[Electroacupuncture with different frequencies for paclitaxel-induced peripheral neuropathy: a randomized controlled trial].

OBJECTIVE: To observe the clinical efficacy of electroacupuncture (EA) at frequencies of 2 Hz, 100 Hz, and 2 Hz/100 Hz for chemotherapy-induced peripheral neuropathy (CIPN). METHODS: One hundred and sixty female breast cancer patients with CIPN induced by paclitaxel were randomly divided into a 2 Hz EA group (40 cases, 1 case dropped out), a 100 Hz EA group (40 cases, 2 cases dropped out), a 2 Hz/100 Hz EA group (40 cases, 3 cases dropped out), and a medication group (40 cases, 2 cases dropped out). The three EA groups received acupuncture at bilateral Quchi (LI 11), Waiguan (TE 5), Hegu (LI 4), Zusanli (ST 36), and Yanglingquan (GB 34). Electrodes of the HANS-200E acupoint nerve stimulator were connected to the same side Hegu (LI 4) and Waiguan (TE 5), and Zusanli (ST 36) and Sanyinjiao (SP 6), with EA stimulation frequencies of 2 Hz, 100 Hz, and 2 Hz/100 Hz, respectively. Each session lasted 30 min, once every other day, three times a week. The medication group received oral mecobalamin tablets, 0.5 mg per dose, three times a day. All groups were treated for four weeks. The functional assessment of cancer therapy/gynaecologic oncology group-neurotoxicity (FACT/GOG-Ntx), peripheral neurotoxicity grading based on the National Cancer Institute-common terminology criteria for adverse events Version 5.0 (NCI-CTCAE V5.0), and peripheral neuropathy pain visual analogue scale (VAS) scores were observed before and after treatment, and at follow-up after 4 weeks of treatment completion, and clinical efficacy was evaluated after theatment. RESULTS: Compared before treatment, FACT/GOG-Ntx scores in all groups were decreased after treatment and during follow-up (P<0.01). The score reduction between before and after treatment in the three EA groups was greater than the medication group (P<0.01, P<0.05), with the 2 Hz and 2 Hz/100 Hz EA groups showing a greater reduction than the 100 Hz EA group (P<0.05). The reduction of FACT/GOG-Ntx score between before treatment and follow-up in the 2 Hz and 2 Hz/100 Hz EA groups was greater than the medication group (P<0.01). Peripheral neurotoxicity grading in the three EA groups were improved after treatment (P<0.01). Compared before treatment, the peripheral neurotoxicity grading in the 2 Hz and 2 Hz/100 Hz EA groups was improved at follow-up (P<0.01, P<0.05). The VAS scores for peripheral neuropathy pain in the three EA groups were decreased after treatment (P<0.01, P<0.05). At follow-up, VAS scores in the 2 Hz, 2 Hz/100 Hz, and medication groups were decreased (P<0.01, P<0.05), with a greater reduction in the 2 Hz/100 Hz EA group than the medication group after treatment and follow-up (P<0.01, P<0.05). The overall effective rates for the 2 Hz, 100 Hz, 2 Hz/100 Hz, and medication groups were 79.5% (31/39), 68.4% (26/38), 81.1% (30/37), and 47.4% (18/38), respectively, with the 2 Hz and 2 Hz/100 Hz groups showing higher effective rates than the medication group (P<0.05). CONCLUSION: EA is effective in treating paclitaxel-induced CIPN. While there is no overall difference in efficacy among the different frequencies, 2 Hz and 2 Hz/100 Hz EA showing potential advantages. For patients with concurrent peripheral neuropathy pain, 2 Hz/100 Hz electroacupuncture is recommended.

Ultra-low-complexity weight-sharing trigonometric nonlinear equalizer for beyond net-200-Gb/s/λ short-reach optical interconnects.

An ultra-low-complexity third-order weight-sharing trigonometric nonlinear equalizer (WS-TNLE) is proposed to eliminate nonlinear signal distortions in short-reach optical interconnects exceeding net 200 Gb/s/λ. By replacing the second- and third-order nonlinear terms in a third-order weight-sharing diagonally pruned Volterra nonlinear equalizer (WS-DP-VNLE) with cosine and sine terms, respectively, the required number of real-valued multiplications per symbol of the proposed third-order WS-TNLE is significantly reduced to the same value as the number of weight-sharing kernels. When transmitting probabilistically shaped 16-level pulse amplitude modulation (PS-PAM-16) signals at net rates ranging from 200.4 Gb/s to 300.4 Gb/s over a 1-km standard single-mode fiber (SSMF), the proposed third-order WS-TNLE requires the lowest number of real-valued multiplications per symbol, ranging from 10 to 44, which reduces the computational complexity by up to 96.2% and 52.4% compared to the third-order WS-DP-VNLE and WS-DP-absolute-term nonlinear equalizer (WS-DP-ATNLE), respectively.

Spotting d-band centers of single-atom catalysts by oxygen intermediate-boosted electrochemiluminescence.

Catalytic activities of single-atom catalysts are strongly dependent on their d-band centers. However, it is a long-standing challenge to provide a cost-effective and accurate evaluation for the positions of d-band centers of these catalysts due to the fact that the widely applicable photoelectron spectroscopy methodologies require complicated sampling and spectral unfolding processes. In this contribution, we have proposed oxygen intermediate-boosted electrochemiluminescence (ECL) for rapid spotting of the d-band centers of single-atom catalysts, involving single atomic Au, Ag, Cu and Fe. It was disclosed that the d-band centers of single-atom catalysts closer to the Fermi level could facilitate the interaction between catalysts and oxygen intermediates, leading to higher luminol ECL intensities as a result of the promoted adsorption and reduction ability towards oxygen intermediates. Moreover, this correlation was also adapted for other metal catalysts such as Au and Ag nanoparticles. This correspondence could be utilized for an accurate identification of d-band centers of single-atom catalysts. It is anticipated that the proposed strategy could be beneficial for a deep understanding of microstructure studies of single-atom catalysts to achieve advanced catalytic performances.

Comparative Study on Mechanical Properties and Microstructure Evolution of Mg-3Zn-1Mn/Sn Alloy through Ca-La-Ce Addition.

This study systematically investigates the influence of the composite addition of Ce, La, and Ca elements on the microstructure evolution and mechanical properties of Mg-3Zn-1Mn/Sn (wt.%) alloys. It indicates that the strength of Mg-Zn-Mn series alloys is superior to that of Mg-Zn-Sn series alloys, due to the stronger restriction of nanosized Mn particles on the recrystallization process and grain growth compared with Mg2Sn phases. The addition of the Ca-La-Ce elements significantly enhances the strength of the Mg-3Zn-1Sn alloy (YS increased by approximately 92.5%, UTS increased by approximately 29.2%, and EL decreased by nearly 52.2%), while for the Mg-3Zn-1Mn alloy, a balanced effect on both the strength and performance can be achieved. This difference mainly lies in the more pronounced refined effect on the grain size and the formation of a bimodal grain structure with strip-like un-DRXed grains and surrounding fine DRXed grains for the Mg-3Zn-1Sn alloy. In contrast, the addition of the Ca-La-Ce elements has a less obvious hindrance on the recrystallization process in the Mg-Zn-Mn series alloy, while significantly weakening the extrusion texture while refining the grains. Through in-depth characterization and experimental analysis, it is found that Sn and Ca can promote the formation of brittle and fine secondary phases. A nanoscale Sn phase (Mg2Sn phase) is more likely to accumulate at the grain boundaries, and the size of the nanoscale Ca2Mg6Zn3 in Mg-Zn-Mn series alloys is finer and more dispersed than that in Mg-Zn-Sn series alloys, thus strongly hindering recrystallization and refining the recrystallized structure of the alloy.

Rapid Size Determination of Quasispherical Gold Nanoparticles by Electrocatalysis Efficiency-Regulated Electrochemiluminescence.

The size of gold nanoparticles (AuNPs) largely decides their properties and applications, making the rapid screening of AuNP size important. Despite the fact that AuNP-amplified electrochemiluminescence (ECL) is widely used in various ECL sensing applications, the mechanism of ECL enhancement remains elusive, especially the quantitative relationship between the enhanced ECL intensity and the size of AuNPs. In this work, taking quasispherical and citrate-stabilized AuNPs as model nanoparticles, we have reported that the ECL intensity of the S2O82--O2 system enhanced significantly with the increasing AuNP size. AuNPs acted as bielectrocatalysts for reducing the S2O82- and O2. The further study of enhancement mechanism demonstrates that AuNPs with increasing size facilitate the electron transfer and promote the generation of radicals required for the ECL emission, which produces more emitters-singlet oxygen. Meanwhile, the high surface density of citrate on small AuNPs suppresses the ECL signal by forming an electrostatic barrier. On the basis of the above phenomena, an ECL-based rapid AuNP size screening approach has been established. The accuracy of this platform is verified by the consistent results in comparison to transmission electron microscopy (TEM) measurements. This work not only provides deep insight into the correlation between the AuNP size and the ECL enhancement but also contributes an alternative to the TEM technique for the rapid AuNP size screening. Additionally, this study also extends the exploration of ECL-based structure analysis techniques toward nanomaterials through clarifying the structure-electrocatalytic activity correlation.

Hypoxanthine Produces Rapid Antidepressant Effects by Suppressing Inflammation in Serum and Hippocampus.

The occurrence and development of depression are closely related to disorders of the brain and peripheral substances. Abnormal metabolites in the blood affect the signal regulation function of the nerve center, which is one of the key factors for depression episodes. This study was focused on metabolites in serum and the mechanism of its antidepressant in the hippocampus. In the present study, serum metabolites in patients with depression were screened by metabolomic techniques. Various depressive mouse models and behavioral tests were used to assess its antidepressant effects. The expressions of inflammatory signaling were detected by using Western blot, ELISA, and immunofluorescence. We found that the metabolite hypoxanthine in the serum of patients with depression was significantly reduced, and the same result was also found in two mouse models of depression such as chronic unpredictable mild stress (CUMS) and social defeat stress (SD). By administering different doses of hypoxanthine (5, 10, 15 mg/kg), we found that only 15 mg/kg was able to significantly reduce the latency and increase food consumption in the novelty suppressed-feeding test (NSF), which was also able to reverse the depressive phenotypes of mice in the CUMS model after a single administration at 2 h later. Hypoxanthine obviously reduced the expressions of inflammation in serum and downregulated the expressions of MAPK and NLRP3-related pathways in the hippocampus in CUMS mice. Moreover, hypoxanthine also suppressed the activations of glial cells including GFAP and IBA-1 in hippocampal CA1, CA3, and dentate gyrus (DG). To sum up, hypoxanthine exerted antidepressant effect relying on the inhibition of peripheral and hippocampal inflammations by regulating MAPK, NLRP3-related pathways, and glial cells. This was the first time that we have found a disordered metabolite in patients with depression and further systematically demonstrated its efficacy and potential mechanism of antidepressants, providing new ideas for antidepressant drug development.

Epigenetic regulation of p63 blocks squamous-to-neuroendocrine transdifferentiation in esophageal development and malignancy.

While cell fate determination and maintenance are important in establishing and preserving tissue identity and function during development, aberrant cell fate transition leads to cancer cell heterogeneity and resistance to treatment. Here, we report an unexpected role for the transcription factor p63 (Trp63/TP63) in the fate choice of the squamous versus neuroendocrine lineage in esophageal development and malignancy. Deletion of p63 results in extensive neuroendocrine differentiation in the developing mouse esophagus and esophageal progenitors derived from human embryonic stem cells. In human esophageal neuroendocrine carcinoma (eNEC) cells, p63 is transcriptionally silenced by EZH2-mediated H3K27 trimethylation (H3K27me3). Up-regulation of the major p63 isoform ΔNp63α, through either ectopic expression or EZH2 inhibition, promotes squamous transdifferentiation of eNEC cells. Together, these findings uncover p63 as a rheostat in coordinating the transition between squamous and neuroendocrine cell fates during esophageal development and tumor progression.

Clinicopathological characteristics of unicentric Castleman disease: A single-center experience of 12 patients.

BACKGROUND: Castleman disease (CD) is an uncommon lymphoproliferative disorder with distinct pathological characteristics. Unicentric Castleman disease (UCD) presents as a single lymph node enlargement, often without significant symptoms. Complete surgical resection is the standard treatment for UCD. This study aimed to explore the clinicopathological features of UCD in a Taiwanese population. METHODS: We retrospectively identified 12 patients with UCD who had undergone surgical treatment between January 1, 2006 and June 30, 2022 at the National Taiwan University Hospital. Clinical and radiological findings were retrieved from medical records. All available pathological slides were reviewed. RESULTS: The patients' mean age was 38.1 years (range, 17 to 69); five (41.7%) were male, and seven (58.3%) were female. Nearly all cases of UCD were in the mediastinum, except for one case in the neck. Most patients were asymptomatic and without abnormal laboratory test results. Computed tomography revealed well-defined tumor borders, contrast enhancement, and occasional calcification. Ten patients underwent en bloc tumor resection, while the remaining two underwent partial resection. Among them, seven (58.3%) underwent video-assisted thoracoscopic surgery (VATS), and four (33.3%) underwent thoracotomy. The mean follow-up duration was 92 months. The patients who underwent total resection had no recurrence. CONCLUSION: Detailed clinicopathological information on UCD in the Taiwanese population is present in our article. Both complete and partial surgery are effective for treatment. VATS may be preferred over thoracotomy due to less operative time and bleeding.

Flexible piezoelectric materials and strain sensors for wearable electronics and artificial intelligence applications.

With the rapid development of artificial intelligence, the applications of flexible piezoelectric sensors in health monitoring and human-machine interaction have attracted increasing attention. Recent advances in flexible materials and fabrication technologies have promoted practical applications of wearable devices, enabling their assembly in various forms such as ultra-thin films, electronic skins and electronic tattoos. These piezoelectric sensors meet the requirements of high integration, miniaturization and low power consumption, while simultaneously maintaining their unique sensing performance advantages. This review provides a comprehensive overview of cutting-edge research studies on enhanced wearable piezoelectric sensors. Promising piezoelectric polymer materials are highlighted, including polyvinylidene fluoride and conductive hydrogels. Material engineering strategies for improving sensitivity, cycle life, biocompatibility, and processability are summarized and discussed focusing on filler doping, fabrication techniques optimization, and microstructure engineering. Additionally, this review presents representative application cases of smart piezoelectric sensors in health monitoring and human-machine interaction. Finally, critical challenges and promising principles concerning advanced manufacture, biological safety and function integration are discussed to shed light on future directions in the field of piezoelectrics.

Development of Minodronic Acid-Loaded Dissolving Microneedles for Enhanced Osteoporosis Therapy: Influence of Drug Loading on the Bioavailability of Minodronic Acid.

Osteoporosis is a metabolic bone disorder with impaired bone microstructure and increased bone fractures, seriously affecting the quality of life of patients. Among various bisphosphonates prescribed for managing osteoporosis, minodronic acid (MA) is the most potent inhibitor of bone context resorption. However, oral MA tablet is the only commercialized dosage form that has extremely low bioavailability, severe adverse reactions, and poor patient compliance. To tackle these issues, we developed MA-loaded dissolving microneedles (MA-MNs) with significantly improved bioavailability for osteoporosis therapy. We investigated the influence of drug loading on the physicochemical properties, transdermal permeation behavior, and pharmacokinetics of MA-MNs. The drug loading of MA-MNs exerted almost no effect on their morphology, mechanical property, and skin insertion ability, but it compromised the transdermal permeability and bioavailability of MA-MNs. Compared with oral MA, MA-MNs with the lowest drug loading (224.9 µg/patch) showed a 9-fold and 25.8-fold increase in peak concentration and bioavailability, respectively. This may be ascribed to the reason that the increased drug loading can generate higher burst release, higher drug residual rate, and drug supersaturation effect in skin tissues, eventually limiting drug absorption into the systemic circulation. Moreover, MA-MNs prolonged the half-life of MA and provided more steady plasma drug concentrations than intravenously injected MA, which helps to reduce dosing frequency and side effects. Therefore, dissolving MNs with optimized drug loading provides a promising alternative for bisphosphonate drug delivery.

Systematic perturbations of SETD2, NSD1, NSD2, NSD3, and ASH1L reveal their distinct contributions to H3K36 methylation.

BACKGROUND: Methylation of histone 3 lysine 36 (H3K36me) has emerged as an essential epigenetic component for the faithful regulation of gene expression. Despite its importance in development and disease, how the molecular agents collectively shape the H3K36me landscape is unclear. RESULTS: We use mouse mesenchymal stem cells to perturb the H3K36me methyltransferases (K36MTs) and infer the activities of the five most prominent enzymes: SETD2, NSD1, NSD2, NSD3, and ASH1L. We find that H3K36me2 is the most abundant of the three methylation states and is predominantly deposited at intergenic regions by NSD1, and partly by NSD2. In contrast, H3K36me1/3 are most abundant within exons and are positively correlated with gene expression. We demonstrate that while SETD2 deposits most H3K36me3, it may also deposit H3K36me2 within transcribed genes. Additionally, loss of SETD2 results in an increase of exonic H3K36me1, suggesting other (K36MTs) prime gene bodies with lower methylation states ahead of transcription. While NSD1/2 establish broad intergenic H3K36me2 domains, NSD3 deposits H3K36me2 peaks on active promoters and enhancers. Meanwhile, the activity of ASH1L is restricted to the regulatory elements of developmentally relevant genes, and our analyses implicate PBX2 as a potential recruitment factor. CONCLUSIONS: Within genes, SETD2 primarily deposits H3K36me3, while the other K36MTs deposit H3K36me1/2 independently of SETD2 activity. For the deposition of H3K36me1/2, we find a hierarchy of K36MT activities where NSD1 > NSD2 > NSD3 > ASH1L. While NSD1 and NSD2 are responsible for most genome-wide propagation of H3K36me2, the activities of NSD3 and ASH1L are confined to active regulatory elements.

Aggregation-induced emission-active supramolecular polymers: from controlled preparation to applications.

Supramolecular polymers are typical self-assemblies, in which repeating monomer units are bonded together with dynamic and reversible noncovalent interactions. Supramolecular polymers can combine the advantages of polymer science and supramolecular chemistry. Aggregation-induced emission (AIE) means that a molecule remains faintly emissive in the dispersed state but intensively luminescent in a highly aggregated state. AIE has brought new opportunities and further development potential to the field of polymeric chemistry. The integration of AIE luminogens with supramolecular interactions can provide new vitality for supramolecular polymers. Therefore, it is essential for scientists to understand the preparation and applications of AIE-active supramolecular polymers. This review focuses on the recent advanced progress in the preparation of AIE-active supramolecular polymers. In addition, we summarize the newly developed supramolecular polymers with an AIE nature and their applications in chemical sensing, and in vitro and in vivo imaging, as well as the visualization of their structure and properties. Finally, the development trends and challenges of AIE-active supramolecular polymers are prospected.

Development of a High-Sensitivity Acoustic Sensor Based on Grating Interferometer Combined with Glass Diaphragm.

In this study, based on the principle of grating interferometer-based acoustic sensors, design guidelines for the grating interferometric module were obtained and analyzed considering various factors in order to obtain high sensitivity, and a glass-based grating interference component and its acoustic sensor device were developed. The key parameters of the grating interference structure were extracted, and their effects on the acoustic response sensitivity were quantified for multiple mechanisms. For the development of the acoustic sensor, the grating-on-convex-platform structure and the micromachining processes of the glass-based components were designed and developed. The developed acoustic sensor samples achieved high sensitivity. In particular, the sample suitable for low-frequency application obtained a sensitivity of 0.776 V/Pa @ 1 kHz, and the spectrum of its sensitivity was flat from 50 Hz to 8 Hz with a deviation less than 1.5 dB and a sensitivity of 0.408 V/Pa @ 20 Hz.

Emerging Trends in Dissolving-Microneedle Technology for Antimicrobial Skin-Infection Therapies.

Skin and soft-tissue infections require significant consideration because of their prolonged treatment duration and propensity to rapidly progress, resulting in severe complications. The primary challenge in their treatment stems from the involvement of drug-resistant microorganisms that can form impermeable biofilms, as well as the possibility of infection extending deep into tissues, thereby complicating drug delivery. Dissolving microneedle patches are an innovative transdermal drug-delivery system that effectively enhances drug penetration through the stratum corneum barrier, thereby increasing drug concentration at the site of infection. They offer highly efficient, safe, and patient-friendly alternatives to conventional topical formulations. This comprehensive review focuses on recent advances and emerging trends in dissolving-microneedle technology for antimicrobial skin-infection therapy. Conventional antibiotic microneedles are compared with those based on emerging antimicrobial agents, such as quorum-sensing inhibitors, antimicrobial peptides, and antimicrobial-matrix materials. The review also highlights the potential of innovative microneedles incorporating chemodynamic, nanoenzyme antimicrobial, photodynamic, and photothermal antibacterial therapies. This review explores the advantages of various antimicrobial therapies and emphasizes the potential of their combined application to improve the efficacy of microneedles. Finally, this review analyzes the druggability of different antimicrobial microneedles and discusses possible future developments.

NA-segformer: A multi-level transformer model based on neighborhood attention for colonoscopic polyp segmentation.

In various countries worldwide, the incidence of colon cancer-related deaths has been on the rise in recent years. Early detection of symptoms and identification of intestinal polyps are crucial for improving the cure rate of colon cancer patients. Automated computer-aided diagnosis (CAD) has emerged as a solution to the low efficiency of traditional methods relying on manual diagnosis by physicians. Deep learning is the latest direction of CAD development and has shown promise for colonoscopic polyp segmentation. In this paper, we present a multi-level encoder-decoder architecture for polyp segmentation based on the Transformer architecture, termed NA-SegFormer. To improve the performance of existing Transformer-based segmentation algorithms for edge segmentation on colon polyps, we propose a patch merging module with a neighbor attention mechanism based on overlap patch merging. Since colon tract polyps vary greatly in size and different datasets have different sample sizes, we used a unified focal loss to solve the problem of category imbalance in colon tract polyp data. To assess the effectiveness of our proposed method, we utilized video capsule endoscopy and typical colonoscopy polyp datasets, as well as a dataset containing surgical equipment. On the datasets Kvasir-SEG, Kvasir-Instrument and KvasirCapsule-SEG, the Dice score of our proposed model reached 94.30%, 94.59% and 82.73%, with an accuracy of 98.26%, 99.02% and 81.84% respectively. The proposed method achieved inference speed with an Frame-per-second (FPS) of 125.01. The results demonstrated that our suggested model effectively segmented polyps better than several well-known and latest models. In addition, the proposed method has advantages in trade-off between inference speed and accuracy, and it will be of great significance to real-time colonoscopic polyp segmentation. The code is available at https://github.com/promisedong/NAFormer .

Epitranscriptomic regulation of lipid oxidation and liver fibrosis via ENPP1 mRNA m6A modification.

BACKGROUND: Dysregulated lipid oxidation occurs in several pathological processes characterized by cell proliferation and migration. Nonetheless, the molecular mechanism of lipid oxidation is not well appreciated in liver fibrosis, which is accompanied by enhanced fibroblast proliferation and migration. METHODS: We investigated the causes and consequences of lipid oxidation in liver fibrosis using cultured cells, animal models, and clinical samples. RESULTS: Increased ecto-nucleotide pyrophosphatase/phosphodiesterase (ENPP1) expression caused increased lipid oxidation, resulting in the proliferation and migration of hepatic stellate cells (HSCs) that lead to liver fibrosis, whereas fibroblast-specific ENPP1 knockout reversing these results. Elevated ENPP1 and N6-methyladenosine (m6A) levels were associated with high expression of Wilms tumor 1 associated protein (WTAP). Mechanistically, WTAP-mediated m6A methylation of the 3'UTR of ENPP1 mRNA and induces its translation dependent of YTH domain family proteins 1 (YTHDF1). Additionally, ENPP1 could interact with hypoxia inducible lipid droplet associated (HILPDA) directly; overexpression of ENPP1 further recruits HILPDA-mediated lipid oxidation, thereby promotes HSCs proliferation and migration, while inhibition of ENPP1 expression produced the opposite effect. Clinically, increased expression of WTAP, YTHDF1, ENPP1, and HILPDA, and increased m6A mRNA content, enhanced lipid oxidation, and increased collagen deposition in human liver fibrosis tissues. CONCLUSIONS: We describe a novel mechanism in which WTAP catalyzes m6A methylation of ENPP1 in a YTHDF1-dependent manner to enhance lipid oxidation, promoting HSCs proliferation and migration and liver fibrosis.

Development of Ampelopsis Radix Ethanolic Extract Loaded Phytosomes for Improved Efficacy in Colorectal Cancer: in vitro and in vivo Assessment Study.

The aim of present work was to develop and evaluate Ampelopsis Radix ethanolic extract loaded phytosomes for improved efficacy in colorectal cancer. Ampelopsis Radix ethanolic extract was prepared by Soxhlet extraction process followed by development of phytosomes using lipids and other excipients. The phytosomes were evaluated for surface morphology, particle size analysis, zeta potential, encapsulation efficiency, drug loading, in vitro drug release, Cytotoxicity assay, cellular uptake studies were performed on HCT-116 and SW480 cell lines. In vivo antitumor activity was performed. The phytosomes were found spherical shape with smooth surface characteristics. The drug loading was observed between 29.27 to 42.10 % while particle size of 85 to 130 nm was found. Phytosomes showed desired release pattern which is required for cancer treatment. Phytosomes showed maximum antiproliferative activity on cell lines over the period of 24 hours and showed highest internalization within both types of cell lines. The survival rate of animals in phytosomes treated group was found to be 100% proving the safety and efficacy. Phytosomes showed highest antitumor activity as compared to other formulations. Study confirms the potential use Ampelopsis Radix ethanolic extract loaded phytosomes for improved efficacy in colorectal cancer.

Healthcare Costs Across Diabetic Kidney Disease Stages: A Veterans Affairs Study.

Background: In the United States, diabetic kidney disease (DKD) affects about one-third of individuals with type 2 diabetes, causing significant economic burdens on the health care system and affecting patients' quality of life. Objective: The aim of the study was to quantify the burden of care in patients at different stages of DKD and to monitor shifts in healthcare costs throughout these stages. Methods: This study used data from the Veterans Affairs National database, focusing on US veterans diagnosed with DKD between January 2016 and March 2022. Aggregated all-cause health care costs per month were summarized using descriptive statistics. We used a generalized linear model to calculate the cost of DKD patent care based on the stages, dialysis phase, and kidney replacement therapy. Results: The cohort of 685,288 patients with DKD was predominantly male (96.51%), White (74.42%), and non-Hispanic (93.54%). The mean (SD) per-patient per-month costs were $1,597 ($3,178), $1,772 ($4,269), $2,857 ($13,072), $3,722 ($12,134), $5,505 ($14,639), and $6,999 ($16,901) for stages 1, 2, 3a, 3b, 4 and 5 respectively. The average monthly expenditure for patients receiving long-term dialysis was $12,299. Costs peaked sharply during the first month of kidney replacement therapy at $38,359 but subsequently decreased to $6,636 after 1 year. Conclusions: The economic implications of DKD are profound, emphasizing the need for efficient early detection and disease management strategies. Preventing patients from progressing to advanced DKD stage will minimize the economic repercussions of DKD and will assist health care systems in optimizing resource allocation.

Diabetic kidney disease (DKD) places a substantial burden on health care systems in the United States. In part of our effort to close the knowledge gap around the disease burden, care cost analysis for the patients with DKD was performed for US veterans. Along with stage progression, overall care costs per-patient per-month drastically increases from $1,597 (stage 1) to $6,999 (stage 5). Monthly costs exceeded $10,000 once veterans started to receive long-term dialysis. The quantitative summary will help health care systems efficiently allocate resources across various disease sectors.

Reversible Molecule Interactions Enable Ultrastretchable and Recyclable Ionogels for Wearable Piezoionic Sensors.

Ionogel-based piezoionic sensors feel motions and strains like human skin relying on reversible ion migrations under external mechanical stimulus and are of great importance to artificial intelligence. However, conventional ion-conductive polymers behave with degraded electrical and mechanical properties after thousands of strain cycles, and the discarded materials and devices become electronic wastes as well. Here, we develop ultrastretchable ionogels with superior electrical properties via the mediation of metal-organic frameworks, whose properties are attributed to reversible molecule interactions inside the material system. Ionogels present excellent mechanical properties with breaking elongation as high as 850%, exceeding most previously reported similar materials, and the high conductivity enables further application in sensor devices. In addition, our ionogels display superior recyclability because of the reversible physical and chemical interactions inside material molecules, which are eco-friendly to the environment. As a result, the ionogel-based piezoionic sensors deliver high sensitivity, flexibility, cyclic stability, and signal reliability, which are of great significance to wearable applications in human-motion detections such as throat vibration, facial expression, joint mobility, and finger movement. Our study paves the way for ultrastretchable and eco-friendly ionogel design for flexible electrochemical devices.

Changes of regional brain activity following Tuina therapy for patients with painful cervical spondylosis: a resting-state fMRI study.

Background: The effectiveness of Tuina therapy has been confirmed in treating pain of patients with cervical spondylosis (CS), however, its therapeutic mechanism is still unclear. This study aimed to observe the changes of regional brain activity following Tuina therapy in patients with painful CS based on resting-state functional magnetic resonance imaging (rs-fMRI) data. Methods: A total of 27 patients with CS and 27 healthy subjects (HCs) were enrolled in this study. All patients received Tuina therapy every 2 days for 2 weeks. The clinical manifestations of patients were evaluated by the Visual Analog Scale (VAS) and Neck Disability Index (NDI) before and after treatment. In addition, rs-fMRI data were collected and preprocessed in all patients before and after treatment, as well as HCs. HCs underwent a 1-time rs-fMRI scan, whereas CS patients underwent 2-times of rs-fMRI scan. The measure of regional homogeneity (ReHo) was calculated and compared between groups. Finally, relationships between altered brain regions and clinical characteristics were evaluated by Pearson's correlation analysis. Results: After Tuina therapy, VAS and NDI scores of patients decreased. Before treatment, CS patients showed higher ReHo values in the left middle temporal gyrus, left thalamus, right anterior and posterior cingulate gyrus, left inferior parietal gyrus and lower ReHo values in the right gyrus rectus when compared with HCs. After treatment, CS patients exhibited higher ReHo values in the left inferior temporal gyrus, right anterior and posterior cingulate gyrus, left inferior parietal gyrus and lower ReHo values in the right rectus gyrus when compared with HCs. CS patients after treatment demonstrated higher ReHo values in the left inferior occipital gyrus when compared with those before treatment. Positive correlations were found between ReHo values of the right rectus gyrus and VAS, NDI scores in CS patients before treatment. Differences of VAS scores between before and after treatment were negatively correlated with ReHo values of the left inferior temporal gyrus in CS patients after treatment. Conclusion: This study demonstrated the presence of asynchronous activity in certain brain regions in CS patients, which might be associated with pain and cervical spine dysfunction. Tuina therapy might modulate asynchronous activity of abnormal brain regions, which might contribute to the effectiveness of Tuina therapy in alleviating pain and cervical spine dysfunction in CS patients.