of 1,674 patients. Results showed that sarcopenia was associated with higher overall mortality (OR, 1.60; 95% CI 1.35-1.90) and lower overall survival (HR, 2.08; 95% CI 1.55-2.80). The sensitivity analysis proved the stability of results in terms of publication years, region, time of diagnosis, sample size, female rate, measurement and follow up period. Conclusions: Sarcopenia is a robust indicator of mortality in spinal metastasis patients and it might be applied to decision-making tools to assess survival probability and adjust the extent of treatment, while a lack of higher level of evidence is existing. Systematic Review Registration: PROSPERO CRD42021283348.

Development of High-Sensitivity Piezoresistive Sensors Based on Highly Breathable Spacer Fabric with TPU/PPy/PDA Coating.

In recent years, the research of flexible sensors has become a hot topic in the field of wearable technology, attracting the attention of many researchers. However, it is still a difficult challenge to prepare low-cost and high-performance flexible sensors by a simple process. Three-dimensional spacer fabric (SF) are the ideal substrate for flexible pressure sensors due to its good compression resilience and high permeability (5747.7 mm/s, approximately 10 times that of cotton). In this paper, Thermoplastic polyurethane/Polypyrrole/Polydopamine/Space Fabric (TPU/PPy/PDA/SF) composite fabrics were prepared in a simple in-situ polymerization method by sequentially coating polydopamine (PDA) and Polypyrrole (PPy) on the surface of SF, followed by spin-coating of different polymers (thermoplastic polyurethane (TPU), polydimethylsiloxane (PDMS) and Ecoflex) on the PPy/PDA/SF surface. The results showed that the TPU/PPy/PDA/SF pressure sensors prepared by spin-coating TPU at 900 rpm at a concentration of 0.3 mol of pyrrole monomer (py) and a polymerization time of 60 min have optimum sensing performance, a wide working range (0−10 kPa), high sensitivity (97.28 kPa−1), fast response (60 ms), good cycling stability (>500 cycles), and real-time motion monitoring of different parts of the body (e.g., arms and knees). The TPU/PPy/PDA/SF piezoresistive sensor with high sensitivity on a highly permeable spacer fabric base developed in this paper has promising applications in the field of health monitoring.

Characterization of the structure, stability, and activity of hypoglycemic peptides from Moringa oleifera seed protein hydrolysates.

Moringa oleifera seed protein hydrolysates exhibit good hypoglycemic activity, but their specific peptide components have not yet been characterized. Here, we identified the ultrafiltration peptide components (<3 kDa) of M. oleifera seed protein hydrolysates. A highly active α-glucosidase inhibitory peptide with an IC50 value of 109.65 µM (MoHpP-2) with the amino acid sequence KETTTIVR was identified. We characterized its structural properties, stability, and hypoglycemic activity. MoHpP-2 was found to be an amphipathic peptide with a ß-turn structure, and the hemolysis of red blood cells was not observed when its concentration was lower than 2 mg mL-1. MoHpP-2 was stable under weakly acidic conditions, at temperatures lower than 60 °C, and at high ion concentrations. Western blotting revealed that MoHpP-2 affected the PI3K and AMPK pathways of HepG2 cells. Molecular docking revealed that MoHpP-2 interacted with α-glucosidase through hydrogen bonding and hydrophobic forces. Thus, MoHpP-2 from M. oleifera seeds could be used to make hypoglycemic functional foods.