Structural and functional insights into the helicase protein E5 of Mpox virus.

Mpox virus (MPXV) can cause mpox in humans. Due to its quick and wide spread in the past two years, mpox has turned into a significant public health concern. Helicase E5 is a multi-domain protein; its primer synthesis and DNA unwinding activity are required for genome uncoating and DNA replication of MPXV. However, the in vitro DNA unwinding activity has never been demonstrated. Here, we report the structural and biochemical studies of MPXV E5, showing that the full-length protein adopts an auto-inhibited conformation. Truncation of the N-terminus can recover the in vitro unwinding activity of E5 towards the forked DNA. Further structural analysis reveals that MPXV E5 shares a conserved mechanism in DNA unwinding and primer synthesis with the homologous proteins. These findings not only advance our understanding on the function of MPXV E5, but also provide a solid basis for the development of anti-poxvirus drugs.

Persistence of dissolved organic matter in sediments influenced by environmental factors：Implication for nutrition and carbon cycle.

The persistence of dissolved organic matter (DOM) plays a crucial role in the cycling and distribution of carbon and nutrients. Nonetheless, our understanding of how environmental alterations affect the persistence of sedimentary DOM remains incomplete. Excitation Emission Fluorescence Matrix-Parallel Factor Analysis (EEM-PARAFAC) was used to examine the fluorescence and compositional characteristics of hydrophilic and hydrophobic DOM (separated using XAD-8 resin) within sediments from twelve lakes and reservoirs. Fluorescence analysis indicated that DOM persistence is dependent on the proportions of the three components derived from PARAFAC. The Mantel test showed that climatic factors had the most significant impact on DOM persistence (Mantel's r = 0.46-0.54, Mantel's p = 0.001-0.007), while anthropogenic (Mantel's r = 0.24-0.32, Mantel's p = 0.03-0.05) and hydrological factors (Mantel's r = 0.03-0.22, Mantel's p = 0.06-0.40) had a somewhat lesser influence. Environmental changes resulted in a consistent decline in DOM persistence from Northeast to Southwest China, accompanied by an increase in gross primary productivity (GPP). Reduced DOM persistence due to climate, hydrological, and anthropogenic factors may lead to elevated concentrations of total phosphorus (TP), contributing to deteriorating water quality and events such as algal blooms. The decline in water quality due to reduced DOM persistence in lakes with high GPP can exacerbate the transition from carbon sinks to carbon sources. Consequently, the persistence of sedimentary DOM significantly influences nutrient and carbon cycling in lakes. Investigating DOM persistence in lakes across diverse geographic locations offers a new perspective on lake eutrophication and carbon emissions. Furthermore, it is crucial to develop targeted recommendations for lake restoration and management.

Reduction of specific enterocytes from loss of intestinal LGR4 improves lipid metabolism in mice.

Whether intestinal Leucine-rich repeat containing G-protein-coupled receptor 4 (LGR4) impacts nutrition absorption and energy homeostasis remains unknown. Here, we report that deficiency of Lgr4 (Lgr4iKO) in intestinal epithelium decreased the proportion of enterocytes selective for long-chain fatty acid absorption, leading to reduction in lipid absorption and subsequent improvement in lipid and glucose metabolism. Single-cell RNA sequencing demonstrates the heterogeneity of absorptive enterocytes, with a decrease in enterocytes selective for long-chain fatty acid-absorption and an increase in enterocytes selective for carbohydrate absorption in Lgr4iKO mice. Activation of Notch signaling and concurrent inhibition of Wnt signaling are observed in the transgenes. Associated with these alterations is the substantial reduction in lipid absorption. Decrement in lipid absorption renders Lgr4iKO mice resistant to high fat diet-induced obesity relevant to wild type littermates. Our study thus suggests that targeting intestinal LGR4 is a potential strategy for the intervention of obesity and liver steatosis.

Prognostic Value of Sublingual Microcirculation in Sepsis: A Systematic Review and Meta-analysis.

Objectives: To investigate the relationship between sublingual microcirculation and the prognosis of sepsis. Data sources: The PubMed, Web of Science, Embase, and China National Knowledge Infrastructure (CNKI) databases were searched to identify studies published from January 2003 to November 2023. Study selection: Clinical studies examining sublingual microcirculation and the prognosis of sepsis were included. Data extraction: Sublingual microcirculation indices included the microvascular blood index (MFI), total vascular density (TVD), perfusion vascular density (PVD), perfusion vascular vessel (PPV), and heterogeneity index (HI). Prognostic outcomes included mortality and severity. Funnel plots and Egger's test were used to detect publication bias. The ability of the small vessel PPV (PPVs) to predict sepsis-related mortality was analyzed based on the summary receiver operating characteristic (SROC) curve, pooled sensitivity, and pooled specificity. Data synthesis: Twenty-five studies involving 1750 subjects were included. The TVD (95% CI 0.11-0.39), PVD (95% CI 0.42-0.88), PPV (95% CI 6.63-13.83), and MFI (95% CI 0.13-0.6) of the survival group were greater than those of the nonsurvival group. The HI in the survival group was lower than that in the nonsurvival group (95% CI -0.49 to -0.03). The TVD (95% CI 0.41-0.83), PVD (95% CI 0.83-1.17), PPV (95% CI 14.49-24.9), and MFI (95% CI 0.25-0.66) of the nonsevere group were greater than those of the severe group. Subgroup analysis revealed no significant difference in TVD between the survival group and the nonsurvival group in the small vessel subgroup. The area under the SROC curve (AUC) was 0.88. Conclusions: Sublingual microcirculation was worse among patients who died and patients with severe sepsis than among patients who survived and patients with nonsevere sepsis. PPV has a good predictive value for the mortality of sepsis patients. This study was recorded in PROSPERO (registration number: CRD42023486349).

Effect of luminescent materials on the aquatic macrophyte Vallisneria natans and periphytic biofilm.

Luminescent materials can adjust the spectrum of light energy utilization by plants. However, current research on the effects of luminescent materials on aquatic plants and periphytic biofilms is limited. This study investigated the effects of the luminescent materials 4-(di-p-tolylamino) benzaldehyde-A (DTB-A) and 4-(di-p-tolylamino) benzaldehyde-M (DTB-M) on the submerged macrophyte Vallisneria natans (V. natans) and periphytic biofilm. Result demonstrated that low concentrations of DTB (0.1 µM) significantly promoted the growth and photosynthetic rate of V. natans. In terms of enzyme activity, exposure to a higher concentration of DTB (10 µM) increased the activities of peroxidase (POD), superoxide dismutase (SOD) and catalase (CAT). A combination of DTB-A and DTB-M treatment significantly changed the V. natans morphology and physiological characteristics, reducing the thickness of the cell wall and subsequently, promoting protein accumulation in leaves. There was no difference in the removal of ammonia or phosphate by V. natans at the 0.1 µM concentration, and the removal of ammonia and phosphate by V. natans decreased significantly as the concentration of luminescent material increased. A total of 3563 OTUs were identified in the biofilm community. The microbial community was dominated by Pseudomonas and Fusobacteria. Furthermore, results showed that an obvious decrease in diversity in the DTB-A and DTB-M mixed treatment group. In addition, the migratory aggregation of DTB molecules in plants was observed by fluorescence imaging. Overall, these findings extend our understanding of the mechanism of effect of luminescent materials on submerged macrophytes and their periphytic microorganisms.

Identifying ALOX15-initiated lipid peroxidation increases susceptibility to ferroptosis in asthma epithelial cells.

Ferroptosis is a programmed form of cell death regulated by iron and has been linked to the development of asthma. However, the precise mechanisms driving ferroptosis in asthma remain elusive. To gain deeper insights, we conducted an analysis of nasal epithelial and sputum samples from the GEO database using three machine learning methods. Our investigation identified a pivotal gene, Arachidonate 15-lipoxygenase (ALOX15), associated with ferroptosis in asthma. Through both in vitro and in vivo experiments, we further confirmed the significant role of ALOX15 in ferroptosis in asthma. Our results demonstrate that ferroptosis manifests in an HDM/LPS-induced allergic airway inflammation (AAI) mouse model, mimicking human asthma, and in HDM/LPS-stimulated 16HBE cells. Moreover, we observed an up-regulation of ALOX15 expression in HDM/LPS-induced mice and cells. Notably, silencing ALOX15 markedly decreased HDM/LPS-induced ferroptosis in 16HBE cells. These findings indicate that ferroptosis may be implicated in the onset and progression of asthma, with ALOX15-induced lipid peroxidation raising the susceptibility to ferroptosis in asthmatic epithelial cells.

Rspo2-LGR4 exacerbates hepatocellular carcinoma progression via activation of Wnt/b-catenin signaling pathway / Rspo2-LGR4 agrava la progresión del carcinoma hepatocelular al activar la vía de señalización Wnt/beta-catenina

Background: The leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4) plays an important role in stem cell differentiation, organ development and cancer. Whether LGR4 affects the progression of hepatocellular carcinoma (HCC) remains unknown. This study aimed to reveal the role of LGR4 in HCC. Methods: Clinical samples of HCC were collected to assess the expression of LGR4 and its correlation with patients’ clinical characteristics. The expression level of LGR4 in HCC cells was altered by pharmacological and genetic methods, and the role of LGR4 in HCC progression was analyzed by in vivo and in vitro assays. HCC was induced by diethylnitrosamine (DEN) and carbon tetrachloride (CCl4) in wild-type and LGR4 deficient mice, the effect of LGR4 on HCC was examined by histopathological evaluation and biochemical assays. Results: LGR4 expression was up-regulated in HCC samples, and its expression level was positively correlated with tumor size, microvascular invasion (MVI), TNM stage and pathological differentiation grade of HCC patients. In the mouse HCC model induced by DEN+CCl4, knockdown of LGR4 effectively inhibited the progression of HCC. Silencing of LGR4 inhibited the proliferation, migration, invasion, stem cell-like properties and Warburg effect of HCC cells. These phenotypes were promoted by R-spondin2 (Rspo2), an endogenous ligand for LGR4. Rspo2 markedly increased the nuclear translocation of β-catenin, whereas IWR-1, an inhibitor of Wnt/β-catenin signaling, reversed its effect. Deficiency of LGR4 significantly reduced the nuclear translocation of β-catenin and the expression of its downstream target genes cyclinD1 and c-Myc. Conclusions: LGR4 promotes HCC progression via Wnt/β-catenin signaling pathway. (AU)

Antecedentes: El receptor de acoplamiento de proteínas G de secuencia repetida 4 (LGR4), rico en leucina, juega un papel importante en la diferenciación de células madre, el desarrollo de órganos y el cáncer. Se desconoce si LGR4 afecta la progresión del carcinoma hepatocelular (HCC). El objetivo de este estudio es revelar el papel de LGR4 en el HCC. Métodos: Se recolectaron muestras clínicas de HCC para evaluar la expresión de LGR4 y su correlación con los resultados clínicos de HCC. Alterar los niveles de expresión de LGR4 en las células de HCC mediante métodos farmacológicos y genéticos y analizar el papel de LGR4 en la progresión del cáncer de hígado mediante mediciones in vivo e in vitro. El HCC fue inducido en ratones de tipo salvaje y con defectos de LGR4 con Nitrosamina de dietilo (DEN) y cloruro de carbono (CCl4), y los efectos de LGR4 sobre el HCC fueron detectados por evaluación histopatológica y determinación bioquímica. Resultados: La expresión de LGR4 está regulada en HCC, y su nivel de expresión está positivamente relacionado con el tamaño tumoral, la infiltración microvascular (MVI), la etapa de TNM y el grado de diferenciación patológica en pacientes con HCC. En el modelo de HCC de ratón inducido por DEN+CCl4, golpear bajo LGR4 inhibió efectivamente la progresión del HCC. El silencio de LGR4 inhibe la proliferación, migración, invasión, propiedades similares a las células madre y el efecto Warburg de las células HCC. Estos fenotipos son promovidos por el ligando endógeno roof slab-specific sponge 2 (Rspo2)de LGR4. El Rspo2 aumentó significativamente la translocación nuclear de la proteína beta-catenina, mientras que el inhibidor de la señalización Wnt/beta-cateninaIWR-1 revirtió su acción... (AU)

High-resolution crystal structure of RNA kinase ArK1 from G. acetivorans.

U47 phosphorylation (Up47) is a novel tRNA modification discovered recently; it can confer thermal stability and nuclease resistance to tRNAs. U47 phosphorylation is catalyzed by Archaeal RNA kinase (Ark1) in an ATP-dependent manner. However, the structural basis for tRNA and/or ATP binding by Ark1 is unclear. Here, we report the expression, purification, and crystallization studies of Ark1 from G. acetivorans (GaArk1). In addition to the Apo-form structure, one GaArk1-ATP complex was also determined in atomic resolution and revealed the detailed basis for ATP binding by GaArk1. The GaArk1-ATP complex represents the only ATP-bound structure of the Ark1 protein. The majority of the ATP-binding residues are conserved, suggesting that GaArk1 and the homologous proteins share similar mechanism in ATP binding. Sequence and structural analysis further indicated that endogenous guanosine will only inhibit the activities of certain Ark1 proteins, such as Ark1 from T. kodakarensis.

Hepatic LGR4 aggravates cholestasis-induced liver injury in mice.

Current therapy for hepatic injury induced by the accumulation of bile acids is limited. Leucine-rich repeat G protein-coupled receptor 4 (LGR4), also known as GPR48, is critical for cytoprotection and cell proliferation. Here, we reported a novel function for the LGR4 in cholestatic liver injury. In the bile duct ligation (BDL)-induced liver injury model, hepatic LGR4 expression was significantly downregulated. Deficiency of LGR4 in hepatocytes (Lgr4LKO) notably decreased BDL-induced liver injury measured by hepatic necrosis, fibrosis, and circulating liver enzymes and total bilirubin. Levels of total bile acids in plasma and liver were markedly reduced in these mice. However, deficiency of LGR4 in macrophages (Lyz2-Lgr4MKO) demonstrated no significant effect on liver injury induced by BDL. Deficiency of LGR4 in hepatocytes significantly attenuated S1PR2 and the phosphorylation of protein kinase B (AKT) induced by BDL. Recombinant Rspo1 and Rspo3 potentiated the taurocholic acid (TCA)-induced upregulation in S1PR2 and phosphorylation of AKT in hepatocytes. Inhibition of S1PR2-AKT signaling by specific AKT or S1PR2 inhibitors blocked the increase of bile acid secretion induced by Rspo1/3 in hepatocytes. Our studies indicate that the R-spondins (Rspos)-LGR4 signaling in hepatocytes aggravates the cholestatic liver injury by potentiating the production of bile acids in a S1PR2-AKT-dependent manner.NEW & NOTEWORTHY Deficiency of LGR4 in hepatocytes alleviates BDL-induced liver injury. LGR4 in macrophages demonstrates no effect on BDL-induced liver injury. Rspos-LGR4 increases bile acid synthesis and transport via potentiating S1PR2-AKT signaling in hepatocytes.

Indole-3-acetic acid alleviates DSS-induced colitis by promoting the production of R-equol from Bifidobacterium pseudolongum.

BACKGROUND: Inflammatory bowel disease (IBD) is characterized by immune-mediated, chronic inflammation of the intestinal tract. The occurrence of IBD is driven by the complex interactions of multiple factors. The objective of this study was to evaluate the therapeutic effects of IAA in colitis. METHOD: C57/BL6 mice were administered 2.5% DSS in drinking water to induce colitis. IAA, Bifidobacterium pseudolongum, and R-equol were administered by oral gavage and fed a regular diet. The Disease Activity Index was used to evaluate disease activity. The degree of colitis was evaluated using histological morphology, RNA, and inflammation marker proteins. CD45+ CD4+ FOXP3+ Treg and CD45+ CD4+ IL17A+ Th17 cells were detected by flow cytometry. Analysis of the gut microbiome in fecal content was performed using 16S rRNA gene sequencing. Gut microbiome metabolites were analyzed using Untargeted Metabolomics. RESULT: In our study, we found IAA alleviates DSS-induced colitis in mice by altering the gut microbiome. The abundance of Bifidobacterium pseudolongum significantly increased in the IAA treatment group. Bifidobacterium pseudolongum ATCC25526 alleviates DSS-induced colitis by increasing the ratio of Foxp3+T cells in colon tissue. R-equol alleviates DSS-induced colitis by increasing Foxp3+T cells, which may be the mechanism by which ATCC25526 alleviates DSS-induced colitis in mice. CONCLUSION: Our study demonstrates that IAA, an indole derivative, alleviates DSS-induced colitis by promoting the production of Equol from Bifidobacterium pseudolongum, which provides new insights into gut homeostasis regulated by indole metabolites other than the classic AHR pathway.

Gastric mechanosensitive channel Piezo1 regulates ghrelin production and food intake.

Ghrelin, produced mainly by gastric X/A-like cells, triggers a hunger signal to the central nervous system to stimulate appetite. It remains unclear whether X/A-like cells sense gastric distention and thus regulate ghrelin production. Here we show that PIEZO1 expression in X/A-like cells decreases in patients with obesity when compared to controls, whereas it increases after sleeve gastrectomy. Male and female mice with specific loss of Piezo1 in X/A-like cells exhibit hyperghrelinaemia and hyperphagia and are more susceptible to overweight. These phenotypes are associated with impairment of the gastric CaMKKII/CaMKIV-mTOR signalling pathway. Activation of PIEZO1 by Yoda1 or gastric bead implantation inhibits ghrelin production, decreases energy intake and induces weight loss in mice. Inhibition of ghrelin production by Piezo1 through the CaMKKII/CaMKIV-mTOR pathway can be recapitulated in a ghrelin-producing cell line mHypoE-42. Our study reveals a mechanical regulation of ghrelin production and appetite by PIEZO1 of X/A-like cells, which suggests a promising target for anti-obesity therapy.

Intermittent fasting promotes type 3 innate lymphoid cells secreting IL-22 contributing to the beigeing of white adipose tissue.

Mechanism underlying the metabolic benefit of intermittent fasting remains largely unknown. Here, we reported that intermittent fasting promoted interleukin-22 (IL-22) production by type 3 innate lymphoid cells (ILC3s) and subsequent beigeing of subcutaneous white adipose tissue. Adoptive transfer of intestinal ILC3s increased beigeing of white adipose tissue in diet-induced-obese mice. Exogenous IL-22 significantly increased the beigeing of subcutaneous white adipose tissue. Deficiency of IL-22 receptor (IL-22R) attenuated the beigeing induced by intermittent fasting. Single-cell sequencing of sorted intestinal immune cells revealed that intermittent fasting increased aryl hydrocarbon receptor signaling in ILC3s. Analysis of cell-cell ligand receptor interactions indicated that intermittent fasting may stimulate the interaction of ILC3s with dendritic cells and macrophages. These results establish the role of intestinal ILC3s in beigeing of white adipose tissue, suggesting that ILC3/IL-22/IL-22R axis contributes to the metabolic benefit of intermittent fasting.

Obesity refers to a condition where a person has excessive fat accumulation, which can have negative impacts on their health. Managing obesity has typically relied on reducing energy intake and increasing energy use through diets and exercise. For example, intermittent fasting is a diet strategy involving periods of time in a day or week where a person does not eat any food. Research has shown that intermittent fasting may improve the metabolism and increase energy use by enhancing a process known as "beigeing" of white fat tissue. In this process, white fat cells or their precursor cells differentiate into beige fat cells, which can consume excess energy by burning fat. Consequently, understanding how beigeing of white fat cells is activated in intermittent fasting may reveal a promising strategy for tackling obesity and metabolic diseases. Immune cells found in the gut known as innate lymphoid cells (ILCs) may play a role in the metabolic benefits from intermittent fasting. However, the roles of ILCs are complex: some types of ILCs can promote obesity, while others show metabolic benefits through their release of proteins like IL-17 and IL-22, which can help the body to metabolise glucose. To find out if these immune cells play a role in intermittent fasting, Chen, Sun et al. used diet-induced obese mice that had to fast every other day. Intermittent fasting was found to cause a form of ILCs (ILC3s) to release IL-22, which resulted in beigeing of white fat cells in obese mice. Single-cell sequencing techniques of gut immune cells further revealed that intermittent fasting increased forms of signalling in ILC3s and caused ILC3s to interact with other immune cells, such as dendritic cells and macrophages. The findings demonstrate how intermittent fasting causes beigeing of white adipose tissue through ILC3s, revealing mechanisms underpinning the metabolic benefits found from intermittent fasting. More research into this process may help identify new targets for treating obesity.

A phase II study of efficacy and safety of the MEK inhibitor tunlametinib in patients with advanced NRAS-mutant melanoma.

BACKGROUND: NRAS-mutant melanoma is an aggressive subtype with poor prognosis; however, there is no approved targeted therapy to date worldwide. METHODS: We conducted a multicenter, single-arm, phase II, pivotal registrational study that evaluated the efficacy and safety of the MEK inhibitor tunlametinib in patients with unresectable, stage III/IV, NRAS-mutant melanoma (NCT05217303). The primary endpoint was objective response rate (ORR) assessed by independent radiological review committee (IRRC) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. The secondary endpoints included progression-free survival (PFS), disease control rate (DCR), duration of response(DOR), overall survival (OS) and safety. FINDINGS: Between November 2, 2020 and February 11, 2022, a total of 100 patients were enrolled. All (n = 100) patients received at least one dose of tunlametinib (safety analysis set [SAS]) and 95 had central laboratory-confirmed NRAS mutations (full analysis set [FAS]). In the FAS, NRAS mutations were observed at Q61 (78.9%), G12 (15.8%) and G13 (5.3%). The IRRC-assessed ORR was 35.8%, with a median DOR of 6.1 months. The median PFS was 4.2 months, DCR was 72.6% and median OS was 13.7 months. Subgroup analysis showed that in patients who had previously received immunotherapy, the ORR was 40.6%. No treatment-related deaths occurred. INTERPRETATION: Tunlametinib showed promising antitumor activity with a manageable safety profile in patients with advanced NRAS-mutant melanoma, including those who had prior exposure to immunotherapy. The findings warrant further validation in a randomized clinical trial.

Differential Diagnosis of Post Pancreatitis Diabetes Mellitus Based on Pancreatic and Gut Hormone Characteristics.

CONTEXT: Distinguishing different types of diabetes is important in directing optimized treatment strategies and correlated epidemiological studies. OBJECTIVE: Through detailed analysis of hormone responses to mixed meal tolerance test (MMTT), we aimed to find representing characteristics of post-acute pancreatitis diabetes mellitus (PPDM-A) and post-chronic pancreatitis diabetes mellitus (PPDM-C). METHODS: Participants with PPDM-A, PPDM-C, type 1 diabetes, type 2 diabetes, and normal controls (NCs) underwent MMTT. Fasting and postprandial responses of serum glucose, C-peptide, insulin, glucagon, pancreatic polypeptide (PP), ghrelin, gastric inhibitory peptide (GIP), glucagon like peptide-1 (GLP-1), and peptide YY (PYY) were detected and compared among different groups. Focused analysis on calculated insulin sensitivity and secretion indices were performed to determine major causes of hyperglycemia in different conditions. RESULTS: Participants with PPDM-A were characterized by increased C-peptide, insulin, glucagon, and PP, but decreased ghrelin, GIP, and PYY compared with NCs. Patients with PPDM-C showed secretion insufficiency of C-peptide, insulin, ghrelin, and PYY, and higher postprandial responses of glucagon and PP than NCs. In particular, both fasting and postprandial levels of ghrelin in PPDM-C were significantly lower than other diabetes groups. PYY responses in patients with PPDM-A and PPDM-C were markedly reduced. Additionally, the insulin sensitivity of PPDM-A was decreased, and the insulin secretion for PPDM-C was decreased. CONCLUSION: Along with the continuum from acute to chronic pancreatitis, the pathological mechanism of PPDM changes from insulin resistance to insulin deficiency. Insufficient PYY secretion is a promising diagnostic marker for distinguishing PPDM from type 1 and type 2 diabetes. Absent ghrelin secretion to MMTT may help identify PPDM-C.

Hormetic effect of a short-chain PFBS on Microcystis aeruginosa and its molecular mechanism.

Short-chain Perfluorinated compounds (PFCs), used as substitutes for highly toxic long-chain PFCs, are increasingly entering the aquatic environment. However, the toxicity of short-chain PFCs in the environment is still controversial. This study investigated the effects of short-chain perfluorobutanesulfonic acid (PFBS) at different concentrations (2.5, 6, 14.4, 36, and 90 mg/L) on M. aeruginosa growth under 12-day exposure and explored the molecular mechanism of toxicity using transcriptomics. The results showed that M. aeruginosa exhibited hormetic effects after exposure to PFBS. Low PFBS concentrations stimulated algal growth, whereas high PFBS concentrations inhibited it, and this inhibitory effect became progressively more pronounced with increasing PFBS exposure concentrations. Transcriptomics showed that PFBS promoted the pathways of photosynthesis, glycolysis, energy metabolism and peptidoglycan synthesis, providing the energy required for cell growth and maintaining cellular morphology. PFBS, on the other hand, caused growth inhibition in algae mainly through oxidative stress, streptomycin synthesis, and genetic damage. Our findings provide new insights into the toxicity and underlying mechanism of short-chain PFCs on algae and inform the understanding of the hormetic effect of short-chain PFCs, which are crucial for assessing their ecological risks in aquatic environments.

A case of hemorrhagic fever with renal syndrome and abnormal serum levels of ferritin, vitamin B12, and folic acid.

INTRODUCTION: Hemorrhagic fever with renal syndrome (HFRS) is a globally prevalent infectious disease caused by the hantavirus in rodents. CASE STUDY: This report describes a case of a 36-year-old male presenting with elevated ferritin, vitamin B12, and folic acid deficiency during the early onset phase of HFRS. Despite normal renal function at admission, the patient exhibited persistent fever and thrombocytopenia, leading to a potential misdiagnosis of an atypical HFRS presentation. Abnormal serum levels of ferritin, vitamin B12, and folic acid served as early indicators of renal dysfunction in patients with HRFS. The patient's condition improved rapidly with a combination of vitamin B6, methyl cobalamin, and folic acid, as evidenced by a subsequent decrease in the ferritin levels, from 3000 to 600 ng/mL, on days 4 and 24, respectively, and an increase in the vitamin B12 and folic acid levels to 200 pg/mL and 36.7 ng/mL, separately. CONCLUSIONS: These findings suggest that ferritin, vitamin B12, and folic acid have the potential to serve as biomarkers for HFRS and play a predictive role in the diagnosis and treatment of the disease.

Sulfite induced degradation of sulfamethoxazole by a silica stabilized ZIF-67(Co) catalyst via non-radical pathways: Formation and role of high-valent Co(IV) and singlet oxygen.

The sulfite (S(IV))-based advanced oxidation process (AOP) has emerged as an appealing alternative to the traditional persulfate-based AOP for the elimination of organic contaminants from diverse water matrices. In this work, a silica reinforced ZIF-67(Co) catalyst (CZS) is fabricated, characterized and tested in the activation of S(IV) for the sulfamethoxazole (SMX) degradation. The prepared CZS demonstrates superior stability and catalytic ability for the degradation of SMX compared to ZIF-67(Co) across a broad pH range. Unlike the conventional radical-dominated oxidation systems, the CZS/S(IV) system for SMX degradation operates through a non-radical mechanism, featuring high-valent Co(IV) and singlet oxygen (1O2) as the predominated reactive species. The hydroxylated Co species exposed on the CZS surface is identified as the pivotal active site, realizing the S(IV) activation through a complexation-electron transfer process, resulting in the production of various reactive intermediates. Co(II) undergoes the conversion to Co(IV) by generated HSO5-, and 1O2 predominantly originates from the intermediate SO4•-. Profiting from the highly selective oxidation capacities of Co(IV) and 1O2, the established oxidative system demonstrates a remarkable interference resistance and exhibits an exceptional decontamination performance under real-world water conditions. In short, this work provides a sustainable S(IV)-based oxidation strategy for environmental remediation via non-radical mechanism.

Effect of luminescent materials on the biochemistry, ultrastructure, and rhizobial microbiota of Spirodela polyrhiza.

Fluorescent materials and technologies have become widely used in scientific research, and due to the ability to convert light wavelengths, their application to photosynthetic organisms can affect their development by altering light quality. However, the impacts of fluorescent materials on aquatic plants and their environmental risks remain unclear. To assess the effects of luminescent materials on floating aquatic macrophytes and their rhizosphere microorganisms, 4-(di-p-tolylamino)benzaldehyde-A (DTB-A) and 4-(di-p-tolylamino)benzaldehyde-M (DTB-M) (emitting blue-green and orange-red light, respectively) were added individually and jointly to Spirodela polyrhiza cultures and set at different concentrations (1, 10, and 100 µM). Both DTB-A and DTB-M exhibited phytotoxicity, which increased with concentration under separate treatment. Moreover, the combined group exhibited obvious stress relief at 10 µM compared to the individually treated group. Fluorescence imaging showed that DTB-A and DTB-M were able to enter the cell matrix and organelles of plant leaves and roots. Peroxidation induced cellular damage, contributing to a decrease in superoxide dismutase (SOD) and peroxidase (POD) activities and malondialdehyde (MDA) accumulation. Decomposition of organelle structures, starch accumulation in chloroplasts, and plasmolysis were observed under the ultrastructure, disrupting photosynthetic pigment content and photosynthesis. DTB-A and DTB-M exposure resulted in growth inhibition, dry weight loss, and leaf yellowing in S. polyrhiza. A total of 3519 Operational Taxonomic Units (OTUs) were identified in the rhizosphere microbiome. The microbial communities were dominated by Alphaproteobacteria, Oxyphotobacteria, and Gammaproteobacteria, with the abundance and diversity varied significantly among treatment groups according to Shannon, Simpson, and Chao1 indices. This study revealed the stress defense response of S. polyrhiza to DTB-A and DTB-M exposures, which provides a broader perspective for the bioremediation of pollutants using aquatic plants and supports the further development of fluorescent materials for applications.

Rspo2-LGR4 exacerbates hepatocellular carcinoma progression via activation of Wnt/ß-catenin signaling pathway.

BACKGROUND: The leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4) plays an important role in stem cell differentiation, organ development and cancer. Whether LGR4 affects the progression of hepatocellular carcinoma (HCC) remains unknown. This study aimed to reveal the role of LGR4 in HCC. METHODS: Clinical samples of HCC were collected to assess the expression of LGR4 and its correlation with patients' clinical characteristics. The expression level of LGR4 in HCC cells was altered by pharmacological and genetic methods, and the role of LGR4 in HCC progression was analyzed by in vivo and in vitro assays. HCC was induced by diethylnitrosamine (DEN) and carbon tetrachloride (CCl4) in wild-type and LGR4 deficient mice, the effect of LGR4 on HCC was examined by histopathological evaluation and biochemical assays. RESULTS: LGR4 expression was up-regulated in HCC samples, and its expression level was positively correlated with tumor size, microvascular invasion (MVI), TNM stage and pathological differentiation grade of HCC patients. In the mouse HCC model induced by DEN+CCl4, knockdown of LGR4 effectively inhibited the progression of HCC. Silencing of LGR4 inhibited the proliferation, migration, invasion, stem cell-like properties and Warburg effect of HCC cells. These phenotypes were promoted by R-spondin2 (Rspo2), an endogenous ligand for LGR4. Rspo2 markedly increased the nuclear translocation of ß-catenin, whereas IWR-1, an inhibitor of Wnt/ß-catenin signaling, reversed its effect. Deficiency of LGR4 significantly reduced the nuclear translocation of ß-catenin and the expression of its downstream target genes cyclinD1 and c-Myc. CONCLUSIONS: LGR4 promotes HCC progression via Wnt/ß-catenin signaling pathway.