Advancements and Challenges in Non-Invasive Sensor Technologies for Swallowing Assessment: A Review.

Dysphagia is a pervasive health issue that impacts diverse demographic groups worldwide, particularly the elderly, stroke survivors, and those suffering from neurological disorders. This condition poses substantial health risks, including malnutrition, respiratory complications, and increased mortality. Additionally, it exacerbates economic burdens by extending hospital stays and escalating healthcare costs. Given that this disorder is frequently underestimated in vulnerable populations, there is an urgent need for enhanced diagnostic and therapeutic strategies. Traditional diagnostic tools such as the videofluoroscopic swallowing study (VFSS) and flexible endoscopic evaluation of swallowing (FEES) require interpretation by clinical experts and may lead to complications. In contrast, non-invasive sensors offer a more comfortable and convenient approach for assessing swallowing function. This review systematically examines recent advancements in non-invasive swallowing function detection devices, focusing on the validation of the device designs and their implementation in clinical practice. Moreover, this review discusses the swallowing process and the associated biomechanics, providing a theoretical foundation for the technologies discussed. It is hoped that this comprehensive overview will facilitate a paradigm shift in swallowing assessments, steering the development of technologies towards more accessible and accurate diagnostic tools, thereby improving patient care and treatment outcomes.

Current Research Status of Respiratory Motion for Thorax and Abdominal Treatment: A Systematic Review.

Malignant tumors have become one of the serious public health problems in human safety and health, among which the chest and abdomen diseases account for the largest proportion. Early diagnosis and treatment can effectively improve the survival rate of patients. However, respiratory motion in the chest and abdomen can lead to uncertainty in the shape, volume, and location of the tumor, making treatment of the chest and abdomen difficult. Therefore, compensation for respiratory motion is very important in clinical treatment. The purpose of this review was to discuss the research and development of respiratory movement monitoring and prediction in thoracic and abdominal surgery, as well as introduce the current research status. The integration of modern respiratory motion compensation technology with advanced sensor detection technology, medical-image-guided therapy, and artificial intelligence technology is discussed and analyzed. The future research direction of intraoperative thoracic and abdominal respiratory motion compensation should be non-invasive, non-contact, use a low dose, and involve intelligent development. The complexity of the surgical environment, the constraints on the accuracy of existing image guidance devices, and the latency of data transmission are all present technical challenges.

Regulable Mixed-Solvent-Induced Phase Separation in Hydrogels for Information Encryption.

The rapid progress of information technology is accompanied by plenty of information embezzlement and forgery, but developing advanced encryption technologies to ensure information security remains challenging. Phase separation commonly leads to a dramatic change in the transmittance of hydrophilic polymer networks, which is a potential method for information security but is often neglected. Here, taking the polyacrylamide (PAAm) hydrogel system as a typical example, facilely adjustable information encryption and decryption via its regulable phase separation process in ethanol/water mixed solvent, are reported. By controlling the osmotic pressure of the external and internal environment, it is demonstrated that the diffusion coefficient during deswelling and reswelling, as well as the corresponding change of transmittance of the gel, can be well controlled. Relatively high osmotic pressure leads to rapid phase separation of the initial gel but slow phase remixing of the phase-separated gel, opening the opportunity of applying the gel as a reversible information encryption device. As proof-of-concept demonstrations, several stable and reversible information encryption and decryption systems by making use of the phase separation process of the gels are designed, which are expected to inspire the development of next-generation soft devices for information technology.

Cellulose nanocrystal/phytic acid reinforced conductive hydrogels for antifreezing and antibacterial wearable sensors.

Common hydrogels containing abundant water are insulating materials and lose stretchability easily below the freezing point of water, holding limited potential in emerging applications such as wearable soft devices. The introduction of compatible biomass-derived materials into hydrogel systems could be a potential solution that simultaneously enables anti-freezing ability, mechanical enhancement, and antibacterial properties. Based on such a hypothesis, here we report the facile development of biocompatible hydrogels that are capable of maintaining satisfying mechanical properties and electrical conductivity well below zero degrees centigrade. The strategy is to reinforce neat polyacrylamide (PAAm) hydrogels with biomass-derived cellulose nanocrystal (CNC) and phytic acid (PA), transforming the originally weak, insulating hydrogels into tough, highly conductive ones. Anti-freezing and antibacterial properties also emerge in the reinforced hydrogels, enabling them to work as efficient wearable sensors below zero degrees centigrade. Considering that numerous polymer hydrogel systems are compatible with CNC and PA, we believe that this simple biomass-based strategy can work universally to enhance and functionalize various weak and insulating hydrogels that are traditionally susceptible to frost and bacteria.

Fe3+-citric acid/sodium alginate hydrogel: A photo-responsive platform for rapid water purification.

As water pollution in human society becomes more and more serious, the demand for materials that can be used for wastewater treatment is increasing. Here, we reported a sodium alginate-based hydrogel (Fe3+-CA/SA hydrogel) that can efficiently photocatalyze the degradation of malachite green. The Fe3+-CA/SA hydrogel is composed of sodium alginate, citric acid, and Fe3+. The hydrogel has multi-leveled pore structure and photochromic ability. Benefiting from the unique microstructure and positive feedback chemical reaction process, the hydrogel has high photocatalytic efficiency. Under 365 nm UV light irradiation, the hydrogel can degrade around 95% of malachite green (20 mg/L) in about 4 min, and there is no need to add H2O2 in the degradation process. The work helps to expand the application of sodium alginate-based hydrogels in the field of water treatment. It also has exploratory significance for the principle of photocatalytic degradation of malachite green.

Preparation of silver nanoparticles by solid-state redox route from hydroxyethyl cellulose for antibacterial strain sensor hydrogel.

As a smart wearable sensor device, the mildew of the biocompatible hydrogel limits its application. In this paper, silver nanoparticles were prepared by solid-state reduction of hydroxyethyl cellulose and compounded into a chemically cross-linked hydrogel as an antibacterial, flexible strain sensor. Because the high surface energy of silver nanoparticles can quench free radicals, we designed three initiators to synthesize hydrogels: ammonium persulfate (APS), 2,2'-Azobis(2-methylpropionitrile) (AIBN) and 2,2'-azobis(2-methylpropionamidine) dihydrochloride (AIBA). Impressively, silver nanoparticles composite hydrogel could only be successfully fabricated and triggered by the AIBN. The mechanical property of the composite hydrogel (0.12 MPa at 704.33 % strain) was significantly improved because of dynamic crosslinking point by HEC. Finally, the composite hydrogels are applied to the field of antibacterial strain sensor and the highest Gauge Factor (GF) reached 4.07. This article proposes a novel, green and simple strategy for preparing silver nanoparticles and compounding them into a hydrogel system for antibacterial strain sensor.

Acid-sensing ion channel 1a mediates acid-induced pyroptosis through calpain-2/calcineurin pathway in rat articular chondrocytes.

The pyroptosis is a causative agent of rheumatoid arthritis, a systemic autoimmune disease merged with degenerative articular cartilage. Nevertheless, the precise mechanism of extracellular acidosis on chondrocyte pyroptosis is largely unclear. Acid-sensing ion channels (ASICs) belong to an extracellular H+ -activated cation channel family. Accumulating evidence has highlighted activation of ASICs induced by extracellular acidosis upregulate calpain and calcineurin expression in arthritis. In the present study, to investigate the expression and the role of acid-sensing ion channel 1a (ASIC1a), calpain, calcineurin, and NLRP3 inflammasome proteins in regulating acid-induced articular chondrocyte pyroptosis, primary rat articular chondrocytes were subjected to different pH, different time, and different treatments with or without ASIC1a, calpain-2, and calcineurin, respectively. Initially, the research results showed that extracellular acidosis-induced the protein expression of ASIC1a in a pH- and time-dependent manner, and the messenger RNA and protein expressions of calpain, calcineurin, NLRP3, apoptosis-associated speck-like protein, and caspase-1 were significantly increased in a time-dependent manner. Furthermore, the inhibition of ASIC1a, calpain-2, or calcineurin, respectively, could decrease the cell death accompanied with the decreased interleukin-1ß level, and the decreased expression of ASIC1a, calpain-2, calcineurin, and NLRP3 inflammasome proteins. Taken together, these results indicated the activation of ASIC1a induced by extracellular acidosis could trigger pyroptosis of rat articular chondrocytes, the mechanism of which might partly be involved with the activation of calpain-2/calcineurin pathway.

Gold-DNA nanosunflowers for efficient gene silencing with controllable transformation.

The development of an efficient delivery system for enhanced and controlled gene interference-based therapeutics is still facing great challenges. Fortunately, the flourishing field of nanotechnology provides more effective strategies for nucleic acid delivery. Here, the triplex-forming oligonucleotide sequence and its complementary strand were used to mediate self-assembly of ultrasmall gold nanoparticles. The obtained sunflower-like nanostructures exhibited strong near-infrared (NIR) absorption and photothermal conversion ability. Upon NIR irradiation, the large-sized nanostructure could disassemble and generate ultrasmall nanoparticles modified with c-myc oncogene silencing sequence, which could directly target the cell nucleus. Moreover, the controlled gene silencing effect could be realized by synergistically controlling the preincubation time with the self-assembled nanostructure (in vitro and in vivo) and NIR irradiation time point. This study provides a new approach for constructing more efficient and tailorable nanocarriers for gene interference applications.

Interleukin-1ß and tumor necrosis factor-α augment acidosis-induced rat articular chondrocyte apoptosis via nuclear factor-kappaB-dependent upregulation of ASIC1a channel.

The acute-phase proinflammatory cytokines interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) demonstrate high-level expression and pleiotropic biological effects, and contribute to the progression and persistence of rheumatoid arthritis (RA). Acid hydrarthrosis is also an important pathological characteristic of RA, and the acid-sensing ion channel 1a (ASIC1a) plays a critical role in acidosis-induced chondrocyte cytotoxicity. However, the roles of IL-1ß and TNF-α in acid-induced apoptosis of chondrocytes remain unclear. Rat adjuvant arthritis and primary articular chondrocytes were used as in vivo and in vitro model systems, respectively. ASIC1a expression in articular cartilage was increased and highly colocalized with nuclear factor (NF)-κB expression in vivo. IL-1ß and TNF-α could upregulate ASIC1a expression. These cytokines activated mitogen-activated protein kinase and NF-κB pathways in chondrocytes, while the respective inhibitors of these signaling pathways could partially reverse the ASIC1a upregulation induced by IL-1ß and TNF-α. Dual luciferase and gel-shift assays and chromatin immunoprecipitation-polymerase chain reaction demonstrated that IL-1ß and TNF-α enhanced ASIC1a promoter activity in chondrocytes by increasing NF-κB DNA-binding activities, which was in turn prevented by the NF-κB inhibitor ammonium pyrrolidinedithiocarbamate. IL-1ß and TNF-α also decreased cell viability but enhanced LDH release, intracellular Ca2+ concentration elevation, loss of mitochondrial membrane potential, cleaved PARP and cleaved caspase-3/9 expression, and apoptosis in acid-stimulated chondrocytes, which effects could be abrogated by the specific ASIC1a inhibitor psalmotoxin-1 (PcTX-1), ASIC1a-short hairpin RNA or calcium chelating agent BAPTA-AM. These results indicate that IL-1ß and TNF-α can augment acidosis-induced cytotoxicity through NF-κB-dependent up-regulation of ASIC1a channel expression in primary articular chondrocytes.

ASIC2a overexpression enhances the protective effect of PcTx1 and APETx2 against acidosis-induced articular chondrocyte apoptosis and cytotoxicity.

Acid hydrarthrosis is another important pathological character in rheumatoid arthritis (RA), and acid-sensing ion channel 1a (ASIC1a) plays a destructive role in acidosis-induced articular chondrocyte cytotoxicity. Recently, ASIC2a has been reported to possess neuroprotective effect on acidosis-induced injury of neuronal cells. However, whether ASIC2a has an enhanced effect on the protective effect of blocking ASIC1a and ASIC3 against acid-induced chondrocyte apoptosis is still unclear. The aim of present study was to investigate the chondroprotective effect of ASIC2a with PcTx1 (ASIC1a specific blocker) and APETx2 (ASIC3 specific blocker) on acidosis-induced chondrocyte apoptosis. Our results revealed that acid (pH 6.0) decreased the cell viability and induced apoptosis of articular chondrocytes. PcTx1 and APETx2 combination significantly attenuated acidosis-induced chondrocyte cytotoxicity due to inhibit apoptosis, and this role could be enhanced by ASIC2a overexpression compared with the PcTx1 and APETx2 combination alone group. Moreover, both the [Ca2+]i levels and the levels of phosphorylated ERK1/2 as well as p38 were further reduced in acidosis-induced chondrocytes after ASIC2a overexpression in the presence of PcTx1 and APETx2. Furthermore, ASIC2a overexpression also reduced acid-induced the expression of ASIC1a. In addition, ASIC2a overexpression further promoted the PcTx1 and APETx2-increased levels of type II collagen in acidosis-induced chondrocytes. Taken together, the current data suggested that ASIC2a overexpression might enhance the anti-apoptotic and protective role of PcTx1 and APETx2 against acid-induced rat articular chondrocyte apoptosis by regulating ASIC1a expression and the [Ca2+]i levels and at least in part, suppressing p38 and ERK1/2 MAPK signaling pathways.

ASIC1a Promotes Acid-Induced Autophagy in Rat Articular Chondrocytes through the AMPK/FoxO3a Pathway.

Acid-sensing ion channel 1a (ASIC1a) is a member of the extracellular H⁺-activated cation channels family. Our previous studies suggested that ASIC1a contributed to acid-induced rat articular chondrocytes autophagy. However, its potential mechanisms remain unclear. The present study demonstrated the effect of ASIC1a on rat articular chondrocytes autophagy and explored the underlying molecular mechanisms. The results demonstrated that ASIC1a contributed to acid-induced autophagy in rat articular chondrocytes, and which was associated with an increase in (Ca2+)i, as indicated that acid-induced increases in mRNA and protein expression of LC3B-II and other autophagy-related markers were inhibited by ASIC1a-specific blocker, PcTx1 and calcium chelating agent, BAPTA-AM. Furthermore, the results showed that extracellular acid increased level of Forkhead box O (FoxO) 3a, but was reversed by inhibition of ASIC1a and Ca2+ influx. Moreover, gene ablation of FoxO3a prevented acid-induced increases in mRNA and protein expression of LC3B-II, Beclin1 and the formation of autophagosome. Finally, it also showed that ASIC1a activated adenine nucleotide (AMP)-activated protein kinase (AMPK). In addition, suppression of AMPK by Compound C and its small interfering RNA (siRNA) prevented acid-induced upregulation of total and nuclear FoxO3a and increases in mRNA and protein expression of LC3B-II, Beclin1, and ATG5. Taken together, these findings suggested that AMPK/FoxO3a axis plays an important role in ASIC1a-mediated autophagy in rat articular chondrocytes, which may provide novel mechanistic insight into ASIC1a effects on autophagy.

Novel Insights into Acid-Sensing Ion Channels: Implications for Degenerative Diseases.

Degenerative diseases often strike older adults and are characterized by progressive deterioration of cells, eventually leading to tissue and organ degeneration for which limited effective treatment options are currently available. Acid-sensing ion channels (ASICs), a family of extracellular H(+)-activated ligand-gated ion channels, play critical roles in physiological and pathological conditions. Aberrant activation of ASICs is reported to regulate cell apoptosis, differentiation and autophagy. Accumulating evidence has highlighted a dramatic increase and activation of ASICs in degenerative disorders, including multiple sclerosis, Parkinson's disease, Huntington's disease, intervertebral disc degeneration and arthritis. In this review, we have comprehensively discussed the critical roles of ASICs and their potential utility as therapeutic targets in degenerative diseases.

Oxazole: A Promising Building Block for the Development of Potent Antitumor Agents.

Oxazole derivatives are found to have a variety of biological activities. A large number of studies have revealed their outstanding anticancer activities. Here we review four different types of oxazole derivatives with anticancer potential reported over the last ten years. We focus our discussion on their activity, selectivity in different cancer cell lines, mechanisms of action, and their structural evolution.

Interleukin-6 enhances acid-induced apoptosis via upregulating acid-sensing ion channel 1a expression and function in rat articular chondrocytes.

The inflammatory cytokine interleukin-6 (IL-6) is a causative agent of rheumatoid arthritis (RA), a chronic inflammatory disease complicated with degenerative arthritic cartilage. However, the precise mechanism of IL-6 on chondrocyte apoptosis is largely unclear. Acid-sensing ion channels (ASICs), a family of extracellular H(+)-activated cation channels, can be transiently activated by extracellular acid and play a pivotal role in acid-induced cell injury. In the present study, to investigate the role of IL-6 in regulating acid-induced articular chondrocyte apoptosis, primary rat articular chondrocytes were subjected to different treatments with or without IL-6 in the presence of acid. The results showed that the mRNA and protein expressions of ASIC1a were significantly increased in articular cartilage and chondrocytes of adjuvant arthritis (AA) rats. IL-6 could dramatically upregulate the level of ASIC1a in a time- and dose-dependent manner, and induce the activation of JAK2, STAT3, ERK, JNK and NF-κB in articular chondrocytes. Moreover, both the respective inhibitors of these signaling pathways and the specific antibody against IL-6 receptor (tocilizumab) could partially abrogate the ASIC1a upregulation induced by IL-6. Furthermore, IL-6 inhibited the cell viability and enhanced LDH release, [Ca(2+)]i elevation, and apoptosis in acid-induced articular chondrocytes, and these changes could be reversed by using psalmotoxin 1(PcTX1), which is the specific antagonist of ASIC1a. In addition, pretreatment with PcTX1 could inhibit the downregulated expression of Bcl-2 and the upregulated expression of Bax induced by IL-6 in acid-induced articular chondrocytes. Taken together, these results indicated that IL-6 could enhance acid-induced articular chondrocyte apoptosis, the mechanism of which might partially be involved with its ability of regulating the activation of ASIC1a-dependent JAK2/STAT3 and MAPK/NF-κB signaling pathways.

Selection and optimization of hits from a high-throughput phenotypic screen against Trypanosoma cruzi.

BACKGROUND: Inhibitors of Trypanosoma cruzi with novel mechanisms of action are urgently required to diversify the current clinical and preclinical pipelines. Increasing the number and diversity of hits available for assessment at the beginning of the discovery process will help to achieve this aim. RESULTS: We report the evaluation of multiple hits generated from a high-throughput screen to identify inhibitors of T. cruzi and from these studies the discovery of two novel series currently in lead optimization. Lead compounds from these series potently and selectively inhibit growth of T. cruzi in vitro and the most advanced compound is orally active in a subchronic mouse model of T. cruzi infection. CONCLUSION: High-throughput screening of novel compound collections has an important role to play in diversifying the trypanosomatid drug discovery portfolio. A new T. cruzi inhibitor series with good drug-like properties and promising in vivo efficacy has been identified through this process.

Effect of ethanol extract of Rhodiola rosea on the early nephropathy in type 2 diabetic rats.

This study aimed to investigate the therapeutical effects of Rhodiola rosea extract on rats with type 2 diabetic nephropathy (DN). The rat type 2 DN model was established by high fat and high calorie feeding and intravenous injection of streptozocin (STZ). Wistar rats were randomly divided into normal group, control group, low dose Rhodiola rosea group, high dose Rhodiola rosea group and Captopril group. Oral glucose tolerance test (OGTT) was performed to determine the impairment of glucose tolerance in the established animal model. A series of parameters including fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), creatinine clearance rate (Ccr), 24-h urinary albumin (UA), the ratio of kidney mass/body weight (renal index) and glomerular area were examined after 8 weeks. Moreover, the expression of transforming growth factor (TGF)-ß1 in renal tissues was detected by using immunohistochemisty. At the end of the eighth week, FBG, TC, TG, Ccr, 24-h urinary albumin, the ratio of kidney mass/body weight and glomerular area were significantly reduced in Rhodiola rosea extract treatment groups as compared with those in control group. TGF-ß1 expression in renal tissues of Rhodiola rosea extract treatment groups was also significantly decreased as compared with that of control group. These results indicate that Rhodiola rosea extract may have a protective effect on early nephropathy in diabetic rats, which might be related to the decrease of the renal expression of TGF-ß1.

[New method of processing on Rhei Radix Et Rhizoma and study on quality control of its processing products].

OBJECTIVE: To establish a simple, rapid and usable new method of processing on Rhei Radix Et Rhizoma and the quality control standard on its processing products. METHODS: The studies of processing on Rhei Radix Et Rhizoma were proceed using yellow rice wine as solvent, through spray, soften and dry at 60-70 degrees C. The contents of total and uncombined chrysophanol and emodin in multi-Rhei Radix Et Rhizoma and its processing products were determined by HPLC. RESULTS: The new method of processing on Rhei Radix Et Rhizoma was simple, rapid and usable. The contents of uncombined chrysophanol and emodin in its processing products was 80%. CONCLUSION: This study provides a new method of processing on Rhei Radix Et Rhizoma and quality control standard on its processing products.