AAV mediated carboxyl terminus of Hsp70 interacting protein overexpression mitigates the cognitive and pathological phenotypes of APP/PS1 mice.

JOURNAL/nrgr/04.03/01300535-202501000-00033/figure1/v/2024-05-14T021156Z/r/image-tiff The E3 ubiquitin ligase, carboxyl terminus of heat shock protein 70 (Hsp70) interacting protein (CHIP), also functions as a co-chaperone and plays a crucial role in the protein quality control system. In this study, we aimed to investigate the neuroprotective effect of overexpressed CHIP on Alzheimer's disease. We used an adeno-associated virus vector that can cross the blood-brain barrier to mediate CHIP overexpression in APP/PS1 mouse brain. CHIP overexpression significantly ameliorated the performance of APP/PS1 mice in the Morris water maze and nest building tests, reduced amyloid-ß plaques, and decreased the expression of both amyloid-ß and phosphorylated tau. CHIP also alleviated the concentration of microglia and astrocytes around plaques. In APP/PS1 mice of a younger age, CHIP overexpression promoted an increase in ADAM10 expression and inhibited ß-site APP cleaving enzyme 1, insulin degrading enzyme, and neprilysin expression. Levels of HSP70 and HSP40, which have functional relevance to CHIP, were also increased. Single nuclei transcriptome sequencing in the hippocampus of CHIP overexpressed mice showed that the lysosomal pathway and oligodendrocyte-related biological processes were up-regulated, which may also reflect a potential mechanism for the neuroprotective effect of CHIP. Our research shows that CHIP effectively reduces the behavior and pathological manifestations of APP/PS1 mice. Indeed, overexpression of CHIP could be a beneficial approach for the treatment of Alzheimer's disease.

Gray matter alterations in Huntington's disease: A meta-analysis of VBM neuroimaging studies.

Increasing neuroimaging studies have attempted to identify biomarkers of Huntington's disease (HD) progression. Here, we conducted voxel-based meta-analyses of voxel-based morphometry (VBM) studies on HD to investigate the evolution of gray matter volume (GMV) alterations and explore the effects of genetic and clinical features on GMV changes. A systematic review was performed to identify the relevant studies. Meta-analyses of whole-brain VBM studies were performed to assess the regional GMV changes in all HD mutation carriers, in presymptomatic HD (pre-HD), and in symptomatic HD (sym-HD). A quantitative comparison was performed between pre-HD and sym-HD. Meta-regression analyses were used to explore the effects of genetic and clinical features on GMV changes. Twenty-eight studies were included, comparing a total of 1811 HD mutation carriers [including 1150 pre-HD and 560 sym-HD] and 969 healthy controls (HCs). Pre-HD showed decreased GMV in the bilateral caudate nuclei, putamen, insula, anterior cingulate/paracingulate gyri, middle temporal gyri, and left dorsolateral superior frontal gyrus compared with HCs. Compared with pre-HD, GMV decrease in sym-HD extended to the bilateral median cingulate/paracingulate gyri, Rolandic operculum and middle occipital gyri, left amygdala, and superior temporal gyrus. Meta-regression analyses found that age, mean lengths of CAG repeats, and disease burden were negatively associated with GMV atrophy of the bilateral caudate and right insula in all HD mutation carriers. This meta-analysis revealed the pattern of GMV changes from pre-HD to sym-HD, prompting the understanding of HD progression. The pattern of GMV changes may be biomarkers for disease progression in HD.

Serological and molecular survey of Toxoplasma gondii infection and associated risk factors in urban cats in Kunming, Southwest China.

Toxoplasma gondii (T. gondii) is a worldwide zoonotic parasite that can infect almost warm-blood animals, including humans, which seriously affect the health of host. Cats are known to be the only definitive host of T. gondii and continuously excrete highly infectious oocysts. This parasite carried by the companion animals leads to a great public health risk. However, there is little information on epidemiology of T. gondii in urban cats in Kunming, Southwest China. In the present study, a total of 231 serum and fecal samples were collected in Kunming aera, and then seroprevalence of T. gondii IgG antibodies in serum and molecular investigation in feces were analyzed to elucidate T. gondii infection in urban cats. The results revealed that 168 of 231 cats (72.7%) were positive for T. gondii antibodies, and 1 of 74 cat feces (1.4%) also showed a positive PCR for T. gondii DNA. The positive fecal sample was sequenced and then phylogenetically analyzed, and the isolate of T. gondii in the present study was closely related to T. gondii strain CN. In addition, the food, water and age of cats were identified as the risk factor for seropositivity. Overall, our findings indicate the widespread occurrence of T. gondii infection in urban cats in Kunming, Southwest China and identify food, water and age are the risk factors associated with T. gondii infection, which can provide effective information for developing strategies to prevent and control this zoonosis.

Desulfovibrio-induced gauzy FeS for efficient hexavalent chromium removal: The influence of SRB metabolism regulated by carbon source and electron carriers.

Biosynthetic metal sulfides showed great application prospects in the environmental treatment against high-valence metal pollutants. However, the efficiency of biosynthesis, agglomeration during the reaction process, and the formation of the passivation layer during the reduction process were always the important factors restricting its development. This study explored the composition of the culture medium to promote the growth of highly corrosive sulfate-reducing bacteria (SRB) and its metabolism to produce FeS nanoparticles (NPs). The results showed that reducing the carbon source (CS) and adding electron carriers in the culture medium effectively promoted the production of small, dispersed, and loose FeS NPs in cells. At pH = 7, 24 °C and 10 min reaction time, 0.1 g/L FeS NPs produced by SRB under the conditions of 10 % CS with 10 ppm cytochrome c medium could achieve 100 % removal efficiency of 1 mM hexavalent chromium (Cr(VI)). Under this condition, FeS NPs could be produced by intracellular metabolism in SRB cells, and environmental factors such as pH, metal cations, and Cl- had little effect on the removal of Cr(VI) by this FeS NPs. The surface proteins of FeS NPs significantly enhanced their antioxidant properties. After 7 days of natural environment exposure, the Cr(VI) removal efficiency of FeS NPs was only reduced by 16 % compared with the initial sample. This work provided an in-depth understanding of Cr(VI) removal by SRB biosynthesis of FeS and contributes to the widespread application of FeS in the future.

Coordination Engineering of Fe-centered Catalysts for Superior Li-S Battery Performance.

Iron-nitrogen functionalized graphene has emerged as a promising cathode host for rechargeable lithium-sulfur batteries (RLSBs) due to its affordability and enhanced battery performance. To optimize its catalytical efficiency, we propose a novel approach involving coordination engineering. Our investigation spans a plethora of catalysts with varied coordination environments, focusing on elements B, C, N and O. We revealed that Fe-C4 and Fe-B2C2-h are particularly effective for promoting Li2S oxidation, whereas Fe-N4 excels in catalyzing the sulfur reduction reaction (SRR). Importantly, our study identified specific descriptors - namely, the Integrated Crystal Orbital Hamilton Population (ICOHP) and the bond length between Fe and S in Li2S adsorbed state - as the most effective predictive descriptors for Li2S oxidation barriers. Meanwhile, Li2S adsorption energy emerges as a reliable descriptor for assessing the SRR barrier. These identified descriptors are expected to be instrumental in rapidly identifying promising cathode hosts across various metal-centered systems with diverse coordination environments. Our findings not only offer valuable insights into the role of coordination environment, but also present an effective path for rapidly identifying high performance catalysts for RLSBs, enabling the acceleration of advanced RLSBs development.

Piperine induces autophagy of colon cancer cells: Dual modulation of AKT/mTOR signaling pathway and ROS production.

BACKGROUND: Colorectal cancer (CRC) is a prevalent malignancy and poses a significant clinical challenge. Piperine, an alkaloid molecule extracted from Piper nigrum and Piper longum, has emerged as a promising anticancer agent. However, the molecular mechanisms of piperine' antitumor effects in CRC need to be further elucidated. METHODS: Human colorectal cancer cells were treated with piperine in vitro. CCK-8 and clone formation assays were adopted to detect cell viability. The accumulation of autophagosomes was assessed by Western blotting and immunofluorescence. Apoptosis and reactive oxygen species (ROS) levels were analyzed by flow. In vivo, a xenograft tumor mouse model was constructed using CT26 cells. RESULTS: Piperine inhibited CRC cell viability and suppressed tumor weight and volume in a mouse model. Additionally, piperine treatment induced the accumulation of autophagosomes in CRC cells. This effect was attributed to the inhibition of the AKT/mTOR pathway and the accumulation of ROS. activation of AKT or clearance of ROS attenuated piperine-mediated tumor suppression. CONCLUSION: This study shows that piperine induces autophagy-dependent cell death in CRC cells by increasing ROS production and inhibiting Akt/mTOR signaling.

Association of the systemic immune-inflammation index with all-cause and cardiovascular mortality in individuals with rheumatoid arthritis.

The systemic immune-inflammation index (SII), a metric reflecting systemic inflammatory response and immune activation, remains underexplored concerning its correlation with mortality among rheumatoid arthritis (RA) patients. This study aimed to delineate the association between SII and both all-cause and cardiovascular mortality within the cohort of American adults diagnosed with RA, utilizing data from the National Health and Nutrition Examination Survey (NHANES) spanning 1999 to 2018. The investigation extracted data from NHANES cycles between 1999 and 2018, identifying RA patients through questionnaire responses. The SII was computed based on complete blood counts, employing the formula: (platelets × neutrophils) / lymphocytes. The optimal SII cutoff value for significant survival outcomes was determined using maximally selected rank statistics. Multivariable Cox proportional hazards models assessed the relationship between SII levels and mortality (all-cause and cardiovascular) among RA patients, with subgroup analyses examining potential modifications by clinical confounders. Additionally, restricted cubic spline (RCS) analyses were conducted to explore the linearity of the SII-mortality association. The study encompassed 2070 American adults with RA, among whom 287 exhibited a higher SII (≥ 919.75) and 1783 a lower SII (< 919.75). Over a median follow-up duration of 108 months, 602 participants died. After adjustments for demographic, socioeconomic, and lifestyle variables, a higher SII was associated with a 1.48-fold increased risk of all-cause mortality (hazard ratio [HR] = 1.48, 95% confidence interval [CI] 1.21-1.81, P < 0.001) and a 1.51-fold increased risk of cardiovascular mortality (HR = 1.51, 95% CI 1.04-2.18, P = 0.030) compared to a lower SII. Kaplan-Meier analyses corroborated significantly reduced survival rates within the higher SII cohort for both all-cause and cardiovascular mortality (Pall-cause mortality < 0.0001 and Pcardiovascular mortality = 0.0004). RCS analyses confirmed a positive nonlinear relationship between SII and mortality rates. In conclusion, the SII offers a straightforward indicator of the equilibrium between detrimental innate inflammation and beneficial adaptive immunity. Our investigation, utilizing a comprehensive and nationally representative sample, reveals that elevated SII levels independently forecast a greater risk of mortality from all causes, as well as cardiovascular-specific mortality, in individuals suffering from RA. These insights underscore the clinical relevance of the SII as an affordable and readily accessible biomarker. Its incorporation into regular clinical practice could significantly enhance the precision of risk assessment and forecasting for patients with RA, facilitating more tailored and effective management strategies. Specifically, patients with high SII levels could be identified for more stringent cardiovascular risk management, including closer monitoring, lifestyle interventions, and aggressive pharmacological treatments to mitigate their increased risk of mortality.

Environmental damping and vibrational coupling of confined fluids within isolated carbon nanotubes.

Because of their large surface areas, nanotubes and nanowires demonstrate exquisite mechanical coupling to their surroundings, promising advanced sensors and nanomechanical devices. However, this environmental sensitivity has resulted in several ambiguous observations of vibrational coupling across various experiments. Herein, we demonstrate a temperature-dependent Radial Breathing Mode (RBM) frequency in free-standing, electron-diffraction-assigned Double-Walled Carbon Nanotubes (DWNTs) that shows an unexpected and thermally reversible frequency downshift of 10 to 15%, for systems isolated in vacuum. An analysis based on a harmonic oscillator model assigns the distinctive frequency cusp, produced over 93 scans of 3 distinct DWNTs, along with the hyperbolic trajectory, to a reversible increase in damping from graphitic ribbons on the exterior surface. Strain-dependent coupling from self-tensioned, suspended DWNTs maintains the ratio of spring-to-damping frequencies, producing a stable saturation of RBM in the low-tension limit. In contrast, when the interior of DWNTs is subjected to a water-filling process, the RBM thermal trajectory is altered to that of a Langmuir isobar and elliptical trajectories, allowing measurement of the enthalpy of confined fluid phase change. These mechanisms and quantitative theory provide new insights into the environmental coupling of nanomechanical systems and the implications for devices and nanofluidic conduits.

An improved Trizol method for extracting total RNA from Eleutherococcus senticosus (Rupr. & Maxim.) Maxim leaves.

INTRODUCTION: High-quality nucleic acids are the basis for molecular biology experiments. Traditional RNA extraction methods are not suitable for Eleutherococcus senticosus Maxim. OBJECTIVE: To find a suitable method to improve the quality of RNA extracted, we modified the RNA extraction methods of Trizol. METHODOLOGY: Based on the conventional Trizol method, the modified Trizol method 1 and modified Trizol method 2 were used as the control for extraction of RNA from E. senticosus Maxim leaves. The modified Trizol method 1 added ß-mercaptoethanol on the conventional Trizol method. After RNA was dissolved, a mixed solution of phenol, chloroform, and isoamyl alcohol was added to denature protein and inhibit the degradation of RNA. The modified Trizol method 2 adds PVPP to grind on the basis of modified Trizol method 1, so as to better remove phenols from leaves, and eliminates the step of incubation at -20°C to reduce extraction time and RNA degradation. Chloroform, CTAB, and CH3COONa were used instead of a phenol, chloroform, and isoamyl alcohol mixed solution to ensure complete separation of nucleic acid from plant tissues and to obtain high-purity RNA. RESULTS: The research results showed that the quality of RNA extracted by conventional Trizol method, modified Trizol method 1, was incomplete, accompanied with different degrees of contamination of polysaccharides, polyphenols, and DNA. The modified Trizol method 2 could better extract RNA from E. senticosus Maxim leaves. The ratio of A260/A280 was in the range of 1.8-2.0, and the yield of RNA was the highest, which was 1.68 and 1.15 times compared with that by conventional Trizol method and modified Trizol method 1 extraction, respectively. The reverse transcription cDNA was further tested through PCR with the specific primers. The amplified fragments are displayed in clear and bright bands in accordance with the expected size. CONCLUSION: The modified Trizol method 2 could better extract RNA from E. senticosus Maxim leaves. High-quality RNA has more advantages in molecular biology study of E. senticosus Maxim.

Corrigendum: Effects of Caragana korshinskii tannin on fermentation, methane emission, community of methanogens, and metabolome of rumen in sheep.

[This corrects the article DOI: 10.3389/fmicb.2024.1334045.].

MAPK4 facilitates angiogenesis by inhibiting the ERK pathway in non-small cell lung cancer.

Background: Angiogenesis plays an important role in the occurrence and development of non-small cell lung cancer (NSCLC). The atypical mitogen-activated protein kinase 4 (MAPK4) has been shown to be involved in the pathogenesis of various diseases. However, the potential role of MAPK4 in the tumor angiogenesis of NSCLC remains unclear. Methods: Adult male C57BL/6 wild-type mice were randomly divided into the control group and p-siMAPK4 intervention group, respectively. The cell proliferation was analyzed with flow cytometry and immunofluorescence staining. The vascular density in tumor mass was analyzed by immunofluorescence staining. The expressions of MAPK4 and related signaling molecules were detected by western blot analysis and immunofluorescence staining, and so on. Results: We found that the expression of MAPK4, which was dominantly expressed in local endothelial cells (ECs), was correlated with tumor angiogenesis of NSCLC. Furthermore, MAPK4 silencing inhibited the proliferation and migration abilities of human umbilical vein ECs (HUVECs). Global gene analysis showed that MAPK4 silencing altered the expression of multiple genes related to cell cycle and angiogenesis pathways, and that MAPK4 silencing increased transduction of the extracellular regulated protein kinases 1/2 (ERK1/2) pathway but not Akt and c-Jun n-terminal kinase pathways. Further analysis showed that MAPK4 silencing inhibited the proliferation and migration abilities of HUVECs cultured in tumor cell supernatant, which was accompanied with increased transduction of the ERK1/2 pathway. Clinical data analysis suggested that the higher expression of MAPK4 and CD34 were associated with poor prognosis of patients with NSCLC. Targeted silencing of MAPK4 in ECs using small interfering RNA driven by the CD34 promoter effectively inhibited tumor angiogenesis and growth of NSCLC in vivo. Conclusion: Our results reveal that MAPK4 plays an important role in the angiogenesis and development of NSCLC. MAPK4 may thus represent a new target for NSCLC.

Single-cell sequencing of the substantia nigra reveals microglial activation in a model of MPTP.

Background: N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin widely used to induce PD models, but the effect of MPTP on the cells and genes of PD has not been fully elucidated. Methods: Single-nucleus RNA sequencing was performed in the Substantia Nigra (SN) of MPTP mice. UMAP analysis was used for the dimensionality reduction visualization of the SN in the MPTP mice. Known marker genes highly expressed genes in each cluster were used to annotate most clusters. Specific Differentially Expressed Genes (DEGs) and PD risk genes analysis were used to find MPTP-associated cells. GO, KEGG, PPI network, GSEA and CellChat analysis were used to reveal cell type-specific functional alterations and disruption of cell-cell communication networks. Subset reconstruction and pseudotime analysis were used to reveal the activation status of the cells, and to find the transcription factors with trajectory characterized. Results: Initially, we observed specific DEGs and PD risk genes enrichment in microglia. Next, We obtained the functional phenotype changes in microglia and found that IGF, AGRN and PTN pathways were reduced in MPTP mice. Finally, we analyzed the activation state of microglia and revealed a pro-inflammatory trajectory characterized by transcription factors Nfe2l2 and Runx1. Conclusion: Our work revealed alterations in microglia function, signaling pathways and key genes in the SN of MPTP mice.

Prognostic insights, immune infiltration, and therapeutic response: Cytoplasmic poly(A) tail regulators in hepatocellular carcinoma.

The presence of a poly(A) tail is indispensable for the post-transcriptional regulation of gene expression in cancer. This dynamic and modifiable feature of transcripts is under the control of various nuclear and cytoplasmic proteins. This study aimed to develop a novel cytoplasmic poly(A)-related signature for predicting prognosis, clinical attributes, tumor immune microenvironment (TIME), and treatment response in hepatocellular carcinoma (HCC). Utilizing RNA sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA), non-negative matrix factorization (NMF), and principal-component analysis (PCA) were employed to categorize HCC patients into three clusters, thus demonstrating the pivotal prognostic role of cytoplasmic poly(A) tail regulators. Furthermore, machine learning algorithms such as least absolute shrinkage and selection operator (LASSO), survival analysis, and Cox proportional hazards modeling were able to distinguish distinct cytoplasmic poly(A) subtypes. As a result, a 5-gene signature derived from TCGA was developed and validated using International Cancer Genome Consortium (ICGC) HCC datasets. This novel classification based on cytoplasmic poly(A) regulators has the potential to improve prognostic predictions and provide guidance for chemotherapy, immunotherapy, and transarterial chemoembolization (TACE) in HCC.

Parathyroid carcinoma located in the thyroid gland: A case report.

BACKGROUND: Parathyroid carcinoma (PC) is a difficult-to-diagnose rare disease with low incidence. Relatively accurate preoperative diagnosis is very important in choosing surgical methods and patient prognosis. CASE SUMMARY: This study reported the clinical diagnosis and treatment of a rare patient with PC located in the thyroid gland and provided a case reference for the diagnosis and treatment of PC. A case of a 64-year-old male patient who presented to our hospital with systemic muscle and joint pain and palpitations is outlined. Subsequently, the patient was admitted to the Department of Nephrology for the treatment of "multiple myeloma nephropathy pending investigation". The patient was diagnosed with "primary hyperparathyroidism and hypercalcemic crisis" using thyroid color ultrasound. CONCLUSION: The intraoperative frozen section report considered the parathyroid tumor. Surgical tumor resection was promptly performed, and the diagnosis of PC was confirmed.

Human herpesvirus 7 meningitis in an adolescent with normal immune function: A case report.

BACKGROUND: Human herpesvirus type 7 (HHV-7) is a less common herpes virus that usually causes mild, self-limiting illnesses. However, in recent years, there have been increasing reports of HHV-7 causing serious central nervous system infections, especially meningitis. The pathogenesis and clinical features of HHV-7 meningitis, particularly in adolescents with normal immune function, remain incompletely studied. Therefore, the purpose of this report is to share a case of HHV-7 meningitis in an immunocompetent adolescent with a view to deepening our understanding of the disease. CASE SUMMARY: A 12-year-old female was admitted with fever, headache, and vomiting. 4 d before admission, the patient developed a fever without obvious induction, with a temperature up to 39.5 °C, no convulsions, accompanied by chills, headaches, fatigue, and no muscle aches. The patient was treated with fever reduction, which could be reduced to 38 °C; repeated high fever, accompanied by vomiting 7-8 times; and no abdominal pain or diarrhea. The patient was diagnosed with "acute suppurative tonsillitis" in a local hospital, and the blood routine was generally normal. The patient was given symptomatic support treatment such as "ceftriaxone sodium" and antiemetic rehydration for 2 d, and his condition did not improve. The patient's physical examination showed pharyngeal congestion, bilateral tonsil grade I hypertrophy, regression of purulent secretions, and cervical resistance. Ocular B-ultrasound: Opacity of the vitreous body and edema of the optic disc in both eyes. Optical coherence tomography examination showed that the macular fovea was generally normal in both eyes, with edema of the optic disc. DNA virus monitoring results: HHV-7. We gave ganciclovir antiviral therapy, dexamethasone anti-inflammatory treatment, mannitol to reduce cranial pressure, omeprazole to protect gastrointestinal mucosa, and calcium and potassium supplementation. CONCLUSION: This study reports a case of HHV-7 meningitis in an adolescent with normal immune function. Through comprehensive analysis of the clinical manifestations, laboratory tests, and treatment methods of the patient, it is found that early identification and antiviral treatment are essential for the outcome of the disease. This case suggests that despite normal immune function, adolescents may still suffer from herpes virus type 7 meningitis, so clinicians should be vigilant and take effective treatment measures in time.

An anti-CRISPR that pulls apart a CRISPR-Cas complex.

In biological systems, the activities of macromolecular complexes must sometimes be turned off. Thus, a wide variety of protein inhibitors has evolved for this purpose. These inhibitors function through diverse mechanisms, including steric blocking of crucial interactions, enzymatic modification of key residues or substrates, and perturbation of post-translational modifications1. Anti-CRISPRs-proteins that block the activity of CRISPR-Cas systems-are one of the largest groups of inhibitors described, with more than 90 families that function through diverse mechanisms2-4. Here, we characterize the anti-CRISPR AcrIF25, and we show that it inhibits the type I-F CRISPR-Cas system by pulling apart the fully assembled effector complex. AcrIF25 binds to the predominant CRISPR RNA-binding components of this complex, comprising six Cas7 subunits, and strips them from the RNA. Structural and biochemical studies indicate that AcrIF25 removes one Cas7 subunit at a time, starting at one end of the complex. Notably, this feat is achieved with no apparent enzymatic activity. To our knowledge, AcrIF25 is the first example of a protein that disassembles a large and stable macromolecular complex in the absence of an external energy source. As such, AcrIF25 establishes a paradigm for macromolecular complex inhibitors that may be used for biotechnological applications.

Wnt signaling in gastric cancer: current progress and future prospects.

Levels of the Wnt pathway components are abnormally altered in gastric cancer cells, leading to malignant cell proliferation, invasion and metastasis, poor prognosis and chemoresistance. Therefore, it is important to understand the mechanism of Wnt signaling pathway in gastric cancer. We systematically reviewed the molecular mechanisms of the Wnt pathway in gastric cancer development; and summarize the progression and the challenges of research on molecular agents of the Wnt pathway.

Sulfur dioxide inhibits mast cell degranulation by sulphenylation of galectin-9 at cysteine 74.

Objectives: Mast cell (MC) degranulation is a key process in allergic reactions and inflammatory responses. Aspartate aminotransferase 1 (AAT1)-derived endogenous sulfur dioxide (SO2) is an important regulator of MC function. However, the mechanism underlying its role in MC degranulation remains unclear. This study aimed to investigate the mechanism by which endogenous SO2 controlled MC degranulation. Methods: HMC-1 and Rat basophilic leukemia cell MC line (RBL-2H3) were used in the cell experiments. SO2 content was detected by in situ fluorescent probe. MC degranulation represented by the release rate of MC ß-hexosaminidase was determined using a colorimetric assay. Sulfenylation of galectin-9 (Gal-9) in MCs and purified protein was detected using a biotin switch assay. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to determine the exact sulfenylation sites of Gal-9 by SO2. Animal models of passive cutaneous anaphylaxis (PCA) and hypoxia-driven pulmonary vascular remodeling were used to investigate the effect of SO2 on mast cell activation in vivo. Site-directed mutation of Gal-9 was conducted to confirm the exact site of SO2 and support the significance of SO2/Gal-9 signal axis in the regulation of MC degranulation. Results: Degranulation was increased in AAT1-knockdowned MCs, and SO2 supplementation reversed the increase in MC degranulation. Furthermore, deficiency of endogenous SO2 contributed to IgE-mediated degranulation in vitro. Besides, SO2 inhibited IgE-mediated and hypoxia-driven MC degranulation in vivo. Mechanistically, LC-MS/MS analysis and site-directed mutation results showed that SO2 sulfenylated Gal-9 at cysteine 74. Sulfenylation of the 74th cysteine of Gal-9 protein was required in the SO2-inhibited MC degranulation under both physiological and pathophysiological conditions. Conclusion: These findings elucidated that SO2 inhibited MC degranulation via sulfenylating Gal-9 under both physiological and pathophysiological conditions, which might provide a novel treatment approach for MC activation-related diseases.

Modeling microbial impact on macrophyte debris decomposition in macrophyte-dominated eutrophic lakes.

The decomposition of macrophytes plays a crucial role in the nutrient cycles of macrophyte-dominated eutrophication lakes. While research on plant decomposition mechanisms and microbial influences has rapid developed, it is curious that plant decomposition models have remained stagnant at the single-stage model from 50 years ago, without endeavor to consider any important factors. Our research conducted in-situ experiments and identified the optimal metrics for decomposition-related microbes, thereby establishing models for microbial impacts on decomposition rates (k_RDR). Using backward elimination in stepwise regression, we found that the optimal subset of independent variables-specifically Gammaproteobacteria-Q-L, Actinobacteriota-Q-L, and Ascomycota-Q-L-increased the adjusted R-squared (Ra2) to 0.93, providing the best modeling for decomposition rate (p = 0.002). Additionally, k_RDR can be modeled by synergic parameters of ACHB-Q-L, LDB-Q-L, and AB-Q-L for bacteria, and SFQ for fungi, albeit with a slightly lower Ra2 of 0.7-0.9 (p < 0.01). The primary contribution of our research lies in two key aspects. Firstly, we introduced optimal metrics for modeling microbes, opting for debris surface microbes over sediment microbes, and prioritizing absolute abundance over relative abundance. Secondly, our model represents a noteworthy advancement in debris modeling. Alongside elucidating the focus and innovative aspects of our work, we also addressed existing limitations and proposed directions for future research. SYNOPSIS: This study explores optimum metrics for decomposition-related microbes, offering precise microbial models for enhanced lake nutrient cycle simulation.

Clinicopathological characteristics and prognosis of uterine sarcoma: a 10-year retrospective single-center study in China.

BACKGROUND: Uterine sarcoma is a rare and heterogeneous gynecological malignancy characterized by aggressive progression and poor prognosis. The current study aimed to investigate the relationship between clinicopathological characteristics and the prognosis of uterine sarcoma in Chinese patients. METHODS: In this single-center retrospective study, we reviewed the medical records of 75 patients with histologically verified uterine sarcoma treated at the First Affiliated Hospital of Xi'an Jiaotong University between 2011 and 2020. Information on clinical characteristics, treatments, pathology and survival was collected. Progression-free survival (PFS) and overall survival (OS) were visualized in Kaplan-Meier curves. Prognostic factors were identified using the log-rank test for univariate analysis and Cox-proportional hazards regression models for multivariate analysis. RESULTS: The histopathological types included 36 endometrial stromal sarcomas (ESS,48%), 33 leiomyosarcomas (LMS,44%) and 6 adenosarcomas (8%). The mean age at diagnosis was 50.2 ± 10.7 years. Stage I and low-grade accounted for the majority. There were 26 recurrences and 25 deaths at the last follow-up. The mean PFS and OS were 89.41 (95% CI: 76.07-102.75) and 94.03 (95% CI: 81.67-106.38) months, respectively. Univariate analysis showed that > 50 years, post-menopause, advanced stage, ≥ 1/2 myometrial invasion, lymphovascular space invasion and high grade were associated with shorter survival (P < 0.05). Color Doppler flow imaging positive signals were associated with shorter PFS in the LMS group (P = 0.046). The ESS group had longer PFS than that of the LMS group (99.56 vs. 76.05 months, P = 0.043). The multivariate analysis showed that post-menopause and advanced stage were independent risk factors of both PFS and OS in the total cohort and LMS group. In the ESS group, diagnosis age > 50 years and high-grade were independent risk factors of PFS, while high-grade and lymphovascular space invasion were independent risk factors of OS. CONCLUSION: In Chinese patients with uterine sarcoma, post-menopause and advanced stage were associated with a significantly poorer prognosis. The prognosis of ESS was better than that of LMS. Color Doppler flow imaging positive signals of the tumor helped to identify LMS, which needs to be further tested in a larger sample in the future.