Recent Trends and Innovations in Bead-Based Biosensors for Cancer Detection.

Demand is strong for sensitive, reliable, and cost-effective diagnostic tools for cancer detection. Accordingly, bead-based biosensors have emerged in recent years as promising diagnostic platforms based on wide-ranging cancer biomarkers owing to the versatility, high sensitivity, and flexibility to perform the multiplexing of beads. This comprehensive review highlights recent trends and innovations in the development of bead-based biosensors for cancer-biomarker detection. We introduce various types of bead-based biosensors such as optical, electrochemical, and magnetic biosensors, along with their respective advantages and limitations. Moreover, the review summarizes the latest advancements, including fabrication techniques, signal-amplification strategies, and integration with microfluidics and nanotechnology. Additionally, the challenges and future perspectives in the field of bead-based biosensors for cancer-biomarker detection are discussed. Understanding these innovations in bead-based biosensors can greatly contribute to improvements in cancer diagnostics, thereby facilitating early detection and personalized treatments.

Incorporating Sodium-Conductive Polymeric Interfacial Adhesive with Inorganic Solid-State Electrolytes for Quasi-Solid-State Sodium Metal Batteries.

Inorganic solid-state electrolytes have attracted enormous attention due to their potential safety, increased energy density, and long cycle-life benefits. However, their application in solid-state batteries is limited by unstable electrode-electrolyte interface, poor point-to-point physical contact, and low utilization of metallic anodes. Herein, interfacial engineering based on sodium (Na)-conductive polymeric solid-state interfacial adhesive is studied to improve interface stability and optimize physical contacts, constructing a robust organic-rich solid electrolyte interphase layer to prevent dendrite-induced crack propagation and security issues. The interfacial adhesive strategy significantly increases the room-temperature critical current density of inorganic Na-ion conductors from 0.8 to 3.2 mA cm-2 and markedly enhances the cycling performance of solid-state batteries up to 500 cycles, respectively. Particularly, the Na3V2(PO4)3-based full solid-state batteries with high cathode loading of 10.16 mg cm-2 also deliver an excellent cycling performance, further realizing the stable operation of solid-state laminated pouch cells. The research provides fundamental perspectives into the role of interfacial chemistry and takes the field a step closer to realizing practical solid-state batteries.

Proteome-wide association study and functional validation identify novel protein markers for pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) remains a lethal malignancy, largely due to the paucity of reliable biomarkers for early detection and therapeutic targeting. Existing blood protein biomarkers for PDAC often suffer from replicability issues, arising from inherent limitations such as unmeasured confounding factors in conventional epidemiologic study designs. To circumvent these limitations, we use genetic instruments to identify proteins with genetically predicted levels to be associated with PDAC risk. Leveraging genome and plasma proteome data from the INTERVAL study, we established and validated models to predict protein levels using genetic variants. By examining 8,275 PDAC cases and 6,723 controls, we identified 40 associated proteins, of which 16 are novel. Functionally validating these candidates by focusing on 2 selected novel protein-encoding genes, GOLM1 and B4GALT1, we demonstrated their pivotal roles in driving PDAC cell proliferation, migration, and invasion. Furthermore, we also identified potential drug repurposing opportunities for treating PDAC. SIGNIFICANCE: PDAC is a notoriously difficult-to-treat malignancy, and our limited understanding of causal protein markers hampers progress in developing effective early detection strategies and treatments. Our study identifies novel causal proteins using genetic instruments and subsequently functionally validates selected novel proteins. This dual approach enhances our understanding of PDAC etiology and potentially opens new avenues for therapeutic interventions.

Comprehensive analysis of fibroblast activation protein expression across 23 tumor indications: insights for biomarker development in cancer immunotherapies.

Introduction: Fibroblast activation protein (FAP) is predominantly upregulated in various tumor microenvironments and scarcely expressed in normal tissues. Methods: We analyzed FAP across 1216 tissue samples covering 23 tumor types and 70 subtypes. Results: Elevated FAP levels were notable in breast, pancreatic, esophageal, and lung cancers. Using immunohistochemistry and RNAseq, a correlation between FAP gene and protein expression was found. Evaluating FAP's clinical significance, we assessed 29 cohorts from 12 clinical trials, including both mono and combination therapies with the PD-L1 inhibitor atezolizumab and chemotherapy. A trend links higher FAP expression to poorer prognosis, particularly in RCC, across both treatment arms. However, four cohorts showed improved survival with high FAP, while in four others, FAP had no apparent survival impact. Conclusions: Our results emphasize FAP's multifaceted role in therapy response, suggesting its potential as a cancer immunotherapy biomarker.

ADAR2 deficiency ameliorates non-alcoholic fatty liver disease and muscle atrophy through modulating serum amyloid A1.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Sarcopenia is a syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength, which is commonly associated with NAFLD. Adenosine-to-inosine editing, catalysed by adenosine deaminase acting on RNA (ADAR), is an important post-transcriptional modification of genome-encoded RNA transcripts. Three ADAR gene family members, including ADAR1, ADAR2 and ADAR3, have been identified. However, the functional role of ADAR2 in obesity-associated NAFLD and sarcopenia remains unclear. METHODS: ADAR2+/+/GluR-BR/R mice (wild type [WT]) and ADAR2-/-/GluR-BR/R mice (ADAR2 knockout [KO]) were subjected to feeding with standard chow or high-fat diet (HFD) for 20 weeks at the age of 5 weeks. The metabolic parameters, hepatic lipid droplet, grip strength test, rotarod test, muscle weight, fibre cross-sectional area (CSA), fibre types and protein associated with protein degradation were examined. Systemic and local tissues serum amyloid A1 (SAA1) were measured. The effects of SAA1 on C2C12 myotube atrophy were investigated. RESULTS: ADAR2 KO mice fed with HFD exhibited lower body weight (-7.7%, P < 0.05), lower liver tissue weight (-20%, P < 0.05), reduced liver lipid droplets in concert with a decrease in hepatic triglyceride content (-24%, P < 0.001) and liver injury (P < 0.01). ADAR2 KO mice displayed protection against HFD-induced glucose intolerance, insulin resistance and dyslipidaemia. Skeletal muscle mass (P < 0.01), muscle strength (P < 0.05), muscle endurance (P < 0.001) and fibre size (CSA; P < 0.0001) were improved in ADAR2 KO mice fed with HFD compared with WT mice fed with HFD. Muscle atrophy-associated transcripts, such as forkhead box protein O1, muscle atrophy F-box/atrogin-1 and muscle RING finger 1/tripartite motif-containing 63, were decreased in ADAR2 KO mice fed with HFD compared with WT mice fed with HFD. ADAR2 deficiency attenuates HFD-induced local liver and skeletal muscle tissue inflammation. ADAR2 deficiency abolished HFD-induced systemic (P < 0.01), hepatic (P < 0.0001) and muscular (P < 0.001) SAA1 levels. C2C12 myotubes treated with recombinant SAA1 displayed a decrease in myotube length (-37%, P < 0.001), diameter (-20%, P < 0.01), number (-39%, P < 0.001) and fusion index (-46%, P < 0.01). Myogenic markers (myosin heavy chain and myogenin) were decreased in SAA1-treated myoblast C2C12 cells. CONCLUSIONS: These results provide novel evidence that ADAR2 deficiency may be important in obesity-associated sarcopenia and NAFLD. Increased SAA1 might be involved as a regulatory factor in developing sarcopenia in NAFLD.

N6-Methyladenosine (m6A) Methylation Is Associated with the Immune Microenvironments in Acute Intracerebral Hemorrhage (ICH).

Researchers have recently found that N6-methyladenosine (m6A) is a type of internal posttranscriptional modification that is essential in mammalian mRNA. However, the features of m6A RNA methylation in acute intracerebral hemorrhage (ICH) remain unknown. To explore differential methylations and to discover their functions in acute ICH patients, we recruited three acute ICH patients, three healthy controls, and an additional three patients and healthy controls for validation. The m6A methylation levels in blood samples from the two groups were determined by ultrahigh-performance liquid chromatography coupled with triple quadruple mass spectrometry (UPLC-QQQ-MS). Methylated RNA immunoprecipitation sequencing (MeRIP-seq) was employed to identify differences in m6A modification, and the differentially expressed m6A-modified genes were confirmed by MeRIP-qPCR. We found no significant differences in the total m6A levels between the two groups but observed differential methylation peaks. Compared with the control group, the coding genes showing increased methylation following acute ICH were mostly involved in processes connected with osteoclast differentiation, the neurotrophin signaling pathway, and the spliceosome, whereas genes with reduced m6A modification levels after acute ICH were found to be involved in the B-cell and T-cell receptor signaling pathways. These results reveal that differentially m6A-modified genes may influence the immune microenvironments in acute ICH.

A novel smart somatosensory wearable assistive device for older adults' home rehabilitation during the COVID-19 pandemic.

Background: Due to the Coronavirus disease 19 (COVID-19) related social distancing measures and health service suspension, physical activity has declined, leading to increased falling risk and disability, and consequently, compromising the older adult health. How to improve the quality of older adult life has become a crucial social issue. Objective: In traditional rehabilitation, manual and repetitive muscle training cannot identify the patient's rehabilitation effect, and increasing the willingness to use it is not easy. Therefore, based on the usability perspective, this study aims to develop a novel smart somatosensory wearable assistive device (called SSWAD) combined with wireless surface electromyography (sEMG) and exergame software and hardware technology. The older adult can do knee extension, ankle dorsiflexion, and ankle plantar flexion rehabilitation exercises at home. Meanwhile, sEMG values can be digitally recorded to assist physicians (or professionals) in judgment, treatment, or diagnosis. Methods: To explore whether the novel SSWAD could improve the older adult willingness to use and motivation for home rehabilitation, 25 frail older adult (12 males and 13 females with an average age of 69.3) perform the rehabilitation program with the SSWAD, followed by completing the system usability scale (SUS) questionnaire and the semi-structured interview for the quantitative and qualitative analyses. In addition, we further investigate whether the factor of gender or prior rehabilitation experience would affect the home rehabilitation willingness or not. Results: According to the overall SUS score, the novel SSWAD has good overall usability performance (77.70), meaning that the SSWAD makes older adult feel interested and improves their willingness for continuous rehabilitation at home. In addition, the individual item scores of SUS are shown that female older adult with prior rehabilitation experience perform better in "Learnability" (t = 2.35, p = 0.03) and "Confidence" (t = -3.24, p = 0.01). On the contrary, male older adult without rehabilitation experience are more willing to adopt new technologies (t = -2.73, p = 0.02), and perform better in "Learnability" (t = 2.18, p = 0.04) and "Confidence" (t = -3.75, p < 0.001) with the SSWAD. In addition, the result of the semi-structured interview shows that the operation of the SSWAD is highly flexible, thus reducing older adult burden during the rehabilitation exercise and using them long-term. Conclusion: This novel SSWAD receives consistently positive feedback regardless of the gender or prior rehabilitation experience of elders. The SSWAD could be used as a novel way of home rehabilitation for elders, especially during the COVID-19 pandemic. Older adult can do rehabilitation exercises at home, and physicians could make proper judgments or adjust suitable treatments online according to the sEMG data, which older adult can know their rehabilitation progress at the same time. Most importantly, older adult do not have to go to the hospital every time for rehabilitation, which significantly reduces time and the risk of infection.

Joint polarization detection and degradation mechanisms for underwater image enhancement.

Light absorption and scattering exist in the underwater environment, which can lead to blurring, reduced brightness, and color distortion in underwater images. Polarized images have the advantages of eliminating underwater scattering interference, enhancing contrast, and detecting material information of the object in underwater detection. In this paper, from the perspective of polarization imaging, different concentrations (0.15 g/ml, 0.30 g/ml, and 0.50 g/ml), different wave bands (red, green, and blue), different materials (copper, wood, high-density PVC, aluminum, cloth, foam, cloth sheet, low-density PVC, rubber, and porcelain tile), and different depths (10 cm, 20 cm, 30 cm, and 40 cm) are set up in a chamber for the experimental environment. By combining the degradation mechanism of underwater images and the analysis of polarization detection results, it is proved that the degree of polarization images have greater advantages than degree of linear polarization images, degree of circular polarization images, S1, S2, and S3 images, and visible images underwater. Finally, a fusion algorithm of underwater visible images and polarization images based on compressed sensing is proposed to enhance underwater degraded images. To improve the quality of fused images, we introduce orthogonal matching pursuit (OMP) in the high-frequency part to improve image sparsity and consistency detection in the low-frequency part to improve the image mutation phenomenon. The fusion results show that the peak SNR values of the fusion result maps using OMP in this paper are improved by 32.19% and 22.14% on average over those using backpropagation and subspace pursuit methods. With different materials and concentrations, the underwater image enhancement algorithm proposed in this paper improves information entropy, average gradient, and standard deviation by 7.76%, 18.12%, and 40.8%, respectively, on average over previous algorithms. The image NIQE value shows that the image quality obtained by this paper's algorithm is improved by about 69.26% over the original S0 image.

Photonic crystal enhanced immunofluorescence biosensor integrated with a lateral flow microchip: Toward rapid tear-based diabetic retinopathy screening.

Diabetic retinopathy (DR) has accounted for major loss of vision in chronic diabetes. Although clinical statistics have shown that early screening can procrastinate or improve the deterioration of the disease, the screening rate remains low worldwide because of the great inconvenience of conventional ophthalmoscopic examination. Instead, tear fluid that contains rich proteins caused by direct contact with eyeballs is an ideal substitute to monitor vision health. Herein, an immunofluorescence biosensor enhanced by a photonic crystal (PhC) is presented to handle the trace proteins suspended in the tear fluid. The PhC was constructed by self-assembled nanoparticles with a thin layer of gold coated on top of it. Then, the PC substrate was conjugated with antibodies and placed in a microchannel. When the capillary-driven tear sample flew over the PC substrate, the immunoassay enabled the formation of a sandwich antibody-antigen-antibody configuration for PhC-enhanced immunofluorescence. The use of PhC resulted in a concentration enhancement of more than tenfold compared to non-PhC, while achieving an equivalent signal intensity. The limit of detection for the target biomarker, lipocalin-1 (LCN-1), reached nearly 3 µg/ml, and the turnaround time of each detection was 15 min. Finally, a preclinical evaluation was conducted using ten tear samples. A clear trend was observed, showing that the concentrations of LCN-1 were at least twofold higher in individuals with chronic diabetes or DR than in healthy individuals. This trend was consistent with their medical conditions. The results provided a direct proof-of-concept for the proposed PhC biosensor in rapid tear-based DR screening.

In Situ Growth of Nano-MoS2 on Graphite Substrates as Catalysts for Hydrogen Evolution Reaction.

In order to synthesize a high-efficiency catalytic electrode for hydrogen evolution reactions, nano-MoS2 was deposited in situ on the surface of graphite substrates via a one-step hydrothermal method. The effects of the reactant concentration on the microstructure and the electrocatalytic characteristics of the nano-MoS2 catalyst layers were investigated in detail. The study results showed that nano-MoS2 sheets with a thickness of about 10 nm were successfully deposited on the surface of the graphite substrates. The reactant concentration had an important effect on uniform distribution of the catalyst layers. A higher or lower reactant concentration was disadvantageous for the electrochemical performance of the nano-MoS2 catalyst layers. The prepared electrode had the best electrocatalytic activity when the thiourea concentration was 0.10 mol·L-1. The minimum hydrogen evolution reaction overpotential was 196 mV (j = 10 mV·cm-2) and the corresponding Tafel slope was calculated to be 54.1 mV·dec-1. Moreover, the prepared electrode had an excellent cycling stability, and the microstructure and the electrocatalytic properties of the electrode had almost no change after 2000 cycles. The results of the present study are helpful for developing low-cost and efficient electrode material for hydrogen evolution reactions.

Sputtered anti-reflection layer on transparent polyimide - substrate improves adhesion strength to - copper layer: effects of layer thickness and sputtering power.

In order to shield the electronic circuits on a transparent polyimide (PI) substrate, an anti-reflection (AR) layer was deposited on a PI film via DC reactive magnetron sputtering. The effects of sputtering power and thickness of AR layer on the optical property and adhesion strength of the PI were investigated. The composition of the AR layer influences the bonding between layers. Sufficient thickness of the AR layer is essential to strengthen the adhesion between the PI and copper (Cu) layers. The sputtered AR layer on the PI also improves the barrier property for water vapor. The AR layer-sputtered PI substrates remain transparent and exhibit high peel strength to the Cu layer, suggesting their potential applications as reliable transparent substrates for modern electronic devices.

Toward Excellent Energy Storage Performance via Well-Aligned and Isolated Interfaces in Multicomponent Polypropylene-Based All-Organic Polymer Dielectric Films.

Polypropylene (PP) serves as an excellent commercialized polymer dielectric film owing to its high breakdown strength, excellent self-healing ability, and flexibility. However, its low dielectric constant causes the large volume of the capacitor. Constructing multicomponent polypropylene-based all-organic polymer dielectric films is a facile strategy for achieving high energy density and efficiency simultaneously. Thereinto, the interfaces between the components become the key factors that determine the energy storage performance of the dielectric films. In this work, we propose to fabricate high-performance polyamide 513 (PA513)/PP all-organic polymer dielectric films via the construction of abundant well-aligned and isolated nanofibrillar interfaces. Laudably, a significant enhancement in the breakdown strength is achieved from 573.1 MV/m of pure PP to 692.3 MV/m with 5 wt % of PA513 nanofibrils. Besides, a maximum discharge energy density of about 4.4 J/cm2 is realized with 20 wt % of PA513 nanofibrils, which is about 1.6-folds higher than pure PP. Simultaneously, the energy efficiency of samples with modulated interfaces maintains higher than 80% up to 600 MV/m, which is much higher than pure PP of about 40.7% at 550 MV/m. This work provides a new strategy to fabricate high-performance multicomponent all-organic polymer dielectric films on an industrial scale.

CDBN-YGXZ, a Novel Small-Molecule Drug, Shows Efficacy against Clostridioides difficile Infection and Recurrence in Mouse and Hamster Infection Models.

Clostridioides difficile infection (CDI) causes severe diarrhea and colitis, leading to significant morbidity, mortality, and high medical costs worldwide. Oral vancomycin, a first-line treatment for CDI, is associated with a high risk of recurrence, necessitating novel therapies for primary and recurrent CDI. A novel small-molecule compound, CDBN-YGXZ, was synthesized by modifying the benzene ring of nitazoxanide with lauric acid. The mechanism of action of CDBN-YGXZ was validated using a pyruvate:ferredoxin/flavodoxin oxidoreductase (PFOR) inhibition assay. The efficacy of CDBN-YGXZ was evaluated using the MIC test and CDI infection model in mice and hamsters. Furthermore, metagenomics was used to reveal the underlying reasons for the effective reduction or prevention of CDI after CDBN-YGXZ treatment. The inhibitory activity against PFOR induced by CDBN-YGXZ. MIC tests showed that the in vitro activity of CDBN-YGXZ against C. difficile ranging from 0.1 to 1.5 µg/mL. In the mouse and hamster CDI models, CDBN-YGXZ provided protection during both treatment and relapse, while vancomycin treatment resulted in severe relapse and significant clinical scores. Compared with global effects on the indigenous gut microbiota induced by vancomycin, CDBN-YGXZ treatment had a mild influence on gut microbes, thus resulting in the disappearance or reduction of CDI recurrence. CDBN-YGXZ displayed potent activity against C. difficile in vitro and in vivo, reducing or preventing relapse in infected animals, which could merit further development as a potential drug candidate for treating CDI.

Circulating Leukocyte as an Inflammatory Biomarker: Association with Fibrinogen and Neuronal Damage in Acute Ischemic Stroke.

Background and Purpose: Leukocytes and fibrinogen are inflammatory markers involved in circulating and central inflammatory response after ischemic stroke. However, the interaction between circulating leukocytes and serum fibrinogen and neuronal injury in acute ischemic stroke (AIS) patients is still unclear. The present study aimed to investigate the association between circulating leukocyte and serum fibrinogen and neuronal injury respectively in AIS. Methods: A cross-section study with 431 hospitalized AIS patients from department of neurology was performed. Circulating leukocytes and fibrinogen were measured, and neuron-specific enolase (NSE) was detected to evaluate central neuronal damage. A propensity score matching method was used to minimize the effects of confounding factors. The relationship between leukocytes and NSE and fibrinogen was analyzed by linear curve fitting analysis and multiple logistic regression models respectively. Results: The mean levels of NSE, leukocyte, and fibrinogen were significantly higher in the matched AIS group (n=89) than those of in the healthy control group (n=89) (all p<0.05). Both serum NSE and fibrinogen were increased with the increasing of leukocyte in AIS patients (both p<0.05). Smoothed plots suggested that there are linear relationships between leukocyte and NSE and fibrinogen respectively. Multiple logistic regression analysis showed the OR (95%) for the relationship between leukocyte and high NSE were 1.13 (1.01-1.26, p=0.031) and 1.13 (1.00-1.28, p=0.048), and between leukocyte and high fibrinogen were 1.40 (1.22-1.61, p<0.001) and 1.35 (1.15-1.58, p<0.001) in all AIS patients before and after adjusting for potential confounders. Conclusion: Our study suggests that elevated circulating leukocyte was associated with high fibrinogen and neuronal injury in AIS. Therefore, there may be potential targets among circulating leukocyte, fibrinogen and NSE that should be intervened to reduce inflammatory reaction after ischemic stroke.

Overexpression of mitogen-activated protein kinase phosphatase-1 in endothelial cells reduces blood-brain barrier injury in a mouse model of ischemic stroke.

Ischemic stroke can cause blood-brain barrier (BBB) injury, which worsens brain damage induced by stroke. Abnormal expression of tight junction proteins in endothelial cells (ECs) can increase intracellular space and BBB leakage. Selective inhibition of mitogen-activated protein kinase, the negative regulatory substrate of mitogen-activated protein kinase phosphatase (MKP)-1, improves tight junction protein function in ECs, and genetic deletion of MKP-1 aggravates ischemic brain injury. However, whether the latter affects BBB integrity, and the cell type-specific mechanism underlying this process, remain unclear. In this study, we established an adult male mouse model of ischemic stroke by occluding the middle cerebral artery for 60 minutes and overexpressed MKP-1 in ECs on the injured side via lentiviral transfection before stroke. We found that overexpression of MKP-1 in ECs reduced infarct volume, reduced the level of inflammatory factors interleukin-1ß, interleukin-6, and chemokine C-C motif ligand-2, inhibited vascular injury, and promoted the recovery of sensorimotor and memory/cognitive function. Overexpression of MKP-1 in ECs also inhibited the activation of cerebral ischemia-induced extracellular signal-regulated kinase (ERK) 1/2 and the downregulation of occludin expression. Finally, to investigate the mechanism by which MKP-1 exerted these functions in ECs, we established an ischemic stroke model in vitro by depriving the primary endothelial cell of oxygen and glucose, and pharmacologically inhibited the activity of MKP-1 and ERK1/2. Our findings suggest that MKP-1 inhibition aggravates oxygen and glucose deprivation-induced cell death, cell monolayer leakage, and downregulation of occludin expression, and that inhibiting ERK1/2 can reverse these effects. In addition, co-inhibition of MKP-1 and ERK1/2 exhibited similar effects to inhibition of ERK1/2. These findings suggest that overexpression of MKP-1 in ECs can prevent ischemia-induced occludin downregulation and cell death via deactivating ERK1/2, thereby protecting the integrity of BBB, alleviating brain injury, and improving post-stroke prognosis.

Anti-reflection Layer-Sputtered Transparent Polyimide Substrate with Reliable Adhesion Strength to the Copper Layer.

Parameters of DC-reactive magnetron sputtering are optimized to deposit anti-reflection (AR) layers on transparent polyimide (PI) substrates, followed by the deposition of the conductive copper layer, to fabricate practically reliable composite films as advanced flexible circuits. When the deposition thickness is controlled and the gas composition during sputtering is adjusted, the resultant AR layer-coated PI film exhibits low reflectance and reveals improved adhesion strength to the copper layer. The adhesion reliability tests confirm that the peel strength between the PI film and the deposited layers could be further improved after thermal processing due to the formation of a worm-like morphology for better mechanical interlocking with layers. The facile sputtering process successfully fabricates a reliable substrate material with low reflectance and sufficient adhesion strength to copper for application as flexible printed circuits.

The effects of low-level laser therapy on muscle strength and functional outcomes in individuals with knee osteoarthritis: a double-blinded randomized controlled trial.

The purpose of this study was to compare the therapeutic effects of low-level laser therapy (LLLT) with 808 and 660 nm wavelength on muscle strength and functional outcomes in individuals with knee osteoarthritis (OA). A total of 47 participants were randomly assigned to the 808 nm, 660 nm, and sham control groups. Two LLLT groups received continuous LLLT with a mean power of 300 mW in different wavelengths at the knee joint 15 min a session three days per week for eight weeks, while the control group received the sham LED treatment. The knee strength and functional performance involving 30-s sit-to-stand, 40 m fast-paced walk, stair climbing, and the TUG test were measured at the baseline and one week after the interventions were completed. The results showed that knee extensor strength was more improved in the 808 nm group as compared to the 660 nm group (p < 0.001, d = 0.57) and the sham control (p < 0.001, d = 0.40), while increased flexor strength was demonstrated in the 808 nm (p = 0.009, d = 0.67) and sham control groups (p < 0.001, d = 0.97). The number of 30-s sit-to-stand was increased only in the 660 nm group (p = 0.006, d = 0.49). All three groups exhibited improvements in the other three functional performance-based tests after the interventions with no statistically significant differences among the groups. In conclusion, both intervention groups improved muscle strength and functional performance as compared to the control group. The 808 nm wavelength group showed better results in knee extensor strength. Therefore, laser therapy is suggested to be integrated into rehabilitation programs to improve muscle strength and functional performance in the population with knee OA.

Positive association between urinary albumin-creatinine ratio and lower extremity peripheral arterial disease in Chinese diabetes patients: A cross-section study with propensity score matching analysis.

BACKGROUND AND AIMS: Elevated urinary albumin-creatinine ratio (ACR) is an established risk factor for lower extremity peripheral arterial disease (PAD) in non-diabetes individual. This study aimed to determine the relationship between urinary ACR level and PAD in diabetes population. METHODS AND RESULTS: A cross-section study with 1396 hospitalized diabetes participants from department of endocrinology and neurology were performed and the propensity score matching method was applied to reduce the effects of confounding factors between the matched PAD and Non-PAD groups. The relationship between urinary ACR and ankle-brachial index (ABI) was analyzed by linear curve fitting analyses and multiple logistic regression models. Our study showed that the prevalence of PAD (low ABI, ABI<0.9) was 7.09% in our diabetes patients. The ABI level was significantly lower in high ACR group compared with those in normal urinary ACR group (1.11 ± 0.17 vs 1.13 ± 0.15, p = 0.010). The prevalence of PAD was increased with the increased tertile's of log2-transformed ACR in total patients before and after propensity score matching (p < 0.001 and p = 0.007, respectively). The OR (95% CI) between log2-transformed ACR and PAD was 1.0 and 1.70 (1.08-2.69, p = 0.022) respectively in normal and high ACR levels in diabetes patients after adjusting for potential confounders. After propensity score matching, the OR (95% CI) between log2-transformed ACR and PAD was 1.0 and 1.85 (1.05-3.23, p = 0.031) respectively in normal and high ACR levels in diabetes patients after adjusting for potential confounders. CONCLUSION: The elevated urinary ACR level was associated with PAD in Chinese diabetes patients.

A novel gut-restricted RIPK1 inhibitor, SZ-15, ameliorates DSS-induced ulcerative colitis.

As a key mediator of cell death and inflammation, receptor-interacting protein kinase 1 (RIPK1) responds to a broad set of inflammatory and pro-death stimuli in human diseases. Inhibitors targeting RIPK1 are being investigated for the treatment of a wide range of human diseases, including ulcerative colitis. In the present study, we designed, synthesized, and investigated the anti-necroptosis and RIPK1-inhibition effects of SZ-15-a symmetrical high-molecular-weight (>500 Da) compound. SZ-15 effectively inhibited necroptosis in U937 and HT-29 cells at concentrations of 1 nM and 10 nM, respectively, and SZ-15 at a concentration of 10 nM almost completely blocked RIPK1, RIPK3, and mixed-lineage kinase domain-like (MLKL) protein phosphorylation induced by necrosis inducers. SZ-15 suppressed the pro-necroptosis function of RIPK1 by downregulating the mRNA expression of pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6. The activities of SZ-15 were effectively restricted to the gut: The percent recovery of the parent form of SZ-15 in mouse feces was 85.75%. Nevertheless, SZ-15 was effectively absorbed and detected in colon tissues after 1 h at a concentration of 3335 ± 868 ng/g, indicating that membrane permeability was maintained. SZ-15 alleviated dextran sulfate sodium (DSS)-induced ulcerative colitis in vivo by decreasing TNF-α, IL-1ß, IL-22, and IL-6 mRNA expression in colonic tissues. Our preclinical study describes a novel gut-restricted RIPK1 inhibitor that shows great potential for use in the clinical treatment of ulcerative colitis.

Osteoregenerative efficacy of a novel synthetic, resorbable Ca/P/S-based bone graft substitute in intra- and peri-articular fractures: a brief medical image-based report.

BACKGROUND: When a fracture goes into or around a joint, it usually damages the cartilage at the ends of bones and other joint tissue. As a result, the affected joints are prone to traumatic arthritis, leading to stiffness. Repairing bone damage, maintaining joint integrity, and avoiding subchondral and metaphyseal defects caused by comminuted fractures is often a great challenge for orthopedic surgeons. Tissue engineering of synthetic bone substitutes has proven beneficial to the attachment and proliferation of bone cells, promoting the formation of mature tissues with sufficient mechanical strength and has become a promising alternative to autograft methods. The purpose of this study is to retrospectively evaluate the clinical outcome and efficacy of a novel synthetic, highly biocompatible, and fully resorbable Ca/P/S-based bone substitute based on medical image findings. MATERIALS AND METHODS: A synthetic, inorganic and highly porous Ca/P/S-based bone-substituting material (Ezechbone® Granule, CBS-400) has been developed by National Cheng-Kung University. We collected fourteen cases of complex intra- and peri-articular fractures with Ezechbone® Granule bone grafting between 2019/11 and 2021/11. We studied the evidence of bone healing by reviewing, interpreting and analyzing the medical image recordings. RESULTS: In the present study, CBS-400 was observed to quickly integrate into surrounding bone within three weeks after grafting during the initial callus formation of the early stage of repair. All of these cases healed entirely within three months. In addition, the patient may return to daily life function after 3.5 months of follow-up and rehabilitation treatment. CONCLUSIONS: Ezechbone® Granule CBS-400 was proved capable of promoting bone healing and early rehabilitation to prevent soft tissue adhesions and joint contractures. Moreover, it has a high potential for avoiding ectopic bone formation or abnormal synostosis. TRIAL REGISTRATION: The Institutional Review Board at National Cheng Kung University Hospital (NCKUH) approved the study protocol (A-ER-109-031, 3-13-2020).