CD133-targeted multifunctional nanomicelles for dual-modality imaging and synergistic high-intensity focus ultrasound (HIFU) ablation on pancreatic cancer in nude mice.

Pancreatic cancer is an aggressive and highly fatal malignant tumor. Recent studies have shown that cancer stem cells (CSCs) play an important role in resisting current therapeutic modalities. Furthermore, CD133 is highly expressed in CSCs. High-intensity focused ultrasound (HIFU) is a promising non-invasive therapeutic strategy for unresectable pancreatic cancers. In our study, we synthesized targeted CD133 organosilane nanomicelles by encapsulating perfluorohexane (PFH). The CD133 antibody on the surface could specifically bind to CD133-positive pancreatic cancer cells and selectively concentrate in pancreatic cancer tumor tissues. PFH was introduced to improve the ablation effect of HIFU due to its liquid-gas phase transition properties. By combining with the dorsal skinfold window chamber model (DSWC) of pancreatic cancer in nude mice, multiphoton fluorescence microscopy was used to evaluate the targeting effect of nanomicelles on pancreatic cancer tumor tissue. These multifunctional nanomicelles synergistically affected HIFU treatment of pancreatic cancer, providing an integrated research platform for diagnosing and treating pancreatic cancer with HIFU.

Enhanced degradation of enrofloxacin in mariculture wastewater based on marine bacteria and microbial carrier.

This study aimed to isolate marine bacteria to investigate their stress response, inhibition mechanisms, and degradation processes under high-load conditions of salinity and enrofloxacin (ENR). The results demonstrated that marine bacteria exhibited efficient pollutant removal efficiency even under high ENR stress (up to 10 mg/L), with chemical oxygen demand (COD), total phosphorus (TP), total nitrogen (TN) and ENR removal efficiencies reaching approximately 88%, 83%, 61%, and 73%, respectively. The predominant families of marine bacteria were Bacillaceae (50.46%), Alcanivoracaceae (32.30%), and Rhodobacteraceae (13.36%). They responded to ENR removal by altering cell membrane properties, stimulating the activity of xenobiotic-metabolizing enzymes and antioxidant systems, and mitigating ENR stress through the secretion of extracellular polymeric substance (EPS). The marine bacteria exhibited robust adaptability to environmental factors and effective detoxification of ENR, simultaneously removing carbon, nitrogen, phosphorus, and antibiotics from the wastewater. The attapulgite carrier enhanced the bacteria's resistance to the environment. When treating actual mariculture wastewater, the removal efficiencies of COD and TN exceeded 80%, TP removal efficiency exceeded 90%, and ENR removal efficiency approached 100%, significantly higher than reported values in similar salinity reactors. Combining the constructed physical and mathematical models of tolerant bacterial, this study will promote the practical implementation of marine bacterial-based biotechnologies in high-loading saline wastewater treatment.

In Situ Quantitative Imaging of Plasma Membrane Stiffness in Live Cells Using a Genetically Encoded FRET Sensor.

Cell membrane stiffness is critical for cellular function, with cholesterol and sphingomyelin as pivot contributors. Current methods for measuring membrane stiffness are often invasive, ex situ, and slow in process, prompting the need for innovative techniques. Here, we present a fluorescence resonance energy transfer (FRET)-based protein sensor designed to address these challenges. The sensor consists of two fluorescent units targeting sphingomyelin and cholesterol, connected by a linker that responds to the proximity of these lipids. In rigid membranes, cholesterol and sphingomyelin are in close proximity, leading to an increased FRET signal. We utilized this sensor in combination with confocal microscopy to explore changes in plasma membrane stiffness under various conditions, including differences in osmotic pressure, the presence of reactive oxygen species (ROS) and variations in substrate stiffness. Furthermore, we explored the impact of SARS-CoV-2 on membrane stiffness and the distribution of ACE2 after attachment to the cell membrane. This tool offers substantial potential for future investigations in the field of mechanobiology.

Exploring the effect of high-pressure processing conditions on the deaggregation of natural major royal jelly proteins (MRJPs) fibrillar aggregates.

High pressure processing is a safe and green novel non-thermal processing technique for modulating food protein aggregation behavior. However, the systematic relationship between high pressure processing conditions and protein deaggregation has not been sufficiently investigated. Major royal jelly proteins, which are naturally highly fibrillar aggregates, and it was found that the pressure level and exposure time could significantly promote protein deaggregation. The 100-200 MPa treatment favoured the deaggregation of proteins with a significant decrease in the sulfhydryl group content. Contrarily, at higher pressure levels (>400 MPa), the exposure time promoted the formation of disordered agglomerates. Notably, the inter-conversion of α-helix and ß-strands in major royal jelly proteins after high pressure processing eliminates the solvent-free cavities inside the aggregates, which exerts a 'collapsing' effect on the fibrillar aggregates. Furthermore, the first machine learning model of the high pressure processing conditions and the protein deaggregation behaviour was developed, which provided digital guidance for protein aggregation regulation.

Sonogenetics-controlled synthetic designer cells for cancer therapy in tumor mouse models.

Bacteria-based therapies are powerful strategies for cancer therapy, yet their clinical application is limited by a lack of tunable genetic switches to safely regulate the local expression and release of therapeutic cargoes. Rapid advances in remote-control technologies have enabled precise control of biological processes in time and space. We developed therapeutically active engineered bacteria mediated by a sono-activatable integrated gene circuit based on the thermosensitive transcriptional repressor TlpA39. Through promoter engineering and ribosome binding site screening, we achieved ultrasound (US)-induced protein expression and secretion in engineered bacteria with minimal noise and high induction efficiency. Specifically, delivered either intratumorally or intravenously, engineered bacteria colonizing tumors suppressed tumor growth through US-irradiation-induced release of the apoptotic protein azurin and an immune checkpoint inhibitor, a nanobody targeting programmed death-ligand 1, in different tumor mouse models. Beyond developing safe and high-performance designer bacteria for tumor therapy, our study illustrates a sonogenetics-controlled therapeutic platform that can be harnessed for bacteria-based precision medicine.

Therapeutic efficacy and safety of JAK inhibitors in treating polymyositis/dermatomyositis: a single-arm systemic meta-analysis.

Introduction: We performed a single-arm meta-analysis to evaluate the efficacy and safety of JAK inhibitors in the treatment of dermatomyositis (DM)/ polymyositis (PM). Methods: Relevant studies from four databases were systematically searched until April 25, 2023. The primary endpoint was Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) and other outcomes were Manual Muscle Testing (MMT) and Creatine Kinase (CK). According to the type of JAK and medication regimen, we conducted subgroup analyses. The registration number in PROSPERO was CRD42023416493. Results: According to the selection criteria, we identified 7 publications with a total of 91 patients. Regarding skin lesions, the CDASI decreased by 17.67 (95% CI: -20.94 ~ -14.41). The CK increased by 8.64 U (95% CI: -28.25 ~ 45.53). About muscle lesions, MMT increased by 10.31 (95% CI: -2.83 ~ 23.46). Subgroup analysis revealed that different types of JAK inhibitors had various degrees of reduction. CDASI in patients treated with RUX had the lowest one [-20.00 (95% CI: -34.9 ~ -5.1)], followed by TOF [-18.29 (95% CI: -21.8 ~ -14.78)] and BAR [-11.2 (95% CI: -21.51 ~ -0.89)]. Additionally, the mean reduction in CDASI in patients treated with TOF alone was 16.16 (95% CI: -21.21 ~ -11.11), in combination with other immunosuppressants was 18.59 (95% CI: -22.74 ~ -14.45). For safety evaluation, one patient developed Orolabial HSV, and two patients developed thromboembolism events. Discussion: In summary, this meta-analysis demonstrated that JAK inhibitors can potentially treat DM/PM without severe adverse reactions. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42023416493, identifier CRD42023416493.

Engineering Nanomedicine for Non-Viral RNA-Based Gene Therapy of Glioblastoma.

Glioblastoma multiforme (GBM) is the most common type of malignant tumor of the central nervous system, characterized by aggressiveness, genetic instability, heterogenesis, and unpredictable clinical behavior. Disappointing results from the current clinical therapeutic methods have fueled a search for new therapeutic targets and treatment modalities. GBM is characterized by various genetic alterations, and RNA-based gene therapy has raised particular attention in GBM therapy. Here, we review the recent advances in engineered non-viral nanocarriers for RNA drug delivery to treat GBM. Therapeutic strategies concerning the brain-targeted delivery of various RNA drugs involving siRNA, microRNA, mRNA, ASO, and short-length RNA and the therapeutical mechanisms of these drugs to tackle the challenges of chemo-/radiotherapy resistance, recurrence, and incurable stem cell-like tumor cells of GBM are herein outlined. We also highlight the progress, prospects, and remaining challenges of non-viral nanocarriers-mediated RNA-based gene therapy.

Extraction, Identification, and In Vitro Anti-Inflammatory Activity of Feruloylated Oligosaccharides from Baijiu Distillers' Grains.

The structure and function of phenoyl oligosaccharides in baijiu distillers' grains (BDGs) have not been identified and investigated yet. This study aimed to elucidate the major phenolic oligosaccharides present in BDGs, optimize their extraction process via a central composite design, and assess their anti-inflammatory properties utilizing the LPS-induced RAW264.7 inflammation model. The main results are as follows: feruloylated oligosaccharides (FOs) were identified as the main phenoyl oligosaccharides in BDGs with a structure of ferulic acid esterified on arabinooligosaccharide xylose. Then, the preparation process of FOs was optimized using the following conditions: pH 5, temperature 55 °C, time 12 h, xylanase addition amount 7 g/L, BDG concentration 120 g/L. Furthermore, the acquired FOs demonstrated notable scavenging activity against DPPH and ABTS free radicals, with Trolox equivalent values of 366.8 ± 10.38 and 0.35 ± 0.01 mM Trolox/mg sample, respectively. However, their efficacy was comparatively lower than that of ferulic acid. Finally, the obtained FOs could effectively inhibit the LPS-induced secretion of TNF-α, IL-6, and IL-1ß and promote the secretion of IL-10 in RAW264.7 cells. Based on the above results, FOs from BDGs were determined to have certain antioxidant and anti-inflammatory activities.

The decreased astrocyte-microglia interaction reflects the early characteristics of Alzheimer's disease.

Alzheimer's disease (AD) is the most common neurodegenerative disease often associated with olfactory dysfunction. Aß is a typical AD hall marker, but Aß-induced molecular alterations in olfactory memory remain unclear. In this study, we used a 5xFAD mouse model to investigate Aß-induced olfactory changes. Results showed that 4-month-old 5xFAD have olfactory memory impairment accompanied by piriform cortex neuron activity decline and no sound or working memory impairment. In addition, synapse and glia functional alteration is consistent across different ages at the proteomic level. Microglia and astrocyte specific proteins showed strong interactions in the conserved co-expression network module. Moreover, this interaction declines only in mild cognitive impairment patients in human postmortem brain proteomic data. This suggests that astrocytes-microglia interaction may play a leading role in the early stage of Aß-induced olfactory memory impairment, and the decreasing of their synergy may accelerate the neurodegeneration.

Single-cell omics identifies inflammatory signaling as a trans-differentiation trigger in mouse embryos.

Trans-differentiation represents a direct lineage conversion; however, insufficient characterization of this process hinders its potential applications. Here, to explore a potential universal principal for trans-differentiation, we performed single-cell transcriptomic analysis of endothelial-to-hematopoietic transition (EHT), endothelial-to-mesenchymal transition, and epithelial-to-mesenchymal transition in mouse embryos. We applied three scoring indexes of entropies, cell-type signature transcription factor expression, and critical transition signals to show common features underpinning the fate plasticity of transition states. Cross-model comparison identified inflammatory-featured transition states and a common trigger role of interleukin-33 in promoting fate conversions. Multimodal profiling (integrative transcriptomic and chromatin accessibility analysis) demonstrated the inflammatory regulation of hematopoietic specification. Furthermore, multimodal omics and fate-mapping analyses showed that endothelium-specific Spi1, as an inflammatory effector, governs appropriate chromatin accessibility and transcriptional programs to safeguard EHT. Overall, our study employs single-cell omics to identify critical transition states/signals and the common trigger role of inflammatory signaling in developmental-stress-induced fate conversions.

Structure elucidation and anticancer activity of a heteropolysaccharide from white tea.

White tea, one of the six traditional teas in China, is made only through natural withering and low-temperature drying processes. It demonstrates diverse pharmacological and health-promoting effects, including antioxidant, antiviral, anticancer, and hypolipidemic activities. Despite the significance of polysaccharides in white tea leaves, their fine structure and physiological functions remain unexplored. In this study, the polysaccharide fragment WTP-80a with anticancer activity was isolated and purified from white tea through water extraction, alcohol precipitation, DEAE-52 ion exchange column chromatography, and sephacryl S-200 dextran gel column chromatography. WTP-80a exhibited a molecular weight of 1.14 × 105 Da and consisted of galactose (Gal), arabinose (Ara), rhamnose (Rha), and glucuronic acid (Glc-UA). The main chain skeleton of WTP-80a contained 3,6)-ß-Galp-(1→, 3)-α-Galp-(1→, 5)-α-Araf-(1 â†’ and 3)-α-Glcp-UA-(1→. Branch chains included α-Araf-(1 â†’ and ß-Rhap-(1 â†’ connected to the C3 and C6 positions of →3,6)-ß-Galp-(1→, respectively. In vitro anticancer experiments revealed that WTP-80a effectively hindered the proliferation, colony formation, migration, and invasion of B16F10 cells. Additionally, it induced apoptosis in B16F10 cells by blocking the G2/M phase, increasing active oxygen content, and reducing mitochondrial membrane potential. These findings provide a solid theoretical foundation for the application of white tea polysaccharides as anticancer products.

Poly-(lactic acid) composite films comprising carvacrol and cellulose nanocrystal-zinc oxide with synergistic antibacterial effects.

Herein, carvacrol (CRV) and modified cellulose nanocrystal-zinc oxide (CNC-ZnO) were incorporated into a poly (lactic acid) (PLA) matrix to prepare a PLA-based composite film using a simple solution casting method to achieve antimicrobial effects for application in antimicrobial food packaging. Compared with films obtained from neat PLA, the PLA@CRV20%@CNC-ZnO3% composite film shows better performance in terms of mechanical properties, ultraviolet (UV) blocking, and antimicrobial effects. The PLA composites containing CRV and 3 wt% CNC-ZnO blends exhibit improved tensile strength (21.8 MPa) and elongation at break (403.1 %) as well as excellent UV resistance. In particular, CRV and the CNC-ZnO hybrid endow the obtained PLA composite films with a synergistic antibacterial effect, resulting in good antibacterial properties for microbes, such as Escherichia coli, Staphylococcus aureus and Aspergillus niger. The diameters of the inhibition zone of the PLA@CRV20%@CNC-ZnO3% composite films against E. coli, S. aureus, and A. niger were 4.9, 5.0, and 3.4 cm, respectively. Appling the PLA@CRV20%@CNC-ZnO3% composite film as an antibacterial food packaging material, the storage period for strawberries was considerably extended. This study provides a theoretical basis for developing new organic/inorganic composite antimicrobial film materials from PLA.

Release of extracellular vesicles triggered by low-intensity pulsed ultrasound: immediate and delayed reactions.

Previous studies have shown that ultrasound may stimulate the release of extracellular vesicles, improving the efficiency of tumor detection. However, it is unclear whether ultrasonic stimulation affects the distribution of extracellular vesicles, and the duration of such stimulation release has not been extensively studied. In this study, we stimulated cells with low-intensity pulsed ultrasound and used liposomes containing black hole quenchers to simulate natural extracellular vesicles, confirming that ultrasound has a destructive effect on vesicles and thus affects particle size distribution. Furthermore, we used proteomics technology to examine the protein expression profile of small vesicles and discovered that the expression of proteins involved in exosome biogenesis was down-regulated. We then looked into the regulation of the actin cytoskeleton and endocytosis pathways, which are required for intracellular vesicle transport, and discovered that ultrasound might induce F-actin depolymerization. The intracellular transport of the cation-independent mannose-6-phosphate receptor (CI-MPR) in the trans-Golgi network (TGN) and the amount of Rab7a protein were proportional to the culture time after LIPUS treatment.

PHPB ameliorates memory deficits and reduces oxidative injury in Alzheimer's disease mouse model by activating Nrf2 signaling pathway.

Alzheimer's disease (AD), a progressive neurodegenerative disorder, is the most common cause of dementia in elderly people and substantially affects patient quality of life. Oxidative stress is considered a key factor in the development of AD. Nrf2 plays a vital role in maintaining redox homeostasis and regulating neuroinflammatory responses in AD. Previous studies show that potassium 2-(1-hydroxypentyl)-benzoate (PHPB) exerts neuroprotective effects against cognitive impairment in a variety of dementia animal models such as APP/PS1 transgenic mice. In this study we investigated whether PHPB ameriorated the progression of AD by reducing oxidative stress (OS) damage. Both 5- and 13-month-old APP/PS1 mice were administered PHPB (100 mg·kg-1·d-1, i.g.) for 10 weeks. After the cognition assessment, the mice were euthanized, and the left hemisphere of the brain was harvested for analyses. We showed that 5-month-old APP/PS1 mice already exhibited impaired performance in the step-down test, and knockdown of Nrf2 gene only slightly increased the impairment, while knockdown of Nrf2 gene in 13-month-old APP/PS1 mice resulted in greatly worse performance. PHPB administration significantly ameliorated the cognition impairments and enhanced antioxidative capacity in APP/PS1 mice. In addition, PHPB administration significantly increased the p-AKT/AKT and p-GSK3ß/GSK3ß ratios and the expression levels of Nrf2, HO-1 and NQO-1 in APP/PS1 mice, but these changes were abolished by knockdown of Nrf2 gene. In SK-N-SH APPwt cells and primary mouse neurons, PHPB (10 µM) significantly increased the p-AKT/AKT and p-GSK3ß/GSK3ß ratios and the level of Nrf2, which were blocked by knockdown of Nrf2 gene. In summary, this study demonstrates that PHPB exerts a protective effect via the Akt/GSK3ß/Nrf2 pathway and it might be a promising neuroprotective agent for the treatment of AD.

Colorful 3D Reconstruction and an Extended Depth of Field for a Monocular Biological Microscope Using an Electrically Tunable Lens.

This paper presents a monocular biological microscope with colorful 3D reconstruction and an extended depth of field using an electrically tunable lens. It is based on a 4f optical system with an electrically tunable lens at the confocal plane. Rapid and extensive depth scanning while maintaining consistent magnification without mechanical movement is achieved. We propose an improved Laplacian operator that considers pixels in diagonal directions to provide enhanced fusion effects and obtain more details of the object. Accurate 3D reconstruction is achieved using the shape-from-focus method by tuning the focal power of the electrically tunable lens. We validate the proposed method by performing experiments on biological samples. The 3D reconstructed images obtained from the biological samples match the actual shrimp larvae and bee antenna samples. Two standard gauge blocks are used to evaluate the 3D reconstruction performance of the proposed method. The experimental results show that the extended depth of fields are 120 µm, 240 µm, and 1440 µm for shrimp larvae, bee tentacle samples, and gauge blocks, respectively. The maximum absolute errors are -39.9 µm and -30.6 µm for the first and second gauge blocks, which indicates 3D reconstruction deviations are 0.78% and 1.52%, respectively. Since the procedure does not require any custom hardware, it can be used to transform a biological microscope into one that effectively extends the depth of field and achieves highly accurate 3D reconstruction results, as long as the requirements are met. Such a microscope presents a broad range of applications, such as biological detection and microbiological diagnosis, where colorful 3D reconstruction and an extended depth of field are critical.

Low-Intensity Pulsed Ultrasound Promotes the Repair of Achilles Tendinopathy by Downregulating the JAK/STAT Signaling Pathway in Rabbits.

Tendinopathy is a complex tendon injury or pathology outcome, potentially leading to permanent impairment. Low-intensity pulsed ultrasound (LIPUS) is emerging as a treatment modality for tendon disorders. However, the optimal treatment duration and its effect on tendons remain unclear. This study aims to investigate the efficacy of LIPUS in treating injured tendons, delineate the appropriate treatment duration, and elucidate the underlying treatment mechanisms through animal experiments. Ninety-six three-month-old New Zealand white rabbits were divided into normal control (NC) and model groups. The model group received Prostaglandin E2 (PGE2) injections to induce Achilles tendinopathy. They were then divided into model control (MC) and LIPUS treatment (LT) groups. LT received LIPUS intervention with a 1-MHz frequency, a pulse repetition frequency (PRF) of 1 kHz, and spatial average temporal average sound intensity ( [Formula: see text]) of 100 mW/cm2. MC underwent a sham ultrasound, and NC received no treatment. Assessments on 1, 4, 7, 14, and 28 days after LT included shear wave elastography (SWE), mechanical testing, histologic evaluation, ribonucleic acid sequencing (RNA-seq), polymerase chain reaction (PCR), and western blot (WB) analysis. SWE results showed that the shear modulus in the LT group was significantly higher than that in the MC group after LT for seven days. Histological results demonstrated improved tendon tissue alignment and fibroblast distribution after LT. Molecular analyses suggested that LIPUS may downregulate the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway and regulate inflammatory and matrix-related factors. We concluded that LT enhanced injured tendon elasticity and accelerated Achilles tendon healing. The study highlighted the JAK/STAT signaling pathway as a potential therapeutic target for LT of Achilles tendinopathy, guiding future research.

Combined Assessment of 2-D Ultrasound and Real-Time Shear Wave Elastography of Low-Intensity Pulsed Ultrasound Therapy Efficacy in Rabbits with Achilles Tendinopathy.

OBJECTIVE: Low-intensity pulsed ultrasound (LIPUS) has been gradually used to treat Achilles tendinopathy. However, there are limited non-invasive and efficient instruments for monitoring LIPUS efficacy in Achilles tendinopathy. The purpose of this study was to assess the therapeutic effectiveness of LIPUS after Achilles tendinopathy by 2-D ultrasound and real-time shear wave elastography (SWE). METHODS: Ninety New Zealand white rabbits were divided into control, sham and LIPUS groups after tendinopathy modeling. On days 1, 4, 7, 14 and 28, the Achilles tendon thickness and SWE Young's modulus on the long axis were measured. The tissues of the Achilles tendon were then evaluated histologically. RESULTS: The mean SWE values increased while the average thickness and histologic scores decreased, especially in the LIPUS group (9.5% and 80.7% on day 28, respectively). The SWE values in the LIPUS group were significantly lower than those in the control group on day 1 (121.0 kPa vs. 177.6 kPa) and peaked on day 7 (173.7 kPa, p < 0.001). By day 28, the SWE value had approached that of the control (191.2 kPa vs. 192.4 kPa), and had been significantly higher than that in the sham group since day 7. SWE values and histologic scores were correlated (r = -0.792, p < 0.01). The average thickness decreased in the three groups but did not differ significantly. CONCLUSION: Two-dimensional ultrasound is beneficial to the diagnosis of Achilles tendinopathy. SWE could quantify changes in Achilles tendon stiffness non-invasively during LIPUS treatment, enabling the study of early Achilles tendon healing after LIPUS treatment.

Optimizing surgical outcomes for elderly gallstone patients with a high body mass index using enhanced recovery after surgery protocol.

BACKGROUND: Rehabilitation of elderly patients with a high body mass index (BMI) after cholecystectomy carries risks and requires the adoption of effective perioperative management strategies. The enhanced recovery after surgery (ERAS) protocol is a comprehensive treatment approach that facilitates early patient recovery and reduces postoperative complications. AIM: To compare the effectiveness of traditional perioperative management methods with the ERAS protocol in elderly patients with gallbladder stones and a high BMI. METHODS: This retrospective cohort study examined data from 198 elderly patients with a high BMI who underwent cholecystectomy at the Shanghai Fourth People's Hospital from August 2019 to August 2022. Among them, 99 patients were managed using the traditional perioperative care approach (non-ERAS protocol), while the remaining 99 patients were managed using the ERAS protocol. Relevant indicator data were collected for patients preoperatively, intraoperatively, and postoperatively, and surgical outcomes were compared between the two groups. RESULTS: The comparison results between the two groups of patients in terms of age, sex, BMI, underlying diseases, surgical type, and preoperative hospital stay showed no statistically significant differences. However, the ERAS group had a significantly shorter preoperative fasting time than the non-ERAS group (4.0 ± 0.9 h vs 7.6 ± 0.9 h). Regarding intraoperative indicators, there were no significant differences between the two groups of patients. However, in terms of postoperative recovery, the ERAS protocol group exhibited significant advantages over the non-ERAS group, including a shorter hospital stay, lower postoperative pain scores and postoperative hunger scores, and higher satisfaction levels. The readmission rate was lower in the ERAS protocol group than in the non-ERAS group (3.0% vs 8.1%), although the difference was not significant. Furthermore, there were significant differences between the two groups in terms of postoperative nausea and vomiting severity, postoperative abdominal distention at 24 h, and daily life ability scores. CONCLUSION: The findings of this study demonstrate that the ERAS protocol confers significant advantages in postoperative outcomes following cholecystectomy, including reduced readmission rates, decreased postoperative nausea and vomiting, alleviated abdominal distension, and enhanced functional capacity. While the protocol may not exhibit significant improvement in early postoperative symptoms, it does exhibit advantages in long-term postoperative symptoms and recovery. These findings underscore the importance of implementing the ERAS protocol in the postoperative management of cholecystectomy patients, as it contributes to improving patients' recovery and quality of life while reducing health care resource utilization.

Polarized macrophages regulate fibro/adipogenic progenitor (FAP) adipogenesis through exosomes.

BACKGROUND: Macrophage polarization has been observed in the process of muscle injuries including rotator cuff (RC) muscle atrophy and fatty infiltration after large tendon tears. In our previous study, we showed that fibrogenesis and white adipogenesis of muscle residential fibro/adipogenic progenitors (FAPs) cause fibrosis and fatty infiltration and that brown/beige adipogenesis of FAPs promotes rotator cuff muscle regeneration. However, how polarized macrophages and their exosomes regulate FAP differentiation remains unknown. METHODS: We cultured FAPs with M0, M1, and M2 macrophages or 2 × 109 exosomes derived from M0, M1 and M2 with and without GW4869, an exosome inhibitor. In vivo, M0, M1, and M2 macrophages were transplanted or purified macrophage exosomes (M0, M1, M2) were injected into supraspinatus muscle (SS) after massive tendon tears in mice (n = 6). SS were harvested at six weeks after surgery to evaluate the level of muscle atrophy and fatty infiltration. RESULTS: Our results showed that M2 rather than M0 or M1 macrophages stimulates brown/beige fat differentiation of FAPs. However, the effect of GW4869, the exosome inhibitor, diminished this effect. M2 exosomes also promoted FAP Beige differentiation in vitro. The transplantation of M2 macrophages reduced supraspinatus muscle atrophy and fatty infiltration. In vivo injections of M2 exosomes significantly reduced muscle atrophy and fatty infiltration in supraspinatus muscle. CONCLUSION: Results from our study demonstrated that polarized macrophages directly regulated FAP differentiation through their exosomes and M2 macrophage-derived exosomes may serve as a novel treatment option for RC muscle atrophy and fatty infiltration.

Prevention and treatment of rheumatoid arthritis through traditional Chinese medicine: role of the gut microbiota.

Recently, despite the increasing availability of treatments for Rheumatoid arthritis (RA), the incidence of RA and associated disability-adjusted life years have been on the rise globally in the late decades. At present, accumulating evidence has been advanced that RA is related to the gut microbiota, therefore, the therapeutic approaches for RA by regulating the gut microbiota are anticipated to become a new means of treatment. Traditional Chinese medicine (TCM) can regulate immunity, reduce inflammation and improve quality of life in various ways. Moreover, it can treat diseases by affecting the gut microbiota, which is a good way to treat RA. In this review, we mainly explore the relationship between TCM and gut microbiota regarding the perspective of treating RA. Moreover, we comprehensively summarize the roles of gut microbiota in the onset, development, progression, and prognosis of RA. Additionally, we elucidate the mechanism of TCM prevention and treatment of RA by the role of microbiota. Finally, we provide an evidence-based rationale for further investigation of microbiota-targeted intervention by TCM.