Spatial functional reorganizations can serve as potential biomarkers of post facial palsy synkinesis.

Facial palsy can result in a serious complication known as facial synkinesis, causing both physical and psychological harm to the patients. There is growing evidence that patients with facial synkinesis have brain abnormalities, but the brain mechanisms and underlying imaging biomarkers remain unclear. Here, we employed functional magnetic resonance imaging (fMRI) to investigate brain function in 31 unilateral post facial palsy synkinesis patients and 25 healthy controls during different facial expression movements and at rest. Combining surface-based mass-univariate analysis and multivariate pattern analysis, we identified diffused activation and intrinsic connection patterns in the primary motor cortex and the somatosensory cortex on the patient's affected side. Further, we classified post facial palsy synkinesis patients from healthy subjects with favorable accuracy using the support vector machine based on both task-related and resting-state functional magnetic resonance imaging data. Together, these findings indicate the potential of the identified functional reorganizations to serve as neuroimaging biomarkers for facial synkinesis diagnosis.

Paired Medicago receptors mediate broad-spectrum resistance to nodulation by Sinorhizobium meliloti carrying a species-specific gene.

Plants have evolved the ability to distinguish between symbiotic and pathogenic microbial signals. However, potentially cooperative plant-microbe interactions often abort due to incompatible signaling. The Nodulation Specificity 1 (NS1) locus in the legume Medicago truncatula blocks tissue invasion and root nodule induction by many strains of the nitrogen-fixing symbiont Sinorhizobium meliloti. Controlling this strain-specific nodulation blockade are two genes at the NS1 locus, designated NS1a and NS1b, which encode malectin-like leucine-rich repeat receptor kinases. Expression of NS1a and NS1b is induced upon inoculation by both compatible and incompatible Sinorhizobium strains and is dependent on host perception of bacterial nodulation (Nod) factors. Both presence/absence and sequence polymorphisms of the paired receptors contribute to the evolution and functional diversification of the NS1 locus. A bacterial gene, designated rns1, is required for activation of NS1-mediated nodulation restriction. rns1 encodes a type I-secreted protein and is present in approximately 50% of the nearly 250 sequenced S. meliloti strains but not found in over 60 sequenced strains from the closely related species Sinorhizobium medicae. S. meliloti strains lacking functional rns1 are able to evade NS1-mediated nodulation blockade.

fMRI, LFP, and anatomical evidence for hierarchical nociceptive routing pathway between somatosensory and insular cortices.

The directional organization of multiple nociceptive regions, particularly within obscure operculoinsular areas, underlying multidimensional pain processing remains elusive. This study aims to establish the fundamental organization between somatosensory and insular cortices in routing nociceptive information. By employing an integrated multimodal approach of high-field fMRI, intracranial electrophysiology, and transsynaptic viral tracing in rats, we observed a hierarchically organized connection of S1/S2 → posterior insula → anterior insula in routing nociceptive information. The directional nociceptive pathway determined by early fMRI responses was consistent with that examined by early evoked LFP, intrinsic effective connectivity, and anatomical projection, suggesting fMRI could provide a valuable facility to discern directional neural circuits in animals and humans non-invasively. Moreover, our knowledge of the nociceptive hierarchical organization of somatosensory and insular cortices and the interface role of the posterior insula may have implications for the development of targeted pain therapies.

Hydroxypropyl Cellulose-Based Orally Dissolving Film Loaded with Insoluble Dexamethasone for Treatment of Oral Ulcers.

Oral ulcers present as recurrent and spontaneous lesions, often causing intolerable burning pain that significantly disrupts patients' daily lives and compromises their quality of life. In addressing this clinical challenge, oral dissolving films (ODFs) have emerged as promising pharmaceutical formulations for oral ulcer management due to their rapid onset of action, ease of administration, and portability. In this study, ODFs containing the insoluble drug dexamethasone (Dex) were formulated for the treatment of oral ulcers in rabbits using a solvent casting method with ethanol as the solvent. To optimize the composition of the ODFs, a Box-Behnken Design (BBD) experiment was employed to investigate the effects of varying concentrations of hydroxypropyl cellulose (HPC), low-substituted hydroxypropyl cellulose (L-HPC), and plasticizer (glycerol) on key parameters, such as disintegration time, tensile strength, and peel-off efficiency of the films. Subsequently, the film properties of the Dex-loaded ODFs (ODF@Dex) were thoroughly assessed, revealing favorable attributes, including homogeneity, mechanical strength, and solubility. Notably, the use of ethanol as the solvent in the ODF preparation facilitated the homogeneous distribution of insoluble drugs within the film matrix, thereby enhancing their solubility and dissolution rate. Leveraging the potent pharmacological activity of Dex, ODF@Dex was further evaluated for its efficacy in promoting ulcer healing and mitigating the expression of inflammatory factors both in vitro and in vivo. The findings demonstrated that the ODF@Dex exerted significant antiulcer effects by modulating the PI3K/Akt signaling pathway, thus contributing to ulcer resolution. In conclusion, our study underscores the potential of HPC-based ODFs formulated with ethanol as a solvent as a promising platform for delivering insoluble drugs, offering a viable strategy for the clinical management of oral ulcers.

Melanin-Concentrating Hormone Is Associated With Delayed Neurocognitive Recovery in Older Adult Patients With Preoperative Sleep Disorders Undergoing Spinal Anesthesia.

BACKGROUND: Aging and preoperative sleep disorders are the main risk factors affecting postoperative cognitive outcomes. However, the pathogenesis of delayed neurocognitive recovery after surgery remains ambiguous, and there is still a lack of potential biomarkers for delayed neurocognitive recovery in older adult patients with preoperative sleep disorders. Our study aimed to explore the relationship between melanin-concentrating hormone (MCH) and delayed neurocognitive recovery early after surgery in older adult patients with preoperative sleep disorders. METHODS: In this monocentric prospective observational study, 156 older adult patients (aged 65 years or older) with preoperative sleep disorders undergoing elective total hip arthroplasty (THA) or total knee arthroplasty (TKA) were included at an academic medical center in Inner Mongolia, China, from October 2021 to November 2022, and all patients underwent spinal anesthesia. The Pittsburgh Sleep Quality Index (PSQI) was applied to assess the preoperative sleep quality of all patients, and preoperative sleep disorders were defined as a score of PSQI >5. We measured the levels of cerebrospinal fluid (CSF) MCH and plasma MCH of all patients. The primary outcome was delayed neurocognitive recovery early after surgery. All patients received cognitive function assessment through the Montreal Cognitive Assessment (MoCA) 1 day before and 7 days after surgery (postoperative day 7 [POD7]). Delayed neurocognitive recovery was defined as a score of POD7 MoCA <26. The potential confounders included variables with P < .2 in the univariate logistic analysis, as well as the important risk factors of delayed neurocognitive recovery reported in the literature. Multivariable logistic regression model based on the Enter method assessed the association of MCH and delayed neurocognitive recovery in older adult patients with preoperative sleep disorders. RESULTS: Fifty-nine (37.8%) older adult patients with preoperative sleep disorders experienced delayed neurocognitive recovery at POD7. Increase in CSF MCH levels (odds ratio [OR] for an increase of 1 pg/mL = 1.16, 95% confidence interval [CI], 1.09-1.23, P < .001) and decrease in plasma MCH levels (OR for an increase of 1 pg/mL = 0.92, 95% CI, 0.86-0.98, P = .003) were associated with delayed neurocognitive recovery, after adjusting for age, sex, education, baseline MoCA scores, American Society of Anesthesiologists (ASA) grade, and coronary heart disease (CHD). CONCLUSIONS: In older adult patients with preoperative sleep disorders, MCH is associated with the occurrence of delayed neurocognitive recovery after surgery. Preoperative testing of CSF MCH or plasma MCH may increase the likelihood of identifying the high-risk population for delayed neurocognitive recovery in older adult patients with preoperative sleep disorders.

Impact of Enhanced Emergency Nursing Processes on the Rescue Outcomes of Emergency Patients with Chest Pain.

Background: Chest pain, a sudden and perilous symptom, is frequently encountered in the emergency department. Prompt and efficient first-aid measures and nursing interventions are crucial for effectively rescuing emergency patients experiencing chest pain. Objective: This study aims to investigate the impact of an enhanced emergency nursing process on the rescue outcomes of emergency patients with chest pain. Design: A randomized controlled study was conducted. Setting: The research was conducted at Suzhou Hospital of Integrated Traditional Chinese and Western Medicine. Participants: A total of 90 emergency chest pain patients admitted between December 2021 and June 2022 were selected and divided into two groups, with 45 cases in each group. Interventions: The control group received routine emergency nursing, while the observation group underwent an improved emergency nursing protocol. Primary Outcome Measures: (1) Treatment initiation time, emergency rescue time, recovery time of vital signs, and hospital stay; (2) curative effect; (3) pain scores; (4) incidence of adverse events; and (5) patient satisfaction. Results: Compared to the control group, the observation group exhibited shorter treatment initiation time, emergency rescue time, recovery time of vital signs, and hospital stay (P < .05). The effective rate in the observation group was higher (P < .05), and pain scores were lower at 30 min, 60 min, 120 min, and 240 min post-rescue (P < .05). The occurrence of adverse events was reduced in the observation group (P = .005), and patient satisfaction was higher at discharge (P < .05). Conclusion: The enhanced emergency nursing process effectively reduces the clinical rescue time for emergency patients with chest pain, enhances rescue efficiency, seizes crucial opportunities for saving lives, and improves patient satisfaction. These findings have significant positive implications for clinical applications.

An iteratively reweighted steered response power approach to multisource localization using a distributed microphone network.

The steered response power (SRP) with phase transform algorithm has been demonstrated to be robust against reverberation and noise for single-source localization. However, when this algorithm is applied to multisource localization (MSL), the "peak missing problem" can occur, namely, that some sources dominate over others over short time intervals, resulting in fewer significant SRP peaks being found than the true number of sources. This problem makes it difficult to detect all the sources among the available SRP peaks. We propose an iteratively reweighted steered response power (IR-SRP) approach that effectively solves the "peak missing problem" and achieves robust MSL in reverberant noisy environments. The initial IR-SRP localization function is computed over the time-frequency (T-F) bins selected by a combination of two weighting schemes, one using coherence, and the other using signal-to-noise ratio. When iterating, our method finds the significant SRP peaks for the dominant sources and eliminates the T-F bins contributed by these sources using inter-channel phase difference information. As a result, the remaining sources can be found in subsequent iterations among the remaining T-F bins. The proposed IR-SRP method is demonstrated using both simulated and measured experiment data.

Increased expression of Nav1.6 of reactive astrocytes in the globus pallidus is closely associated with motor deficits in a model of Parkinson's disease.

Parkinson's disease (PD) is a common neurodegenerative disease in elderly people, which is characterized by motor disabilities in PD patients. Nav1.6 is the most abundant subtype of voltage-gated sodium channels (VGSCs) in the brain of adult mammals and rodents. Here we investigated the role of Nav1.6 in the external globus pallidus (GP) involved in the pathogenesis of motor deficits in unilateral 6-OHDA(6-hydroxydopamine)lesioned rats. The results show that Nav1.6 is dramatically increased in reactive astrocytes of the ipsilateral GP in the middle stage, but not different from the control rats in the later stage of the pathological process in 6-OHDA lesioned rats. Furthermore, the down-regulation of Nav1.6 expression in the ipsilateral GP can significantly improve motor deficits in 6-OHDA lesioned rats in the middle stage of the pathological process. The electrophysiological experiments show that the down-regulation of Nav1.6 expression in the ipsilateral GP significantly decreases the abnormal high synchronization between the ipsilateral M1 (the primary motor cortex) and GP in 6-OHDA lesioned rats. Ca2+ imaging reveals that the down-regulation of Nav1.6 expression reduces the intracellular concentration of Ca2+ ([Ca2+ ]i) in primary cultured astrocytes. These findings suggest that the increased Nav1.6 expression of reactive astrocytes in the GP play an important role in the pathogenesis of motor dysfunction in the middle stage in 6-OHDA lesioned rats, which may participate in astrocyte-neuron communication by regulating [Ca2+ ]i of astrocytes, thereby contributing to the formation of abnormal electrical signals of the basal ganglia (BG) in 6-OHDA lesioned rats.

Smart Ratiometric SERS Nanoprobe for Real-Time Monitoring Hydrogen Peroxide in Living Cells during NADH Treatment Associated with Ferroptosis.

Studying the oxidative stress, especially the reactive oxygen species (ROS) response of ferroptosis, is crucial for the diagnosis and treatment of cancer based on ferroptosis. However, reliable quantitative analysis of intracellular ROS in cancer treatment for drug screening is still a challenge. Herein, a superior ratiometric SERS nanoprobe was developed for in situ, real-time, and highly sensitive detection of content variation of H2O2 within living cells. The SERS nanoprobe was prepared by coassembly of the internal standard molecule p-mercaptobenzonitrile and the reporter molecule p-mercaptophenylboronic acid on the surface of gold nanoparticles, used for synergistic calibration and detection of H2O2, which enables reliable detection of the true content of intracellular H2O2 without the interference of other substances in cells. Based on the nanoprobe, we found that the level of intracellular H2O2 of cancer cells was increased after the nicotinamide adenine dinucleotide (NADH) treatment, with a dose-dependence to the concentration of NADH. High doses of NADH (above 20 mM) can induce cell death by means of ferroptosis associated with the level elevation of intracellular lipid hydroperoxides. This study highlights the potential of the SERS nanoprobe for tracking content variation of cellular H2O2 and understanding its roles in screening new anticancer drugs.

Strong antibunching effect under the combination of conventional and unconventional photon blockade.

Photon blockade (PB), an effective method of generating antibunching effect, is a critical way to construct a single photon source. The PB effect can be divided into conventional PB effect (CPB) and unconventional PB effect (UPB). Most studies focus on designing systems to successfully enhance CPB or UPB effect individually. However, CPB extremely depends on the nonlinearity strength of the Kerr materials to achieve strong antibunching effect while UPB relies on quantum interference beset with the high probability of the vacuum state. Here, we propose a method to utilize the relevance and complementarity of CPB and UPB to realize these two types simultaneously. We employ a hybrid Kerr nonlinearity two-cavity system. Because of the mutual assistance of two cavities, CPB and UPB can coexist in the system under certain states. In this way, for the same Kerr material, we reduce the value of the second-order correlation function due to CPB by three orders of magnitude without losing the mean photon number due to the presence of UPB, so the advantages of both PB effects are fully reflected in our system, which is a huge performance boost for single photons.

Polyaspartic Acid-Stabilized CaCO3-Containing In Situ Hydrogel for Protection and Treatment of Gastric Ulcer.

The lack of effective oral drug delivery systems to treat gastric ulcer is an urgent challenge in clinical practice. Herein, a gastric acid pH-responsive hydrogel of curcumin/sodium alginate/polyaspartic acid@CaCO3 (Cur/SA/PC) was developed for sustained release of Cur, exerting effective protection and treatment of gastric ulcers. The in vitro gelatinization properties and the corresponding gel characteristics of the SA/PC delivery system demonstrated the successful construction of the in situ hydrogel with uniform strength. The cellular uptake illustrated the successful uptake and sustained release of Cur. Besides, Cur effectively inhibited NLRP3-mediated pyroptosis both in vitro and in vivo, exhibited an excellent pro-healing effect by regulating the PI3K/Akt signaling pathway, and alleviated acetic acid-induced chronic gastric injury in rats. Moreover, the relative bioavailability of Cur in the SA/PC hydrogel could effectively increase in the pharmacokinetic study. Importantly, the protective barrier formed by the SA/PC hydrogel could effectively protect against alcohol-induced acute gastric ulcers in rats. Overall, the designed SA/PC oral delivery system is a promising strategy to overcome gastric barriers for oral drug delivery.

Targeting ATP Synthase by Bedaquiline as a Therapeutic Strategy to Sensitize Ovarian Cancer to Cisplatin.

Cisplatin is a common chemotherapeutic drug for treating ovarian cancer, but its clinical efficacy is hampered by intrinsic and acquired resistance. Previous studies had shown inhibiting oxidative phosphorylation overcomes cisplatin resistance in ovarian cancer. Studies reveal that bedaquiline, a clinically available antimicrobial drug, inhibits cancer via targeting mitochondria. This study systematically assessed the efficacy of bedaquiline in ovarian cancer and its underlying mechanism. Using a panel of ovarian cancer cell lines and normal ovary cells, we demonstrated bedaquiline is selective for anti-ovarian cancer activities. Furthermore, the sensitivity varied among different ovarian cancer cell lines regardless of their sensitivity to cisplatin. Bedaquiline inhibited growth, survival and migration, through decreasing levels of ATP synthase subunit, complex V activity, mitochondrial respiration and ATP. We further found that ovarian cancer displayed increased levels of ATP, oxygen consumption rate (OCR), complex V activity and ATP synthase subunits compared to normal counterpart. Combination index analysis showed that bedaquiline and cisplatin is synergistic. Bedaquiline remarkably enhanced the efficacy of cisplatin in inhibiting ovarian cancer growth in mice. Our study provides evidence to repurpose bedaquiline for ovarian cancer treatment and suggests that ATP synthase is a selective target to overcome cisplatin resistance in ovarian cancer.

[Nomographic Model for Predicting Severe Foot Pain in Nurses from Tertiary Hospitals in China].

Objective: To investigate the prevalence and common sites of severe foot pain among nurses, to define the risk factors of severe foot pain in nurses in tertiary hospital in China, and to construct a nomograph model for predicting individuals' risks for severe foot pain. Methods: Between August 2019 and December 2019, a stratified global sampling method was used to select 10691 nurses from 351 tertiary hospitals in China to investigate the incidence of severe foot pain among them. The variables that may affect the occurrence of severe foot pain were analyzed by single factor analysis to identify the influencing factors of severe foot pain in nurses. Furthermore, the independent risk factors of severe foot pain were analyzed by stepwise logistic regression analysis. The statistically significant factors identified in the multivariate regression analysis were incorporated into the nomograph prediction model. The predictive performance of the nomograph was measured by the consistency index (C-index) and calibrated with 1000 Bootstrap samples. Results: A total of 3419 nurses out of the 10691 had foot pain, resulting in an incidence of 31.98%. The incidence of severe pain (VAS score 7-10) was 2.27% (243 of 10691). The locations of severe pain were more commonly found in the soles and heels of both feet. Six factors, including age, education, the material of the work shoes, comfortableness of the work shoes, number of complications, and foot injure history, were incorporated in the nomograph predicting model. The C-index value was 0.706 and the standard curve fitted well with the calibrated prediction curve. Conclusion: The risk prediction model constructed in this study showed sound performance in predicting the risk of severe foot pain in nurses, and all the indicators involved are simple and the relevant data are easily obtained. The model can provide reference for preventing severe foot pain in nurses.

Sequential Dual Delivery System Based on siCOX-2-Loaded Gold Nanostar and Thermal-Sensitive Liposomes Overcome Hypoxia-Mediated Multidrug Resistance in Tumors.

Reversing hypoxia-mediated multidrug resistance (MDR) presents a unique challenge in clinical chemotherapy. Here, a sequential dual delivery system composited with Cyclooxygenase-2 siRNA (siCOX-2) in poly-d-arginine (9R)/2-deoxyglucose (DG)-loaded gold nanostar (GNS) (siCOX-2@RDG) and paclitaxel (PTX)-loaded thermosensitive liposome (PTSL) was proposed to conquer the hypoxia-mediated MDR in tumors. As a result, the prepared siCOX-2@RDG exhibited a starlike morphology with a uniform particle size of 194.36 ± 1.44 nm and a ζ-potential of -11.83 ± 2.01 mV. In vitro, PTSL displayed expected thermal-responsive release properties. As expected, siCOX-2@RDG displayed exceptional DG-mediated hypoxia-targeting capability both in vitro and in vivo and downregulated the expression of COX-2 successfully. Meanwhile, GNS-triggered hyperthermia elevated the cellular uptake of PTSL in PTX-resistant HepG2(HepG2/PTX) cells in vitro and enhanced the permeability of tumor tissues, thus elevating the valid retention of PTX into solid tumors. Finally, we demonstrated that the sequential dual systems composed of siCOX-2@RDG and PTSL could reverse hypoxia-mediated MDR and exhibit excellent synergistic antitumor effects both in vitro and in vivo, prolonging the survival of tumor-bearing mice. The devised sequential dual systems, composed of two independent nanosystems, have a promising potential to overcome hypoxia-mediated MDR in clinical practice.

A SERS and fluorescence dual-channel microfluidic droplet platform for exploring telomerase activity at the single-cell level.

Telomerase is a significant biomarker for potential early cancer diagnosis and therapy. Exploring telomerase activity in single cells presents great challenges due to the complexity and small amount of total proteins in telomerase as well as the lack of an effective amplification method for its analysis. Herein, we developed a surface-enhanced Raman spectroscopy (SERS) and fluorescence dual-channel microfluidic droplet platform for the in situ and highly sensitive determination of low-abundance telomerase activity in single cells. In this work, the nanoprobe is composed of gold nanoparticles (AuNPs) functionalized by a telomerase primer and signal sequence (a Cy5-labeled DNA strand). The dual-signal switching of the SERS turn-off and fluorescence turn-on mechanisms for the Cy5 response to telomerase allows for the highly sensitive and reliable determination of telomerase at the single-cell level. As a result, the SERS-fluorescence microdroplet platform exhibits an excellent performance for the efficient investigation of cell heterogeneity upon telomerase expression and the dynamic monitoring of variations in intracellular telomerase activity during treatment with a telomerase inhibitor. The proposed platform will help to decipher the heterogeneity of cell populations and is potentially applicable in the clinical diagnosis of diseases related to telomerase activity.

Aronia melanocarpa polysaccharide ameliorates liver fibrosis through TGF-ß1-mediated the activation of PI3K/AKT pathway and modulating gut microbiota.

The purpose of this experiment was to investigate the anti-hepatic fibrosis effect of Aronia melanocarpa polysaccharide (AMP) on TAA-induced liver fibrosis mice and its mechanism, as well as the changes in intestinal flora in vivo. This was established with a dose of 200 mg/kg TAA (i.p) once every three days, lasting for eight weeks. Colchicine with 0.4 mg/kg, and AMP (200 and 400 mg/kg) were given by intragastric administration (i.g) after 28 days of intraperitoneal injection of TAA. AMP treatment significantly inhibited the activities of liver injury markers ALT and AST in serum. Histopathological staining demonstrated that AMP significantly reversed TAA-induced hepatocyte necrosis and collagen deposition. In addition, AMP treatment block TGF- ß1/Smads pathway inhibited the production of ECM and alleviates liver fibrosis. Furthermore, AMP treatment enhanced the phosphorylation of PI3K/AKT and decreased the expression of its downstream apoptosis-related proteins in liver, thus effectively alleviating TAA-induced liver fibrosis. In addition, 16S rDNA gene sequencing analysis showed that AMP treatment helped restore the imbalanced ecosystem of gut microbes, increased the proportion of Bacteroidetes and Proteobacteria, and increased species richness. Above findings clearly show that AMP is an effective method for treating liver fibrosis, possibly by improving the gut microbiota.

Multiplexed lateral flow assay integrated with orthogonal CRISPR-Cas system for SARS-CoV-2 detection.

The development of field-deployable detection platform amenable for multiplexed genes testing will significantly improve the efficiency and reliability during point-of-care testing (POCT) applications. In this regard, an orthogonal CRISPR-Cas-mediated multiplexed lateral flow assay (designated as OC-MLFA) is proposed for SARS-CoV-2 genome detection. Taking the advantage of activation and cleavage preferences between Cas12a and Cas13a, orthogonal (two-independent-channel signal readout) CRISPR-Cas system is investigated. Lateral flow strips with two target lines are designed to accommodate the orthogonal CRISPR system. The interference between Cas12a and Cas13a channels can be effectively eliminated via the elaborate nucleic acids and lateral flow strips design. The high preamplification efficiency from reverse transcription recombinase polymerase amplification (RT-RPA) and Cas enzyme mediated trans-cleavage process bring the sensitivity of our OC-MLFA method to 10 copies per test (30 µL). Nasopharyngeal swab clinical samples with different cycle threshold (Ct) values according to the RT-PCR method were analyzed with the proposed OC-MLFA, during which 76 out of 76 detection accuracy was obtained. Featured with the multiplexed genes detection simultaneously in one reaction and colorimetric readout through single strip, the OC-MLFA we proposed herein ensures great accuracy and efficiency, which endows promising field-deployable POCT application feasibility.

Docetaxel-loaded M1 macrophage-derived exosomes for a safe and efficient chemoimmunotherapy of breast cancer.

The conversion of tumor-promoting M2 macrophage phenotype to tumor-suppressing M1 macrophages is a promising therapeutic approach for cancer treatment. However, the tumor normally provides an abundance of M2 macrophage stimuli, which creates an M2 macrophage-dominant immunosuppressive microenvironment. In our study, docetaxel (DTX) as chemotherapeutic modularity was loaded into M1 macrophage-derived exosomes (M1-Exo) with M1 proinflammatory nature to establish DTX-M1-Exo drug delivery system. We found that DTX-M1-Exo induced naïve M0 macrophages to polarize to M1 phenotype, while failed to repolarize to M2 macrophages upon Interleukin 4 restimulation due to impaired mitochondrial function. This suggests that DTX-M1-Exo can achieve long-term robust M1 activation in immunosuppressive tumor microenvironment. The in vivo results further confirmed that DTX-M1-Exo has a beneficial effect on macrophage infiltration and activation in the tumor tissues. Thus, DTX-M1-Exo is a novel macrophage polarization strategy via combined chemotherapy and immunotherapy to achieve great antitumor therapeutic efficacy.

Citri Reticulatae Pericarpium alleviates postmyocardial infarction heart failure by upregulating PPARγ expression.

Heart failure after myocardial infarction (MI) is the leading cause of death worldwide. Citri Reticulatae Pericarpium (CRP) is a traditional Chinese herbal medicine that has been used in the clinic for centuries. In this study, we aimed to investigate the roles of CRP in cardiac remodelling and heart failure after MI, as well as the molecular mechanisms involved. Male C57BL/6 mice aged 8 weeks were subjected to coronary artery ligation to mimic the clinical situation in vivo. Echocardiography was used to assess the systolic function of the mouse heart. Masson trichrome staining and Wheat germ agglutinin (WGA) staining were utilised to determine the fibrotic area and cross-sectional area of the mouse heart, respectively. Cardiomyocytes and fibroblasts were isolated from neonatal rats aged 0-3 days in vitro using enzyme digestion. TUNEL staining and EdU staining were performed to evaluate apoptosis and proliferation, respectively. Gene expression changes were analysed by qRT-PCR, and protein expression changes were assessed by Western blotting. Our findings revealed that CRP attenuated cardiac hypertrophy, fibrosis and apoptosis and alleviated heart failure after MI in vivo. Furthermore, CRP mitigated cardiomyocyte apoptosis and fibroblast proliferation and differentiation into myofibroblasts. In addition, the PPARγ inhibitor T0070907 completely abolished the abovementioned beneficial effects of CRP, and the PPARγ activator rosiglitazone failed to further ameliorate cardiac apoptosis and fibrosis in vitro. CRP alleviates cardiac hypertrophy, fibrosis, and apoptosis and can ameliorate heart failure after MI via activation of PPARγ.

Does a beautiful environment make food better - The effect of environmental aesthetics on food perception and eating intention.

Generally, people prefer to dine in beautiful environments. Previous studies have reported that environmental factors affect an individual's perception of food; however, little is known about the effect of environmental aesthetics on food perception. In Experiment 1, we used photographs of restaurant (1a) or non-restaurant (1b) environments with high or low aesthetic value, paired with images of foods, and participants were asked to rate the visual, olfactory, and gustatory aesthetic value of the food. Results showed significantly higher ratings for food perception in all three sensory modalities in the high aesthetic value environment, together with positive emotion and the desire to eat, compared with the low aesthetic environment. Experiment 2 extended the study to two real-world environments (one high and one low aesthetic value) and actual food consumption. The results also found higher aesthetic ratings in the olfactory and gustatory systems and greater desire to eat again in an environment with high aesthetic value than in an environment with low aesthetic value. This research also explored the mediating role of emotion in the relationship between environmental aesthetics and food perception and found a significant mediating relationship. In conclusion, environmental aesthetics play an important role in food perception, and these findings provide insights into increasing positive food perception in daily life.