The combination of a PTP1B inhibitor, TNFR2 blocker, and PD­1 antibody suppresses the progression of non­small cell lung cancer tumors by enhancing immunocompetence.

Lung cancer is increasingly recognized as a leading cause of cancer­related mortality. Immunotherapy has emerged as a promising therapeutic approach for lung cancer, particularly non­small cell lung cancer (NSCLC). Nonetheless, the response rate to programmed cell death 1 (PD­1) inhibitors remains less than optimal. It has been suggested that protein tyrosine phosphatase 1B (PTP1B) plays a crucial role in the development and progression of cancer by facilitating T cell expansion and cytotoxicity. Our previous research demonstrated that the combination of tumor necrosis factor receptor 2 (TNFR2) with immune activity treatments synergistically suppresses tumor growth. This insight led to exploring the efficacy of a combined treatment strategy involving PD­1 inhibitors, PTP1B inhibitors and TNFR2 antibodies (triple therapy) in NSCLC. In this context, the therapeutic effectiveness of these combination immunotherapies was validated in mouse models with NSCLC by analyzing the expansion and function of immune cells, thereby assessing their impact on tumor growth. The results indicated that inhibiting PTP1B decreases the expression of PD­L1 and TNFR2 on LLC cells, along with an increase in the proportion of CD4+T and CD8+T cells. Compared with other treatment groups, the triple therapy significantly reduced tumor volume in mice with NSCLC and extended their survival. Moreover, this combination therapy altered the distribution of myeloid­derived suppressor cells, dendritic cells, B cells and M1 macrophages, while increasing the proportion of CD8+T cells and reducing the proportion of Treg cells in the spleens, lymph nodes, and tumors of NSCLC models. The triple therapy also resulted in a decrease in PD­L1, PTP1B and TNFR2 expression within NSCLC tumor tissues in mice. Overall, the triple therapy effectively suppressed tumor growth and improved outcomes in mice with NSCLC by modulating immune cell distribution and reducing levels of target immune proteins.

Curative care expenditure of outpatient anxiety disorder in Liaoning Province, 2015-2020-based on "System of Health Accounts 2011".

Introduction: Anxiety disorders are the most common mental disorder, experienced by more than a quarter of the population. This study examines total outpatient curative care expenditures (CCE) for anxiety disorders and changes in their composition based on the System of Health Accounts 2011 (SHA 2011). Methods: This study used multi-stage stratified random from a total of 9,318,513 outpatient sample data by 920 healthcare organizations, a total of 109,703 cases of anxiety disorders from 53 sample organizations (5.76%) from 2015 to 2020. Univariate analysis, multifactor analysis and structural equation modeling (SEM) were used to explore the influential factors affecting outpatient CCE for anxiety disorders. Results: Anxiety disorder outpatient CCE from 2015 to 2020 continued to increase from CNY 99.39million in 2015 to CNY 233.84 million in 2020, mainly concentrated in western medicine costs, 15-64 years, general hospital, generalized anxiety disorder and public financing. The results of univariate analysis showed statistically significant differences in all subgroups, and the results of multivariate analysis and SEM showed that the choice to purchase western drugs, purchase prepared Chinese drugs, choice to have a checkup, urban employees' basic medical insurance, and 0-14 years old were associated with high anxiety disorder outpatient CCE. Conclusion: Initiatives to improve the essential drug system, reduce the out-of-pocket (OOP) ratio, and strengthen primary health care to effectively reduce the medical burden on patients.

Differential impacts of microplastics on carbon and nitrogen cycling in plant-soil systems: A meta-analysis.

Microplastics (MPs) are widely present in terrestrial ecosystems. However, how MPs impact carbon (C) and nitrogen (N) cycling within plant-soil system is still poorly understood. Here, we conducted a meta-analysis utilizing 3338 paired observations from 180 publications to estimate the effects of MPs on plant growth (biomass, nitrogen content, nitrogen uptake and nitrogen use efficiency), change in soil C content (total carbon (TC), soil organic carbon (SOC), dissolved organic carbon (DOC), microbial biomass carbon (MBC)), C losses (carbon dioxide (CO2) and methane), soil N content (total nitrogen, dissolved organic nitrogen, microbial biomass nitrogen, total dissolve nitrogen, ammonium, nitrate (NO3--N) and nitrite) and nitrogen losses (nitrous oxide, ammonia (NH3) volatilization and N leaching) comprehensively. Results showed that although MPs significantly increased CO2 emissions by 25.7 %, they also increased TC, SOC, MBC, DOC and CO2 by 53.3 %, 25.4 %, 19.6 % and 24.7 %, respectively, and thus increased soil carbon sink capacity. However, MPs significantly decreased NO3--N and NH3 volatilization by 14.7 % and 43.3 %, respectively. Meanwhile, MPs significantly decreased plant aboveground biomass, whereas no significant changes were detected in plant belowground biomass and plant N content. The impacts of MPs on soil C, N and plant growth varied depending on MP types, sizes, concentrations, and experimental durations, in part influenced by initial soil properties. Overall, although MPs enhanced soil carbon sink capacity, they may pose a significant threat to future agricultural productivity.

Heteroaggregation and deposition behaviors of carboxylated nanoplastics with different types of clay minerals in aquatic environments: Important role of calcium(II) ion-assisted bridging.

The widespread utilization of plastic products ineluctably leads to the ubiquity of nanoplastics (NPs), causing potential risks for aquatic environments. Interactions of NPs with mineral surfaces may affect NPs transport, fate and ecotoxicity. This study aims to investigate systematically the deposition and aggregation behaviors of carboxylated polystyrene nanoplastics (COOH-PSNPs) by four types of clay minerals (illite, kaolinite, Na-montmorillonite, and Ca-montmorillonite) under various solution chemistry conditions (pH, temperature, ionic strength and type). Results demonstrate that the deposition process was dominated by electrostatic interactions. Divalent cations (i.e., Ca2+, Mg2+, Cd2+, or Pb2+) were more efficient for screening surface negative charges and compressing the electrical double layer (EDL). Hence, there were significant increases in deposition rates of COOH-PSNPs with clay minerals in suspension containing divalent cations, whereas only slight increases in deposition rates of COOH-PSNPs were observed in monovalent cations (Na+, K+). Negligible deposition occurred in the presence of anions (F-, Cl-, NO3-, CO32-, SO42-, or PO43-). Divalent Ca2+ could incrementally facilitate the deposition of COOH-PSNPs through Ca2+-assisted bridging with increasing CaCl2 concentrations (0-100 mM). The weakened deposition of COOH-PSNPs with increasing pH (2.0-10.0) was primarily attributed to the reduce in positive charge density at the edges of clay minerals. In suspensions containing 2 mM CaCl2, increased Na+ ionic strength (0-100 mM) and temperature (15-55 ◦C) also favored the deposition of COOH-PSNPs. The ability of COOH-PSNPs deposited by four types of clay minerals followed the sequence of kaolinite > Na-montmorillonite > Ca-montmorillonite > illite, which was related to their structural and surface charge properties. This study revealed the deposition behaviors and mechanisms between NPs and clay minerals under environmentally representative conditions, which provided novel insights into the transport and fate of NPs in natural aquatic environments.

Understanding the relationship between pore size, surface charge density, and Cu2+ adsorption in mesoporous silica.

This research delved into the influence of mesoporous silica's surface charge density on the adsorption of Cu2+. The synthesis of mesoporous silica employed the hydrothermal method, with pore size controlled by varying the length of trimethylammonium bromide (CnTAB, n = 12, 14, 16) chains. Gas adsorption techniques and transmission electron microscopy characterized the mesoporous silica structure. Surface charge densities of the mesoporous silica were determined through potentiometric titration, while surface hydroxyl densities were assessed using the thermogravimetric method. Subsequently, batch adsorption experiments were conducted to study the adsorption of Cu2+ in mesoporous silica, and the process was comprehensively analyzed using Atomic absorption spectrometry (AAS), Fourier transform infrared (FTIR), and L3 edge X-ray absorption near edge structure (XANES). The research findings suggest a positive correlation between the pore size of mesoporous silica, its surface charge density, and the adsorption capacity for Cu2+. More specifically, as the pore size increases within the 3-4.1 nm range, the surface charge density and the adsorption capacity for Cu2+ also increase. Our findings provide valuable insights into the relationship between the physicochemical properties of mesoporous silica and the adsorption behavior of Cu2+, offering potential applications in areas such as environmental remediation and catalysis.

Representing Context and Priority in Working Memory.

The ability to prioritize among contents in working memory (WM) is critical for successful control of thought and behavior. Recent work has demonstrated that prioritization in WM can be implemented by representing different states of priority in different representational formats. Here, we explored the mechanisms underlying WM prioritization by simulating the double serial retrocuing task with recurrent neural networks. Visualization of stimulus representational dynamics using principal component analysis revealed that the network represented trial context (order of presentation) and priority via different mechanisms. Ordinal context, a stable property lasting the duration of the trial, was accomplished by segregating representations into orthogonal subspaces. Priority, which changed multiple times during a trial, was accomplished by separating representations into different strata within each subspace. We assessed the generality of these mechanisms by applying dimensionality reduction and multiclass decoding to fMRI and EEG data sets and found that priority and context are represented differently along the dorsal visual stream and that behavioral performance is sensitive to trial-by-trial variability of priority coding, but not context coding.

Regulating Tumor-Associated Macrophage Polarization by Cyclodextrin-Modified PLGA Nanoparticles Loaded with R848 for Treating Colon Cancer.

Purpose: This study aimed to develop a novel and feasible modification strategy to improve the solubility and antitumor activity of resiquimod (R848) by utilizing the supramolecular effect of 2-hydroxypropyl-beta-cyclodextrin (2-HP-ß-CD). Methods: R848-loaded PLGA nanoparticles modified with 2-HP-ß-CD (CD@R848@NPs) were synthesized using an enhanced emulsification solvent-evaporation technique. The nanoparticles were then characterized in vitro by several methods, such as scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, particle size analysis, and zeta potential analysis. Then, the nanoparticles were loaded with IR-780 dye and imaged using an in vivo imaging device to evaluate their biodistribution. Additionally, the antitumor efficacy and underlying mechanism of CD@R848@NPs in combination with an anti-TNFR2 antibody were investigated using an MC-38 colon adenocarcinoma model in vivo. Results: The average size of the CD@R848@NPs was 376 ± 30 nm, and the surface charge was 21 ± 1 mV. Through this design, the targeting ability of 2-HP-ß-CD can be leveraged and R848 is delivered to tumor-supporting M2-like macrophages in an efficient and specific manner. Moreover, we used an anti-TNFR2 antibody to reduce the proportion of Tregs. Compared with plain PLGA nanoparticles or R848, CD@R848@NPs increased penetration in tumor tissues, dramatically reprogrammed M1-like macrophages, removed tumors and prolonged patient survival. Conclusion: The new nanocapsule system is a promising strategy for targeting tumor, reprogramming tumor -associated macrophages, and enhancement immunotherapy.

Combinational delivery of TLR4 and TLR7/8 agonist enhanced the therapeutic efficacy of immune checkpoint inhibitors to colon tumor.

Immunotherapy is regarded as a potent cancer treatment, with DC vaccines playing a crucial role. Although clinical trials have demonstrated the safety and efficacy of DC vaccines, loading antigens in vitro is challenging, and their therapeutic effects remain unpredictable. Moreover, the diverse subtypes and maturity states of DCs in the body could induce both immune responses and immune tolerance, potentially affecting the vaccine's efficacy. Hence, the optimization of DC vaccines remains imperative. Our study discovered a new therapeutic strategy by using CT26 and MC38 mouse colon cancer models, as well as LLC mouse lung cancer models. The strategy involved the synergistic activation of DCs through intertumoral administration of TLR4 agonist high-mobility group nucleosome binding protein 1 (HMGN1) and TLR7/8 agonist (R848/resiquimod), combined with intraperitoneal administration of TNFR2 immunosuppressant antibody. The experimental results indicated that the combined use of HMGN1, R848, and α-TNFR2 had no effect on LLC cold tumors. However, it was effective in eradicating CT26 and MC38 colon cancer and inducing long-term immune memory. The combination of these three drugs altered the TME and promoted an increase in anti-tumor immune components. This may provide a promising new treatment strategy for colon cancer.

Estimating the economic burden of stroke in China: a cost-of-illness study.

OBJECTIVES: Stroke imposes a heavy economic burden and loss of productivity on individuals and society. This study assessed a range of crucial factors, including direct costs and indirect costs, to gauge the economic implications of stroke in China. These outcomes were evaluated with specific reference to the year 2018, using the Chinese yuan (¥) as the unit of measurement and providing the corresponding purchasing power parity dollar ($PPP) currency value. METHODS: A cost-of-illness methodology was used to ascertain the economic implications of stroke in 2018. Within the constraints of this approach, economic costs were defined as 'direct costs' or 'indirect costs'. We estimated direct costs from sample data, the National Health Service Survey and the National Health Account and Health Statistical Yearbook. A human capital method was used to conservatively estimate indirect costs. RESULTS: In 2018, of the economic burden of stroke in China, the direct costs were ¥247.8 billion ($PPP 58.6 billion) and indirect costs were ¥704.4 billion ($PPP 166.5 billion). The curative care expenditure for stroke was ¥193.1 billion ($PPP 45.7 billion), consuming nearly 5.5% of curative expenditure. The cost of stroke treatment relied heavily on public financing, with 58% from social health insurance and 14% from government sources. CONCLUSIONS: A significant economic burden is imposed by stroke on China's economy, and there is a risk of underestimating this burden if indirect costs are not comprehensively considered. The importance of implementing effective preventive measures and screening strategies for stroke, with a particular focus on high-risk populations, is underscored by this study's findings. Such investments in public health have the potential to yield substantial benefits.

Injectable Bombyx mori (B. mori) silk fibroin/MXene conductive hydrogel for electrically stimulating neural stem cells into neurons for treating brain damage.

Brain damage is a common tissue damage caused by trauma or diseases, which can be life-threatening. Stem cell implantation is an emerging strategy treating brain damage. The stem cell is commonly embedded in a matrix material for implantation, which protects stem cell and induces cell differentiation. Cell differentiation induction by this material is decisive in the effectiveness of this treatment strategy. In this work, we present an injectable fibroin/MXene conductive hydrogel as stem cell carrier, which further enables in-vivo electrical stimulation upon stem cells implanted into damaged brain tissue. Cell differentiation characterization of stem cell showed high effectiveness of electrical stimulation in this system, which is comparable to pure conductive membrane. Axon growth density of the newly differentiated neurons increased by 290% and axon length by 320%. In addition, unfavored astrocyte differentiation is minimized. The therapeutic effect of this system is proved through traumatic brain injury model on rats. Combined with in vivo electrical stimulation, cavities formation is reduced after traumatic brain injury, and rat motor function recovery is significantly promoted.

Design of Bombyx mori (B. mori) Silk Fibroin Microspheres for Developing Biosafe Sunscreen.

Sunscreens play a crucial role in protecting the skin from ultraviolet (UV) damage. However, present commercial sunscreens have a tendency to generate free radicals in the UV window, resulting in serious inflammatory responses and health problems. In this study, we demonstrate that silk fibroin microspheres (SFMPs) assembled from regenerated silk fibroin (SF) could scavenge free radicals while preventing UV irradiation and thus present a promising sunscreen. The SFMP reflected more UV light than SF and presented a higher stability than that of organic commercial sunscreens. In vitro analysis proved that SFMP could more efficiently scavenge the hydroxy radical and reduce the intracellular reactive oxygen than titanium dioxide (TiO2). In vivo experiments exhibited that SFMP provided stronger skin protection against UV irradiation than commercial sunscreens and TiO2. Furthermore, SFMP treatment significantly inhibited the skin inflammatory response. This work suggests that the SFMP has great potential to be developed into a biosafe sunscreen.

Chemerin promotes invasion of oral squamous cell carcinoma by stimulating IL-6 and TNF-α production via STAT3 activation.

AIMS: Elevated levels of adipokine chemerin have been identified in oral squamous cell carcinoma (OSCC) and found to be associated with metastasis to the cervical lymph nodes. The underlying mechanism through which chemerin affects OSCC progression is unclear. The aims of this study were firstly to determine chemerin levels and cytokine concentrations in serum from patients with OSCC and in OSCC cell cultures, and secondly to observe chemerin effects on OSCC cell cytokine secretion, migration, and invasion in vitro. METHODS: Serum samples were collected from 20 patients diagnosed with OSCC, including groups with (LN+) and without (LN-) cervical lymph node metastasis. A Luminex liquid suspension assay was used to quantify serum concentrations of 27 types of cytokines. Correlations between chemerin and cytokines (i.e., IL-6, IL-15, GM-CSF, RANTES, TNF-α, and VEGF) were analyzed. ELISAs (enzyme-linked immunosorbent assays) were used to determine concentrations of chemerin and selected cytokines in serum and in supernatants of OSCC cell cultures (SCC9 and SCC25 cell lines). OSCC cells were stimulated with human recombinant chemerin, STAT3 inhibitor, or IL-6 together with TNF-α neutralizing antibodies. Phosphorylated STAT3 protein levels were measured with western blot analysis. OSCC cell migration and invasion were investigated with Transwell assays. RESULTS: Compared to the LN- group, OSCC patients with cervical lymph node metastasis had higher levels of IL-6 (P = 0.006), IL-15 (P = 0.020), GM-CSF (P = 0.036), RANTES (P = 0.032), TNF-α (P = 0.005), VEGF (P = 0.006), and chemerin (P = 0.001). Patients' serum chemerin levels correlated directly with IL-6, GM-CSF, TNF-α, and VEGF levels in OSCC patients. Exogenous recombinant chemerin treatment promoted secretion of IL-6 and TNF-α via activation of STAT3 in OSCC cells. Chemerin induced OSCC-cell migration and invasion, and these effects were reduced by IL-6 and TNF-α neutralizing antibodies. CONCLUSION: Our findings indicate that chemerin may play a role in advancing OSCC progression by increasing production of IL-6 and TNF-α, perhaps via a mechanism involving STAT3 signaling.

Regenerated silk fibroin coating stable liquid metal nanoparticles enhance photothermal antimicrobial activity of hydrogel for wound infection repair.

The integration of liquid metal (LM) and regenerated silk fibroin (RSF) hydrogel holds great potential for achieving effective antibacterial wound treatment through the LM photothermal effect. However, the challenge of LM's uncontrollable shape-deformability hinders its stable application. To address this, we propose a straightforward and environmentally-friendly ice-bath ultrasonic treatment method to fabricate stable RSF-coated eutectic gallium indium (EGaIn) nanoparticles (RSF@EGaIn NPs). Additionally, a double-crosslinked hydrogel (RSF-P-EGaIn) is prepared by incorporating poly N-isopropyl acrylamide (PNIPAAm) and RSF@EGaIn NPs, leading to improved mechanical properties and temperature sensitivity. Our findings reveal that RSF@EGaIn NPs exhibit excellent stability, and the use of near-infrared (NIR) irradiation enhances the antibacterial behavior of RSF-P-EGaIn hydrogel in vivo. In fact, in vivo testing demonstrates that wounds treated with RSF-P-EGaIn hydrogel under NIR irradiation completely healed within 14 days post-trauma infection, with the formation of new skin and hair. Histological examination further indicates that RSF-P-EGaIn hydrogel promoted epithelialization and well-organized collagen deposition in the dermis. These promising results lay a solid foundation for the future development of drug release systems based on photothermal-responsive hydrogels utilizing RSF-P-EGaIn.

Unveiling the exciton dissociation dynamics steered by built-in electric fields in conjugated microporous polymers for photoreduction of uranium (VI) from seawater.

Developing highly efficient photocatalysts based on conjugated microporous polymers (CMPs) are often impeded by the intrinsically large exciton binding energy and sluggish charge transfer kinetics that result from their vulnerable driving force. Herein, a family of pyrene-based nitrogen-implanted CMPs were constructed, where the nitrogen gradient was regulated. Accordingly, the built-in electric field endowed by the nitrogen gradient dramatically accelerates the dissociation of exciton into free carriers, thereby enhancing charge separation efficiency. As a result, PyCMP-3N generated by polymerization of 1,3,6,8-tetrakis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrene and 2,4,6-tris(4-bromophenyl)-1,3,5-triazine featured an optimized built-in electric field and exhibited the highest photocatalytic removal efficiency of uranium (VI) (99.5 %). Our proposed strategy not only provides inspiration for constructing the built-in electric field by controlling nitrogen concentration gradients, but also offers an in-depth understanding the crucial role of built-in electric field in exciton dissociation and charge transfer, efficiently promoting CMPs photocatalysis.

Heavy metal migration dynamics and solid-liquid distribution strategy in abandoned tailing soils.

The tailings soil originating from an abandoned sulfur-iron mine in Sichuan Province, China, exhibits elevated concentrations of heavy metals (HMs) and possesses limited soil conservation capacity. Variability soil particle size fractions (PSFs) contributes to an increased risk of HMs ion migration. Existing research on HMs behavior has focused on the bulk soil scale, resulting in a dearth of comprehensive information concerning different particle sizes and colloid scales. We collected soil samples from upstream source (XWA), migration path (XWB), and downstream farmland (XWC) of an abandoned tailing and categorized into sand, silt, clay, colloid and dissolved, respectively. The investigation primarily aimed to elucidate the solid-liquid distribution trade-off strategies of soil HMs along migration pathway. Results show that PSFs composition predominantly influences HMs solid-liquid distribution. In the mining area, large particles serve as the principal component for HMs enrichment. However, along the migration pathway, the proportion of highly mobile fine particles increases, shifting HMs from solid to liquid phase. Furthermore, inorganic elements such as Mg, Al, and Fe influence on HMs distribution within PSFs through various reactions, whereas organic matter and glomalin-related soil protein (GRSP) also exert regulatory roles. Increasing the proportion of large particles can reduce the risk of HMs migration.

Outpatient depression current care expenditure changes in Liaoning Province from 2015 to 2020: a study based on the "system of health accounts 2011".

Introduction: Depression is the leading cause of disability worldwide and has become a health issue of global concern. Based on the "System of Health Accounts 2011" (SHA 2011) for patients with depression, this paper studies the changes in the current curative expenditure (CCE) of outpatient depression in Liaoning Province, China, and provides policy recommendations. Method: A stratified multistage random sample of 56,994 patients with depression included from 1,227 healthcare facilities in Liaoning Province were included. The significance of differences in variables within groups was analyzed by univariate analysis (including descriptive statistics analysis, Mann-Whitney U test and Kruskal-Wallis H test), and factors influencing depression outpatient CCE were analyzed by multiple linear regression analysis and constructing structural equation models (SEM). Results: The CCE of outpatient depression was ranging from CNY 75.57 million to CNY 100.53 million in 2015-2020, with the highest of CNY 100.53 million in 2018, CNY 103.28 million in 2019. Medical expenditures are mainly concentrated in general hospitals and provincial healthcare institutions, accounting for about 90% of all provincial scope expenditures. The multiple regression results show that provincial healthcare institutions, purchase of drug, select medical treatment for depression, general hospitals and urban employees' health insurance are the main influencing factors for depression outpatient CCE. The results of SEM show that insurance status negative impact outpatient expenditure. Conclusion: Health insurance is an important factor in equitable access to healthcare resources for patients, and medication expenditure is the influential factor affecting the high expenditure of outpatient clinics. It is of great importance to reduce the medical burden of patients by increasing the coverage of medical insurance, increasing the proportion of bills that are eligible for reimbursement, and improving the system by guaranteeing the supply of psychotropic medication.

Ultrafast Bi-Directional Bending Moisture-Responsive Soft Actuators through Superfine Silk Rod Modified Bio-Mimicking Hierarchical Layered Structure.

Development of stimulus-responsive materials is crucial for novel soft actuators. Among these actuators, the moisture-responsive actuators are known for their accessibility, eco-friendliness, and robust regenerative attributes. A major challenge of moisture-responsive soft actuators (MRSAs) is achieving significant bending curvature within short response times. Many plants naturally perform large deformation through a layered hierarchical structure in response to moisture stimuli. Drawing inspiration from the bionic structure of Delosperma nakurense (D. nakurense) seed capsule, here the fabrication of an ultrafast bi-directional bending MRSAs is reported. Combining a superfine silk fibroin rod (SFR) modified graphene oxide (GO) moisture-responsive layer with a moisture-inert layer of reduced graphene oxide (RGO), this actuator demonstrated large bi-directional bending deformation (-4.06 ± 0.09 to 10.44 ± 0.00 cm-1) and ultrafast bending rates (7.06 cm-1 s-1). The high deformation rate is achieved by incorporating the SFR into the moisture-responsive layers, facilitating rapid water transmission within the interlayer structure. The complex yet predictable deformations of this actuator are demonstrated that can be utilized in smart switch, robotic arms, and walking device. The proposed SFR modification method is simple and versatile, enhancing the functionality of hierarchical layered actuators. It holds the potential to advance intelligent soft robots for application in confined environments.

Posterior Percutaneous Endoscopic Cervical Discectomy for Single-Level Soft, Huge Central Disc Herniation.

BACKGROUND: Posterior percutaneous endoscopic cervical discectomy (PPECD) has been proven safe and effective for foraminal cervical disc herniation (CDH). However, central CDH has long been considered as the contraindication of PPECD, because the path is obstructed by the spinal cord and nerve root. OBJECTIVES: To preliminarily assess the feasibility, safety, and effectiveness of PPECD for single-level soft, huge central CDH. STUDY DESIGN: A retrospective cohort study. SETTING: Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College). METHODS: Between 2017 and 2020, 31 patients diagnosed with single-level soft, huge central CDH were treated by PPECD. Primary outcomes included the measures of neck and radicular pain based on the numeric rating scale (NRS) and cervical neurologic status based on the Japanese Orthopedic Association (JOA) score. The global outcome was assessed using the Odom's criteria at one-year follow-up. RESULTS: Compared to the baseline, there was a constant and significant reduction of NRS-rated pain and improvement of JOA-rated cervical neurologic status postoperatively (P < 0.01). According to the Odom's criteria, 96.8% (30/31) of patients had satisfactory postoperative clinical improvement (excellent or good outcomes) at one-year follow-up. Complications included C5 nerve root palsy and spinal cord injury. The total complication rate was 16.5% (2/31), but these complications were temporary and not catastrophic. LIMITATIONS: The limitations of this study include the volume of the sample, a short follow-up period, and the lack of a control group. CONCLUSIONS: Our preliminary experience indicates that PPECD is a feasible and promising alternative for symptomatic single-level soft, huge central CDH.

Phytochemical analysis and hepatotoxicity assessment of braised Polygoni Multiflori Radix (Wen-He-Shou-Wu).

Polygoni Multiflori Radix (PMR) is a medicinal herb commonly used in China and Eastern Asia. Recently, the discovery of hepatotoxicity in PMR has received considerable attention from scientists. Processing is a traditional Chinese medicine technique used for the effective reduction of toxicity. One uncommon technique is the braising method-also known as 'Wen-Fa' in Chinese-which is used to prepare tonics or poisonous medications. Braised PMR (BPMR)-also known as 'Wen-He-Shou-Wu'-is one of the processed products of the braising method. However, the non-volatile components of BPMR have not been identified and examined in detail, and therefore, the hepatotoxic advantage of BPMR remains unknown. In this study, we compared the microscopic characteristics of different samples in powder form using scanning electron microscopy (SEM), investigated the non-volatile components, assessed the effects of different processed PMR products on the liver, and compared the differences between BPMR and PMR Praeparata recorded in the Chinese Pharmacopoeia (2020 edition). We found that the hepatotoxicity of BPMR was dramatically decreased, which may be related to an increase in polysaccharide content and a decrease in toxic substances. The present study provides an important foundation for future investigations of the processing mechanisms of BPMR.

Botulinum toxin type A ameliorates rat dorsal root ganglia neuron pyroptosis in postherpetic neuralgia by upregulating cathelicidin antimicrobial peptide to inhibit neutrophil elastase.

Botulinum toxin type A (BoNT/A) has exhibited efficacy in postherpetic neuralgia (PHN) treatment, and this study aims to uncover its underlying mechanisms. Resiniferatoxin (RTX)-induced PHN rats were given BoNT/A. Rat postoperative pain behaviors were assessed by Von Frey test. Cleaved-synaptosomal protein 25 kDa (cl-SNAP-25) or cathelicidin antimicrobial peptide (CAMP) expression in rat dorsal root ganglia (DRG) was detected by immunofluorescence or immunohistochemistry. Healthy rat-derived DRG neurons were transfected, incubated with lipopolysaccharides (LPS)/adenosine 5'-triphosphate (ATP) to stimulate pyroptosis and treated with BoNT/A. The CCK-8, Western blot, ELISA, and qRT-PCR were used to assess the viability, levels of pyroptosis-related proteins proinflammatory cytokine levels, as well as CAMP and ELANE mRNA levels. BoNT/A (30 U/kg) promoted cl-SNAP-25 expression in rat DRG and reversed RTX-induced decrease of rat paw withdrawal thresholds and CAMP expression and increase of pyroptosis-associated protein and inflammatory factor expression in rat DRG. CAMP interacted with ELANE in rat DRG neurons. BoNT/A attenuated LPS/ATP-stimulated inhibition of viability and CAMP expression and upregulation of inflammatory mediators, pyroptosis-related proteins, and ELANE expression in rat DRG neurons, which was counteracted by CAMP silencing. However, ELANE knockdown offset the effect of CAMP silencing in LPS/ATP/BoNT/A-treated rat DRG neurons. On the whole, BoNT/A alleviates rat DRG neuron pyroptosis during PHN by upregulating CAMP to inhibit ELANE.