Blood soluble CD89-IgA complex may be a potential biomarker for predicting multi-organ involvement, especially renal involvement in children with immunoglobulin A vasculitis.

BACKGROUND: Immunoglobulin A vasculitis (IgAV) is a kind of systemic vasculitis mediated by IgA immune complexes (IgA-ICs). Soluble CD89-IgA complex (sCD89-IgA) as a type of IgA-IC associated with renal involvement in IgAV, the ability of blood sCD89-IgA as a biomarker to predict renal or multi-organ involvement in children with IgAV is not evident, and this study mainly focused on this. METHODS: The clinical characteristics and blood samples of 57 pediatric patients with IgAV were collected. ELISA was used to detect plasma IgA-ICs and sCD89-IgA levels. Serum IgA levels were detected by Nephelometry method. Statistical analysis was conducted to analyze the relationship between sex, age, serum IgA levels, plasma IgA-ICs levels, plasma sCD89-IgA levels and the involvement of multiple organs (except skin) including kidneys in these patients. RESULTS: Compared to patients with simple skin involvement, patients with multi-organ involvement, especially kidneys, had higher levels of plasma IgA-ICs and sCD89-IgA, and the statistical difference was significant. In addition, a high level of plasma sCD89-IgA was a high-risk factor for patients to develop multi-organ or renal involvement in addition to the skin. ROC curve analysis showed that the AUC was 0.861 (Sensitivity: 83 %, Specificity: 88 %, p < 0.0001) when plasma sCD89-IgA predicted multi-organ involvement, and AUC 0.926 (Sensitivity: 94 %, Specificity: 88 %, p < 0.0001) for predicting renal involvement. CONCLUSIONS: The results suggested that plasma sCD89-IgA may be a potential biomarker for predicting multi-organ involvement (in addition to skin), especially renal involvement in IgAV pediatric patients.

Discovery of a urea-based hit compound as a novel inhibitor of transforming growth factor-ß type 1 receptor: in silico and in vitro studies.

Transforming growth factor ß type 1 receptor (TGFßR1), a crucial serine-threonine kinase, is central to the TGFß/Smad signaling pathway, governing cellular processes like growth, differentiation, apoptosis, and immune response. This pathway is closely linked to the epithelial-mesenchymal transition (EMT) process, which plays an important role in the metastasis of hepatocellular carcinoma (HCC). To date, only limited inhibitors targeting TGFßR1 have entered clinical trials, yet they encounter challenges, notably high toxicity, in clinical applications. Herein, an efficient virtual screening pipeline was developed. Eighty compounds were screened from a pool of over 17 million molecules based on docking scores and binding free energy. Four compounds were manually selected with the assistance of enhanced sampling method BPMD (binding pose metadynamics). The binding stability of these four compounds complexed with TGFßR1 was subsequently studied through long-timescale conventional molecular dynamics simulations. The three most promising compounds were subjected to in vitro bioactivity assays. Cpd272 demonstrated moderate inhibitory activity against TGFßR1, with an IC50 value of 1.57 ± 0.33 µM. Moreover, it exhibited cytotoxic effects on human hepatocellular carcinoma cell line Bel-7402. By shedding light on the binding mode of the receptor-ligand complexes, Cpd272 was identified as a hit compound featuring a novel urea-based scaffold capable of effectively inhibiting TGFßR1.

Mitochondria-encoded peptide MOTS-c participates in plasma membrane repair by facilitating the translocation of TRIM72 to membrane.

Rationale: An impairment of plasma membrane repair has been implicated in various diseases such as muscular dystrophy and ischemia/reperfusion injury. MOTS-c, a short peptide encoded by mitochondria, has been shown to pass through the plasma membrane into the bloodstream. This study determined whether this biological behavior was involved in membrane repair and its underlying mechanism. Methods and Results: In human participants, the level of MOTS-c was positively correlated with the abundance of mitochondria, and the membrane repair molecule TRIM72. In contrast to high-intensity eccentric exercise, moderate-intensity exercise improved sarcolemma integrity and physical performance, accompanied by an increase of mitochondria beneath the damaged sarcolemma and secretion of MOTS-c. Furthermore, moderate-intensity exercise increased the interaction between MOTS-c and TRIM72, and MOTS-c facilitated the trafficking of TRIM72 to the sarcolemma. In vitro studies demonstrated that MOTS-c attenuated membrane damage induced by hypotonic solution, which could be blocked by siRNA-TRIM72, but not AMPK inhibitor. Co-immunoprecipitation study showed that MOTS-c interacted with TRIM72 C-terminus, but not N-terminus. The dynamic membrane repair assay revealed that MOTS-c boosted the trafficking of TRIM72 to the injured membrane. However, MOTS-c itself had negligible effects on membrane repair, which was recapitulated in TRIM72-/- mice. Unexpectedly, MOTS-c still increased the fusion of vesicles with the membrane in TRIM72-/- mice, and dot blot analysis revealed an interaction between MOTS-c and phosphatidylinositol (4,5) bisphosphate [PtdIns (4,5) P2]. Finally, MOTS-c blunted ischemia/reperfusion-induced membrane disruption, and preserved heart function. Conclusions: MOTS-c/TRIM72-mediated membrane integrity improvement participates in mitochondria-triggered membrane repair. An interaction between MOTS-c and plasma lipid contributes to the fusion of vesicles with membrane. Our data provide a novel therapeutic strategy for rescuing organ function by facilitating membrane repair with MOTS-c.

Effect of straw decomposition on hexavalent chromium removal by straw: Significant roles of surface potential and dissolved organic matter.

Mobility and bioavailability of hexavalent chromium (Cr(VI)) in agricultural soils are affected by interactions between Cr(VI) and returned crop straws. However, the effect of straw decomposition on Cr(VI) removal and underlying mechanisms remain unclear. In this study, Cr(VI) removal by pristine and decomposed rice/rape straws was investigated by batch experiments and a series of spectroscopies. The results showed that straw decomposition inhibited Cr(VI) removal, regardless of straw types. However, the potential mechanisms of the inhibition were distinct for the two straws. For the rice straw, a lower zeta potential after decomposition suppressed Cr(VI) sorption and subsequent reduction. In addition, less Cr(VI) was reduced by the decomposed rice straw-derived dissolved organic matter (DOM) than the pristine one. In contrast, for the rape straw, due to the increased zeta potential after decomposition, the decreased Cr(VI) removal was mainly ascribed to less Cr(VI) reduction by the rape straw-derived DOM. These results emphasized the significant roles of straw surface potential and DOM in Cr(VI) removal, depending on straw types and decomposition, which facilitate the fundamental understanding of Cr(VI) removal by straws and are helpful for predicting the environmental risk of Cr and rational straw return in Cr(VI)-contaminated fields.

Efficacy and safety of bronchoscopic lung volume reduction for chronic obstructive pulmonary disease: a systematic review and network meta-analysis.

BACKGROUND: Various bronchoscopic lung volume reduction (BLVR) methods have been developed to treat chronic obstructive pulmonary disease (COPD). The efficacy and safety of these interventions remain unclear. This study assessed the efficacy and safety of various BLVR interventions in COPD patients. METHODS: PubMed and Embase were searched from inception to 21 October 2023. The primary outcomes assessed included the 6-min walking distance (6MWD), St. George Respiratory Questionnaire (SGRQ) score, lung function, and adverse events (AE). A frequentist approach with a random-effects model was used for a network meta-analysis. RESULTS: Twelve randomized controlled trials (RCTs) with 1646 patients were included in this meta-analysis. Patients treated with an endobronchial valve (EBV) achieved a minimum clinically important difference (MCID) in 6MWD and SGRQ at 6 months. Patients treated with coils achieved MCID in the SGRQ score at 12 months. Patients with aspiration valve system and bronchoscopic thermal vapor ablation (BTVA) achieved MCID in the SGRQ score at 6 months. CONCLUSIONS: In COPD patients, EBV should be considered first, while being wary of pneumothorax. Coil and BTVA are potential therapeutic alternatives. Although BTVA demonstrates a safer procedural profile than coils, additional studies are imperative to clarify its efficacy.

Relationship between the length of macular Bruch's membrane on fundus photograph and myopia occurrence in pre-myopia children aged 3-6 years: A 3-year longitudinal study.

PURPOSE: To evaluate the occurrence and influencing factors of myopia occurrence in pre-myopia children aged 3-6 years. METHODS: This study included 204 pre-myopia (-0.50D-0.50D). The length of macular BM was shorter in Myopia group than that in Non-myopia group (P < 0.001). Baseline SE and the length of macular BM were independent influencing factors which associated with myopia occurrence (OR, 0.031; 95 % CI, 0.008-0.117, P < 0.001 and OR, 0.204; 95 % CI, 0.055-0.763, P = 0.018, respectively) by multivariate binary logistic regression analysis. SE changing process represented the changes of SE, Myopia group had bigger SE changes (P < 0.001). And in the multivariate liner regression analysis, age was the common influencing factor of SE changing process in total participants, Non-myopia group and Myopia group (B = 0.234, P < 0.001; B = 0.078, P = 0.010; B = 0.161, P = 0.046, respectively) CONCLUSIONS: Initial SE and the length of macular BM in pre-myopia children aged 3-6 years were the independent factors of the occurrence of myopia. And initial age was the common factor that associated with SE changing process.

Network pharmacology-based mechanism analysis of dauricine on the alleviating Aß-induced neurotoxicity in Caenorhabditis elegans.

BACKGROUND: Dauricine (DAU), a benzyl tetrahydroisoquinoline alkaloid isolated from the root of Menispermum dauricum DC, exhibits promising anti-Alzheimer's disease (AD) effects, but its underlying mechanisms remain inadequately investigated. This paper aims to identify potential targets and molecular mechanisms of DAU in AD treatment. METHODS: Network pharmacology and molecular docking simulation method were used to screen and focus core targets. Various transgenic Caenorhabditis elegans models were chosen to validate the anti-AD efficacy and mechanism of DAU. RESULTS: There are 66 potential DAU-AD target intersections identified from 100 DAU and 3036 AD-related targets. Subsequent protein-protein interaction (PPI) network analysis identified 16 core targets of DAU for anti-AD. PIK3CA, AKT1 and mTOR were predicted to be the central targets with the best connectivity through the analysis of "compound-target-biological process-pathway network". Molecular docking revealed strong binding affinities between DAU and PIK3CA, AKT1, and mTOR. In vivo experiments demonstrated that DAU effectively reduced paralysis in AD nematodes caused by Aß aggregation toxicity, downregulated expression of PIK3CA, AKT1, and mTOR homologues (age-1, akt-1, let-363), and upregulated expression of autophagy genes and the marker protein LGG-1. Simultaneously, DAU increased lysosomal content and enhanced degradation of the autophagy-related substrate protein P62. Thioflavin T（Th-T）staining experiment revealed that DAU decreased Aß accumulation in AD nematodes. Further experiments also confirmed DAU's protein scavenging activity in polyglutamine (polyQ) aggregation nematodes. CONCLUSION: Collectively, the mechanism of DAU against AD may be related to the activation of the autophagy-lysosomal protein clearance pathway, which contributes to the decrease of Aß aggregation and the restoration of protein homeostasis.

Pathologic Features of Primary Colon, Rectal, and Anal Malignancies.

In USA, colorectal cancer is the third most commonly diagnosed cancer in men, second in women, as well as the third leading cause of cancer deaths (Siegel et al. in Cancer J Clin 73:1-112, 2023 [109]). Worldwide, colorectal cancer is the second leading cause of death and causes almost 916,000 deaths each year (Ferlay in Global cancer observatory: cancer today. International Agency for Research on Cancer, Lyon, 2020 [28]). Fortunately, due to the colon's surgical and endoscopic accessibility and functional redundancy, colorectal cancer is very treatable. Colonoscopic surveillance has the potential for not only providing tissue for the diagnosis of precancerous polyps and invasive carcinoma, but also preventing development of invasive carcinoma by the removal of precancerous lesions. This chapter discusses the clinical and pathologic features of the spectrum of epithelial, hematolymphoid, and mesenchymal malignant tumors of the colon, rectum, appendix, and anus.

Chemo-enzymatic Functionalization of Bovine Milk Exosomes with an EGFR Nanobody for Target-specific Drug Delivery.

Bovine milk exosomes (BmExo) have been identified as versatile nanovesicles for anti-cancer drugs delivery due to their natural availability and biocompatibility. However, tumor-specific delivery based on BmExo often requires post-isolation modifications of the membrane surface with active-targeting ligands. In this study, we report an alternative approach to functionalize BmExo with nanobody using Sortase A-mediated site-specific ligation for drug delivery. The BmExo membrane was first coated with a diglycine-containing amphiphile molecule, NH2-GG-PEG2000-DSPE, through hydrophobic insertion, following by ligation with EGFR nanobody (7D12) by Sortase A (SrtA). The successful construction of BmExo-7D12 was confirmed by Western blotting analysis, electron microscopy, and dynamic light scattering (DLS). As a demonstration model, BmExo-7D12 loaded with the chemotherapeutic drug doxorubicin (Dox) was shown to be able to deliver Dox to cancer cells in response to the expression of EGFR as manifested by immunocytochemistry and flow cytometry analysis. Finally, the cytotoxicity assay showed that BmExo-7D12-Dox was more effective in killing tumor cells with high EGFR expression while significantly reduced the non-specific toxicity to EGFR negative cells. This study developed an effective approach to functionalize BmExo with nanobody for target-specific drug delivery. This approach should prove to be versatile and efficient for the generation of protein-ligands modified BmExo.

Therapeutic effect of oxidized bletilla striata polysaccharide-natamycin eye drops on fungal keratitis.

OBJECTIVE: Fungal keratitis (FK) usually develops to a poor clinical prognosis due to the fungal invasion and excessive inflammatory reaction. In order to enhance the therapeutic effect of natamycin (NAT), we used the anti-inflammatory biological polysaccharide bletilla striata polysaccharide (BSP) combined with NAT to prepare a new eye drop -- oxidized bletilla striata polysaccharide-natamycin (OBN). METHODS: UV-vis, FT-IR, and fluorescence spectroscopy were used to identify the synthesis of OBN. Biocompatibility of OBN was determined by CCK-8, scratch assay, and corneal toxicity test. RAW264.7 cells and C57BL/6 mice were stimulated with A. fumigatus and treated with PBS, OBN, or NAT. The anti-inflammatory activity of OBN was detected by RT-PCR and ELISA. In mice with FK, the clinical scores were used to evaluate the effect of OBN; HE staining was performed to assess the corneal pathological changes; MPO assay and immunofluorescence staining were used to investigate neutrophil infiltration. RESULTS: OBN was synthesized by combining oxidized bletilla striata polysaccharide (OBSP) with NAT through Schiff base reaction. OBN did not affect cell viability at a concentration of 160 µg/mL in HCECs, RAW264.7 cells, and mouse corneas. OBN versus NAT significantly improved the prognosis of A. fumigatus keratitis by reducing disease severity, neutrophil infiltration, and expression of inflammatory factors in vivo. Additionally, OBN treatment down-regulated the mRNA and protein expression levels of inflammatory factors IL-1ß, TNF-α, and IL-6 in RAW264.7 and mouse models. CONCLUSION: OBN is a compound prepared by covalently linking OBSP to the imino group of NAT through Schiff base reaction. OBN treatment down-regulated inflammation and improved the prognosis of mice with A. fumigatus keratitis.

Temporal vascular arcade angle in fundus image was associated with the rate of spherical equivalent refractive error and axial length changes in myopia children with young school age.

PURPOSE: To evaluate temporal vascular arcade angle and its influencing factors in myopic children. METHODS: It was a retrospective study, we reviewed the records of 119 patients aged 6-10 years with myopia (spherical equivalent refractive error (SER) ≤ -0.05D) in the third year of follow-up in Beijing Hyperopia Reserve Research. We measured temporal vascular arcade angles on the fundus photographs and measured 3-year rate of spherical equivalent(D/year) and axial length (AXL) changes(mm/year). RESULTS: Mean age at initial visit was 7.71±1.20 years and mean SER was -1.32±1.09D. Children were divided into two groups according to the refractive status of children at baseline: Myopia onset group (SER>-0.50D at baseline) (n = 107) and Myopia progression group (SER≤-0.50D at baseline) (n = 12). The mean SER in Myopia progression group was much smaller than Myopia onset group (P < 0.001) and mean AXL in Myopia progression group was much longer than Myopia onset group (P = 0.042). AXL (r=-0.320, P < 0.001), SER change rate (r=-0.209, P = 0.022) and AXL change rate (r=-0.232, P = 0.011) were associated with temporal vascular arcade angle in all participants. In Myopia onset group, AXL (r=-0.317, P < 0.001) and AXL change rate (r=-0.190, P = 0.05) were associated with temporal vascular arcade angle. There were no parameters were associated with temporal vascular arcade angle (all P > 0.05) in Myopia progression group. Only AXL (r=-0.306, P = 0.018) was associated with temporal vascular arcade angle in girls while AXL (r=-0.370, P = 0.004), SER change rate (r=-0.317, P = 0.013) and AXL change rate (r=-0.365, P = 0.004) were all associated with the Angle in boys. CONCLUSION: Temporal vascular arcade angle was associated with the rate of SER and AXL changes in myopia onset children, and showed gender differences. These may suggest that lamina cribrosa location has different influencing factors in different genders and different stages of myopia development. Due to the small number of people in Myopia progression group, large sample size studies are still needed in the future.

RNA-binding proteins potentially regulate alternative splicing of immune/inflammatory-associated genes during the progression of generalized pustular psoriasis.

Generalized pustular psoriasis (GPP) is a rare but severe form of psoriasis. However, the pathogenesis of GPP has not been fully elucidated. Although RNA-binding proteins (RBPs) and the alternative splicing (AS) process are essential for regulating post-transcriptional gene expression, their roles in GPP are still unclear. We aimed to elucidate the regulatory mechanisms to identify potential new therapeutic targets. Here, We analyzed an RNA sequencing (RNA-seq) dataset (GSE200977) of peripheral blood mononuclear cells (PBMCs) of 24 patients with GPP, psoriasis vulgaris (PV), and healthy controls (HCs) from the Gene Expression Omnibus (GEO) database. We found that the abnormal alternative splicing (AS) events associated with GPP were mainly "alt3p/alt5p", and 15 AS genes were differentially expressed. Notably, the proportions of different immune cell types were correlated with the expression levels of regulatory alternatively spliced genes (RASGs): significant differences were observed in expression levels of DTD2, NDUFAF3, NBPF15, and FBLN7 in B cells and ARFIP1, IPO11, and RP11-326L24.9 in neutrophils in the GPP samples. Furthermore, We identified 32 differentially expressed RNA-binding proteins (RBPs) (18 up-regulated and 14 down-regulated). Co-expression networks between 14 pairs of differentially expressed RBPs and RASGs were subsequently constructed, demonstrating that these differentially expressed RBPs may affect the progression of GPP by regulating the AS of downstream immune/inflammatory-related genes such as LINC00989, ENC1 and MMP25-AS1. Our results were innovative in revealing the involvement of inflammation-related RBPs and RASGs in the development of GPP from the perspective of RBP-regulated AS.

Melatonin Priming Promotes Crop Seed Germination and Seedling Establishment Under Flooding Stress by Mediating ABA, GA, and ROS Cascades.

Both seed germination and subsequent seedling establishment are key checkpoints during the life cycle of seed plants, yet flooding stress markedly inhibits both processes, leading to economic losses from agricultural production. Here, we report that melatonin (MT) seed priming treatment enhances the performance of seeds from several crops, including soybean, wheat, maize, and alfalfa, under flooding stress. Transcriptome analysis revealed that MT priming promotes seed germination and seedling establishment associated with changes in abscisic acid (ABA), gibberellin (GA), and reactive oxygen species (ROS) biosynthesis and signaling pathways. Real-time quantitative RT-PCR (qRT-PCR) analysis confirmed that MT priming increases the expression levels of GA biosynthesis genes, ABA catabolism genes, and ROS biosynthesis genes while decreasing the expression of positive ABA regulatory genes. Further, measurements of ABA and GA concentrations are consistent with these trends. Following MT priming, quantification of ROS metabolism-related enzyme activities and the concentrations of H2O2 and superoxide anions (O2 -) after MT priming were consistent with the results of transcriptome analysis and qRT-PCR. Finally, exogenous application of GA, fluridone (an ABA biosynthesis inhibitor), or H2O2 partially rescued the poor germination of non-primed seeds under flooding stress. Collectively, this study uncovers the application and molecular mechanisms underlying MT priming in modulating crop seed vigor under flooding stress.

Dual domain distribution disruption with semantics preservation: Unsupervised domain adaptation for medical image segmentation.

Recent unsupervised domain adaptation (UDA) methods in medical image segmentation commonly utilize Generative Adversarial Networks (GANs) for domain translation. However, the translated images often exhibit a distribution deviation from the ideal due to the inherent instability of GANs, leading to challenges such as visual inconsistency and incorrect style, consequently causing the segmentation model to fall into the fixed wrong pattern. To address this problem, we propose a novel UDA framework known as Dual Domain Distribution Disruption with Semantics Preservation (DDSP). Departing from the idea of generating images conforming to the target domain distribution in GAN-based UDA methods, we make the model domain-agnostic and focus on anatomical structural information by leveraging semantic information as constraints to guide the model to adapt to images with disrupted distributions in both source and target domains. Furthermore, we introduce the inter-channel similarity feature alignment based on the domain-invariant structural prior information, which facilitates the shared pixel-wise classifier to achieve robust performance on target domain features by aligning the source and target domain features across channels. Without any exaggeration, our method significantly outperforms existing state-of-the-art UDA methods on three public datasets (i.e., the heart dataset, the brain dataset, and the prostate dataset). The code is available at https://github.com/MIXAILAB/DDSPSeg.

Chronic recurrent multifocal osteomyelitis: Case report and review of the literature.

BACKGROUNDS: Chronic recurrent multifocal osteomyelitis (CRMO) is a rare inflammatory disease. OBJECTIVE: This report aims to analyze the clinical characteristics of CRMO and enhance clinicians' comprehension. We present 3 atypical cases, highlighting their unique clinical features, diagnostic challenges, and effective treatment strategies. METHODS: We retrieved 3 CRMO cases in our hospital from September 2019 to August 2022. The clinical features were analyzed retrospectively, and relevant literatures were reviewed. RESULTS: All 3 cases initially presented with bone pain, normal leucocyte counts, negative rheumatoid factors and no signs of sclerotic or hyperostotic lesions. Case 1, a 12-year-old girl, exhibited concurrent acne on the forehead and historic necrotizing lymphadenitis, a previously unreported association with CRMO. Case 2, a 14-year-old boy, tested positive for human leukocyte antigen-B27 and displayed scoliosis along with multifocal osteomyelitis. Case 3, a 9-year-old girl, presented with scoliosis, and chest computed tomography revealed changes in the T8 vertebral body, initially suggesting Langerhans cell histiocytosis. Bone biopsy was conducted in case 1 and case 3, revealing chronic inflammation. All 3 cases affected long bones, pelvis, and vertebra, involving 8, 6 and 5 bones, respectively, identified by magnetic resonance imaging. Genetic analysis was undertaken in cases 1 and 2 but no pathogenic mutations were identified. Upon the confirmation of a CRMO diagnosis, all patients were initiated on a treatment regimen comprising nonsteroidal anti-inflammatory drugs and tumor necrosis factor-α inhibitors. In cases 1 and 2, due to the severity of their bone pain, they were also administered to disease-modifying anti-rheumatic drugs, specifically methotrexate. All 3 patients achieved remission of bone pain. To gain a more comprehensive understanding of CRMO, we conducted a thorough review of relevant literature. CONCLUSION: CRMO is a rare autoinflammatory bone disorder with diverse clinical presentations and a lack of specific laboratory tests, which leads to potency to misdiagnosis or delayed diagnosis. By raising awareness and improving diagnostic criteria, physicians are now better equipped to identify CRMO. We contribute to share our understanding of CRMO by presenting 3 cases with untypical clinical features, highlighting the importance of recognizing this rare condition for timely and effective management.

Inter-cellular mRNA Transfer Alters Human Pluripotent Stem Cell State.

Inter-cellular transmission of mRNA is being explored in mammalian species using immortal cell lines (1-3). Here, we uncover an inter-cellular mRNA transfer phenomenon that allows for the adaptation and reprogramming of human primed pluripotent stem cells (hPSCs). This process is induced by the direct cell contact-mediated coculture with mouse embryonic stem cells (mESCs) under the condition impermissible for human primed PSC culture. Mouse-derived mRNA contents are transmitted into adapted hPSCs only in the coculture. Transfer-specific mRNA analysis show the enrichment for divergent biological pathways involving transcription/translational machinery and stress-coping mechanisms, wherein such transfer is diminished when direct cell contacts are lost. After 5 days of mESC culture, surface marker analysis, and global gene profiling confirmed that mRNA transfer-prone hPSC efficiently gains a naïve-like state. Furthermore, transfer-specific knockdown experiments targeting mouse-specific transcription factor-coding mRNAs in hPSC show that mouse-derived Tfcp2l1, Tfap2c, and Klf4 are indispensable for human naïve-like conversion. Thus, inter-species mRNA transfer triggers cellular reprogramming in mammalian cells. Our results support that episodic mRNA transfer can occur in cell cooperative and competitive processes(4), which provides a fresh perspective on understanding the roles of mRNA mobility for intra- and inter-species cellular communications.

The mechanism of RGS5 regulating gastric cancer mismatch repair protein.

The incidence and mortality rates of gastric cancer (GC) remain alarmingly high worldwide, imposing a substantial healthcare burden. In this study, we utilized data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A 4-gene prognostic model was developed to predict patient prognosis, and its accuracy was validated across multiple datasets. Patients with a low-risk score exhibited improved prognosis, elevated tumor mutation burden, heightened sensitivity to both immunotherapy and conventional chemotherapy. Notably, our investigation revealed that the key gene RGS5 positively modulates the expression of mismatch repair proteins via c-Myc. Furthermore, co-immunoprecipitation (COIP) assays demonstrated the interaction between RGS5 and c-Myc. Additionally, we confirmed that RGS5 regulates c-Myc through the ubiquitin-proteasome pathway. Moreover, RGS5 was identified as a positive regulator of PD-L1 expression and exhibited a negative correlation with the majority of immune cells. These findings underscore the potential of RGS5 as a novel biomarker and therapeutic target in the context of GC.

Non-lactational mastitis with multiple sinus wounds treated by integrated traditional Chinese and Western medicine.

OBJECTIVE: Non-lactational mastitis (NLM) is a benign inflammatory disease of the mammary gland, with pain, swelling and redness as the main clinical manifestations. There is no unified and effective standard treatment plan for this disease at present. In addition to breast cancer, non-lactational mastitis is also becoming a presenting complaint in an increasing number of outpatients at the authors' clinic. This case report summarises the treatment and management of a 35-year-old female patient with NLM complicated with multiple sinus wounds after surgery. METHOD: The patient was treated as follows, with: timely debridement according to the local condition of the wound, with manual compression to drain exudate from the sinus wound; selected wound dressings according to their performance and characteristics to fill the sinus tract for drainage and infection control; psychological care of the patient and their family to ensure that patients actively participate in the treatment; family support to the patient to deal with negative emotions; integrated traditional Chinese and Western medicine to prevent/manage infection; dietary care and control; posture management and health education to facilitate the patient's wound healing process. RESULTS: After local management with systemic treatment and management using integrated traditional Chinese and Western medicine, the wound healed after 46 days, with no recurrence during a follow-up period of one year. CONCLUSION: As shown in this case report, the wound should be cut and drained as soon as possible in order to prevent obstruction of the sinus drainage. Modern wound dressings are selected for the 'external' treatment of local wounds. Integrated traditional Chinese and Western medicine may help in systemic therapy of the whole patient.

3-MCPD Induces Renal Cell Pyroptosis and Inflammation by Inhibiting ESCRT-III-Mediated Cell Repair and Mitophagy.

3-Monochloropropane-1,2-diol (3-MCPD) is a chloropropyl alcohol contaminant mainly from the thermal processing of food and could affect kidneys. Pyroptosis is programmed cell death mediated by inflammasomes and gasdermins, and excessive cellular pyroptosis and inflammation can lead to tissue injury. In the present study, we found that 3-MCPD increased lactate dehydrogenase (LDH) levels in vitro and in vivo, increased the protein expression of NOD-like receptor family pyrin domain containing 3 (NLRP3), N-terminal domain of GSDMD (GSDMD-N), and cleaved caspase-1 and promoted the release of interleukin-1ß (IL-1ß) and interleukin-18 (IL-18), which induced renal cell pyroptosis and inflammation. Mechanistic studies indicated that the addition of N-acetylcysteine (NAC), a ROS scavenger, inhibited NLRP3 activation and attenuated pyroptosis. Furthermore, we revealed that 3-MCPD induced ROS accumulation by inhibiting ESCRT-III-mediated mitophagy. These results were further validated by the overexpression of charged multivesicular body protein 4B (CHMP4B), a key subunit of ESCRT-III, and the addition of the mitophagy activator carbonyl cyanide m-chlorophenylhydrazone (CCCP) and rapamycin (Rapa). Thus, our results showed that 3-MCPD could induce mitochondrial damage and produce ROS. 3-MCPD suppressed mitophagy, leading to the accumulation of damaged mitochondria and ROS, thereby activating NLRP3 and pyroptosis. Meanwhile, 3-MCPD-mediated suppression of ESCRT-III hindered the repair of GSDMD-induced cell membrane rupture, which further caused the occurrence of pyroptosis. Our findings provide new perspectives for studying the mechanisms underlying 3-MCPD-induced renal injury.

Earthworm gut bacteria facilitate cadmium immobilization through the formation of CdS nanoparticles.

Gut bacteria of earthworm Amynthas hupeiensis exhibit significant potential for the in-situ remediation of cadmium (Cd)-contaminated soil. However, the mechanisms by which these gut bacteria immobilize and tolerate Cd remain elusive. The composition of the gut bacterial community was characterized by high-throughput sequencing. Cd-tolerant bacteria were isolated from the gut, and their roles in Cd immobilization, as well as their tolerance mechanisms, were explored through chemical characterization and transcriptome analysis. The predominant taxa in the gut bacterial community included unclassified Enterobacteriaceae, Citrobacter, and Bacillus, which were distinctly different from those in the surrounding soil. Notably, the most Cd-tolerant gut bacterium, Citrobacter freundii DS strain, immobilized 63.61% of Cd2+ within 96 h through extracellular biosorption and intracellular bioaccumulation of biosynthetic CdS nanoparticles, and modulation of solution pH and NH4+ concentration. Moreover, the characteristic signals of CdS were also observed in the gut content of A. hupeiensis when the sterilized Cd-contaminated soil was inoculated with C. freundii. The primary pathways involved in the response of C. freundii to Cd stress included the regulation of ABC transporters, bacterial chemotaxis, cell motility, oxidative phosphorylation, and two-component system. In conclusion, C. freundii facilitates Cd immobilization both in vitro and in vivo, thereby enhancing the host earthworm's adaptation to Cd-contaminated soil.