One case of spinal bulbar muscular atrophy misdiagnosed as polymyositis: Case report.

RATIONALE: Spinal bulbar muscular atrophy (SBMA) is a rare X-linked recessive motor neuron degenerative disease. Due to the lack of specificity in its early clinical manifestations, SBMA is easily misdiagnosed. Herein, we present a case in which SBMA was misdiagnosed as polymyositis. PATIENT CONCERNS: A 58-year-old patient began to develop symptoms of limb weakness 20 years ago and was admitted to the Second Hospital of Hebei Medical University 10 years ago without special treatment. Two years ago, the above symptoms worsened and he was admitted to Peking Union Medical College Hospital. The patient was misdiagnosed as polymyositis. According to the gene mutation characteristics of SBMA, the patient was diagnosed with SBMA. DIAGNOSES: The result of the Kennedy gene test was positive, and the patient was diagnosed with Kennedy disease. INTERVENTIONS: After the diagnosis of SBMA, the patient was given symptomatic treatment to alleviate the condition. OUTCOMES: Conservative treatment after discharge was requested. It is recommended that patients avoid bucking to prevent complications. LESSONS: This is a case of milder SBMA being misdiagnosed as polymyositis. For patients with weak limbs, the possibility of SBMA should be considered.

Screening of potentially active compounds against rheumatoid arthritis in the Juan-Bi decoction using systems pharmacology and animal experiments.

Background: The Juan-Bi decoction (JBD) is a classic traditional Chinese medicines (TCMs) prescription for the treatment of rheumatoid arthritis (RA). However, the active compounds of the JBD in RA treatment remain unclear. Aim: The aim of this study is to screen effective compounds in the JBD for RA treatment using systems pharmacology and experimental approaches. Method: Botanical drugs and compounds in the JBD were acquired from multiple public TCM databases. All compounds were initially screened using absorption, distribution, metabolism, excretion, and toxicity (ADMET) and physicochemical properties, and then a target prediction was performed. RA pathological genes were acquired from the DisGeNet database. Potential active compounds were screened by constructing a compound-target-pathogenic gene (C-T-P) network and calculating the cumulative interaction intensity of the compounds on pathogenic genes. The effectiveness of the compounds was verified using lipopolysaccharide (LPS)-induced RAW.264.7 cells and collagen-induced arthritis (CIA) mouse models. Results: We screened 15 potentially active compounds in the JBD for RA treatment. These compounds primarily act on multiple metabolic pathways, immune pathways, and signaling transduction pathways. Furthermore, in vivo and in vitro experiments showed that bornyl acetate (BAC) alleviated joint damage, and inflammatory cells infiltrated and facilitated a smooth cartilage surface via the suppression of the steroid hormone biosynthesis. Conclusion: We screened potential compounds in the JBD for the treatment of RA using systems pharmacology approaches. In particular, BAC had an anti-rheumatic effect, and future studies are required to elucidate the underlying mechanisms.

Solar-driven water evaporation using a collaborative photothermal conversion material system based on carbonized waste polyphenylene sulfide and copper sulfide.

Recently, water resources have become scarce due to the growing global population and human impact on the environment, coupled with the effects of climate change. For solving the problem of global freshwater shortage and increasing the value of discarded polyphenylene sulfide (PPS) filter bags, in this study, balsa wood was used as the base of a photothermal solar evaporator, chitosan solution was used as the binder, and the main photothermal conversion materials used were polyphenylene sulfide (CP) carbide and copper sulfide. In order to create synergistic photothermal conversion materials, freeze-drying and in situ precipitation were used to deposit the photothermal conversion materials on top of the balsa wood. The prepared CP/CuS-wood evaporator has excellent water evaporation performance and light conversion capability, with a water evaporation rate of 2.68 kg m-2 h-1 and a photothermal conversion efficiency of 93.2% under simulated one solar intensity irradiation. In addition, the evaporator can effectively remove organic dyes such as methylene blue and methyl orange. The evaporator's durability and seawater desalination capability have also been confirmed through seawater desalination experiments and outdoor tests. Studies have shown that solar interface photothermal evaporators are a viable solution for desalination and wastewater treatment. This eco-friendly, economically viable and stable photothermal evaporator mentioned in this paper has pioneering features and will be a new paradigm for desalination and wastewater treatment.

Efficacy of multicomponent interventions on injury risk among ice and snow sports participants-a systematic review and meta-analysis.

BACKGROUND: Ice and snow sports, which are inherently high risk due to their physically demanding nature, pose significant challenges in terms of participant safety. These activities increase the likelihood of injuries, largely due to reduced bodily agility and responsiveness in cold, often unpredictable winter environments. The critical need for effective injury prevention in these sports is emphasized by the considerable impact injuries have on the health of participants, alongside the economic and social costs associated with medical and rehabilitative care. In the context of ice and snow sports environments, applying the E principles of injury prevention to evaluate intervention measures can guide the implementation of future sports safety and other health promotion intervention measures in this field. When well executed, this approach can substantially reduce both the frequency and severity of injuries, thereby significantly enhancing the safety and long-term viability of these challenging sports. OBJECTIVE: The objective of this study was to rigorously assess and statistically substantiate the efficacy of diverse injury prevention strategies in ice and snow sports, aiming to bolster future safety measures with solid empirical evidence. DESIGN: Systematic review and meta-analysis. METHODS: The overarching aim of this research was to meticulously aggregate and scrutinize a broad spectrum of scholarly literature, focusing on the quantifiable efficacy of diverse, multicomponent intervention strategies in mitigating the incidence of injuries within the realm of ice and snow sports. This endeavour entailed an exhaustive extraction of data from esteemed academic databases, encompassing publications up to September 30, 2023. In pursuit of methodological excellence and analytical rigor, the study employed advanced bias assessment methodologies, notably the AMSTAR 2 and GRADE approaches, alongside sophisticated random-effects statistical modelling. This comprehensive approach was designed to ensure the utmost validity, reliability, and scholarly integrity of the study's findings. RESULTS: Fifteen papers, including 9 randomized controlled trials, 3 case‒control studies, and 3 cohort studies with 26,123 participants and 4,382 injuries, were analysed. The findings showed a significant reduction in injury rates through various interventions: overall injury prevention (RR = 0.50, 95% CI 0.42-0.63), educational training (RR = 0.50, 95% CI 0.34-0.73), educational videos (RR = 0.53, 95% CI 0.34-0.81), protective equipment (RR = 0.64, 95% CI 0.46-0.87), and policy changes (RR = 0.28, 95% CI 0.16-0.49). Subgroup analysis revealed potential heterogeneity in compliance (p = 0.347). Compared to controls, multicomponent interventions effectively reduced injury rates. CONCLUSION: This systematic review and meta-analysis demonstrated that multicomponent interventions significantly prevent injuries in ice and snow sports. By applying the E principles of injury prevention and constructing a framework for practical injury prevention research in ice and snow sports, we can gradually shift towards a systemic paradigm for a better understanding of the development and prevention of sports injuries. Moreover, sports injury prevention is a complex and dynamic process. Therefore, high-quality experiments in different scenarios are needed in future research to provide more reliable evidence, offer valuable and relevant prevention information for practitioners and participants, and help formulate more effective preventive measures in practice.

Adaptation to an acid microenvironment promotes pancreatic cancer organoid growth and drug resistance.

Harsh environments in poorly perfused tumor regions may select for traits driving cancer aggressiveness. Here, we investigated whether tumor acidosis interacts with driver mutations to exacerbate cancer hallmarks. We adapted mouse organoids from normal pancreatic duct (mN10) and early pancreatic cancer (mP4, KRAS-G12D mutation, ± p53 knockout) from extracellular pH 7.4 to 6.7, representing acidic niches. Viability was increased by acid adaptation, a pattern most apparent in wild-type (WT) p53 organoids, and exacerbated upon return to pH 7.4. This led to increased survival of acid-adapted organoids treated with gemcitabine and/or erlotinib, and, in WT p53 organoids, acid-induced attenuation of drug effects. New genetic variants became dominant during adaptation, yet they were unlikely to be its main drivers. Transcriptional changes induced by acid and drug adaptation differed overall, but acid adaptation increased the expression of gemcitabine resistance genes. Thus, adaptation to acidosis increases cancer cell viability after chemotherapy.

Real-Time Monitoring of Tyrosine Hydroxylase Activity with a Ratiometric Fluorescent Probe.

Parkinson's disease (PD) represents the second most widespread neurodegenerative disease, and early monitoring and diagnosis are urgent at present. Tyrosine hydroxylase (TH) is a key enzyme for producing dopamine, the levels of which can serve as an indicator for assessing the severity and progression of PD. This renders the specific detection and visualization of TH a strategically vital way to meet the above demands. However, a fluorescent probe for TH monitoring is still missing. Herein, three rationally designed wash-free ratiometric fluorescent probes were proposed. Among them, TH-1 exhibited ideal photophysical properties and specific dual-channel bioimaging of TH activity in SH-SY5Y nerve cells. Moreover, the probe allowed for in vivo imaging of TH activity in zebrafish brain and living striatal slices of mice. Overall, the ratiometric fluorescent probe TH-1 could serve as a potential tool for real-time monitoring of PD in complex biosystems.

Study of ultraviolet light emitting diodes with InGaN quantum dots and lattice matched superlattice electron blocking layers.

Ultraviolet light emitting diodes (UV-LEDs) face the challenges including insufficient hole injection and severe electron leakage. Quantum dots (QDs) have been proven to provide three-dimensionally localized states for carriers, thereby enhancing carrier confinement. Therefore, UV-LEDs employing InGaN QDs are designed and studied in this paper. The APSYs software is used to simulate UV-LEDs. Simulation results indicate that the QDs effectively improve the electron and hole concentration in the active region. However, UV-LEDs with QDs experience efficiency droop due to serious electron leakage. What's more, the lattice mismatch between last quantum barrier (LQB) and electron blocking layer (EBL) leads to the polarization field, which induces the downward band bending at the LQB/EBL interface and reduces effective barrier height of EBL for electrons. The AlInGaN/AlInGaN lattice matched superlattice (LMSL) EBL is designed to suppress electron leakage while mitigating lattice mismatch between LQB and EBL. The results indicate that the utilization of QDs and LMSL EBL contributes to increasing the electron and hole concentration in the active region, reducing electron leakage, enhancing radiative recombination rate, and reducing turn-on voltage. The efficiency droop caused by electron leakage is mitigated. When the injection current is 120 mA, the external quantum efficiency is increased to 9.3% and the output power is increased to 38.3 mW. This paper provides a valuable reference for addressing the challenges of insufficient hole injection and severe electron leakage.

Spontaneous Skyrmion Bubbles in an Iron-Silicon Alloy with Uniaxial Magnetic Anisotropy.

The magnetic skyrmions exhibit intriguing topological behaviors, holding promise for future applications in the realm of spintronic devices. Despite recent advancements, achieving spontaneous magnetic skyrmions and topological transitions in magnets featuring uniaxial magnetic anisotropy, particularly at elevated temperatures (>100 K), remains a challenging endeavor. Here, single-crystal Fe5Si3 nanorods with the central symmetry and uniaxial magnetic anisotropy were successfully synthesized on a mica substrate through chemical vapor deposition, which exhibit a high Curie temperature (TC) of about 372 K. The real-time observation, facilitated by Lorentz transmission electron microscopy, revealed the spontaneous formation of magnetic skyrmions and evolution of domains in focused ion beam-prepared Fe5Si3 thin foils. Moreover, Fe5Si3 device transport measurements expose notable magnetoresistance (MR) effects, enabling the interchange between positive and negative MR across specific temperature settings. These results offer various potential avenues for exploring diverse topological spin textures and their formation mechanisms, indicating inventive applications for iron-silicon alloy in the realm of spintronics.

Lactate-Induced CCL8 in Tumor-Associated Macrophages Accelerates the Progression of Colorectal Cancer through the CCL8/CCR5/mTORC1 Axis.

Tumor-associated macrophages (TAMs) play a pivotal role in shaping the tumor microenvironment. Lactic acid (LA) has been identified as an influential factor in promoting immune escape and tumor progression. However, the mechanisms through which LA modulates TAMs in colorectal cancer (CRC) remain poorly understood. We used qRT-PCR to quantify the expression of LA-related genes (LDHA and LAMP2) in CRC tumor tissues and adjacent nontumor tissues (n = 64). The biological effects and mechanisms of LA on macrophages and tumors were evaluated via qRT-PCR, Western blot, RNA-seq, wound healing assay, colony formation assay in vitro, and allograft mouse tumor models in vivo. We found the expression of LDHA and LAMP2 was highly elevated in the tumor regions and positively associated with a poor clinical stage of CRC. A high concentration of LA was generated under hypoxia; it could promote tumor progression and metastasis with the involvement of macrophages. The inhibition of LA release impaired this protumor phenomenon. Mechanically, LA induced M2 macrophages through the AKT/ERK signaling pathway; subsequently, M2 macrophages secreted CCL8 and facilitated the proliferation and metastasis of CRC cells by activating the CCL8/CCR5/mTORC1 axis. This effect was inhibited by the antagonist or knockdown of CCR5. In conclusion, lactate-induced CCL8 in TAMs accelerated CRC proliferation and metastasis through the CCL8/CCR5/mTORC1 axis.

Lactate receptor GPR81 drives breast cancer growth and invasiveness through regulation of ECM properties and Notch ligand DLL4.

BACKGROUND: The lactate receptor GPR81 contributes to cancer development through unclear mechanisms. Here, we investigate the roles of GPR81 in three-dimensional (3D) and in vivo growth of breast cancer cells and study the molecular mechanisms involved. METHODS: GPR81 was stably knocked down (KD) in MCF-7 human breast cancer cells which were subjected to RNA-seq analysis, 3D growth, in situ- and immunofluorescence analyses, and cell viability- and motility assays, combined with KD of key GPR81-regulated genes. Key findings were additionally studied in other breast cancer cell lines and in mammary epithelial cells. RESULTS: GPR81 was upregulated in multiple human cancer types and further upregulated by extracellular lactate and 3D growth in breast cancer spheroids. GPR81 KD increased spheroid necrosis, reduced invasion and in vivo tumor growth, and altered expression of genes related to GO/KEGG terms extracellular matrix, cell adhesion, and Notch signaling. Single cell in situ analysis of MCF-7 cells revealed that several GPR81-regulated genes were upregulated in the same cell clusters. Notch signaling, particularly the Notch ligand Delta-like-4 (DLL4), was strikingly downregulated upon GPR81 KD, and DLL4 KD elicited spheroid necrosis and inhibited invasion in a manner similar to GPR81 KD. CONCLUSIONS: GPR81 supports breast cancer aggressiveness, and in MCF-7 cells, this occurs at least in part via DLL4. Our findings reveal a new GPR81-driven mechanism in breast cancer and substantiate GPR81 as a promising treatment target.

Attentional suppression of weight-related distractors among females with weight dissatisfaction.

Although many studies have investigated attentional biases toward weight-related information among individuals with weight dissatisfaction, the mechanisms underlying the processing of task-irrelevant and spatial-irrelevant weight-related information as distractors remain unclear. Participants were assigned to groups according to their levels of weight dissatisfaction to address this question. Participants with high weight dissatisfaction (HWD) were assigned to the experimental group; those with low weight dissatisfaction (LWD) were assigned to a control group. By recording event-related potentials during a visual search task along the median vertical line, fatness-related/thinness-related/neutral words and scrambled strokes were presented horizontally in pairs as task-irrelevant distractors. The results showed that intact words facilitated fast attentional orienting compared to scrambled strokes, as revealed by the significant N2pc for all types of intact words for both the HWD and LWD groups. More importantly, only fatness- and thinness-related words elicited the evident PD in the HWD group, and the PD amplitudes were larger in the HWD group compared to the LWD group. These findings suggest that weight-related distractors were actively suppressed after initial attentional orienting among females with HWD. This reveals the mechanisms of attentional biases toward weight-related information among females with HWD and contributes to the model of the cognitive-behavioral theory of body image disturbance. These results may help enhance prevention and interventions for reducing weight dissatisfaction.

Attentional biases toward auditory weight-related information among females with weight dissatisfaction.

Although there is substantial evidence of visual attentional biases in processing weight-related information among individuals with weight dissatisfaction, few studies have examined auditory attentional biases in these individuals. The identification of attentional biases may provide an impetus for interventions to reduce distress, negative body image, and pathological eating patterns among weight-dissatisfied individuals. Therefore, the present study aimed to investigate the attentional biases, as well as the neural consequences, toward auditory weight-related information among weight-dissatisfied young females. In this experiment, young female participants were assigned to an experimental group with high weight dissatisfaction (HWD) and a control group with low weight dissatisfaction (LWD) according to the levels of weight dissatisfaction. Using a spatial cueing paradigm, auditory fatness-related, thinness-related, and neutral household words were presented laterally as cue stimuli, followed by visual stimuli presented at either the cued or uncued location. The results revealed that auditory fatness-related words elicited significantly larger N2ac amplitudes than auditory thinness-related and neutral words in the HWD group. However, for the LWD group, thinness-related words elicited a significantly larger N2ac than fatness-related and neutral words. These results suggest an orienting attentional bias toward auditory fatness-related body words among females with HWD and an orienting attentional bias toward auditory thinness-related words among females with LWD.

ANXA2 as a novel substrate of FBXW7 promoting esophageal squamous cell carcinoma via ERK phosphorylation.

Our recent study suggests that FBXW7 loss of function plays a critical function in esophageal cancer. However, the mechanism of FBXW7 in promoting esophageal cancer is still unclear. Here, we explored the interaction protein of FBXW7 by screening of GST-pulldown and LC-MS/MS analysis in esophageal squamous cell carcinoma (ESCC) and identified ANXA2 as a potential target of FBXW7. FBXW7 loss of function could restore the expression of ANXA2 and promote the malignant biological characteristics of ESCC cells in vitro. Up-regulation of ANXA2 enhances the ERK pathway in ESCC. Furthermore, the 23rd tyrosine residue of ANXA2, phosphorylated by SRC, was regarded as playing important roles in the FBXW7-related degradation system. In clinical samples, we found that ANXA2 had high expression in ESCC tissues. High ANXA2 was associated with poor tumor staging. More importantly, we designed a combination regimen including SCH779284, a clinical ERK inhibitor against the phosphorylation of EKR and siRNA targeting ANXA2 by intratumor injection, and it produced potent inhibitory effects on the growth of xenograft tumors in vivo. In conclusion, this study provided evidence that FBXW7 loss of function could promote esophageal cancer through ANXA2 overexpression, and this novel regulation pathway may be used as an efficient target for ESCC treatment.

Crosstalk between tumor acidosis, p53 and extracellular matrix regulates pancreatic cancer aggressiveness.

Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive malignancy with minimal treatment options and a global rise in prevalence. PDAC is characterized by frequent driver mutations including KRAS and TP53 (p53), and a dense, acidic tumor microenvironment (TME). The relation between genotype and TME in PDAC development is unknown. Strikingly, when wild type (WT) Panc02 PDAC cells were adapted to growth in an acidic TME and returned to normal pH to mimic invasive cells escaping acidic regions, they displayed a strong increase of aggressive traits such as increased growth in 3-dimensional (3D) culture, adhesion-independent colony formation and invasive outgrowth. This pattern of acidosis-induced aggressiveness was observed in 3D spheroid culture as well as upon organotypic growth in matrigel, collagen-I and combination thereof, mimicking early and later stages of PDAC development. Acid-adaptation-induced gain of cancerous traits was further increased by p53 knockout (KO), but only in specific extracellular matrix (ECM) compositions. Akt- and Transforming growth factor-ß (TGFß) signaling, as well as expression of the Na+ /H+ exchanger NHE1, were increased by acid adaptation. Whereas Akt inhibition decreased spheroid growth regardless of treatment and genotype, stimulation with TGFßI increased growth of WT control spheroids, and inhibition of TGFß signaling tended to limit growth under acidic conditions only. Our results indicate that a complex crosstalk between tumor acidosis, ECM composition and genotype contributes to PDAC development. The findings may guide future strategies for acidosis-targeted therapies.

Chronic acidosis rewires cancer cell metabolism through PPARα signaling.

The mechanisms linking tumor microenvironment acidosis to disease progression are not understood. Here, we used mammary, pancreatic, and colon cancer cells to show that adaptation to growth at an extracellular pH (pHe ) mimicking acidic tumor niches is associated with upregulated net acid extrusion capacity and elevated intracellular pH at physiological pHe , but not at acidic pHe . Using metabolic profiling, shotgun lipidomics, imaging and biochemical analyses, we show that the acid adaptation-induced phenotype is characterized by a shift toward oxidative metabolism, increased lipid droplet-, triacylglycerol-, peroxisome content and mitochondrial hyperfusion. Peroxisome proliferator-activated receptor-α (PPARA, PPARα) expression and activity are upregulated, at least in part by increased fatty acid uptake. PPARα upregulates genes driving increased mitochondrial and peroxisomal mass and ß-oxidation capacity, including mitochondrial lipid import proteins CPT1A, CPT2 and SLC25A20, electron transport chain components, peroxisomal proteins PEX11A and ACOX1, and thioredoxin-interacting protein (TXNIP), a negative regulator of glycolysis. This endows acid-adapted cancer cells with increased capacity for utilizing fatty acids for metabolic needs, while limiting glycolysis. As a consequence, the acid-adapted cells exhibit increased sensitivity to PPARα inhibition. We conclude that PPARα is a key upstream regulator of metabolic changes favoring cancer cell survival in acidic tumor niches.

Single-Cell RNA-Seq Identifies Dynamic Cardiac Transition Program from ADCs Induced by Leukemia Inhibitory Factor.

Adipose-derived cells (ADCs) from white adipose tissue are promising stem cell candidates because of their large regenerative reserves and the potential for cardiac regeneration. However, given the heterogeneity of ADC and its unsolved mechanisms of cardiac acquisition, ADC-cardiac transition efficiency remains low. In this study, we explored the heterogeneity of ADCs and the cellular kinetics of 39,432 single-cell transcriptomes along the leukemia inhibitory factor (LIF)-induced ADC-cardiac transition. We identified distinct ADC subpopulations that reacted differentially to LIF when entering the cardiomyogenic program, further demonstrating that ADC-myogenesis is time-dependent and initiates from transient changes in nuclear factor erythroid 2-related factor 2 (Nrf2) signaling. At later stages, pseudotime analysis of ADCs navigated a trajectory with 2 branches corresponding to activated myofibroblast or cardiomyocyte-like cells. Our findings offer a high-resolution dissection of ADC heterogeneity and cell fate during ADC-cardiac transition, thus providing new insights into potential cardiac stem cells.

Serum Tenascin-C and Alarin Levels Are Associated with Cardiovascular Diseases in Type 2 Diabetes Mellitus.

Background: Tenascin-C (TNC), an extracellular matrix glycoprotein, is elevated in inflammatory and cardiovascular pathologies, whereas alarin, a novel orexigenic peptide, participates in insulin resistance and glycometabolism. The roles of these molecules in individuals with cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM), clinical conditions associating with metabolic disorders, and chronic inflammation, remain controversial. Our study aimed at determining the potential role of TNC and alarin in CVD adult patients with T2DM. Methods: This was a cross-sectional study. Basic and clinical information for 250 patients with T2DM were analyzed. Based on their cardiovascular disease status, participants were assigned into the CVD and non-CVD groups. Serum TNC and alarin levels were assessed by enzyme-linked immunosorbent assay (ELISA). Results: Serum TNC and alarin concentrations in the CVD group were significantly higher than those of the non-CVD group. Moreover, serum TNC levels were positively correlated with age, waist circumference, and waist-hip ratio; however, they were negatively correlated with TC, LDL-C, and eGFR levels. Alarin levels were positively correlated with BMI, waist circumference, and hip circumference. In logistic regression models, TNC and alarin were also established to be independent determinants for CVD in T2DM patients and their increases were associated with CVD severity. Receiver operating characteristic (ROC) curve analysis showed that the area under curve (AUC) values for TNC and alarin were 0.68 and 0.67, respectively. TNC and alarin were good predictors of CVD occurrence. When the cutoff value for TNC was 134.05 pg/mL, its sensitivity was 69.47% while its specificity was 61.29%. When the cutoff value for alarin was 142.69 pg/mL, sensitivity and specificity were 38.95% and 90.97%, respectively. Conclusion: Elevated TNC and alarin levels are independently associated with the occurrence and severity of CVD in T2DM individuals. Therefore, these two biomarkers are potential diagnostic and prognostic indicators for CVD in diabetics.

Progenitor cells from brown adipose tissue undergo neurogenic differentiation.

Multipotent cells derived from white adipose tissue have been shown to differentiate into multiple lineages including neurogenic lineages. However, the high innervation of brown adipose tissue by the sympathetic nervous system suggest it might be a better source of neural precursor cells. To investigate potential differences between white and brown progenitors, we cultured white and brown dedifferentiated fat (wDFAT and brDFAT) cells from mouse and human adipose tissue and compared marker expression of neural precursors, and neuronal and glial cells, using fluorescence-activated cell sorting, bright-field imaging, immunofluorescence, and RNA analysis by qPCR. The results showed that both wDFAT and brDFAT cells had the capacity to generate neuronal and glial-like cells under neurogenic conditions. However, the brDFAT cells exhibited enhanced propensity for neurogenic differentiation. The neurogenic cells were at least in part derived from Adiponectin-expressing cells. TdTomato-expressing cells derived from Adiponectin (Adipoq) Cre ERT2 -tdTomato flox/flox mice gave rise to individual cells and cell clusters with neurogenic characteristics. Moreover, human brDFAT cells demonstrated a similar ability to undergo neurogenic differentiation after treatment with neurogenic medium, as assessed by immunofluorescence and qPCR. Together, our results support that brDFAT cells have ability to undergo neurogenic differentiation.

Combinational Chemoimmunotherapy for Breast Cancer by Codelivery of Doxorubicin and PD-L1 siRNA Using a PAMAM-Incorporated Liposomal Nanoplatform.

Chemoimmunotherapy can synergistically enhance the therapeutic effects and decrease the side effects by a combined method. However, the effective targeted codelivery of various chemotherapeutic agents and siRNAs remains challenging. Although nanomedicine-based chemoimmunotherapy has shown great potential in cancer treatment in recent years, further effort is needed to simplify the nanocarrier designs and maintain their effective functions. Here, we report a simple but robust multifunctional liposomal nanocarrier that contains a pH-sensitive liposome (LP) shell and a dendritic core for tumor-targeted codelivery of programmed cell death ligand 1 (PD-L1) siRNA and doxorubicin (DOX) (siPD-L1@PM/DOX/LPs). siPD-L1@PM/DOX/LPs had a suitable particle size and zeta potential, excellent stability in serum, and pH-sensitive drug release in vitro. They exhibited significant cell proliferation inhibition compared to free DOX and DOX-loaded LPs and could escape endosomes, effectively release siRNA into the cytoplasm of MCF-7 cells, and significantly reduce the PD-L1 expression on tumor cells. In vivo imaging confirmed high accumulation of siPD-L1@PM/DOX/LPs at the tumor site. More importantly, compared with siPD-L1@PM/LPs or DOX alone, siPD-L1@PM/DOX/LPs were more effective in inhibiting tumor growth and activating cytotoxic T cells in vivo. In conclusion, this nanocarrier may hold promise as a codelivery nanoplatform to improve the treatment of various solid tumors.