Extracellular pectin-RALF phase separation mediates FERONIA global signaling function.

The FERONIA (FER)-LLG1 co-receptor and its peptide ligand RALF regulate myriad processes for plant growth and survival. Focusing on signal-induced cell surface responses, we discovered that intrinsically disordered RALF triggers clustering and endocytosis of its cognate receptors and FER- and LLG1-dependent endocytosis of non-cognate regulators of diverse processes, thus capable of broadly impacting downstream responses. RALF, however, remains extracellular. We demonstrate that RALF binds the cell wall polysaccharide pectin. They phase separate and recruit FER and LLG1 into pectin-RALF-FER-LLG1 condensates to initiate RALF-triggered cell surface responses. We show further that two frequently encountered environmental challenges, elevated salt and temperature, trigger RALF-pectin phase separation, promiscuous receptor clustering and massive endocytosis, and that this process is crucial for recovery from stress-induced growth attenuation. Our results support that RALF-pectin phase separation mediates an exoskeletal mechanism to broadly activate FER-LLG1-dependent cell surface responses to mediate the global role of FER in plant growth and survival.

FERONIA controls pectin- and nitric oxide-mediated male-female interaction.

Species that propagate by sexual reproduction actively guard against the fertilization of an egg by multiple sperm (polyspermy). Flowering plants rely on pollen tubes to transport their immotile sperm to fertilize the female gametophytes inside ovules. In Arabidopsis, pollen tubes are guided by cysteine-rich chemoattractants to target the female gametophyte1,2. The FERONIA receptor kinase has a dual role in ensuring sperm delivery and blocking polyspermy3. It has previously been reported that FERONIA generates a female gametophyte environment that is required for sperm release4. Here we show that FERONIA controls several functionally linked conditions to prevent the penetration of female gametophytes by multiple pollen tubes in Arabidopsis. We demonstrate that FERONIA is crucial for maintaining de-esterified pectin at the filiform apparatus, a region of the cell wall at the entrance to the female gametophyte. Pollen tube arrival at the ovule triggers the accumulation of nitric oxide at the filiform apparatus in a process that is dependent on FERONIA and mediated by de-esterified pectin. Nitric oxide nitrosates both precursor and mature forms of the chemoattractant LURE11, respectively blocking its secretion and interaction with its receptor, to suppress pollen tube attraction. Our results elucidate a mechanism controlled by FERONIA in which the arrival of the first pollen tube alters ovular conditions to disengage pollen tube attraction and prevent the approach and penetration of the female gametophyte by late-arriving pollen tubes, thus averting polyspermy.

Inducing a Synergistic Effect on Ptδ+/Electron-Rich Sites via a Platinization Strategy: Generating Hyper-High Current Density in Hydrogen Evolution Reaction.

Herein, we propose a platinization strategy for the preparation of Pt/X catalysts with low Pt content on substrates possessing electron-rich sites (Pt/X: X = Co3O4, NiO, CeO2, Covalent Organic Framework (COF), etc.). In examples with inorganic and organic substrates, respectively, Pt/Co3O4 possesses remarkable catalytic ability toward HER, achieving a current density at an overpotential of 500 mV that is 3.22 times higher than that of commercial Pt/C. It was also confirmed by using operando Raman spectroscopy that the enhancement of catalytic activity was achieved after platinization of the COF, with a reduction of overpotential from 231 to 23 mV at 10 mA cm-2. Density functional theory (DFT) reveals that the improved catalytic activity of Pt/Co3O4 and Pt/COF originated from the re-modulation of Ptδ+ on the electronic structure and the synergistic effect of the interfacial Ptδ+/electron-rich sites. This work provides a rapid synthesis strategy for the synthesis of low-content Pt catalysts for electrocatalytic hydrogen production.

Isoliquiritigenin diminishes invasiveness of human nasopharyngeal carcinoma cells associating with inhibition of MMP-2 expression and STAT3 signalling.

Nasopharyngeal carcinoma (NPC) is prevalent in Asia and exhibits highly metastatic characteristics, leading to uncontrolled disease progression. Isoliquiritigenin (ISL) have attracted attention due to their diverse biological and pharmacological properties, including anticancer activities. However, the impact of ISL on the invasive and migratory ability of NPC remains poorly understood. Hence, this study aimed to investigate the in vitro anti-metastatic effects of ISL on NPC cells and elucidate the underlying signalling pathways. Human NPC cell NPC-39 and NPC-BM were utilized as cell models. Migratory and invasive capabilities were evaluated through wound healing and invasion assays, respectively. Gelatin zymography was employed to demonstrate matrix metalloproteinase-2 (MMP-2) activity, while western blotting was conducted to analyse protein expression levels and explore signalling cascades. Overexpression of signal transducer and activator of transcription 3 (STAT3) was carried out by transduction of STAT3-expressing vector. Our findings revealed that ISL effectively suppressed the migration and invasion of NPC cells. Gelatin zymography and Western blotting assays demonstrated that ISL treatment led to a reduction in MMP-2 enzyme activity and protein expression. Investigation of signalling cascades revealed that ISL treatment resulted in the inhibition of STAT3 phosphorylation. Moreover, overexpression of STAT3 restored the migratory ability of NPC cells in the presence of ISL. Collectively, these findings indicate that ISL inhibits the migration and invasion of NPC cells associating with MMP-2 downregulation through suppressing STAT3 activation. This suggests that ISL has an anti-metastatic effect on NPC cells and has potential therapeutic benefit for NPC treatment.

Differential regulation of phosphorylation, structure, and stability of circadian clock protein FRQ isoforms.

Neurospora crassa is an important model organism for circadian clock research. The Neurospora core circadian component FRQ protein has two isoforms, large FRQ (l-FRQ) and small FRQ (s-FRQ), of which l-FRQ bears an additional N-terminal 99-amino acid fragment. However, how the FRQ isoforms operate differentially in regulating the circadian clock remains elusive. Here, we show l-FRQ and s-FRQ play different roles in regulating the circadian negative feedback loop. Compared to s-FRQ, l-FRQ is less stable and undergoes hypophosphorylation and faster degradation. The phosphorylation of the C-terminal l-FRQ 794-aa fragment was markedly higher than that of s-FRQ, suggesting the l-FRQ N-terminal 99-aa region may regulate the phosphorylation of the entire FRQ protein. Quantitative label-free LC/MS analysis identified several peptides that were differentially phosphorylated between l-FRQ and s-FRQ, which were distributed in FRQ in an interlaced fashion. Furthermore, we identified two novel phosphorylation sites, S765 and T781; mutations S765A and T781A showed no significant effects on conidiation rhythmicity, although T781 conferred FRQ stability. These findings demonstrate that FRQ isoforms play differential roles in the circadian negative feedback loop and undergo different regulations of phosphorylation, structure, and stability. The l-FRQ N-terminal 99-aa region plays an important role in regulating the phosphorylation, stability, conformation, and function of the FRQ protein. As the FRQ circadian clock counterparts in other species also have isoforms or paralogues, these findings will also further our understanding of the underlying regulatory mechanisms of the circadian clock in other organisms based on the high conservation of circadian clocks in eukaryotes.

Recurrent Occupational Hantavirus Infections Linked to Feeder Rodent Breeding Farm, Taiwan, 2022.

We investigated 2 acute cases and 1 previous case of Seoul hantavirus infection in workers in a feeder rodent breeding farm in Taiwan. Prevalence of hantavirus IgG among the tested feeder rats was 37.5%. Appropriate prevention measures, including using disinfection protocols and personal protective equipment, are crucial to lowering risk.

Diabetes and further risk of cancer: a nationwide population-based study.

BACKGROUND: Individuals with diabetes have a significantly higher risk of developing various forms of cancer, and the potential biological links between these two diseases are not completely understood. METHODS: This was a longitudinal retrospective nationwide cohort study, a study design that allows us to examine the natural course of cancer development over an extended period of time with a large sample size. Initially, 3,111,975 and 22,208,395 eligible patients aged ≥ 20 years with and without diabetes, respectively, were matched by age, sex, and the Charlson comorbidity index. Ultimately, 1,751,457 patients were selected from each group. Stratified populations for diabetic retinopathy (DR) (n = 380,822) and without DR (n = 380,822) as well as proliferative DR (PDR) (n = 141,150) and non-proliferative DR (NPDR) (n = 141,150) were analyzed in this study. The main outcome measure was the first-time diagnosis of cancer during the follow-up period. RESULTS: We observed a 20% higher risk of total cancer incidence [hazard ratios (HR), 1.20; p < 0.001] in the diabetes cohort compared to the non-diabetes cohort. The highest HR was observed for liver and pancreas cancers. Moderately increased risks were observed for oral, colon, gallbladder, reproductive (female), kidney, and brain cancer. Furthermore, there was a borderline significantly increased risk of stomach, skin, soft tissue, female breast, and urinary tract (except kidney) cancers and lymphatic and hematopoietic malignancies. The stratified analysis revealed that the total cancer incidence was significantly higher in the DR cohort compared to the non-DR cohort (HR, 1.31; p < 0.001), and there was a borderline increased risk in the PDR cohort compared to the NPDR cohort (HR, 1.13; p = 0.001). CONCLUSIONS: This study provides large-scale, nationwide, population-based evidence that diabetes is independently associated with an increased risk of subsequent development of total cancer and cancer at specific sites. Notably, this risk may further increase when DR develops.

Propofol improves survival in a murine model of sepsis via inhibiting Rab5a-mediated intracellular trafficking of TLR4.

BACKGROUND: Propofol is a widely used anesthetic and sedative, which has been reported to exert an anti-inflammatory effect. TLR4 plays a critical role in coordinating the immuno-inflammatory response during sepsis. Whether propofol can act as an immunomodulator through regulating TLR4 is still unclear. Given its potential as a sepsis therapy, we investigated the mechanisms underlying the immunomodulatory activity of propofol. METHODS: The effects of propofol on TLR4 and Rab5a (a master regulator involved in intracellular trafficking of immune factors) were investigated in macrophage (from Rab5a-/- and WT mice) following treatment with lipopolysaccharide (LPS) or cecal ligation and puncture (CLP) in vitro and in vivo, and peripheral blood monocyte from sepsis patients and healthy volunteers. RESULTS: We showed that propofol reduced membrane TLR4 expression on macrophages in vitro and in vivo. Rab5a participated in TLR4 intracellular trafficking and both Rab5a expression and the interaction between Rab5a and TLR4 were inhibited by propofol. We also showed Rab5a upregulation in peripheral blood monocytes of septic patients, accompanied by increased TLR4 expression on the cell surface. Propofol downregulated the expression of Rab5a and TLR4 in these cells. CONCLUSIONS: We demonstrated that Rab5a regulates intracellular trafficking of TLR4 and that propofol reduces membrane TLR4 expression on macrophages by targeting Rab5a. Our study not only reveals a novel mechanism for the immunomodulatory effect of propofol but also indicates that Rab5a may be a potential therapeutic target against sepsis.

Characteristics of tandem repeat inheritance and sympathetic nerve involvement in GAA-FGF14 ataxia.

BACKGROUND: Intronic GAA repeat expansion ([GAA] ≥250) in FGF14 is associated with the late-onset neurodegenerative disorder, spinocerebellar ataxia 27B (SCA27B, GAA-FGF14 ataxia). We aim to determine the prevalence of the GAA repeat expansion in FGF14 in Chinese populations presenting late-onset cerebellar ataxia (LOCA) and evaluate the characteristics of tandem repeat inheritance, radiological features and sympathetic nerve involvement. METHODS: GAA-FGF14 repeat expansion was screened in an undiagnosed LOCA cohort (n = 664) and variations in repeat-length were analyzed in families of confirmed GAA-FGF14 ataxia patients. Brain magnetic resonance imaging (MRI) was used to evaluate the radiological feature in GAA-FGF14 ataxia patients. Clinical examinations and sympathetic skin response (SSR) recordings in GAA-FGF14 patients (n = 16) were used to quantify sympathetic nerve involvement. RESULTS: Two unrelated probands (2/664) were identified. Genetic screening for GAA-FGF14 repeat expansion was performed in 39 family members, 16 of whom were genetically diagnosed with GAA-FGF14 ataxia. Familial screening revealed expansion of GAA repeats in maternal transmissions, but contraction upon paternal transmission. Brain MRI showed slight to moderate cerebellar atrophy. SSR amplitude was lower in GAA-FGF14 patients in pre-symptomatic stage compared to healthy controls, and further decreased in the symptomatic stage. CONCLUSIONS: GAA-FGF14 ataxia was rare among Chinese LOCA cases. Parental gender appears to affect variability in GAA repeat number between generations. Reduced SSR amplitude is a prominent feature in GAA-FGF14 patients, even in the pre-symptomatic stage.

CCCTC-binding factor: the specific transcription factor of ß-galactoside α-2,6-sialyltransferase 1 that upregulates the sialylation of anti-citrullinated protein antibodies in rheumatoid arthritis.

OBJECTIVE: Sialylation of the crystallizable fragment (Fc) of ACPAs, which is catalysed by ß-galactoside α-2,6-sialyltransferase 1 (ST6GAL1) could attenuate inflammation of RA. In this study, we screened the transcription factor of ST6GAL1 and elucidated the mechanism of transcriptionally upregulating sialylation of ACPAs in B cells to explore its role in the progression of RA. METHODS: Transcription factors interacting with the P2 promoter of ST6GAL1 were screened by DNA pull-down and liquid chromatography with tandem mass spectrometry (LC-MS/MS), and verified by chromatin immunoprecipitation (ChIP), dual luciferase reporter assay and electrophoretic mobility shift assay (EMSA). The function of the CCCTC-binding factor (CTCF) on the expression of ST6GAL1 and the inflammatory effect of ACPAs were verified by knocking down and overexpressing CTCF in B cells. The CIA model was constructed from B cell-specific CTCF knockout mice to explore the effect of CTCF on arthritis progression. RESULTS: We observed that the levels of ST6GAL1 and ACPAs sialylation decreased in the serum of RA patients and were negatively correlated with DAS28 scores. Subsequently, CTCF was screened and verified as the transcription factor interacting with the P2 promoter of ST6GAL1, which enhances the sialylation of ACPAs, thus weakening the inflammatory activity of ACPAs. Furthermore, the above results were also verified in the CIA model constructed from B cell-specific CTCF knockout mice. CONCLUSION: CCCTC-binding factor is the specific transcription factor of ß-galactoside α-2,6-sialyltransferase 1 in B cells that upregulates the sialylation of ACPAs in RA and attenuates the disease progression.

Defect engineering on electrocatalysts for sustainable nitrate reduction to ammonia: Fundamentals and regulations.

Electrocatalytic nitrate (NO3 -) reduction to ammonia (NH3) is a "two birds-one stone" method that targets remediation of NO3 --containing sewage and production of valuable NH3. The exploitation of advanced catalysts with high activity, selectivity, and durability is a key issue for the efficient catalytic performance. Among various strategies for catalyst design, defect engineering has gained increasing attention due to its ability to modulate the electronic properties of electrocatalysts and optimize the adsorption energy of reactive species, thereby enhancing the catalytic performance. Despite previous progress, there remains a lack of mechanistic insights into the regulation of catalyst defects for NO3 - reduction. Herein, this review presents insightful understanding of defect engineering for NO3 - reduction, covering its background, definition, classification, construction, and underlying mechanisms. Moreover, the relationships between regulation of catalyst defects and their catalytic activities are illustrated by investigating the properties of electrocatalysts through the analysis of electronic band structure, charge density distribution, and controllable adsorption energy. Furthermore, challenges and perspectives for future development of defects in NO3RR are also discussed, which can help researchers to better understand the defect engineering in catalysts, and also inspire scientists entering into this promising field.

Hepatitis A Exposure Response and Outbreak Prevention in a Large Urban Jail - Los Angeles County, California, May-July 2023.

Correctional settings provide a high-risk environment for hepatitis A transmission because of the high proportion of homelessness and injection drug use among persons who are incarcerated. On May 30, 2023, Los Angeles County Department of Public Health informed the Communicable Disease Surveillance and Control (CDSC) unit of the Los Angeles County Jail system that a symptomatic incarcerated person had received a positive test result for acute hepatitis A. Upon learning the next day that the patient was a food handler, CDSC staff members identified 5,830 potential contacts of the index patient, 1,702 of whom had been released from the jail. During June 1-12, a total of 2,766 contacts who did not have a documented history of hepatitis A serology or vaccination that could be confirmed from the electronic health record or state immunization registry were identified. These persons were offered hepatitis A vaccination as postexposure prophylaxis; 1,510 (54.6%) accepted vaccination. Contacts who were food handlers without confirmed evidence of immunity and who declined vaccination were removed from food-handling duties for the duration of their potential incubation period. No additional cases were identified. Identifying contacts promptly and using immunization and serology records to ensure rapid delivery of postexposure prophylactic vaccine can help prevent hepatitis A transmission during exposures among incarcerated populations.

A comparative study of hypothalamic involvement in patients with myelin oligodendrocyte glycoprotein antibody-associated disease, neuromyelitis optica spectrum disorder, and multiple sclerosis.

BACKGROUND AND PURPOSE: We aimed to characterize hypothalamic involvement in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and compare it with neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS). METHODS: A retrospective study was performed to identify hypothalamic lesions in patients diagnosed with MOGAD, NMOSD, or MS from January 2013 to May 2020. The demographic, clinical, and radiological features were recorded. Hypothalamic dysfunction and prognosis were assessed through physical examination, biochemical testing, sleep monitoring, and magnetic resonance imaging. RESULTS: Hypothalamic lesions were observed in seven of 96 patients (7.3%) with MOGAD, 34 of 536 (6.3%) with NMOSD, and 16 of 356 (4.5%) with MS (p = 0.407). The time from disease onset to development of hypothalamic lesions was shortest in MOGAD (12 months). The frequency of bilateral hypothalamic lesions was the lowest in MOGAD (p = 0.008). The rate of hypothalamic dysfunction in MOGAD was 28.6%, which was lower than that in NMOSD (70.6%) but greater than that in MS patients (18.8%; p = 0.095 and p = 0.349, respectively). Hypothalamic dysfunction in MOGAD manifests as hypothalamic-pituitary-adrenal axis dysfunction and hypersomnia. The proportion of complete regression of hypothalamic lesions in MOGAD (100%) was much greater than that in NMOSD (41.7%) and MS patients (18.2%; p = 0.007 and p = 0.001, respectively). An improvement in hypothalamic dysfunction was observed in all MOGAD patients after immunotherapy. CONCLUSIONS: MOGAD patients have a relatively high incidence of asymptomatic hypothalamic lesions. The overall prognosis of patients with hypothalamic involvement is good in MOGAD, as the lesions completely resolve, and dysfunction improves after immunotherapy.

Effect of minoxidil combined with triamcinolone acetonide on alopecia areata by microneedle injection.

OBJECTIVE: Alopecia areata (AA) is often characterized by sudden onset of patchy hair loss. Topical corticosteroid injection is the most common treatment. This study retrospectively observed the clinical efficacy of microneedle minoxidil combined with triamcinolone acetonide in the treatment of AA. METHODS: A total of 230 patients with AA were selected. The experimental group (n = 120) received physician training and home microneedle treatment with minoxidil combined with triamcinolone acetonide once a week. Topical minoxidil and triamcinolone acetonide were used twice daily at other times. The control group (n = 110) was treated with minoxidil combined with triamcinolone acetonide, twice a day. Cure rate, response rate, SALT, dermatological Quality of Life Index (DLQI), visual analogue (VAS), and cost were assessed at weeks 4 and 12. RESULTS: Treated group SALT score(Severity of Alopecia Tool) remarkable lower than control group after treated 4 and 12 weeks. After 12 weeks treatment, DLQI score of the treated group (1.8 ± 1.67) were significantly lower than those of the control group (2.45 ± 1.88) (p < 0.05). VAS score and adverse reaction between two group showed no significant different (p = 0.823, p = 0.484 respectively). The total cost was 53.93 ± 15.85 in the treatment group and 53.26 ± 11.51 in the control group. There was no significant difference between the two groups (p = 0.72). In the treated group, the complete response rate (CR: 78.33%) and total effective rate (CR+PR: 95%) were significantly higher than those in the control group (CR: 40.91% and CR+PR: 51.82%), with statistically significant differences (p < 0.001). CONCLUSION: Microneedle introduction of minoxidil and triamcinolone acetonide in the treatment of AA is a safe, effective, economical, and convenient method, with few adverse reactions, and has a good application prospect.

Application of cantharidin, retinoic acid cream and salicylic acidy in multiple palmoplantar warts.

OBJECTIVE: Multiple palmoplantar warts, caused by human papillomavirus (HPV) infection, were investigated for clinical efficacy using cantharidin, retinoic acid cream, and salicylic acid cream. METHODS: A total of 110 patients with multiple palmoplantar warts were enrolled. The experimental group (54 cases) received a 1:1:1 combination (CRS) of 0.25% cantharidin, 0.1% retinoic acid cream, and 5% salicylic acid, applied with pressurized encapsulation for 8 h every night, three times per week. The control group (56 cases) underwent conventional liquid nitrogen freezing. Monthly follow-ups assessed cure rate, effective rate, dermatological life quality index (DLQI), visual analog scale (VAS), and cost, with evaluations conducted after 3 months. RESULTS: The treatment group exhibited a cure rate of 85.19% and a total effective rate of 96.30%, surpassing the control group with rates of 39.29% and 51.79%, respectively (p < 0.05). The treatment group's DLQI score (1.84 ± 1.06) was significantly lower than the control group's score (6.04 ± 1.78) (p = 0.0005). Additionally, the treatment group's VAS score (1.84 ± 1.06) was notably lower than the control group's score (8.56 ± 1.07) (p < 0.0001). The treatment group's total cost (43.20 ± 2.85) was markedly lower than the control group's cost (206.38 ± 90.81), with a statistically significant difference (p < 0.0001). CONCLUSION: The combination of cantharidin, retinoic acid cream, and salicylic acid with local encapsulation is a safe, effective, economical, and convenient treatment method for multiple palmoplantar warts, exhibiting few side effects and showing promise.

Magnetic resonance imaging features for differentiating tuberculous from pyogenic spondylitis: a meta-analysis.

OBJECTIVE: To perform a meta-analysis comparing the MRI features of tuberculous and pyogenic spondylitis, using histopathological results and/or blood culture as the standard reference. MATERIALS AND METHODS: PubMed, Embase, Web of Science, and Cochrane Library were searched for English-language studies on the MRI features of tuberculous and pyogenic spondylitis published between January 2010 and February 2023. Risk for bias and concerns regarding applicability were assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Pooled MRI features' proportions were calculated using a bivariate random-effects model. RESULTS: Thirty-two studies met the inclusion criteria: 21 for tuberculous spondylitis, three for pyogenic spondylitis, and eight for both. Of the nine informative MRI features comparing tuberculous spondylitis to pyogenic spondylitis, involvement of ≥ 2 vertebral bodies (92% vs. 88%, P = .004), epidural extension (77% vs. 25%, P < .001), paravertebral collection (91% vs. 84%, P < .001), subligamentous spread (93% vs. 24%, P < .001), thin and regular abscess wall (94% vs. 18%, P < .001), vertebral collapse (68% vs. 24%, P < .001), and kyphosis (39% vs. 3%, P < .01) were more suggestive of tuberculous spondylitis, while disc signal change (82% vs. 95%, P < .001) and disc height loss (22% vs. 59%, P < .001) were more suggestive of pyogenic spondylitis. CONCLUSION: Involvement of ≥ 2 vertebral vertebral bodies, soft tissue attribution, thin and regular abscess wall, vertebral collapse, and kyphosis were MRI features more common in tuberculous spondylitis, while disc signal change and height loss were more common in pyogenic spondylitis.

Clinical and pathological analyses of 14 cases of angiomatoid fibrous histiocytoma.

Angiomatoid fibrous histiocytoma (AFH) is a soft tissue tumor of uncertain differentiation. Although its prognosis is good, its diagnosis and differential diagnosis remain a challenge, particularly for tumors with an atypical morphology. We evaluated the clinicopathological characteristics of 14 AFH cases and examined the key factors in its diagnosis or differential diagnosis. The cohort comprised 6 men and 8 women aged 9-65 years (average age: 31.2 years). Most of the tumors (11/14, 79%) were located in soft tissues, whereas 3/14 (21%) were located in the lung (1 case) and brain (2 cases). Tumor cells were spindle-shaped to epithelioid, with a visible fibrous capsule (9/14, 64%), hemorrhagic gap (9/14, 64%), lymphocyte sleeve (7/14, 50%), necrosis (3/14, 21%), and infiltrative boundary (4/14, 29%). The tumors expressed desmin (10/14, 71%) and exhibited low levels of Ki-67. 13 cases (93%) displayed ESWSR1 gene rearrangement. At follow-up, 1 case (7%) experienced local tumor recurrence. AFH is a rare intermediate tumor. Its pathological diagnosis requires a comprehensive analysis of histological, immunophenotypic, and molecular genetic features to avoid misdiagnosis. Our study has further enriched the histological features of AFH, emphasizing the importance of differential diagnosis and providing a reference for clinical practice.

Aqueous extracts of Ocimum gratissimum mitigate colitis and protect against AOM/DSS-induced colorectal cancer in mice.

In this study, we explored the in vivo effects of Ocimum gratissimum aqueous extracts (OGE) on colorectal cancer (CRC) development provoked by azoxymethane/dextran sodium sulfate (AOM/DSS). The results showed a significant reduction in the tumor load and tumor number for the OGEH group that received continued administration of OGE compared to the AOM/DSS group, with P values of <0.01, but this was not observed in the OGEHs group that received separated administration of OGE. All groups except the control group exhibited aberrant crypt foci (ACF) and adenocarcinoma of lesion pathology in colon, and both conditions were significantly reduced in the OGEH group (P < 0.01) as compared to the AOM/DSS group. Subsequent investigation into whether OGE exhibits eliminative effects on DSS-induced severe colitis (SC) in mice showed that the disease activity index score was significantly reduced in the OGE-treated groups (P < 0.01), also colon colitis histological score was reversed. These data suggest that OGE may be potentially effective in preventing CRC when administered throughout the promotional stages of carcinogenesis by inhibiting inflammatory SC.

Serum neurofilament light chain is associated with disturbed limbic-based functional connectivity in patients with anti-NMDAR encephalitis.

Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis shows a predilection for affecting the limbic system, but structural MRI in most patients is usually unremarkable. However, the functional connectivity reorganization of limbic nodes remains unknown. Serum neurofilament light chains (sNfL) are clinically linked with the disease severity and neurological disability of anti-NMDAR encephalitis. However, the relationship between sNfL and limbic-based functional architecture has not been explored. We consecutively recruited 20 convalescent patients with anti-NMDAR encephalitis and 24 healthy controls from March 2018 to March 2021. Resting-state functional MRI metrics, including fractional amplitude of low-frequency fluctuation (fALFF), regional homogeneity (ReHo), and atlas-based seed functional connectivity, were analyzed to investigate regional activities and functional connectivity alterations. Correlation analysis among functional connectivity, sNfL, Mini-Mental State Examination (MMSE), and Montreal cognitive assessment outcomes were explored in patients. Compared with those of healthy controls, the fALFF and ReHo were consistently increased in regions of the posterior default mode network (DMN) hub, mainly the bilateral supramarginal gyrus and precuneus, in patients with anti-NMDAR encephalitis (FWE-corrected p < 0.05). Patients demonstrated disturbed functional organization characterized by reduced connectivity of the posterior DMN hub with the sensorimotor cortex and hypoconnectivity of the parahippocampal gyrus (PHG) with the right fusiform gyrus but extensively enhanced thalamocortical connectivity (FWE-corrected p < 0.05). Furthermore, convalescent sNfL showed a positive correlation with enhanced thalamocortical connectivity (r = 0.4659, p = 0.0384). Onset sNfL with an independent linear correlation to convalescent MMSE performance (B coefficient, -0.013, 95% CI, -0.025 ~ -0.002, p = 0.0260) was positively correlated with intra-DMN connectivity (r = 0.8969, p < 0.0001) and limbic-sensory connectivity (r = 0.4866, p = 0.0346 for hippocampus seed and r = 0.5218, p = 0.0220 for PHG seed). Patients with anti-NMDAR encephalitis demonstrated disturbed functional organization with substantial thalamocortical hyperconnectivity, that was positively correlated with convalescent sNfL. Onset sNfL showed a positive correlation with intra-DMN connectivity and limbic-sensory connectivity.

Microbiota-derived tryptophan metabolites indole-3-lactic acid is associated with intestinal ischemia/reperfusion injury via positive regulation of YAP and Nrf2.

BACKGROUND: Lactobacillus has been demonstrated to serve a protective role in intestinal injury. However, the relationship between Lactobacillus murinus (L. murinus)-derived tryptophan metabolites and intestinal ischemia/reperfusion (I/R) injury yet to be investigated. This study aimed to evaluate the role of L. murinus-derived tryptophan metabolites in intestinal I/R injury and the underlying molecular mechanism. METHODS: Liquid chromatograph mass spectrometry analysis was used to measure the fecal content of tryptophan metabolites in mice undergoing intestinal I/R injury and in patients undergoing cardiopulmonary bypass (CPB) surgery. Immunofluorescence, quantitative RT-PCR, Western blot, and ELISA were performed to explore the inflammation protective mechanism of tryptophan metabolites in WT and Nrf2-deficient mice undergoing intestinal I/R, hypoxia-reoxygenation (H/R) induced intestinal organoids. RESULTS: By comparing the fecal contents of three L. murinus-derived tryptophan metabolites in mice undergoing intestinal I/R injury and in patients undergoing cardiopulmonary bypass (CPB) surgery. We found that the high abundance of indole-3-lactic acid (ILA) in the preoperative feces was associated with better postoperative intestinal function, as evidenced by the correlation of fecal metabolites with postoperative gastrointestinal function, serum I-FABP and D-Lactate levels. Furthermore, ILA administration improved epithelial cell damage, accelerated the proliferation of intestinal stem cells, and alleviated the oxidative stress of epithelial cells. Mechanistically, ILA improved the expression of Yes Associated Protein (YAP) and Nuclear Factor erythroid 2-Related Factor 2 (Nrf2) after intestinal I/R. The YAP inhibitor verteporfin (VP) reversed the anti-inflammatory effect of ILA, both in vivo and in vitro. Additionally, we found that ILA failed to protect epithelial cells from oxidative stress in Nrf2 knockout mice under I/R injury. CONCLUSIONS: The content of tryptophan metabolite ILA in the preoperative feces of patients is negatively correlated with intestinal function damage under CPB surgery. Administration of ILA alleviates intestinal I/R injury via the regulation of YAP and Nrf2. This study revealed a novel therapeutic metabolite and promising candidate targets for intestinal I/R injury treatment.