TET3 is a common epigenetic immunomodulator of pathogenic macrophages.

Through a combination of single-cell/single-nucleus RNA-sequencing (sc/snRNA-seq) data analysis, immunohistochemistry, and primary macrophage studies, we have identified pathogenic macrophages characterized by TET3 overexpression (Toe-Macs) in three major human diseases associated with chronic inflammation: metabolic dysfunction-associated steatohepatitis (MASH), non-small cell lung cancer (NSCLC), and endometriosis. These macrophages are induced by common factors present in the disease microenvironment (DME). Crucially, the universal reliance on TET3 overexpression among these macrophages enables their selective elimination as a single population, irrespective of heterogeneity in other molecular markers.

Additions of trastuzumab to preoperative chemotherapy or chemoimmunotherapy for patients with potentially resectable stage III to IV HER2-positive gastric cancer.

Background: Whether the addition of trastuzumab to chemo(immuno)therapy for the preoperative treatment of patients with potentially resectable HER2-positive gastric cancer has clinical benefits remains to be explored. This real-world observational study was designed to evaluate the efficacy and safety of trastuzumab plus chemo(immuno)therapy for neoadjuvant or conversion therapy in patients with potentially resectable HER2-positive gastric cancer.

Methods: We retrospectively collected the clinical data of treatment-naïve patients with potentially resectable stage III to IV HER2-positive gastric cancer who received preoperative therapy prior to D2 gastrectomy.

Insight into the transformation of phosphorus in soil affected by microplastics: A review.

The presence of microplastics (MPs) exerts detrimental effects on soil ecosystems worldwide, subsequently affecting the soil phosphorus (P) cycling. However, the effects of MPs on soil P availability and speciation remain inconsistent, and the underlying factors and mechanisms have not been systematically discussed. Therefore, the impact of MPs on the availability and speciation of P should be clarified for the efficient management of P in the MP-polluted farmland soil.

Biliary adenofibroma and cholangiocarcinoma: neighbors or relatives? A systematic and critical review.

Biliary adenofibroma (BAF) is currently classified as a benign intrahepatic biliary tumor. However, a growing body of literature has documented BAFs with invasive components or associated cholangiocarcinoma. To better characterize this challenging entity, we performed a systematic review of BAF.

Prevalence, Production and the Role of Superantigens in Cystic Fibrosis Lung Disease.

Staphylococcus aureus (SA), the most common cystic fibrosis (CF) lung pathogen, is uniquely capable of producing superantigen (SAg) exotoxins, which are the most potent activators of the immune system. Although the proinflammatory roles of SA-SAgs is well-established, their role in the immunopathogenesis of CF lung disease is unexplored. Herein, we demonstrate that 60-80% of pediatric and adult CF SA isolates carried at least one SA-SAg gene, with the former harboring potent SA-SAgs (Staphylococcal enterotoxin A and B) more frequently (30-60%).

Characterization of Cholangiocarcinomas With Tubulocystic Morphology Associated With Biliary Adenofibroma or Biliary Adenofibroma-Like Lesions.

Hepatic biliary adenofibroma (BAF) is a benign neoplasm composed of tubuloglandular and microcystic structures within a fibrous stroma, resembling von Meyenburg complexes or ductal plate malformation (DPM). Intrahepatic cholangiocarcinoma (iCCA) with a DPM pattern (iCCA-DPM) is an established variant of iCCA, whereas adenofibroma-like tubulocystic carcinoma (AL-TCC) is a newly proposed iCCA variant associated with BAF-type lesions. We hypothesize that BAF, AL-TCC, and iCCA-DPM form a tumorigenic spectrum.

Clinicopathologic Features of Untreated Colorectal Cancer with Acellular Mucin-Only Lymph Nodes.

Lymph nodes (LNs) containing only acellular mucin are considered negative for metastasis in treated colorectal cancers (CRCs). However, no data exist on how to stage these LNs in untreated CRCs. We collected 63 untreated CRC cases with LNs containing only acellular mucin from 27 US institutions and 23 additional cases from the Dutch Nationwide Pathology Databank.

Histopathologic Progression of Autoimmune Atrophic Gastritis: A Retrospective Review of 180 Specimens From 32 Patients.

Context.—: Autoimmune atrophic gastritis (AIAG) is a chronic, immune-mediated inflammation restricted to the gastric body. Despite well-defined histologic features, the pathologic progression is still not fully understood.

Intrahepatic cholangiocarcinoma: Insights on molecular testing, targeted therapies, and future directions from a multidisciplinary panel.

Biliary tract cancers (BTCs) are a histologically and molecularly diverse group of malignancies arising from the gallbladder and the ductal epithelium of the biliary tree. Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver malignancy in the United States. Surgical resection with negative margins is the only recognized curative treatment option for iCCA; however, most patients will present with advanced or unresectable disease.

Epidermal Growth Factor Receptor Regulates Beclin-1 in Hyperoxic Acute Lung Injury.

Unlabelled: While delivery of supplemental oxygen is a life-saving therapy, exposure to high levels of oxygen, called hyperoxia, is associated with increased mortality in the intensive care unit (ICU). Hyperoxia leads to oxidant-mediated acute lung injury (ALI) and pulmonary cell death, called hyperoxic acute lung injury (HALI). Elucidation of molecular mechanisms in HALI could identify therapeutic targets in ALI.

Salt-alkali-tolerant growth-promoting Streptomyces sp. Jrh8-9 enhances alfalfa growth and resilience under saline-alkali stress through integrated modulation of photosynthesis, antioxidant defense, and hormone signaling.

Streptomyces is a group of plant growth-promoting microorganisms with considerable potential for enhancing plant tolerance to environmental stress. However, the mechanisms by which Streptomyces strains induce systemic tolerance to saline-alkaline stress remain unclear. Here, we evaluated the properties of Streptomyces sp.

Portal and Hepatic Vein Embolization versus Portal Venous Embolization Alone in Cirrhotic and Noncirrhotic Swine: A Pilot Study.

Purpose: To evaluate the effectiveness of combined portal vein embolization (PVE) and hepatic vein embolization (HVE) compared with that of PVE alone in cirrhotic and noncirrhotic swine.

Materials And Methods: Sixteen Yorkshire pigs were included in this study. In the cirrhotic group (n = 8) and noncirrhotic group (n = 8), subjects underwent embolization according to established protocols.

Hepatic Biliary Adenofibroma: Histological Characteristics, Diagnostic Challenges, and Its Role as a Precursor to Intrahepatic Cholangiocarcinoma.

Hepatic biliary adenofibroma is an exceedingly rare biliary neoplasm that primarily affects adults. It typically presents as a solitary mass composed of low-grade microcystic and tubuloglandular bile duct structures, which are lined by low columnar to cuboidal non-mucin-producing biliary epithelium and supported by abundant fibrous stroma. Histologically, it resembles the Von Meyenburg complex but is much larger in size and often shows cytologic atypia.

Hepatic Arterial Flow-Induced Portal Tract Fibrosis in Portal Hypertension: The Role of VCAM-1 and Osteopontin-Expressing Macrophages.

Background: The liver undergoes significant hemodynamic changes during surgery, transplantation, or cirrhosis with portal hypertension(PH). The hepatic artery buffer response(HABR), which compensates for reduced portal venous flow by increasing hepatic artery(HA) flow, is hypothesized to induce pathological portal tract remodeling. This study investigates the molecular mechanisms underlying this process.

Steatotic Liver Disease: Navigating Pathologic Features, Diagnostic Challenges, and Emerging Insights.

Steatotic liver disease (SLD) is now used as an overarching category encompassing five subcategories: metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic and alcohol related/associated liver disease (MetALD), alcohol-related/associated liver disease (ALD), SLD with specific etiology, and cryptogenic SLD. This review summarizes foundational and recent advances in the histologic evaluation of SLD, including common pathologic features across all subcategories, distinctions associated with different etiologies, scoring and grading systems, and the evolution of digital pathology techniques for SLD assessment.

Colorectal adenosquamous carcinoma: clinicopathologic analysis of two large cohorts and literature review confirm poor prognosis and reveal prognostic aspects.

Aims: We compiled two cohorts of colorectal adenosquamous carcinoma (ASC) to describe its histologic and molecular aspects using modern parameters to compare them with literature reports using meta-analysis of cohorts and individual case series.

Methods And Results: We identified 53 colorectal ASC from 19 North American academic medical centres, in addition to national database reports on 94 Dutch cases. We analysed available clinical, histologic, and immunohistochemical features and patient outcome.

Liver Lymphatic Dysfunction as a Driver of Fibrosis and Cirrhosis Progression.

The liver lymphatic system plays a critical role in maintaining interstitial fluid balance and immune regulation. Efficient lymphatic drainage is essential for liver homeostasis, but its role in liver disease progression remains poorly understood. In cirrhosis, lymphangiogenesis initially compensates for increased lymph production, but impaired lymphatic drainage in advanced stages may lead to complications such as ascites and portal hypertension.

Reconstitution of synaptic junctions orchestrated by teneurin-latrophilin complexes.

Synapses are organized by trans-synaptic adhesion molecules that coordinate assembly of pre- and postsynaptic specializations, which, in turn, are composed of scaffolding proteins forming liquid-liquid phase-separated condensates. Presynaptic teneurins mediate excitatory synapse organization by binding to postsynaptic latrophilins; however, the mechanism of action of teneurins, driven by extracellular domains evolutionarily derived from bacterial toxins, remains unclear. In this work, we show that only the intracellular sequence, a dimerization sequence, and extracellular bacterial toxin-derived latrophilin-binding domains of Teneurin-3 are required for synapse organization, suggesting that teneurin-induced latrophilin clustering mediates synaptogenesis.

The evolving role of liver biopsy: Current applications and future prospects.

Histopathologic evaluation of liver biopsy has played a longstanding role in the diagnosis and management of liver disease. However, the utility of liver biopsy has been questioned by some, given the improved imaging modalities, increased availability of noninvasive serologic tests, and development of artificial intelligence over the past several years. In this review, we discuss the current and future role of liver biopsy in both non-neoplastic and neoplastic liver diseases in the era of improved noninvasive laboratory, radiologic, and digital technologies.

Conversion therapy with chemoimmunotherapy induced pCR in a stage IV lung squamous cell carcinoma patient harboring exon 20 insertion.

This case study details an innovative conversion therapy strategy in a 58-year-old Asian male with baseline stage cTNM advanced lung squamous cell carcinoma (SCC) harboring a rare exon 20 insertion mutation with concurrent high PD-L1 expression who achieved a pathologic complete response (pCR) after preoperative immunotherapy plus chemotherapy. The patient initially presented with coughing and bloody sputum and was comprehensively diagnosed via PET/CT scanning, bronchoscopic biopsy and next-generation sequencing. After four cycles of platinum‒paclitaxel chemotherapy plus immunotherapy with pembrolizumab (a PD-1 blockade), significant primary tumor shrinkage and the disappearance of oligometastasis in the right adrenal gland were discovered via CT scans.

Neoadjuvant PD-(L)1 blockade with or without chemotherapy versus chemotherapy alone in mismatch repair-deficient, potentially resectable stage III-IV gastric cancer patients: a single-center retrospective study.

Background: Currently, PD-(L)1 blockade-based neoadjuvant treatment has shown promising outcomes in patients with potentially resectable gastric cancer. In this real-world study, we aimed to retrospectively observe the efficacy including tumor response and event-free survival (EFS), and safety of PD-(L)1 blockade-based neoadjuvant treatment versus chemotherapy alone in potentially resectable gastric cancer patients with microsatellite instability-high (MSI-H) or mismatch-repair deficient (dMMR) status.

Methods: We retrospectively collected the clinical data of patients with potentially resectable gastric cancer and MSI-H/dMMR status who received neoadjuvant treatment followed by D2 gastrectomy at the Affiliated Hospital of Qingdao University from January 2019 to June 2023.

Clinicopathologic features and prognosis of steatohepatitic hepatocellular carcinoma based on varying cutoffs of tumoral steatohepatitic changes.

Objectives: Steatohepatitic hepatocellular carcinoma (SH-HCC) is currently recognized as a distinct histologic subtype of HCC. The prognosis and specific criteria for determining the amount of steatohepatitis required to define SH-HCC are still unclear.

Methods: After excluding all recognized HCC subtypes from 505 HCC cases (2010-2019), the remaining cases were categorized as conventional HCC (CV-HCC) (n = 223).