Novel assaying method for the accurate and rapid analysis of antioxidant total capacity based on hexachloroiridate(IV).

We introduce a novel method, namely IrRAC, for assessing total antioxidant capacity utilizing the single electron oxidant hexachloroiridate(IV). This method leverages the 488 nm absorption band of [IrCl6]2- largely reducing interferences from antioxidants and their oxidation products. [IrCl6]2- is stable 6 h in phosphate-buffered saline (PBS) ensuring consistent and reproducible absorbance readings and rendering spectrophotometric determinations under physiological neutrality. Individual assessments of 23 antioxidants reveal a linear correlation between decreasing absorbance and increasing antioxidant concentration. When the IrRAC assay was compared with several established water-based methods, strong correlations were found. Importantly, [IrCl6]2- shows a minimal oxidation of non-antioxidative substances. Moreover, IrRAC performs well with synthetic antioxidant mixtures and real samples, highlighting that the nature of antioxidants dominates the assay without much disturbance. Commercial availability of K2[IrCl6] eliminates the need of pretreatment of the oxidant. Undoubtedly, the new method confers a compelling and cost-effective alternative to the existing electron transfer-based methodologies.

Genome-wide characterization and expression profiling of the HD-ZIP gene family in Acoraceae under salinity and cold stress.

The Homeodomain-Leucine Zipper (HD-ZIP) transcription factors play a pivotal role in governing various aspects of plant growth, development, and responses to abiotic stress. Despite the well-established importance of HD-ZIPs in many plants, their functions in Acoraceae, the basal lineage of monocots, remain largely unexplored. Using recently published whole-genome data, we identified 137 putative HD-ZIPs in two Acoraceae species, Acorus gramineus and Acorus calamus. These HD-ZIP genes were further classified into four subfamilies (I, II, III, IV) based on phylogenetic and conserved motif analyses, showcasing notable variations in exon-intron patterns among different subfamilies. Two microRNAs, miR165/166, were found to specifically target HD-ZIP III genes with highly conserved binding sites. Most cis-acting elements identified in the promoter regions of Acoraceae HD-ZIPs are involved in modulating light and phytohormone responsiveness. Furthermore, our study revealed an independent duplication event in Ac. calamus and a one-to-multiple correspondence between HD-ZIP genes of Ac. calamus and Ac. gramineus. Expression profiles obtained from qRT-PCR demonstrated that HD-ZIP I genes are strongly induced by salinity stress, while HD-ZIP II members have contrasting stress responses in two species. HD-ZIP III and IV genes show greater sensitivity in stress-bearing roots. Taken together, these findings contribute valuable insights into the roles of HD-ZIP genes in stress adaptation and plant resilience in basal monocots, illuminating their multifaceted roles in plant growth, development, and response to abiotic stress.

Intraocular mRNA delivery with endogenous MmPEG10-based virus-like particles.

Virus-like particles (VLP) are a promising tool for intracellular gene delivery, yet their potential in ocular gene therapy remains underexplored. In this study, we bridged this knowledge gap by demonstrating the successful generation and application of vesicular stomatitis virus glycoprotein (VSVG)-pseudotyped mouse PEG10 (MmPEG10)-VLP for intraocular mRNA delivery. Our findings revealed that PEG10-VLP can efficiently deliver GFP mRNA to adult retinal pigment epithelial cell line-19 (ARPE-19) cells, leading to transient expression. Moreover, we showed that MmPEG10-VLP can transfer SMAD7 to inhibit epithelial-mesenchymal transition (EMT) in RPE cells effectively. In vivo experiments further substantiated the potential of these vectors, as subretinal delivery into adult mice resulted in efficient transduction of retinal pigment epithelial (RPE) cells and GFP reporter gene expression without significant immune response. However, intravitreal injection did not yield efficient ocular expression. We also evaluated the transduction characteristics of MmPEG10-VLP following intracameral delivery, revealing transient GFP protein expression in corneal endothelial cells without significant immunotoxicities. In summary, our study established that VSVG pseudotyped MmPEG10-based VLP can transduce mitotically inactive RPE cells and corneal endothelial cells in vivo without triggering an inflammatory response, underscoring their potential utility in ocular gene therapy.

Increased visceral fat area to skeletal muscle mass ratio is positively associated with the risk of metabolic dysfunction-associated steatotic liver disease in a Chinese population.

BACKGROUND: The diagnosis and comprehension of nonalcoholic fatty liver disease (NAFLD), recently redefined as metabolic dysfunction-associated steatotic liver disease (MASLD) are gaining a better understanding. In this study, we examined the association between visceral fat area and skeletal muscle mass ratio (VSR) and the prevalence of MASLD in a Chinese population. METHODS: A cross-sectional study was conducted involving 10,916 individuals who underwent bioelectrical impedance analysis, along with anthropometric and biochemical measurements, from January 2022 to June 2023. According to the VSR distribution, sex-specific quartiles of VSR within the study population were defined. Linear trend tests were performed for the categorized VSR variables. Logistic regression models were performed to estimate the odds ratio and 95% confidence intervals between VSR distribution and MASLD prevalence stratified by sex. RESULTS: The prevalence of MASLD was 37.94% in the overall population (56.34% male), and it gradually increased with higher VSR levels in both genders (P < 0.001). Logistic regression analysis demonstrated a significant association between VSR and MASLD prevalence after adjusting for confounders. The odds ratio (95% confidence interval) for MASLD, comparing the lowest to the highest VSR quartile, was 3.159 (2.671, 3.736) for men and 2.230 (1.764, 2.819) for women (all P < 0.001). Restricted cubic splines also indicated significant non-linear relationships between VSR and MASLD prevalence. CONCLUSIONS: VSR is positively associated with the prevalence of MASLD in this Chinese population, with a notably higher risk for men as VSR increases compared to women.

A Recyclable Electrochemical Reduction of Aldehydes and Ketones to Alcohols Using Water as the Hydrogen Source and Solvent.

There are several challenging problems such as the usage of combustible and hazardous hydrogen sources and severe environmental pollution in the conventional reduction of aldehydes/ketones to alcohols. We report here a practical, safe, and green electrochemical reduction, which solves these problems to a large extent. Through an undivided cell, Zn(+) and Sn(-) as the electrode, tetrabutylammonium chloride (TBAC) as the electrolyte, water as the solvent and hydrogen source, a wide range of aldehydes and ketones are converted into the corresponding alcohols in mild conditions. Furthermore, the electrolytes and water can be recycled, and reductive deuteration can be achieved by simply using D2O as the solvent. Finally, the reduction can be smoothly scaled up to a kilogram level.

Surufatinib combined with photodynamic therapy induces ferroptosis to inhibit cholangiocarcinoma in vitro and in tumor models.

The curative effect of single therapy for advanced cholangiocarcinoma (CCA) is poor, thus investigating combined treatment strategies holds promise for improving prognosis. Surufatinib (SUR) is a novel multikinase inhibitor that has been confirmed to prolong survival of patients with advanced CCA. Photodynamic therapy (PDT) can also ablate advanced CCA and relieve biliary obstruction. In this study, we explored the anti-CCA effect of SUR combined with PDT, and explored the underlying mechanism. We found that SUR could effectively inhibit the abilities of proliferation, migration and metastasis in CCA cells (HUCCT-1, RBE). The ability of SUR to inhibit CCA was also confirmed by the HUCCT-1 cell xenograft model in Balb/c nude mice and CCA patient-derived organoids. SUR combined with PDT can significantly enhance the inhibitory effect on CCA, and can be alleviated by two ferroptosis inhibitors (Ferrostatin-1, Deferoxamine). By detecting the level of reactive oxygen species, lipid peroxides, malondialdehyde and glutathione, we further confirmed that SUR combined with PDT can inhibit CCA cells by inducing ferroptosis. Glutathione peroxidase 4 (GPX4) belongs to the glutathione peroxidase family and is mainly responsible for the metabolism of intracellular hydrogen peroxide. GPX4 inhibits ferroptosis by reducing cytotoxic lipid peroxides (L-OOH) to the corresponding alcohols (L-OH). Acyl-CoA synthetase long-chain family member 4 (ACSL4) is a member of the long-chain fatty acid coenzyme a synthetase family and is mainly involved in the biosynthesis and catabolism of fatty acids. ACSL4 induces ferroptosis by promoting the accumulation of lipid peroxides. Both SUR and PDT can induce ferroptosis by promoting ACSL4 and inhibiting GPX4. The regulation effect is found to be more significant in combined treatment group. In conclusion, SUR combined with PDT exerted an anti-CCA effect by inducing ferroptosis. Combination therapy provides a new idea for the clinical treatment of CCA.

P2X7 receptor is essential for ST36-attenuated cardiac fibrosis upon beta-adrenergic insult.

P2X7 receptor (P2X7R) plays an important role in modulating inflammation and fibrosis, but information is limited whether Zusanli (ST36) can inhibit inflammation and fibrosis by regulating P2X7R. Isoprenaline at 5 mg/kg was subcutaneously injected to wild-type and P2X7R knockout mice for 7 days, while treatment groups received electroacupuncture (EA) stimulation at ST36 for 7 sessions. Following 7-session treatment, Masson's trichrome staining was performed to assess the fibrosis. Morphology, electrocardiogram, and echocardiography were carried out to evaluate the cardiac function and structure. Western blotting, hematoxylin and eosin staining, immunohistochemistry, and biochemical analysis of inflammatory cytokine and transmission electron microscopy were carried out to characterize the effect of ST36 on inflammation. P2X7R was overexpressed in ISO-treated mice. EA at ST36, but not at non-points, reduced ISO-induced cardiac fibrosis, increases in HW/BW, R+S wave relative to mice in ISO groups. In addition, EA at ST36 downregulated ISO-upregulated P2X7R and NLRP3 in ventricle. Moreover, EA reduced cytokines of IL-1ß, IL-6, and IL-18 in serum, and inhibited foam cell gathering, inflammatory cell infiltration, and autophagy. However, EA at ST36 failed to attenuate the cardiac fibrosis and hypertrophy in P2X7R knockout mice. In conclusion, EA at ST36 attenuated ISO-induced fibrosis possibly via P2X7R.

Depletion of regulatory T cells enhancing the anti-tumor effect of in situ vaccination in solid tumors.

The emergence of immune checkpoint inhibitors (ICIs) has revolutionized the clinical treatment for tumor. However, the low response rate of ICIs remains the major obstacle for curing patients and effective approaches for patients with primary or secondary resistance to ICIs remain lacking. In this study, immune stimulating agent unmethylated CG-enriched (CpG) oligodeoxynucleotide (ODN) was locally injected into the tumor to trigger a robust immune response to eradicate cancer cells, while anti-CD25 antibody was applied to remove immunosuppressive regulatory T cells, which further enhanced the host immune activity to attack tumor systematically. The combination of CpG and anti-CD25 antibody obtained notable regression in mouse melanoma model. Furthermore, rechallenge of tumor cells in the xenograft model has resulted in smaller tumor volume, which demonstrated that the combinational treatment enhanced the activity of memory T cells. Remarkably, this combinational therapy presented significant efficacy on multiple types of tumors as well and was able to prevent relapse of tumor partially. Taken together, our combinational immunotherapy provides a new avenue to enhance the clinical outcomes of patients who are insensitive or resistant to ICIs treatments.

Statistical Genomics Analysis of Simple Sequence Repeats from the Paphiopedilum Malipoense Transcriptome Reveals Control Knob Motifs Modulating Gene Expression.

Simple sequence repeats (SSRs) are found in nonrandom distributions in genomes and are thought to impact gene expression. The distribution patterns of 48 295 SSRs of Paphiopedilum malipoense are mined and characterized based on the first full-length transcriptome and comprehensive transcriptome dataset from 12 organs. Statistical genomics analyses are used to investigate how SSRs in transcripts affect gene expression. The results demonstrate the correlations between SSR distributions, characteristics, and expression level. Nine expression-modulating motifs (expMotifs) are identified and a model is proposed to explain the effect of their key features, potency, and gene function on an intra-transcribed region scale. The expMotif-transcribed region combination is the most predominant contributor to the expression-modulating effect of SSRs, and some intra-transcribed regions are critical for this effect. Genes containing the same type of expMotif-SSR elements in the same transcribed region are likely linked in function, regulation, or evolution aspects. This study offers novel evidence to understand how SSRs regulate gene expression and provides potential regulatory elements for plant genetic engineering.

[Curcumin Combined with Thalidomide Inhibits Proliferation of KG-1 Cells and Its Related Mechanisms].

OBJECTIVE: To investigate the effects of curcumin combined with thalidomide on the proliferation and apoptosis of acute myeloid leukemia KG-1 cells, and its correlation with B-cell lymphoma-xL (Bcl-xL), signal transducer and activator of transcription 3 (STAT3). METHODS: MTT assay was used to detect the proliferation of KG-1 cells and screen the optimal combined concentration of curcumin and thalidomide. The effects of curcumin, thalidomide and their combination on the proliferation and apoptosis of KG-1 cells were analyzed by MTT method and flow cytometry, respectively. The mRNA expression levels of STAT3 and Bcl-xL in single-drug group, two-drug combination group and control group (untreated cells) were detected by real-time quantitative PCR. RESULTS: Both curcumin and thalidomide inhibited the proliferation of KG-1 cells in a concentration-dependent manner in the range of 20-100 µmol/L (r =0.657, r =0.681). The IC50 value of curcumin and thalidomide at 48 h was (42.07±0.50) µmol/L and (57.01±2.39) µmol/L, respectively. The cell proliferation inhibition rate of curcumin (40 µmol/L) + thalidomide (60 µmol/L) was (86.67±1.53)%, which was significantly higher than (51.67±1.15)% of curcumin (40 µmol/L) and (55.33±1.53)% of thalidomide (60 µmol/L) (both P < 0.05). Treated with curcumin and thalidomide alone or in combination, the apoptosis rate of KT-1 cells was (18.67±2.08)%, (21.33±2.52)%, and (46.67±1.53)%, respectively, which was significantly higher than (0.72±0.03)% of control group (all P < 0.05). The cell apoptosis rate of two-drug combination group was significantly higher than that of single-drug group (both P < 0.05). Compared with the control group, the mRNA expressions of STAT3 and Bcl-xL in single-drug group, two-drug combination group were significantly decreased (both P < 0.05). Compared with single-drug group, the mRNA expressions of STAT3 and Bcl-xL in two-drug combination group were also significantly decreased (both P < 0.05). CONCLUSION: Curcumin combined with thalidomide can synergistically down-regulate the expression of STAT3 and Bcl-xL, inhibit the proliferation of KG-1 cells, and induce apoptosis.

Radical Three-Component Nitro Spiro-Cyclization of Unsaturated Sulfonamides/Amides to Access NO2-Featured 4-Azaspiro[4.5]decanes.

Free radical three-component nitration/spirocyclization of unsaturated sulfonamides/amides with tert-butyl nitrite was developed for the construction of diverse NO2-revised 4-azaspiro[4.5]decanes. This tandem system featured metal-free participation, simple operation, good selectivity/yields, and a green/low-cost O source. Meanwhile, one nitro-containing complex molecule and a scaled-up operation were performed well to test the synthetic potential of the cascade reaction. Isotopic labeling, radical inhibition experiments, and DFT analysis were carried out to gain insight into the reaction process.

Bi-path color tunable plasmonic micro-nano hybrid structures for encrypted printing.

Colored information is crucial for humans to perceive the world. Plasmonic spectra modulation can serve as an effective means to create different colors. Although several solutions for plasmonic color-printing have been proposed, further information encryption has not received any attention. Herein, we exhibit a fine color modulation strategy to construct noble-metal-based micro-nano hybrid structures in the bi-path of photo-thermal deformation and liquid-phase-chemical reaction. Ag/Ta2O5 bi-layer films are ablated at the center of the machined lines of nanosecond pulsed laser, while silver nanoparticles are formed in other regions by thermal radiation of the infrared laser, which can be further dissolved and shape-modulated in KCl solution under different periods. The variation of size and spacing of nano-Ag particles results in a precise shift of plasmonic spectra in visible region. Colored information can be hidden by adjusting the scan number and the energy density during laser processing, and will emerge after the subsequent chemical dissolution reactions. The bi-path color adjustment strategy is easy to operate and can play a role in key information protection and color image switching.

Phenotypic comparison and the potential antitumor function of immortalized bone marrow-derived macrophages (iBMDMs).

Introduction: Macrophages are an important component of innate immunity and involved in the immune regulation of multiple diseases. The functional diversity and plasticity make macrophages to exhibit different polarization phenotypes after different stimuli. During tumor progression, the M2-like polarized tumor-associated macrophages (TAMs) promote tumor progression by assisting immune escape, facilitating tumor cell metastasis, and switching tumor angiogenesis. Our previous studies demonstrated that functional remodeling of TAMs through engineered-modifying or gene-editing provides the potential immunotherapy for tumor. However, lack of proliferation capacity and maintained immune memory of infused macrophages restricts the application of macrophage-based therapeutic strategies in the repressive tumor immune microenvironment (TIME). Although J2 retrovirus infection enabled immortalization of bone marrow-derived macrophages (iBMDMs) and facilitated the mechanisms exploration and application, little is known about the phenotypic and functional differences among multi kinds of macrophages. Methods: HE staining was used to detect the biosafety of iBMDMs, and real-time quantitative PCR, immunofluorescence staining, and ELISA were used to detect the polarization response and expression of chemokines in iBMDMs. Flow cytometry, scratch assay, real-time quantitative PCR, and crystal violet staining were used to analyze its phagocytic function, as well as its impact on tumor cell migration, proliferation, and apoptosis. Not only that, the inhibitory effect of iBMDMs on tumor growth was detected through subcutaneous tumor loading, while the tumor tissue was paraffin sectioned and flow cytometry was used to detect its impact on the tumor microenvironment. Results: In this study, we demonstrated iBMDMs exhibited the features of rapid proliferation and long-term survival. We also compared iBMDMs with RAW264.7 cell line and mouse primary BMDMs with in vitro and in vivo experiments, indicating that the iBMDMs could undergo the same polarization response as normal macrophages with no obvious cellular morphology changes after polarization. What's more, iBMDMs owned stronger phagocytosis and pro-apoptosis functions on tumor cells. In addition, M1-polarized iBMDMs could maintain the anti-tumor phenotypes and domesticated the recruited macrophages of receptor mice, which further improved the TIME and repressed tumor growth. Discussion: iBMDMs can serve as a good object for the function and mechanism study of macrophages and the optional source of macrophage immunotherapy.

Finding Natural, Dense, and Stable Frustrated Lewis Pairs on Wurtzite Crystal Surfaces for Small-Molecule Activation.

The surface frustrated Lewis pairs (SFLPs) open up new opportunities for substituting noble metals in the activation and conversion of stable molecules. However, the applications of SFLPs on a larger scale are impeded by the complex construction process, low surface density, and sensitivity to the reaction environment. Herein, wurtzite-structured crystals such as GaN, ZnO, and AlP are found for developing natural, dense, and stable SFLPs. It is revealed that the SFLPs can naturally exist on the (100) and (110) surfaces of wurtzite-structured crystals. All the surface cations and anions serve as the Lewis acid and Lewis base in SFLPs, respectively, contributing to the surface density of SFLPs as high as 7.26×1014 cm-2. Ab initio molecular dynamics simulations indicate that the SFLPs can keep stable under high temperatures and the reaction atmospheres of CO and H2O. Moreover, outstanding performance for activating the given small molecules is achieved on these natural SFLPs, which originates from the optimal orbital overlap between SFLPs and small molecules. Overall, these findings not only provide a simple method to obtain dense and stable SFLPs but also unfold the nature of SFLPs toward the facile activation of small molecules.

A Cross-Sectional Study on Awareness of Tuberculosis Control Among Post-Treatment Tuberculosis Patients in a City in China.

Purpose: This study aimed to investigate awareness of tuberculosis control among post-treatment tuberculosis patients, in order to provide a basis for future preventive and control work in this population. Patients and Methods: A cross-sectional descriptive study was conducted on post-treatment patients with tuberculosis in seven districts of Jinan City between July 2021 and December 2022. A face-to-face or telephone interviews using structured questionnaires for the research subjects were conducted by data collectors. Analyses were carried out first for all subjects, and then separately for male and female subjects. Results: A total of 837 valid questionnaires were collected, of which 495 were males and 342 were females. The awareness rate of the core TB knowledge was 82.46%. The ≥65 year group in the total group (OR=0.43, 95% CI: (0.28, 0.68)), male (OR=0.47, 95% CI: (0.27, 0.83)) and female group (OR=0.40, 95% CI: (0.19, 0.86)) was lower than that of the control group. Educational level and monthly income are the main factors of TB cognition in total group. People with university or higher education (OR=2.05, 95% CI: (1.38, 3.05)) and with a monthly income of ≥6,000 (OR=1.89, 95% CI: (1.10, 3.25)) had a higher awareness rate. The group with current residence in the city was more aware than the reference group. Conclusion: In the future, the communication of the main transmission route, suspicious symptoms, and cure of TB needs to be strengthened for the post-treatment TB patients. The elderly, those with secondary school education or below, agricultural workers and low-income people are the groups with weak knowledge of TB, and they are also the groups that need to be focused on health education. The above information should be focused on the above groups of people in order to educate them in a way that is easily acceptable to them.

Impact of metabolic syndrome on bone mineral density in men over 50 and postmenopausal women according to U.S. survey results.

Metabolic Syndrome (MetS) and bone mineral density (BMD) have shown a controversial link in some studies. This research aims to study their association in males over 50 and postmenopausal females using National Health and Nutrition Examination Survey (NHANES) data. Postmenopausal females and males over 50 were included in the study. MetS was defined by the National Cholesterol Education Program Adult Treatment Panel III guidelines. BMD values were measured at the thoracic spine, lumbar spine, and pelvis as the primary outcome. Weighted multivariate general linear models have been employed to explore the status of BMD in patients with MetS. Additionally, interaction tests and subgroup analyses were conducted. Utilizing the NHANES database from 2003 to 2006 and 2011-2018, we included 1924 participants, with 1029 males and 895 females. In postmenopausal women, after adjusting for covariates, we found a positive correlation between MetS and pelvic (ß: 0.030 [95%CI 0.003, 0.06]) and thoracic (ß: 0.030 [95%CI 0.01, 0.06]) BMD, though not for lumbar spine BMD (ß: 0.020 [95%CI - 0.01, 0.05]). In males over 50 years old, MetS was positively correlated with BMD in both Model 1 (without adjusting for covariates) and Model 2 (considering age and ethnicity). Specifically, Model 2 revealed a positive correlation between MetS and BMD at the pelvis (ß: 0.046 [95%CI 0.02, 0.07]), thoracic spine (ß: 0.047 [95%CI 0.02, 0.07]), and lumbar spine (ß: 0.040 [95%CI 0.02, 0.06]). Subgroup analysis demonstrated that the relationship between MetS and BMD remained consistent in all strata, underscoring the stability of the findings. In postmenopausal women, after adjusting for all covariates, a significant positive correlation was observed between MetS and BMD in the pelvis and thoracic spine, whereas this correlation was not significant for lumbar spine BMD. Conversely, in males, positive correlations between MetS and BMD at the lumbar spine, thoracic spine, and pelvis were identified in Model 2, which adjusted for age and ethnicity; however, these correlations disappeared after fully adjusting for all covariates. These findings highlight the potential moderating role of gender in the impact of MetS on BMD.

Extracorporeal photopheresis reduces inflammation and joint damage in a rheumatoid arthritis murine model.

BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammatory reactions and tissue damage in the joints. Long-term drug use in clinical practice is often accompanied by adverse reactions. Extracorporeal photopheresis (ECP) is an immunomodulatory therapy with few side effects, offering a potential and safe therapeutic alternative for RA through the induction of immune tolerance. This study aimed to investigate the therapeutic effects of ECP on RA using a collagen-induced arthritis (CIA) murine model, as well as to explore its immunomodulatory effects in vivo. Additionally, particular attention was given to the significant role of monocytes during the ECP process. METHODS: A murine model of rheumatoid arthritis was established by administering two injections of bovine type II collagen to DBA/1J mice. ECP, ECP-MD (mononuclear cells were depleted during the ECP), MTX, and PBS treatment were applied to the CIA mice. During the treatment process, clinical scores and body weight changes of CIA mice were closely monitored. After six treatment sessions, micro-CT images of the hind paws from live mice were captured. Ankle joints and paws of the mice were collected and processed for histological evaluation. Spleen samples were collected to measure the Th17/Treg cells ratio, and serum samples were collected to assess cytokine and anti-type II collagen IgG levels. Monocytes and dendritic cells populations before and after ECP in vitro were detected by flow cytometry. RESULT: ECP therapy significantly attenuated the progression of CIA, alleviated the severity of clinical symptoms in CIA mice and effectively suppressed synovial hyperplasia, inflammation, and cartilage damage. There was an expansion in the percentage of CD3 + CD4 + CD25 + FoxP3 + Tregs and a decrease in CD3 + CD4 + IL17A + Th17 cells in vivo. Furthermore, ECP reduced the serum levels of pro-inflammatory cytokines IL-6 (53.47 ± 7.074 pg/mL vs 5.142 ± 1.779 pg/mL, P < 0.05) and IL-17A (3.077 ± 0.401 pg/mL vs 0.238 ± 0.082 pg/mlL, P < 0.0001) compared with PBS. Interestingly, the depletion of monocytes during the ECP process did not lead to any improvement in clinical symptoms or histological scores in CIA mice. Moreover, the imbalance in the Th17/Treg cells ratio became even more pronounced, accompanied by an augmented secretion of pro-inflammatory cytokines IL-6 and IL-17A. In vitro, compared with cells without ECP treatment, the proportion of CD11b + cells were significantly reduced (P < 0.01), the proportion of CD11c + cells were significantly elevated (P < 0.001) 24 h after ECP treatment. Additionally, the expression of MHC II (P < 0.0001), CD80 (P < 0.01), and CD86 (P < 0.001) was downregulated in CD11c + cells 24 h after ECP treatment. CONCLUSION: Our study demonstrates that ECP exhibits a therapeutic effect comparable to conventional therapy in CIA mice, and the protective mechanisms of ECP against RA involve Th17/Treg cells ratio, which result in decreased IL-6 and IL-17A. Notably, monocytes derived from CIA mice are an indispensable part to the efficacy of ECP treatment, and the proportion of monocytes decreased and the proportion of tolerogenic dendritic cells increased after ECP treatment in vitro.

Prevalence of intestinal trichomonads in captive non-human primates in China.

Trichomonads are protozoan symbionts with the capacity to infect vertebrates including humans and non-human primates (NHPs), sometimes with pathogenic effects. However, their diversity and prevalence in NHPs in China are poorly understood. A total of 533 fecal samples were collected from captive NHPs in Yunnan Province, China, of which 461 samples from Macaca fascicularis and 72 from Macaca mulatta. Trichomonadidae species were identified using PCR amplification of the ITS-1/5.8S/ITS-2 sequences. The overall prevalence of trichomonads in NHPs was determined to be 11.4% (61/533), with gender, diarrhea, and region identified as potential risk factors for the infections. Sequence alignment and phylogenetic analysis identified three species of trichomonads, i.e., Trichomitopsis minor (n = 45), Pentatrichomonas hominis (n = 11), and Tetratrichomonas sp. (n = 5). To the best of our knowledge, this is the first study to report Trichomitopsis minor infection in NHPs in China. Of note, Pentatrichomonas hominis is generally recognized as a parasitic organism affecting humans. Collectively, our results suggest that NHPs are potential sources of zoonotic trichomonad infections, highlighting the importance of surveillance and control measures to protect human and animal populations.

Title: Prévalence des Trichomonadidae intestinaux chez les primates non humains captifs en Chine. Abstract: Les Trichomonadidae sont des symbiotes protozoaires capables d'infecter les vertébrés, notamment les humains et les primates non humains (PNH), parfois avec des effets pathogènes. Cependant, leur diversité et leur prévalence chez les PNH en Chine sont mal comprises. Au total, 533 échantillons fécaux ont été collectés sur des PNH captifs dans la province du Yunnan, en Chine, dont 461 échantillons de Macaca fascicularis et 72 de Macaca mulatta. Les espèces de Trichomonadidae ont été identifiées par amplification PCR des séquences ITS-1/5.8S/ITS-2. La prévalence globale des Trichomonadidae dans les PNH a été déterminée à 11,4 % (61 / 533) et le sexe, la diarrhée et la région ont été identifiés comme facteurs de risque potentiels d'infection. L'alignement des séquences et l'analyse phylogénétique ont identifié trois espèces de Trichomonadidae, à savoir Trichomitopsis minor (n = 45), Pentatrichomonas hominis (n = 11) et Tetratrichomonas sp. (n = 5). À notre connaissance, il s'agit de la première étude à signaler une infection par Trichomitopsis minor chez les PNH en Chine. Il convient de noter que Pentatrichomonas hominis est généralement reconnu comme un organisme parasitaire affectant les humains. Collectivement, nos résultats suggèrent que les PNH sont des sources potentielles d'infections zoonotiques à Trichomonadidae, soulignant l'importance des mesures de surveillance et de contrôle pour protéger les populations humaines et animales.

The Effectiveness of Exercise-based Rehabilitation in People with Hand Osteoarthritis: A Systematic Review with Meta-analysis.

OBJECTIVE: To investigate the effectiveness of exercise-based rehabilitation programs compared with non-exercise intervention or no intervention for people with hand osteoarthritis (OA). DESIGN: Intervention systematic review with meta-analysis. LITERATURE SEARCH: We searched five databases on 23/07/2023. STUDY SELECTION CRITERIA: We included randomized controlled trials that compared the effectiveness of rehabilitation programs that included an exercise component, with non-exercise intervention or no intervention for people with hand OA. DATA SYNTHESIS: Standardized mean differences (SMD) were pooled using a random effects model. The risk of bias was assessed using the Cochrane Risk of Bias 2.0 tool. The certainty of the evidence was evaluated using the GRADE approach. RESULTS: Fourteen trials were included in the meta-analysis (n = 1341 participants). In the immediate-term (<24 weeks) there was low-certainty evidence of an effect of exercise-based rehabilitation on improving pain (13 trials; SMD -0.65, 95%CI: -1.06, -0.25), function (11 trials; SMD -0.35, 95%CI: -0.54, -0.15), and grip strength (14 trials; SMD 0.21, 95%CI: 0.03, 0.38). There was moderate-certainty evidence of an effect on reducing stiffness (7 trials; SMD -0.33, 95%CI: -0.51, -0.16). There was low-certainty evidence of no effect on improving pinch strength and quality of life. For the long-term ⩾24 weeks), there was low-certainty evidence that exercise-based rehabilitation had no additional effect on improving pain, function, and stiffness. CONCLUSION: Exercise-based rehabilitation improved pain, function, stiffness, and grip strength in people with hand OA in the immediate-term; the benefits were not maintained in the long-term.

The role of dermal fibroblasts in autoimmune skin diseases.

Fibroblasts are an important subset of mesenchymal cells in maintaining skin homeostasis and resisting harmful stimuli. Meanwhile, fibroblasts modulate immune cell function by secreting cytokines, thereby implicating their involvement in various dermatological conditions such as psoriasis, vitiligo, and atopic dermatitis. Recently, variations in the subtypes of fibroblasts and their expression profiles have been identified in these prevalent autoimmune skin diseases, implying that fibroblasts may exhibit distinct functionalities across different diseases. In this review, from the perspective of their fundamental functions and remarkable heterogeneity, we have comprehensively collected evidence on the role of fibroblasts and their distinct subpopulations in psoriasis, vitiligo, atopic dermatitis, and scleroderma. Importantly, these findings hold promise for guiding future research directions and identifying novel therapeutic targets for treating these diseases.