Hasty Briefsbeta

Bilingual

Agonistic anti-CD40 antibody treatment converts resident regulatory T cells into activated type 1 effectors within the tumor microenvironment - PubMed
8 days ago
- Agonistic anti-CD40 antibody treatment reduces regulatory T cells in pancreatic ductal adenocarcinoma.
- The reduction occurs via CD40-activated dendritic cells and cytokines like IL-12 and IFN-γ.
- Regulatory T cells lose Foxp3 expression, acquiring Th1-like features (e.g., Tbet+ IFN-γ+).
- Treatment reorganizes the tumor microenvironment, relocating Treg and ExTreg cells to the periphery.
- ExTreg cells show high antigen-driven activation and anti-tumor effector capacity.
Robot-assisted versus conventional minimally invasive oesophagectomy for oesophageal squamous cell carcinoma (RAMIE): a multicentre, open-label, randomised, phase 3, non-inferiority trial - PubMed
8 days ago
- The RAMIE trial is a phase 3, non-inferiority study comparing robot-assisted and thoracoscopic oesophagectomy for oesophageal squamous cell carcinoma.
- It involved 362 patients in China, randomized into two groups, with a median follow-up of 71.5 months.
- 5-year overall survival was 69.4% with robot-assisted surgery versus 56.2% with thoracoscopic surgery, confirming non-inferiority and suggesting superiority.
- Complication rates and conversions to open surgery were similar between the two groups, with one treatment-related death in each.
Microphthalmos, rudimentary iris tissue, fundal coloboma and anophthalmos in ectrodactyly ectodermal dysplasia cleft lip/palate syndrome - PubMed
8 days ago
- EEC syndrome involves claw-like hands/feet, ectodermal dysplasia, and cleft lip/palate.
- Complete triad presentation is rare, and intraocular involvement is seldom reported.
- A case exhibited microphthalmos, rudimentary iris tissue, fundal coloboma, and anophthalmos.
Treatable traits in interstitial lung disease: towards precision medicine - PubMed
8 days ago
- Current ILD pharmacotherapies include systemic glucocorticoids, steroid-sparing immunosuppressants, and antifibrotic drugs, each targeting major biological components.
- Treatment is based on a treatable traits approach, integrating clinical, lab, radiological, and pathological features to match biology with medication strategy.
- Acute inflammatory presentations typically receive systemic glucocorticoids; chronic inflammatory disease gets long-term steroid-sparing immunosuppression; progressive fibrotic disease receives antifibrotics.
- Emerging therapies like nerandomilast (a PDE4B inhibitor with antifibrotic/immunomodulatory effects) are being introduced, approved recently in the USA.
- Future goals include integrating molecular endotypes to enable precision-based ILD management, addressing knowledge gaps in current approaches.
Lactic acid drives NLRP3 inflammasome activation and caspase-1-like cytokine cleavage via intracellular acidification - PubMed
8 days ago
- NLRP3 activators like nigericin or ATP trigger lactic acid production and efflux in macrophages via lactate dehydrogenase.
- Intracellular lactic acid accumulation causes cytoplasmic acidification, promoting NLRP3 inflammasome activation and leading to ASC speck formation, caspase-1 activation, and IL-1β secretion.
- Extracellular lactic acid buildup impairs lactate efflux, worsening intracellular acidification and amplifying inflammasome activation, which can be prevented by alkalinization of the extracellular environment.
- Mechanistically, intracellular acidification induces mitochondrial dysfunction, ROS production, and PKR phosphorylation, facilitating PKR-NLRP3 interaction and inflammasome assembly through parallel pathways.
- Independently, lactic acid directly cleaves pro-IL-1β and pro-IL-18 into mature forms by mimicking caspase-1 activity, specifically at Asp116 in pro-IL-1β as confirmed by mass spectrometry.
- In a murine sepsis model, lactate administration increased inflammation, IL-1β levels, neutrophil infiltration, hypothermia, and worsened survival, highlighting lactic acid's role in promoting inflammation.
Distinct mechanisms of replication stress induced by oncogenic RAS and cyclin E1 converge on R-loop-dependent fork reversal - PubMed
8 days ago
- Oncogenic RAS (HRASV12) and cyclin E1 overexpression induce replication stress, primarily via R-loops during S-phase.
- HRASV12-induced replication stress is ROS-dependent, mediated by the ROS sensor PRDX2 and linked to TIMELESS release.
- Fork reversal inhibition in HRASV12 or cyclin E1 cells leads to MUS81- and PRIMPOL-mediated DNA synthesis, aiding chromosome segregation.
- PRIMPOL repriming is part of a MUS81-dependent restart mechanism for R-loop-mediated conflicts to maintain genomic stability.
- Persistent reversed forks can impair mitosis, causing DNA breaks and chromosomal rearrangements despite protective roles in S-phase.
Activation of α7nAChR reduces inflammation and apoptosis, promoting muscle regeneration through the AKT-FOXO1 pathway - PubMed
8 days ago
- Activation of α7nAChR reduces inflammation and apoptosis, promoting muscle regeneration via the AKT-FOXO1 pathway.
- Denervation decreases α7nAChR expression, increasing inflammation and apoptosis, which leads to muscle atrophy.
- Treatment with PNU120596 or electroacupuncture restores α7nAChR function and alleviates muscle atrophy.
- Targeting α7nAChR offers a promising therapeutic approach for muscle wasting after denervation.
The exposome of brain aging across 34 countries - PubMed
8 days ago
- Study examines the exposome's impact on brain aging across 34 countries using multimodal brain age measures.
- Aggregated exposome models explained significantly more variance in brain aging than individual exposures.
- Physical exposome factors are primarily linked to accelerated structural brain aging in limbic, subcortical, and cerebellar regions.
- Social exposome factors are more strongly associated with accelerated functional brain aging in frontotemporal and limbic networks.
- Exposome burden increased the risk of accelerated brain aging by 3.3 to 9.1-fold, exceeding the effects of clinical diagnoses.
- Findings were validated out-of-sample and remained consistent across clinical subgroups and after controlling for multiple confounders.
- Highlights the need to address physical, social, and political inequities to mitigate accelerated brain aging.
Irisin ameliorates obesity and insulin resistance via adipose tissue IL-33 and regulatory T cells - PubMed
8 days ago
- Irisin, an exercise-induced myokine, improves obesity and insulin resistance in mice.
- Irisin increases IL-33 production in visceral adipose tissue (VAT) mesenchymal stromal cells.
- It preserves ST2+ regulatory T cells in VAT, which are crucial for immunomodulation.
- These changes reduce adipose tissue inflammation and upregulate thermogenic genes in subcutaneous fat.
- The effects lead to better glucose tolerance, increased energy expenditure, without affecting food intake or muscle mass.
Leptomeningeal metastatic cancer cells induce a permissive choroid plexus vasculature through extracellular-vesicle-derived 5-HIAA signaling - PubMed
8 days ago
- Leptomeningeal metastasis (LM) involves cancer cells colonizing the meninges, with the choroid plexus serving as a key barrier.
- The study finds that cancer cells remodel the metabolic microenvironment to create a supportive premetastasis niche in the choroid plexus.
- Extracellular vesicles containing 5-hydroxyindoleacetic acid (5-HIAA) target choroid plexus vessels before initial cancer cell invasion.
- 5-HIAA causes vascular distortion, abnormal hemodynamics, increased permeability, and facilitates cancer cell traversal through the vasculature.
- Mechanistically, 5-HIAA activates the aryl hydrocarbon receptor pathway, leading to aberrant expression of mechanoreceptors and tight junction proteins.
- Elevated 5-HIAA levels in cerebrospinal fluid and choroid plexus indicate a predisposition for metastatic colonization.
- These findings highlight 5-HIAA's role in niche formation and suggest metabolic targets to prevent LM initiation by modulating choroidal plasticity.
Lipid accumulation in tuberculosis granulomas inhibits macrophage-CD4+ T cell interactions and infection control - PubMed
8 days ago
- Lipid accumulation, specifically cholesterol, in tuberculosis granulomas impairs macrophage-CD4+ T cell interactions and infection control.
- Infection or exposure to mycolic acids disrupts cholesterol trafficking in macrophages, leading to cholesterol build-up and sequestration of MHC class II in lysosomes.
- This cholesterol overload reduces antigen presentation and weakens anti-Mtb CD4+ T cell responses, particularly in necrotic granulomas.
- Restoring cholesterol homeostasis pharmacologically during late-stage infection improves Mtb control in mice, suggesting a therapeutic target.
Aberrant amino acid-sensing promotes immunotherapy resistance via the inflammatory cytokine-ZBTB5-mTORC1 axis - PubMed
8 days ago
- Inflammatory cytokines in the tumor microenvironment hijack mTORC1 signaling even under nutrient insufficiency.
- ZBTB5, phosphorylated at S127, degrades NPRL2 in the GATOR1 complex to reactivate mTORC1 and boost tumor amino acid uptake.
- Increased tumor amino acid uptake worsens nutrient restriction and death of CD8+ T cells, promoting immunotherapy resistance.
- Blocking ZBTB5-pS127 alleviates resistance to immune checkpoint inhibitors, suggesting a potential therapeutic strategy.
Gut microbiota-associated nutritional-immune status predicts prognosis in postoperative NSCLC patients - PubMed
8 days ago
- High prognostic nutritional index (PNI ≥46.2) predicts improved 5-year survival in postoperative NSCLC patients.
- High PNI associates with enrichment of SCFA-producing gut bacteria (e.g., Akkermansia, Eubacterium hallii) and higher butyrate/isovalerate levels.
- SCFA levels correlate with increased CD8+ T cell infiltration in tumors.
- Fecal microbiota transplantation from high-PNI patients reduces lung tumor growth in mice.
- Oral administration of A. muciniphila, E. hallii, or butyrate suppresses tumor growth and enhances CD8+ tumor-infiltrating lymphocytes.
- PNI and gut microbiota-SCFA axis are prognostic biomarkers and potential immunomodulatory targets for early-stage NSCLC.
Olorofim in combination with azole antifungals: results from the Phase 2 salvage therapy study - PubMed
9 days ago
- Preclinical studies indicated unidirectional antagonism where azoles reduce olorofim's antifungal effect against Aspergillus fumigatus.
- Phase 2b salvage study results showed similar outcomes for olorofim with and without concomitant azoles in aspergillosis, coccidioidomycosis, and other fungal infections at Days 42 and 84.
- No increased rate of drug-induced liver injury was observed in patients receiving olorofim-azole combination therapy.
- Analysis did not show reduced clinical efficacy or tolerability of olorofim when combined with mould-active azoles or fluconazole, despite study size limitations.
The Diverse Roles of Heparan Sulfate in RNA Virus Infections: Insights From Enterovirus A71, Severe Acute Respiratory Syndrome Coronavirus 2, and Chikungunya Virus - PubMed
9 days ago
- Heparan sulfate (HS) serves as an attachment and internalization factor for many RNA and DNA viruses due to its structural heterogeneity.
- HS facilitates viral attachment for EV-A71, SARS-CoV-2, and CHIKV, and additionally aids SARS-CoV-2 internalization in the absence of ACE2.
- Viral affinity for HS is determined by positively charged residues on the virion, influencing infectivity and plaque size in vitro for EV-A71 and SARS-CoV-2.
- Higher HS affinity correlates with viral attenuation, reduced inflammation, lower capsid stability, and increased sensitivity to antibodies in vivo for EV-A71 and CHIKV.
- HS mimetics targeting virus-HS interactions show promise as broad-spectrum antivirals, with some already in clinical trials.
Food Variety Score and Geriatric Nutritional Risk Index Mediate the Relationship Between Masticatory Function and Osteoporosis - PubMed
9 days ago
- Higher Functional Tooth Units (FTUs) are associated with a lower prevalence of osteoporosis.
- Food Variety Score (FVS) and Geriatric Nutritional Risk Index (GNRI) mediate the relationship between masticatory function and osteoporosis.
- Maintaining adequate masticatory function may reduce osteoporosis risk through improved nutrition and food variety.
Emergence of Carbapenem-Resistant Putative Hypervirulent Klebsiella pneumoniae ST147 with a Distinct Hybrid Plasmid in Türkiye - PubMed
9 days ago
- CR-hvKp prevalence in Türkiye increased from 20.7% in 2018 to 33.1% by 2023.
- Dominant clone shifted from ST2096 (mainly blaOXA-232) before 2022 to ST147 (co-carrying blaNDM-5 and blaOXA-48, KL64 capsule).
- ST147 carries a 364-kb hybrid plasmid (pPF302_hybrid) with IncHI1B_pNDM and IncFIB_pNDM replicons, including novel resistance genes rmtF1 and arr-2.
Harnessing AlphaFold3 to Elucidate BBSome Structure and Protein Partners - PubMed
9 days ago
- AlphaFold3 generated a structural model of the BBSome complex that closely matches recent cryo-EM data (Cα RMSD: 1.203 Å).
- BBS1 and BBS9 were identified as central interaction hubs, BBS2 and BBS7 showed the most polar contacts, and the pathogenic mutation BBS1M390R was predicted to destabilize the complex.
- BBS4 stably interacts with pericentriolar material 1, suggesting a role in centriolar satellite localization.
- Interaction analysis with GPCRs identified contact hotspots on BBS1, BBS4, and BBS5, supported by immunoprecipitation and peptide competition assays.
- Modeling suggested plausible interfaces between specific BBS proteins and metabolic signaling proteins (e.g., MRAP2, leptin receptor, insulin receptor), aligning with reported biochemical associations.
- The findings provide new insights into BBSome structure and receptor interactions, offering a predictive framework for exploring its role in ciliary trafficking and human disease.
Sex-specific links between dietary fat intake, dementia risk, and cognitive decline in central obesity: a UK biobank cohort study - PubMed
9 days ago
- Study finds sex-specific links between dietary fat intake and dementia risk in central obesity, using data from 128,160 UK Biobank participants.
- In women with central obesity, a moderately high percentage of energy from fat (MHF) is associated with lower risk of all-cause dementia and Alzheimer's disease, and higher cognitive test scores.
- No significant association between dietary fat intake and dementia risk was observed in men, but MHF was linked to higher scores in some cognitive tests.
- Results highlight potential benefits of dietary interventions, especially for women with central obesity, in reducing dementia risk and improving cognitive function.
No-reflow phenomenon after vessel recanalization in acute ischemic stroke: mechanisms, diagnosis, and treatment directions - PubMed
9 days ago
- The no-reflow phenomenon (NRP) is a condition where, despite successful recanalization of large vessels in acute ischemic stroke, microvascular tissue reperfusion remains impaired, leading to poor clinical outcomes.
- NRP prevalence after reperfusion therapy ranges from 3.3% to 63%, with mechanisms including intraluminal occlusion (e.g., distal embolization, microthrombus formation) and extraluminal constriction, along with inflammatory responses and neurovascular unit dysfunction.
- Diagnostic methods for NRP involve clinical, imaging, and other assessments, while explored treatments include targeted therapy, pericyte modulators, post-ischemic conditioning, and traditional Chinese medicine, aiming to improve patient management and guide future research.

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Bilingual

Agonistic anti-CD40 antibody treatment converts resident regulatory T cells into activated type 1 effectors within the tumor microenvironment - PubMed
8 days ago
- Agonistic anti-CD40 antibody treatment reduces regulatory T cells in pancreatic ductal adenocarcinoma.
- The reduction occurs via CD40-activated dendritic cells and cytokines like IL-12 and IFN-γ.
- Regulatory T cells lose Foxp3 expression, acquiring Th1-like features (e.g., Tbet+ IFN-γ+).
- Treatment reorganizes the tumor microenvironment, relocating Treg and ExTreg cells to the periphery.
- ExTreg cells show high antigen-driven activation and anti-tumor effector capacity.
Robot-assisted versus conventional minimally invasive oesophagectomy for oesophageal squamous cell carcinoma (RAMIE): a multicentre, open-label, randomised, phase 3, non-inferiority trial - PubMed
8 days ago
- The RAMIE trial is a phase 3, non-inferiority study comparing robot-assisted and thoracoscopic oesophagectomy for oesophageal squamous cell carcinoma.
- It involved 362 patients in China, randomized into two groups, with a median follow-up of 71.5 months.
- 5-year overall survival was 69.4% with robot-assisted surgery versus 56.2% with thoracoscopic surgery, confirming non-inferiority and suggesting superiority.
- Complication rates and conversions to open surgery were similar between the two groups, with one treatment-related death in each.
Microphthalmos, rudimentary iris tissue, fundal coloboma and anophthalmos in ectrodactyly ectodermal dysplasia cleft lip/palate syndrome - PubMed
8 days ago
- EEC syndrome involves claw-like hands/feet, ectodermal dysplasia, and cleft lip/palate.
- Complete triad presentation is rare, and intraocular involvement is seldom reported.
- A case exhibited microphthalmos, rudimentary iris tissue, fundal coloboma, and anophthalmos.
Treatable traits in interstitial lung disease: towards precision medicine - PubMed
8 days ago
- Current ILD pharmacotherapies include systemic glucocorticoids, steroid-sparing immunosuppressants, and antifibrotic drugs, each targeting major biological components.
- Treatment is based on a treatable traits approach, integrating clinical, lab, radiological, and pathological features to match biology with medication strategy.
- Acute inflammatory presentations typically receive systemic glucocorticoids; chronic inflammatory disease gets long-term steroid-sparing immunosuppression; progressive fibrotic disease receives antifibrotics.
- Emerging therapies like nerandomilast (a PDE4B inhibitor with antifibrotic/immunomodulatory effects) are being introduced, approved recently in the USA.
- Future goals include integrating molecular endotypes to enable precision-based ILD management, addressing knowledge gaps in current approaches.
Lactic acid drives NLRP3 inflammasome activation and caspase-1-like cytokine cleavage via intracellular acidification - PubMed
8 days ago
- NLRP3 activators like nigericin or ATP trigger lactic acid production and efflux in macrophages via lactate dehydrogenase.
- Intracellular lactic acid accumulation causes cytoplasmic acidification, promoting NLRP3 inflammasome activation and leading to ASC speck formation, caspase-1 activation, and IL-1β secretion.
- Extracellular lactic acid buildup impairs lactate efflux, worsening intracellular acidification and amplifying inflammasome activation, which can be prevented by alkalinization of the extracellular environment.
- Mechanistically, intracellular acidification induces mitochondrial dysfunction, ROS production, and PKR phosphorylation, facilitating PKR-NLRP3 interaction and inflammasome assembly through parallel pathways.
- Independently, lactic acid directly cleaves pro-IL-1β and pro-IL-18 into mature forms by mimicking caspase-1 activity, specifically at Asp116 in pro-IL-1β as confirmed by mass spectrometry.
- In a murine sepsis model, lactate administration increased inflammation, IL-1β levels, neutrophil infiltration, hypothermia, and worsened survival, highlighting lactic acid's role in promoting inflammation.
Distinct mechanisms of replication stress induced by oncogenic RAS and cyclin E1 converge on R-loop-dependent fork reversal - PubMed
8 days ago
- Oncogenic RAS (HRASV12) and cyclin E1 overexpression induce replication stress, primarily via R-loops during S-phase.
- HRASV12-induced replication stress is ROS-dependent, mediated by the ROS sensor PRDX2 and linked to TIMELESS release.
- Fork reversal inhibition in HRASV12 or cyclin E1 cells leads to MUS81- and PRIMPOL-mediated DNA synthesis, aiding chromosome segregation.
- PRIMPOL repriming is part of a MUS81-dependent restart mechanism for R-loop-mediated conflicts to maintain genomic stability.
- Persistent reversed forks can impair mitosis, causing DNA breaks and chromosomal rearrangements despite protective roles in S-phase.
Activation of α7nAChR reduces inflammation and apoptosis, promoting muscle regeneration through the AKT-FOXO1 pathway - PubMed
8 days ago
- Activation of α7nAChR reduces inflammation and apoptosis, promoting muscle regeneration via the AKT-FOXO1 pathway.
- Denervation decreases α7nAChR expression, increasing inflammation and apoptosis, which leads to muscle atrophy.
- Treatment with PNU120596 or electroacupuncture restores α7nAChR function and alleviates muscle atrophy.
- Targeting α7nAChR offers a promising therapeutic approach for muscle wasting after denervation.
The exposome of brain aging across 34 countries - PubMed
8 days ago
- Study examines the exposome's impact on brain aging across 34 countries using multimodal brain age measures.
- Aggregated exposome models explained significantly more variance in brain aging than individual exposures.
- Physical exposome factors are primarily linked to accelerated structural brain aging in limbic, subcortical, and cerebellar regions.
- Social exposome factors are more strongly associated with accelerated functional brain aging in frontotemporal and limbic networks.
- Exposome burden increased the risk of accelerated brain aging by 3.3 to 9.1-fold, exceeding the effects of clinical diagnoses.
- Findings were validated out-of-sample and remained consistent across clinical subgroups and after controlling for multiple confounders.
- Highlights the need to address physical, social, and political inequities to mitigate accelerated brain aging.
Irisin ameliorates obesity and insulin resistance via adipose tissue IL-33 and regulatory T cells - PubMed
8 days ago
- Irisin, an exercise-induced myokine, improves obesity and insulin resistance in mice.
- Irisin increases IL-33 production in visceral adipose tissue (VAT) mesenchymal stromal cells.
- It preserves ST2+ regulatory T cells in VAT, which are crucial for immunomodulation.
- These changes reduce adipose tissue inflammation and upregulate thermogenic genes in subcutaneous fat.
- The effects lead to better glucose tolerance, increased energy expenditure, without affecting food intake or muscle mass.
Leptomeningeal metastatic cancer cells induce a permissive choroid plexus vasculature through extracellular-vesicle-derived 5-HIAA signaling - PubMed
8 days ago
- Leptomeningeal metastasis (LM) involves cancer cells colonizing the meninges, with the choroid plexus serving as a key barrier.
- The study finds that cancer cells remodel the metabolic microenvironment to create a supportive premetastasis niche in the choroid plexus.
- Extracellular vesicles containing 5-hydroxyindoleacetic acid (5-HIAA) target choroid plexus vessels before initial cancer cell invasion.
- 5-HIAA causes vascular distortion, abnormal hemodynamics, increased permeability, and facilitates cancer cell traversal through the vasculature.
- Mechanistically, 5-HIAA activates the aryl hydrocarbon receptor pathway, leading to aberrant expression of mechanoreceptors and tight junction proteins.
- Elevated 5-HIAA levels in cerebrospinal fluid and choroid plexus indicate a predisposition for metastatic colonization.
- These findings highlight 5-HIAA's role in niche formation and suggest metabolic targets to prevent LM initiation by modulating choroidal plasticity.
Lipid accumulation in tuberculosis granulomas inhibits macrophage-CD4+ T cell interactions and infection control - PubMed
8 days ago
- Lipid accumulation, specifically cholesterol, in tuberculosis granulomas impairs macrophage-CD4+ T cell interactions and infection control.
- Infection or exposure to mycolic acids disrupts cholesterol trafficking in macrophages, leading to cholesterol build-up and sequestration of MHC class II in lysosomes.
- This cholesterol overload reduces antigen presentation and weakens anti-Mtb CD4+ T cell responses, particularly in necrotic granulomas.
- Restoring cholesterol homeostasis pharmacologically during late-stage infection improves Mtb control in mice, suggesting a therapeutic target.
Aberrant amino acid-sensing promotes immunotherapy resistance via the inflammatory cytokine-ZBTB5-mTORC1 axis - PubMed
8 days ago
- Inflammatory cytokines in the tumor microenvironment hijack mTORC1 signaling even under nutrient insufficiency.
- ZBTB5, phosphorylated at S127, degrades NPRL2 in the GATOR1 complex to reactivate mTORC1 and boost tumor amino acid uptake.
- Increased tumor amino acid uptake worsens nutrient restriction and death of CD8+ T cells, promoting immunotherapy resistance.
- Blocking ZBTB5-pS127 alleviates resistance to immune checkpoint inhibitors, suggesting a potential therapeutic strategy.
Gut microbiota-associated nutritional-immune status predicts prognosis in postoperative NSCLC patients - PubMed
8 days ago
- High prognostic nutritional index (PNI ≥46.2) predicts improved 5-year survival in postoperative NSCLC patients.
- High PNI associates with enrichment of SCFA-producing gut bacteria (e.g., Akkermansia, Eubacterium hallii) and higher butyrate/isovalerate levels.
- SCFA levels correlate with increased CD8+ T cell infiltration in tumors.
- Fecal microbiota transplantation from high-PNI patients reduces lung tumor growth in mice.
- Oral administration of A. muciniphila, E. hallii, or butyrate suppresses tumor growth and enhances CD8+ tumor-infiltrating lymphocytes.
- PNI and gut microbiota-SCFA axis are prognostic biomarkers and potential immunomodulatory targets for early-stage NSCLC.
Olorofim in combination with azole antifungals: results from the Phase 2 salvage therapy study - PubMed
9 days ago
- Preclinical studies indicated unidirectional antagonism where azoles reduce olorofim's antifungal effect against Aspergillus fumigatus.
- Phase 2b salvage study results showed similar outcomes for olorofim with and without concomitant azoles in aspergillosis, coccidioidomycosis, and other fungal infections at Days 42 and 84.
- No increased rate of drug-induced liver injury was observed in patients receiving olorofim-azole combination therapy.
- Analysis did not show reduced clinical efficacy or tolerability of olorofim when combined with mould-active azoles or fluconazole, despite study size limitations.
The Diverse Roles of Heparan Sulfate in RNA Virus Infections: Insights From Enterovirus A71, Severe Acute Respiratory Syndrome Coronavirus 2, and Chikungunya Virus - PubMed
9 days ago
- Heparan sulfate (HS) serves as an attachment and internalization factor for many RNA and DNA viruses due to its structural heterogeneity.
- HS facilitates viral attachment for EV-A71, SARS-CoV-2, and CHIKV, and additionally aids SARS-CoV-2 internalization in the absence of ACE2.
- Viral affinity for HS is determined by positively charged residues on the virion, influencing infectivity and plaque size in vitro for EV-A71 and SARS-CoV-2.
- Higher HS affinity correlates with viral attenuation, reduced inflammation, lower capsid stability, and increased sensitivity to antibodies in vivo for EV-A71 and CHIKV.
- HS mimetics targeting virus-HS interactions show promise as broad-spectrum antivirals, with some already in clinical trials.
Food Variety Score and Geriatric Nutritional Risk Index Mediate the Relationship Between Masticatory Function and Osteoporosis - PubMed
9 days ago
- Higher Functional Tooth Units (FTUs) are associated with a lower prevalence of osteoporosis.
- Food Variety Score (FVS) and Geriatric Nutritional Risk Index (GNRI) mediate the relationship between masticatory function and osteoporosis.
- Maintaining adequate masticatory function may reduce osteoporosis risk through improved nutrition and food variety.
Emergence of Carbapenem-Resistant Putative Hypervirulent Klebsiella pneumoniae ST147 with a Distinct Hybrid Plasmid in Türkiye - PubMed
9 days ago
- CR-hvKp prevalence in Türkiye increased from 20.7% in 2018 to 33.1% by 2023.
- Dominant clone shifted from ST2096 (mainly blaOXA-232) before 2022 to ST147 (co-carrying blaNDM-5 and blaOXA-48, KL64 capsule).
- ST147 carries a 364-kb hybrid plasmid (pPF302_hybrid) with IncHI1B_pNDM and IncFIB_pNDM replicons, including novel resistance genes rmtF1 and arr-2.
Harnessing AlphaFold3 to Elucidate BBSome Structure and Protein Partners - PubMed
9 days ago
- AlphaFold3 generated a structural model of the BBSome complex that closely matches recent cryo-EM data (Cα RMSD: 1.203 Å).
- BBS1 and BBS9 were identified as central interaction hubs, BBS2 and BBS7 showed the most polar contacts, and the pathogenic mutation BBS1M390R was predicted to destabilize the complex.
- BBS4 stably interacts with pericentriolar material 1, suggesting a role in centriolar satellite localization.
- Interaction analysis with GPCRs identified contact hotspots on BBS1, BBS4, and BBS5, supported by immunoprecipitation and peptide competition assays.
- Modeling suggested plausible interfaces between specific BBS proteins and metabolic signaling proteins (e.g., MRAP2, leptin receptor, insulin receptor), aligning with reported biochemical associations.
- The findings provide new insights into BBSome structure and receptor interactions, offering a predictive framework for exploring its role in ciliary trafficking and human disease.
Sex-specific links between dietary fat intake, dementia risk, and cognitive decline in central obesity: a UK biobank cohort study - PubMed
9 days ago
- Study finds sex-specific links between dietary fat intake and dementia risk in central obesity, using data from 128,160 UK Biobank participants.
- In women with central obesity, a moderately high percentage of energy from fat (MHF) is associated with lower risk of all-cause dementia and Alzheimer's disease, and higher cognitive test scores.
- No significant association between dietary fat intake and dementia risk was observed in men, but MHF was linked to higher scores in some cognitive tests.
- Results highlight potential benefits of dietary interventions, especially for women with central obesity, in reducing dementia risk and improving cognitive function.
No-reflow phenomenon after vessel recanalization in acute ischemic stroke: mechanisms, diagnosis, and treatment directions - PubMed
9 days ago
- The no-reflow phenomenon (NRP) is a condition where, despite successful recanalization of large vessels in acute ischemic stroke, microvascular tissue reperfusion remains impaired, leading to poor clinical outcomes.
- NRP prevalence after reperfusion therapy ranges from 3.3% to 63%, with mechanisms including intraluminal occlusion (e.g., distal embolization, microthrombus formation) and extraluminal constriction, along with inflammatory responses and neurovascular unit dysfunction.
- Diagnostic methods for NRP involve clinical, imaging, and other assessments, while explored treatments include targeted therapy, pericyte modulators, post-ischemic conditioning, and traditional Chinese medicine, aiming to improve patient management and guide future research.

Hasty Briefsbeta

Agonistic anti-CD40 antibody treatment converts resident regulatory T cells into activated type 1 effectors within the tumor microenvironment - PubMed

Robot-assisted versus conventional minimally invasive oesophagectomy for oesophageal squamous cell carcinoma (RAMIE): a multicentre, open-label, randomised, phase 3, non-inferiority trial - PubMed

Microphthalmos, rudimentary iris tissue, fundal coloboma and anophthalmos in ectrodactyly ectodermal dysplasia cleft lip/palate syndrome - PubMed

Treatable traits in interstitial lung disease: towards precision medicine - PubMed

Lactic acid drives NLRP3 inflammasome activation and caspase-1-like cytokine cleavage via intracellular acidification - PubMed

Distinct mechanisms of replication stress induced by oncogenic RAS and cyclin E1 converge on R-loop-dependent fork reversal - PubMed

Activation of α7nAChR reduces inflammation and apoptosis, promoting muscle regeneration through the AKT-FOXO1 pathway - PubMed

The exposome of brain aging across 34 countries - PubMed

Irisin ameliorates obesity and insulin resistance via adipose tissue IL-33 and regulatory T cells - PubMed

Leptomeningeal metastatic cancer cells induce a permissive choroid plexus vasculature through extracellular-vesicle-derived 5-HIAA signaling - PubMed

Lipid accumulation in tuberculosis granulomas inhibits macrophage-CD4+ T cell interactions and infection control - PubMed

Aberrant amino acid-sensing promotes immunotherapy resistance via the inflammatory cytokine-ZBTB5-mTORC1 axis - PubMed

Gut microbiota-associated nutritional-immune status predicts prognosis in postoperative NSCLC patients - PubMed

Olorofim in combination with azole antifungals: results from the Phase 2 salvage therapy study - PubMed

The Diverse Roles of Heparan Sulfate in RNA Virus Infections: Insights From Enterovirus A71, Severe Acute Respiratory Syndrome Coronavirus 2, and Chikungunya Virus - PubMed

Food Variety Score and Geriatric Nutritional Risk Index Mediate the Relationship Between Masticatory Function and Osteoporosis - PubMed

Emergence of Carbapenem-Resistant Putative Hypervirulent Klebsiella pneumoniae ST147 with a Distinct Hybrid Plasmid in Türkiye - PubMed

Harnessing AlphaFold3 to Elucidate BBSome Structure and Protein Partners - PubMed

Sex-specific links between dietary fat intake, dementia risk, and cognitive decline in central obesity: a UK biobank cohort study - PubMed

No-reflow phenomenon after vessel recanalization in acute ischemic stroke: mechanisms, diagnosis, and treatment directions - PubMed

Agonistic anti-CD40 antibody treatment converts resident regulatory T cells into activated type 1 effectors within the tumor microenvironment - PubMed

Robot-assisted versus conventional minimally invasive oesophagectomy for oesophageal squamous cell carcinoma (RAMIE): a multicentre, open-label, randomised, phase 3, non-inferiority trial - PubMed

Microphthalmos, rudimentary iris tissue, fundal coloboma and anophthalmos in ectrodactyly ectodermal dysplasia cleft lip/palate syndrome - PubMed

Treatable traits in interstitial lung disease: towards precision medicine - PubMed

Lactic acid drives NLRP3 inflammasome activation and caspase-1-like cytokine cleavage via intracellular acidification - PubMed

Distinct mechanisms of replication stress induced by oncogenic RAS and cyclin E1 converge on R-loop-dependent fork reversal - PubMed

Activation of α7nAChR reduces inflammation and apoptosis, promoting muscle regeneration through the AKT-FOXO1 pathway - PubMed

The exposome of brain aging across 34 countries - PubMed

Irisin ameliorates obesity and insulin resistance via adipose tissue IL-33 and regulatory T cells - PubMed

Leptomeningeal metastatic cancer cells induce a permissive choroid plexus vasculature through extracellular-vesicle-derived 5-HIAA signaling - PubMed

Lipid accumulation in tuberculosis granulomas inhibits macrophage-CD4+ T cell interactions and infection control - PubMed

Aberrant amino acid-sensing promotes immunotherapy resistance via the inflammatory cytokine-ZBTB5-mTORC1 axis - PubMed

Gut microbiota-associated nutritional-immune status predicts prognosis in postoperative NSCLC patients - PubMed

Olorofim in combination with azole antifungals: results from the Phase 2 salvage therapy study - PubMed

The Diverse Roles of Heparan Sulfate in RNA Virus Infections: Insights From Enterovirus A71, Severe Acute Respiratory Syndrome Coronavirus 2, and Chikungunya Virus - PubMed

Food Variety Score and Geriatric Nutritional Risk Index Mediate the Relationship Between Masticatory Function and Osteoporosis - PubMed

Emergence of Carbapenem-Resistant Putative Hypervirulent Klebsiella pneumoniae ST147 with a Distinct Hybrid Plasmid in Türkiye - PubMed

Harnessing AlphaFold3 to Elucidate BBSome Structure and Protein Partners - PubMed

Sex-specific links between dietary fat intake, dementia risk, and cognitive decline in central obesity: a UK biobank cohort study - PubMed

No-reflow phenomenon after vessel recanalization in acute ischemic stroke: mechanisms, diagnosis, and treatment directions - PubMed