Preparation of low molecular weight chondroitin sulfate from different sources by H2O2/ascorbic acid degradation and its degradation mechanism.

Low molecular weight chondroitin sulfate (LMCS) has attention for enhanced bioavailability and bioactivity compared to native CS. We optimized H2O2/ ascorbic acid (Vc) degradation conditions to prepare LMCS from chicken, bovine, and shark cartilages. Degradation kinetics models and chemical composition data of LMCS showed the GlcA residues of chondroitin-4-sulfate (CSA) may be preferentially attacked. Nuclear magnetic resonance (NMR) spectroscopy and high-performance liquid chromatography-electrospray mass spectrometry (HPLC-MS) indicated that the CH of GlcA in CS was broken through a hydrogen abstraction reaction to break the ß-(1 â†’ 3) bond and form the hexendioic acid product. Standard density functional theory (DFT) calculations indicated that the energy required for the hydrogen abstraction from the C1-H bond in GlcA was lower than that of GalNAc. Molecular dynamics (MD) showed that CSA was more likely to interact with hydroxyl radicals (·OH) than non-sulfated chondroitin (CSO) and chondroitin-6-sulfate (CSC). These results provide guidance for producing LMCS.

Assembly of soy protein-corn starch composite gels by thermal induction: Structure, and properties.

The effect of different corn starch (CS) concentrations on the gel formation of soybean isolate protein (SPI) was investigated. Moreover, the texture, rheological properties of the gel were determined, and the spatial structure and interactions of the composite gel system were analyzed. The composite system transitioned from liquid to solid-like with an increase in the CS concentration and did not backflow when inverted for 24 h. With the addition of CS, the gel strength, water holding capacity (WHC), G', and G'' increased significantly. The maximum was reached at 10 % starch concentration with gel strength of (228.96 ± 29.86) g and WHC of (98.93 ± 2.02)  %. According to low-field 1H nuclear magnetic resonance (LF-NMR) results, CS has a high water absorption capacity, which improved the WHC. The scanning electron microscopy results revealed that composite gels with a high CS concentration had a more dense and small void network structure. According to the results of molecular force interaction, infrared spectroscopy, Raman spectroscopy, and free sulfhydryl group analysis, the added starch promoted the unfolding of SPI molecules, exposure of hydrophobic groups, transformation of free sulfhydryl groups into disulfide bonds, and hydrogen bond formation. Hydrophobic interactions, disulfide bonding, and hydrogen bonding function together to form the SPI-CS composite gel system. The study results provide the basis for applying soy protein and CS gels.

Fe/S oxidation-coupled arsenic speciation transformation mediated by AMD enrichment culture under different pH conditions.

Arsenic (As) speciation transformation in acid mine drainage (AMD) is comprehensively affected by biological and abiotic factors, such as microbially mediated Fe/S redox reactions and changes in environmental conditions (pH and oxidation-reduction potential). However, their combined impacts on arsenic speciation transformation remain poorly studied. Therefore, we explored arsenic transformation and immobilization during pyrite dissolution mediated by AMD enrichment culture under different acidic pH conditions. The results for incubation and mineralogical transformation of solid residues show that in the presence of AMD enrichment culture, pH 2.0, 2.5, and 3.0 are more conducive to the formation of jarosites and ferric arsenate, which could immobilize high quantities of dissolved arsenic by adsorption and coprecipitation. The pH conditions significantly affect the initial adsorption of microbial cells to the minerals and the evolution of microbial community structure, further influencing the biodissolution of pyrite and the release and oxidation process of Fe/S. The results of Fe/S/As speciation transformation of the solid residues show that the transformation of Fe, S, and As in solution is mainly regulated by pH and potential values, which imposed significantly different effects on the formation of secondary minerals and thus arsenic oxidation and immobilization. The above results indicated that arsenic transformation is closely related to the Fe/S oxidation associated with pyrite bio-oxidation, and this correlation is critically regulated by the pH conditions of the system.

A near-infrared light-promoted self-healing photothermally conductive polycarbonate elastomer based on Prussian blue and liquid metal for sensors.

Composite elastomers with elasticity, conductivity, and self-healing properties have gained tremendous interest due to the imperative demands in the fields of stretchable electronics and soft robotics. However, the self-healing performance and the amount of filler are contradictory. Herein, a new conductive self-healing composite elastomer is developed by uniformly dispersing EGaIn droplets and Prussian blue nanoparticles (PBNPs) in a bran-new elastomer which cross-linked the linear polymer that obtained by ring-opening polymerization of trimethylene carbonate and 5-methyl-5-carboxytrimethylene carbonate initiated by polyethylene glycol by aluminum chloride. As confirmed by FT-IR and XPS, the cross-linking network of the composite elastomer is composed of hydrogen bonds and coordination bonds sheared between aluminum and carboxyl groups, and the coordination process was revealed by DFT calculations. This elastomer exhibits excellent light-to-heat conversion properties, thermal conductivity (1.207 W/mK), electrical conductivity (202.34 S·m-1), and good tensile properties that meet application requirements. The good photothermal performance enables the elastomer to self-heal rapidly under NIR irradiation (90.3 %), and accelerate the shape recovery of the elastomer. As a sensor, the elastomer demonstrates good sensitivity, capable of monitoring human movements and recognizing handwriting. This self-healable conductive elastomer has significant potential in the fields of damage-resistant flexible sensors and human-machine interface applications.

Guben Xiezhuo Decoction inhibits M1 polarization through the Raf1/p-Elk1 signaling axis to attenuate renal interstitial fibrosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Guben Xiezhuo Decoction (GBXZD) is an herbal compound used to treat chronic kidney disease (CKD) under the guidance of traditional Chinese medicine (TCM). Its main components are Astragalus membranaceus (Fisch.) Bunge, Codonopsis pilosula (Franch.) Nannf., Centella asiatica (L.) Urb., Salvia miltiorrhiza Bunge, Cuscuta chinensis Lam., and Rheum palmatum L.. Clinical studies have shown that it can relieve fatigue, nausea and other symptoms and improve kidney function in patients; however, its specific mechanism of action requires further study. AIM OF THE STUDY: Renal interstitial fibrosis (RIF) is the ultimate characteristic manifestation of various CKD, that cannot be cured, and appropriate treatments to delay its progression require further exploration. GBXZD, widely used in clinical practice for RIF treatment, can effectively relieve the syndrome in patients with CKD. However, the specific mechanism of action of GBXZD in RIF is unknown and requires further study. This study aimed to explore the specific effects of GBXZD on RIF through the regulation of M1 macrophages. MATERIALS AND METHODS: An in vivo RIF model was obtained through unilateral ureteral obstruction (UUO), and the Sprague-Dawley (SD) rats were randomly divided into sham operation, UUO, UUO + GBXZD-low dose (GBXZD-L) and UUO + GBXZD-high dose (GBXZD-H) groups. Pathological changes in rat kidney specimens were observed using hematoxylin and eosin (HE) and Masson staining. The expression of collagen I (COL I), fibronectin (FN), α-smooth muscle actin (α-SMA), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumour necrosis factor-α (TNF-α) was detected using immunohistochemistry, and immunofluorescence was used to detect the expression of CD86 and inducible nitric-oxide synthase (iNOS) in kidney tissue. An in vitro experiment was performed using M1 polarization model in RAW264.7 macrophages induced by lipopolysaccharide (LPS). Cells were divided into control, LPS, LPS + GBXZD-low dose (GBXZD-L) and LPS + GBXZD-high dose (GBXZD-H) groups. The changes in expression of CD86, iNOS, IL-1ß, IL-6, and TNF-α were measured using western blotting, flow cytometry, immunofluorescence and enzyme-linked immunosorbent assay (ELISA). We analyzed the action pathway of GBXZD in regulating M1 polarization of macrophages using antibody microarray and verified the results using western blotting. RESULTS: Histopathological results showed that the UUO group exhibited significant fibrotic injury compared to the sham group. After GBXZD treatment, the degree of kidney injury, RIF, and inflammatory factor expression were lower than those in the UUO group. Compared with LPS-treated cells, the expression of the M1 markers CD86, iNOS, and pathway proteins Raf1 and p-Elk1 was down-regulated in RAW 264.7 cells treated with LPS and GBXZD. The secretion of the inflammatory factors IL-1ß, IL-6, and TNF-α in the LPS group was more than that in the control group. However, the levels of these factors were significantly reduced in the GBXZD-H group compared to those in the LPS group. CONCLUSIONS: This study indicates that GBXZD ameliorates RIF and inhibits the inflammatory response and macrophage M1 polarization by a potential mechanism related to the downregulation of Raf1 and p-Elk1. GBXZD therefore has therapeutic potential value for patients with CKD.

Construction of an ultrasensitive dual-mode chiral molecules sensing platform based on molecularly imprinted polymer modified bipolar electrode.

Chiral molecules are abundant in nature. Phenylketonuria (PKU) is caused by the abnormal transformation of chiral molecules L-phenylalanine (L-Phe) in the human blood, which can cause irreversible harm to the human body. In this work, we documented an electrochemiluminescent (ECL) dual-mode sensor platform based on molecularly imprinted polymer (MIP) modified closed bipolar electrodes for high sensitivity detection of L-Phe and D-phenylalanine (D-Phe). In the anode chamber of a bipolar electrode modified with phenylalanine imprinting, Ru (bpy)32+ underwent a redox reaction to produce a chemiluminescence response under the stimulation of a driving voltage. At the same time, the reduction of the cathode film of the bipolar electrode was promoted, and the color changed from dark blue to nearly white. Thus, the dual-mode detection of target molecules is realized. The detection range of the sensor for phenylalanine reached 0.01-10,000 nM, and the detection limits of L-Phe and D-Phe were 3.9 pM and 4.6 pM (S/N = 3), respectively. This dual-mode system achieved high stability and high specificity, and also successfully realized the detection of actual samples, which is expected to achieve future clinical applications.

The incidence and risk factors of unplanned removal of peripherally inserted central catheters among adult patients: A multi-centre cohort study.

AIMS AND OBJECTIVES: (i) To estimate the national incidence of unplanned removal of peripherally inserted central catheters (PICCs) in China. (ii) To explore the associated risk factors to provide evidence for the prevention. DESIGN: A multi-centre prospective cohort study. METHODS: A representative sample of 3222 Chinese adult patients with successful PICC insertion was recruited for the PICC Safety Management Research (PATH) using a two-stage cluster sampling method from December 2020 to June 2022. Sixty hospitals from seven Chinese provinces representing all geographical regions were selected. Demographic information and PICC characteristics were collected using a standard online case report form. Risk factors for the unplanned removal of PICCs were assessed using a cause-specific hazard model and verified using a sub-distribution hazard model. STROBE guidelines were followed in reporting this study. RESULTS: Three thousand one hundred and sixty-six patients were included in the final analysis with a mean age of 59 years and a total of 344,247 catheter days. The incidence of unplanned removal was 10.04%. Female, with thrombosis history, PICC insertion due to infusion failure, valved catheter and double-lumen catheter were risk factors, whereas longer insertion and exposure length were protective factors in the cause-specific hazard model. Higher BMI became an independent risk factor in the sub-distribution hazard model. CONCLUSIONS: Unplanned removal of PICCs is a serious clinical challenge in China. Our findings call for prevention strategies targeting the identified risk factors. RELEVANCE TO CLINICAL PRACTICE: Our study characterised the epidemiology of unplanned removal of PICCs among Chinese adult inpatients, highlighting the need for prevention among this population and providing a basis for the formulation of relevant prevention strategies. PATIENT OR PUBLIC CONTRIBUTION: Patients contributed through sharing their information required for the case report form. Healthcare professionals who provide direct care to the patient at each medical centre contributed by completing the online case report form.

Heat and force coupling analysis during precision glass molding of free-form optical elements.

As an effective method for mass production of glass lenses, precision glass molding (PGM) technology has been mature in aspherical lens technology. However, glass molding of complex surfaces such as free-form optical elements is still in its infancy. For mass-produced glass lenses, the energy consumption is mainly concentrated on the heating stage, and the cost is also a key concern. In this paper, an X Y polynomial free-form optical element is simulated by the finite element method. In view of the long heating and molding time, finite element models were established, respectively, at the optimum molding temperature and a temperature point before the optimum temperature. The stress distribution and variation trend of the two methods were analyzed, and the single cycle time of the two methods was compared. The results showed that, under the premise of the maximum stress increase of 3.91 MPa, this method reduces the heating and molding time from 1000 to 910 s, which has significant advantages in terms of time and cost.

The Role of Necroptosis in Cerebral Ischemic Stroke.

Cerebral ischemia, also known as ischemic stroke, accounts for nearly 85% of all strokes and is the leading cause of disability worldwide. Due to disrupted blood supply to the brain, cerebral ischemic injury is trigged by a series of complex pathophysiological events including excitotoxicity, oxidative stress, inflammation, and cell death. Currently, there are few treatments for cerebral ischemia owing to an incomplete understanding of the molecular and cellular mechanisms. Accumulated evidence indicates that various types of programmed cell death contribute to cerebral ischemic injury, including apoptosis, ferroptosis, pyroptosis and necroptosis. Among these, necroptosis is morphologically similar to necrosis and is mediated by receptor-interacting serine/threonine protein kinase-1 and -3 and mixed lineage kinase domain-like protein. Necroptosis inhibitors have been shown to exert inhibitory effects on cerebral ischemic injury and neuroinflammation. In this review, we will discuss the current research progress regarding necroptosis in cerebral ischemia as well as the application of necroptosis inhibitors for potential therapeutic intervention in ischemic stroke.

Engineered Extracellular Vesicles: A potential treatment for regeneration.

Extracellular vesicles (EVs) play a critical role in various physiological and pathological processes. EVs have gained recognition in regenerative medicine due to their biocompatibility and low immunogenicity. However, the practical application of EVs faces challenges such as limited targeting ability, low yield, and inadequate therapeutic effects. To overcome these limitations, engineered EVs have emerged. This review aims to comprehensively analyze the engineering methods utilized for modifying donor cells and EVs, with a focus on comparing the therapeutic potential between engineered and natural EVs. Additionally, it aims to investigate the specific cell effects that play a crucial role in promoting repair and regeneration, while also exploring the underlying mechanisms involved in the field of regenerative medicine.

Aspirin intervention before ICU admission reduced the mortality in critically ill patients with acute kidney injury: results from the MIMIC-IV.

Background: Aspirin, with its pleiotropic effects such as anti-inflammatory and anti-platelet aggregation, has been widely used for anti-inflammatory, analgesic, and cardiovascular diseases. However, the association between the use of aspirin before the intensive care unit (ICU) and clinical outcomes in critically ill patients with acute kidney injury (AKI) is unknown. Methods: Patients with AKI in this retrospective observational study were selected from the Marketplace for Medical Information in Intensive Care IV (MIMIC-IV). The association between aspirin intervention and 30-day mortality was assessed using Cox proportional hazards model. Logistic regression models were used to assess the association of aspirin intervention with the risks of intracranial hemorrhage, gastrointestinal bleeding and blood transfusion. The propensity score matching (PSM) method was adopted to balance the baseline variables. Sensitivity analysis was performed to validate the results by multiple interpolations for the missing data. Results: The study included 4237 pre-ICU aspirin users and 9745 non-users. In multivariate models, we found a decreased risk of mortality in those who received aspirin before ICU compared to those who did not (30-day:hazard ratio [HR], 0.70; 95% CI, 0.62-0.79; p < 0.001; 90-day:HR, 0.70; 95% CI, 0.63-0.77, p < 0.001; 180-day:HR, 0.72; 95%CI,0.65-0.79, p < 0.001). This benefit was consistent in the post-PSM analyses, sensitivity analyses, and subgroup analyses. Moreover, aspirin intervention was associated with a reduced risk of intracranial hemorrhage and gastrointestinal bleeding (HR, 0.16; 95% CI, 0.10-0.25; p < 0.001; HR, 0.59; 95% CI, 0.38-0.88, p = 0.012) after being adjusted by relating covariates, whereas with a increased risk of blood transfusion (HR, 1.28; 95% CI, 1.16-1.46; p < 0.001). Conclusion: Patients with AKI treated with aspirin before ICU admission might have reduced 30-day, 90-day and 180-day mortality without increasing the risk of intracranial hemorrhage (ICH) or gastrointestinal bleeding, but may increase the risk of transfusion.

A Simple and Rapid High-Performance Liquid Chromatography Method for Preparation and Content Detection of the Mainly Numbing Taste Substances of Zanthoxylum bungeanum Maxim.

As the characteristic numbing taste substances, hydroxyl-α-sanshool (HAS) and hydroxyl-ß-sanshool (HBS) were considered vital indicators to evaluate the quality of Zanthoxylum bungeanum Maxim. However, it is very difficult to obtain their high-purity monomers individually, as the only difference between HAS and HBS is that C-6 cis-trans isomerism. In our study, a simple and rapid Ag +-HPLC method was developed to pure the standard chemicals of Z. bungeanum with numbing taste, and 1H NMR and 13C NMR were employed to determine the purity and structure. Moreover, an HPLC method was established to determine the content of numbing taste components of 16 varieties of Z. bungeanum from different regions. The analytical methods were validated for accuracy, precision, and linearity, respectively. The validated method was accurate (spiked recoveries 0.94-1.10), precise in terms of peak area (intra-day RSDs <1.25% and inter-day RSDs <1.61%), and linear (r2 ≥ 0.999). It was found that there were significant differences in the content of HAS and HBS among different types of Z. bungeanum, with HAS content ranging from 60.06 ± 1.14 to 164.13 ± 3.28 mg/g and HBS ranging from 7.81 ± 0.36 to 21.11 ± 0.75 mg/g. The RSDs of HAS range were 1.73-3.80% and that of HBS range 2.03-4.73% (RSDs ≤5%), which indicated that the measurements of HAS and HBS were reliable.

Cerebral venous thrombosis caused by spontaneous intracranial hypotension due to spontaneous spinal cerebrospinal fluid leakage in the high cervical region: a case report.

Spontaneous intracranial hypotension (SIH) may lead to cerebral venous thrombosis (CVT). This case report describes the diagnostic and treatment processes used for a patient with CVT caused by SIH due to spontaneous spinal cerebrospinal fluid (CSF) leakage in the high cervical region. Clinical data were collected from a 37-year-old man with an initial symptom of spontaneous posterior cervical pain. The diagnostic and treatment processes of SIH-induced CVT were described. A magnetic resonance imaging (MRI) study showed superior sagittal sinus thrombosis, and a lumbar puncture revealed a low initial CSF pressure of less than 60 mmH2O. The patient underwent anticoagulation and fluid rehydration therapies. No abnormalities were observed in the thoracic MRI scan, but a cervical MRI scan revealed a spontaneous CSF leak. An epidural blood patch with autologous blood was performed, and symptoms completely resolved 3 days after the procedure. This report proposes a diagnostic procedure for detecting rare cases of SIH-induced CVT, thereby preventing future misdiagnoses and delayed treatment. When a patient presenting with CVT in conjunction with intracranial hypotension has no history of trauma or piercing, SIH caused by spontaneous spinal CSF leakage should be considered as a potential cause of secondary low intracranial pressure. For detection of CSF leaks at rare sites, an MRI of the whole spine rather than a localized MRI of the spine needs to be performed to avoid misdiagnosis. An epidural blood patch should be performed as soon as possible as it may shorten the length of hospitalization and improve prognosis.

Analysis of inpatient cost burden and influencing factors of seniors' patients with mental illness in Dalian, China.

BACKGROUND: As China's aging population continues to grow, the prevalence of mental illness among the seniors has been steadily increasing. The aim of this study is to reveal the changing trends and characteristics of economic burden among seniors patients with long-term hospitalization for mental illness, and to analyze the influencing factors. METHODS: The data for this study were gathered from seniors' patients with mental illness who were hospitalized and aged 60 years or older. The patients were admitted to four specialized and general hospitals located in Dalian city between January 2018 and December 2020. The types of diseases include affective mental disorders (mood disorders), Schizophrenia, schizotypal, and delusional disorders, Organic (including symptomatic) mental disorders, Neurotic, stress-related and somatoform disorders, Mental retardation, Mental and behavioral disorders due to substance use. (Identify the main diagnosis at discharge using ICD-10 coding). This study analyzed the basic characteristics and disease-related information of seniors patients with long-term psychiatric disorders who were hospitalized, and explored the factors influencing hospitalization costs among patients with different illnesses. RESULTS: Among the 3871 study subjects, the average length of hospital stay was 127.51 days. The average hospitalization expenses per case were 33,656.07 yuan. Seniors' patients with mental illness who receives treatment in specialized hospitals have higher hospitalization costs. Long-term hospitalization increases the total hospitalization costs. Age has an impact on hospitalization costs for patients with organic mental disorders. Patients with affective disorders (mood disorders) and neurotic, stress-related, and somatoform disorders who are covered by urban employee medical insurance have higher hospitalization costs.Patients with severe psychiatric disorders who have a 31-day readmission plan, as well as senior patients with somatoform disorders comorbid with other illnesses, incur higher hospitalization costs. CONCLUSIONS: We should take corresponding measures to reduce the number of readmissions for patients with severe mental illnesses. The impact of treatment methods and differences in healthcare institutions on total hospitalization costs deserves further research. It is necessary to strengthen the prevention and diagnosis of comorbid physical illnesses in patients with mental disorders. The burden of mental illnesses in the seniors is significant, and medical insurance policies should be inclined towards providing support.

Prognostic evaluation of oral squamous cell carcinoma based on pleiotrophin, urokinase plasminogen activator, and glycoprotein nonmetastatic melanoma protein B expression.

This study investigated the expression of pleiotrophin (PTN), urokinase plasminogen activator (uPA), and glycoprotein nonmetastatic melanoma protein B (GPNMB) in oral squamous cell carcinoma (OSCC) tissues and their correlation with prognosis. From February 2017 to January 2020, PTN, uPA, and GPNMB expression in cancer tissues and adjacent tissues of 93 patients with OSCC was determined using immunohistochemistry. The diagnostic value of the combined detection of OSCC and its relationship with clinicopathological characteristics were analyzed, as well as the prognostic potential of PTN, uPA, and GPNMB. Cancer tissues from patients with OSCC exhibited high expression of PTN, uPA, and GPNMB. The AUC for the combined detection of PTN, uPA, and GPNMB for diagnosis and prognosis was greater than that of each index alone. The rates of expression of PTN, uPA, and GPNMB were higher in the death group than in the survival group. Patients with PTN, uPA, and GPNMB expression had lower 3-year survival rates. PTN expression was a risk factor affecting the prognosis of patients with OSCC. The rate of PTN, uPA, and GPNMB expression in OSCC tissues was high, and their expression was related to clinicopathological features such as lymph node metastasis and tumor invasion depth. The combined detection of each index has a predictive value for the prognosis of patients.

Diverse Structural Design Strategies of MXene-Based Macrostructure for High-Performance Electromagnetic Interference Shielding.

There is an urgent demand for flexible, lightweight, mechanically robust, excellent electromagnetic interference (EMI) shielding materials. Two-dimensional (2D) transition metal carbides/nitrides (MXenes) have been potential candidates for the construction of excellent EMI shielding materials due to their great electrical electroconductibility, favorable mechanical nature such as flexibility, large aspect ratios, and simple processability in aqueous media. The applicability of MXenes for EMI shielding has been intensively explored; thus, reviewing the relevant research is beneficial for advancing the design of high-performance MXene-based EMI shields. Herein, recent progress in MXene-based macrostructure development is reviewed, including the associated EMI shielding mechanisms. In particular, various structural design strategies for MXene-based EMI shielding materials are highlighted and explored. In the end, the difficulties and views for the future growth of MXene-based EMI shields are proposed. This review aims to drive the growth of high-performance MXene-based EMI shielding macrostructures on basis of rational structural design and the future high-efficiency utilization of MXene.

Evaluating the effectiveness of video-game based swallowing function training in patients with dysphagia: study protocol for a randomized controlled trial.

BACKGROUND: Dysphagia can lead to serious complications such as aspiration and aspiration pneumonia, timely and effective rehabilitation training can improve the swallowing function of patients. However, the conventional rehabilitation training methods used in clinical settings have shortcomings such as poor adherence of patients. We present the study design of a randomized controlled trial that evaluated whether video-game based swallowing rehabilitation training can effectively improve swallowing in patients with dysphagia and whether it has additional benefits compared with conventional training methods to improve swallowing function and training compliance among patients with dysphagia. METHODS: A randomized controlled trial with 4 weeks of intervention and 4 weeks of follow-up will be conducted in a rehabilitation center in Beijing, China. We will enroll 78 patients aged 18-80 years with dysphagia. Participants will be randomly assigned to the experimental group (video-game based swallowing function training) and the control group (conventional swallowing function training). All participants will receive 30 min of training per day, 5 times per week, for a total of 4 weeks. The primary outcome is swallowing function. Secondary outcomes include patients' quality of life, training compliance, and training satisfaction. Outcomes are assessed at baseline (pre-treatment), 4 weeks of treatment (post-treatment), and 8 weeks (follow-up), and the assessor is not aware of the participants' grouping. DISCUSSION: The protocol describes a new rehabilitation training method for dysphagia, which involves participant eligibility recruitment, recruitment strategies, and data analysis plan. The results of the study will inform the rehabilitation training and clinical care management of swallowing function in patients with dysphagia. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05978700. Registered on 28 July 2023.

A human pluripotent stem cell-based somitogenesis model using microfluidics.

Emerging human pluripotent stem cell (hPSC)-based embryo models are useful for studying human embryogenesis. Particularly, there are hPSC-based somitogenesis models using free-floating culture that recapitulate somite formation. Somitogenesis in vivo involves intricately orchestrated bio-chemical and -mechanical events. However, none of the current somitogenesis models controls biochemical gradients or biomechanical signals in the culture, limiting their applicability to untangle complex biochemical-biomechanical interactions that drive somitogenesis. Here we report a new human somitogenesis model by confining hPSC-derived presomitic mesoderm (PSM) tissues in microfabricated trenches. Exogenous microfluidic morphogen gradients imposed on PSM cause axial patterning and trigger spontaneous rostral-to-caudal somite formation. A mechanical theory is developed to explain the size dependency between somites and PSM. The microfluidic somitogenesis model is further exploited to reveal regulatory roles of cellular and tissue biomechanics in somite formation. This study presents a useful microengineered, hPSC-based model for understanding the bio-chemical and -mechanical events that guide somite formation.

A new N/Fe doped carbon dot nanosurface molecularly imprinted polymethacrylate nanoprobe for trace fipronil with SERS/RRS dimode technique.

The N and Fe doped carbon dot (CDNFe) was prepared by microwave procedure. Using CDNFe as the nano-substrate, fipronil (FL) as the template molecule and α-methacrylic acid as the functional monomer, the molecular imprinted polymethacrylic acid nanoprobe (CDNFe@MIP) with difunction was synthesized by microwave procedure. The CDNFe@MIP was characterized by transmission electron microscopy, X-ray photoelectron spectroscopy, Fourier infrared spectroscopy, and other techniques. The results show that the nanoprobe not only distinguish FL but also has a strong catalytic effect on the HAuCl4-Na2C2O4 nanogold indicator reaction. When the nanoprobes specifically recognize FL, their catalytic effect is significantly reduced. Since the AuNPs generated by HAuCl4 reduction have strong surface-enhanced Raman scattering (SERS) and resonance Rayleigh scattering (RRS) effects, a SERS/RRS dual-mode sensing platform for detecting 5-500 ng/L FL was constructed. The new analytical method was applied to detect FL in food samples with a relative standard deviation (RSD) of 3.3-8.1 % and a recovery rate of 94.6-104.5 %.

The presumable effects of hydroxychloroquine and its metabolites in the treatment of systemic lupus erythematosus.

OBJECTIVE: Hydroxychloroquine (HCQ) is an essential drug in the treatment of systemic lupus erythematosus (SLE). This study aimed to detect the concentrations of HCQ and its metabolites from peripheral blood of SLE patients and to investigate the relationship between those concentrations and SLE disease activity. METHODS: 176 SLE patients treated with HCQ were enrolled in this study. The concentrations of HCQ and its metabolites in their peripheral blood were measured by high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). Patients' disease activity was evaluated with the systemic lupus erythematosus disease activity index (SLEDAI). The variables between different concentrations or treatments were statistically analyzed. Linear regression was employed to explore relationships between the concentrations of HCQ and its metabolites with the disease activity. RESULTS: The SLEDAI was lower in patients with higher concentrations of HCQ, desethylhydroxychloroquine (DHCQ), and desethylchloroquine (DCQ) (P = 0.024, P = 0.018, and P = 0.003, respectively). There were no significant differences in SLEDAI and the concentrations of HCQ and its metabolites among groups with different treatments (P > 0.05). After adjusting age, gender, disease duration, HCQ dose adjusted to actual body weight, and glucocorticoid (GC) dose, the SLEDAI was negatively correlated with the concentrations of HCQ, DHCQ, DCQ and bisdesethylchloroquine (BDCQ) (P = 0.007, P = 0.011, P = 0.029, and P = 0.008, respectively). After grouping analysis, in patients treated with HCQ and GC, the SLEDAI was negatively correlated with concentrations of HCQ, DHCQ and BDCQ (P = 0.011, P = 0.035, and P = 0.036, respectively). CONCLUSIONS: The concentrations of HCQ and metabolites were correlated with the SLE disease activity after adjusting possible confounding factors, indicating that HCQ and its metabolites might play certain immunoregulatory roles in SLE treatment. Moreover, GC might have a synergistic effect with HCQ. It is helpful in clinical management and follow-up to monitor the concentrations of HCQ and its metabolites in SLE patients.