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In gastric cancer (GC), intestinal metaplasia (IM) is a common precursor lesion, but its relationship to the MUC2/MUC5AC/CDX2 axis is not completely understood. Although V-set and immunoglobulin domain containing 1 (VSIG1) is supposed to be a specific marker for gastric mucosa and GC, respectively, no data about its relationship with IM or mucin phenotype have been published. The aim of our study was to explore the possible linkage between IM and these four molecules. The clinicopathological features of 60 randomly selected GCs were examined in association with VSIG1, MUC2, MUC5AC and CDX2. Two online database platforms were also used to establish the transcription factors (TFs) network involved in MUC2/MUC5AC/CDX2 cascade. IM was more frequently encountered in females (11/16 cases) and in patients below 60 years old (10/16 cases). Poorly differentiated (G3) carcinomas tended to show a loss of CDX2 (27/33 cases) but not of MUC2 and MUC5AC. MUC5AC and CDX2 were lost in parallel with the depth of invasion of the pT4 stage (28/35 and 29/35 cases), while an advanced Dukes-MAC-like stage was only correlated with CDX2 and VSIG1 loss (20/37 and 30/37 cases). VSIG1 was directly correlated with MUC5AC (p = 0.04) as an indicator of gastric phenotype. MUC2-negative cases showed a propensity towards lymphatic invasion (37/40 cases) and distant metastases, while CDX2-negative cases tended to associate with hematogenous dissemination (30/40 cases). Regarding the molecular network, only 3 of the 19 TFs involved in this carcinogenic cascade (SP1, RELA, NFKB1) interacted with all targeted genes. In GC, VSIG1 can be considered an indicator of gastric phenotype carcinomas, where carcinogenesis is mainly driven by MUC5AC. Although infrequently encountered in GC, CDX2 positivity might indicate a locally advanced stage and risk for vascular invasion, especially in tumors developed against the background of IM. The loss of VSIG1 indicates a risk for lymph node metastases.

V-set and Immunoglobulin domain containing 1 (VSIG1) is a cell-cell adhesion molecule which role in the genesis and evolution of gastric cancer (GC) is not understood. Only three Medline-indexed papers have focused on the role of VSIG1 in GC. The clinicopathological features of 94 GCs were examined in association with immunohistochemical (IHC) patterns of VSIG1, E-cadherin, and β-catenin which were assessed in the tumor core (central) vs. invasive edge. Cases were classified depending on the VSIG1 expression: membrane/membrane in both core and invasive front; null/negative staining in both core and invasive front; and cases with translocational patterns: membrane core/cytoplasmic buds and cytoplasmic core/null buds. Most of the tumors showed null pattern (n = 54). Cases with translocational patterns (n = 20) were GCs with a high lymph node ratio value (≥ 0.26) and advanced Dukes-MAC-like stage. Of the 20 total cases, 9 showed membrane-to-nuclear translocation of β-catenin and loss of E-cadherin, as indicators of epithelial-mesenchymal transition. All cases with membrane/membrane pattern (n = 20) involved the distal stomach. The poorest overall survival was registered in patients with subcellular translocation of VSIG1, compared to those with either membrane/membrane or null patterns (p = 0.002). In GC, VSIG1 acts as an adhesion membrane protein but its membrane-cytoplasmic translocation can be an indicator of epithelial-mesenchymal transition due to cytoplasmic VSIG1-mediated activation of canonical Wnt/β-catenin signaling pathway.

Mycobacterium avium complex (MAC) organisms have been isolated from water and soil. It is now generally accepted that environmental sources, especially natural waters, are the reservoirs for most human infections caused by MAC. Previously, we reported that M. avium and M. intracellular were distributed predominantly in the eastern and western part of Japan, respectively. To clarify the factor(s) of the difference, the following experiment was undertaken. MAC was isolated from soil samples collected in Tokai, Kinki and Chugoku districts, by the method of Ichiyama et al. MAC isolates were identified by AccuProbe Confirmation and Identification tests, together with some conventional tests. Seven (11.7%) of 60 isolates were identified as M. avium, twenty (33%) as M. intracellulaer and 33 (55%) as MAC-like organisms. Therefore, it was not found that the difference in the geographical distribution between soil MAC and disease-associated MAC. MAC-like strains possess MAC-specific alpha antigen, and biological and biochemical features of MAC. They reacted with the AccuProbe MAC but not with the AccuProbe M. avium and M. intracellulare. Sequencing analysis of 16s RNA gene implies that MAC-like strains show an intermediate sequence pattern of M. avium and M. intracellulare. HPLC patterns of these strains were compatible with those of MAC. It is known that the major serovars of MAC isolates from patients with or without AIDS are different. Serological aspects in this respect are not yet elucidated well in Japan. The major serovars of MAC from patients with AIDS are 4 and 8 in the USA and Australia, 6 and 4 in Sweden, and 8/21 and 8 in Germany. On the other hand, the major serovars of MAC from patients without AIDS are 8 and 16 (15) in the USA and 6 and 1 in Sweden. According to out recent study the major serovars of MAC from non-AIDS patients are 1 and 8 in the eastern part and 16 and 14 in the western part of Japan. In the present study, 38 MAC isolates from sputum, stool and blood and AIDS patients were identified. All of the isolates were identified as M. avium. Serovars of 15 strains were 4 (4 strains), 8 (3 strains), 9 (3 strains), 3 (2 strains), Darkin (2 strains) and 1 (1 strain). Therefore, it seems that the major serovars of the Japanese MAC strains from AIDS patients are similar to those of the American MAC strains from such patients.

Malignancy associated changes (MAC) can be defined as subtle morphological and physiologic changes that are found in ostensibly normal cells of patients harboring malignant disease. It has been postulated that MAC have a potential to become a useful tool in detection, diagnosis and prognosis of malignant diseases. An in vitro cell culture model system was designed to study interactions between non-small cell lung cancer (NSCLC) and the normal bronchial epithelium of the human respiratory tract in vivo to see if the MAC-like phenomenon can be detected in such a system. In this study we examined changes in nuclear features of normal human bronchial epithelial cells (NHBE) when they were co-cultured with cells derived from a lung cancer cell line NCI-H460. Using discriminant function analysis, nuclear features were determined which allow maximal discrimination between normal cells incubated with or without cancerous cells. Our results demonstrate that MAC appear to be specific to changes induced by malignancy, and that these changes differ from those induced by growth factors in the serum. This study provides evidence in support to the hypothesis that MAC are induced by a soluble factor(s) released by malignant cells. Colour figure can be viewed on http://www.esacp.org/acp/2003/25-2/sun.htm

α-Crystallin is the archetypical chaperone of the small heat-shock protein family, all members of which contain the so-called "α-crystallin domain" (ACD). This domain and the N- and C-terminal extensions are considered the main functional units in its chaperone function. Previous studies have shown that a 19-residue fragment of the ACD of human αA-crystallin called mini-αA-crystallin (MAC) shows chaperone properties similar to those of the parent protein. Subsequent studies have confirmed the function of this peptide, but no studies have addressed the mechanistic basis for the chaperone function of MAC. Using human γD-crystallin (HGD), a key substrate protein for parent α-crystallin in the ocular lens, we show here that MAC not only protects HGD from aggregation during thermal and chemical unfolding but also binds weakly and reversibly to HGD (Kd ≈ 200-700 μM) even when HGD is in the native state. However, at temperatures favoring the unfolding of HGD, MAC forms a stable complex with HGD similar to parent α-crystallin. Using nuclear magnetic resonance spectroscopy, we identify the residues in HGD that are involved in these two modes of binding and show that MAC protects HGD from aggregation by binding to Phe 56 and Val 132 at the domain interface of the target protein, and residues Val 164 to Leu 167 in the core of the C-terminal domain. Furthermore, we suggest that the low-affinity, reversible binding of MAC on the surface of HGD in the native state is involved in facilitating its binding to both the domain interface and core regions during the early stages of the unfolding of HGD. This work highlights some structural features of MAC and MAC-like peptides that affect their chaperone activity and can potentially be manipulated for translational studies.

Mice from the MRL strain are prone to develop systemic lupus erythematosus (SLE) and have demonstrated accelerated wound healing and scarless tissue regeneration; however, many of the mechanisms involved in these clinically relevant pathologies are unclear. Prior studies have described macrophage accumulation and functional defects in mice prone to lupus. Monocyte-macrophages have also been shown to have a high degree of plasticity. To determine whether there might be innate differences in the hematopoietic systems of MRL mice, we evaluated hematopoietic progenitor cell content in a variety of tissues and the proliferative responses of derived marrow and thioglycolate (TG)-elicited peritoneal macrophages. Our experiments reveal that MRL mice have significantly lower numbers of circulating blood leukocytes and platelets. Even more strikingly, we found that MRL blood and marrow contain an unusually robust number of unique and assayable macrophage colony-stimulating factor responsive cells which have the characteristics of macrophage colony-forming cell precursors. In culture, in contrast to cells derived from control C57BL/6 mice, this cell type and thioglycolate-elicited peritoneal macrophages from MRL mice can be extensively expanded with just macrophage colony-stimulating factor to acquire an in situ "f-mac-like" (see Y. Zhao, D. Glesne and E. Huberman, A human peripheral blood monocyte-derived subset acts as pluripotent stem cells. Proc. Natl. Acad. Sci. U.S.A. 100, (2003) 2426-2431.) morphology when plated on plastic surfaces. Our results suggest that these increased numbers of macrophage progenitor cells and their potential differentiation plasticity may play a functional role in the onset of systemic lupus erythematosus and may also contribute to the accelerated and scarless tissue regenerative repair response observed in MRL mice.

Although the role of p53 in the evolution and prognosis of gastric cancer (GC) has been extensively examined, the exact mechanism of action is incompletely understood. In the last years, p53-target genes were supposed to be involved in the p53 pathway. One of them is the tumor-suppressor gene Maspin, which codifies the protein with the same name. Maspin activity depends on its subcellular localization. To our knowledge, the possible role of TP53 gene in Maspin subcellular localization, in GC cells, has not yet been studied in a large number of human samples. To evaluate the possible role of wild-type and mutated p53 in Maspin subcellular localization. The present study included 266 consecutive patients with GC in which TP53 gene status, and mutations in exons 2 to 11, respectively, were analyzed and correlated with immunohistochemical expression of p53 and Maspin. None of the 266 cases showed mutations in exon 9. The rate of TP53 mutations was 33.83%. The mutation rate was slightly higher in distally-located GCs, with a lower degree (&#x2264; 5 buds/ high power fields) of dyscohesivity (P < 0.01). The wild-type cases had a longer survival, compared with mutant GCs, especially in patients without lymph node metastases, despite the high depth of tumor infiltration (P = 0.01). The Dukes-MAC-like staging system was proved to have the most significant independent prognostic value (P < 0.01). The statistical correlations proved that TP53 gene mutations in exon 7 might induce knockdown of Maspin, but wild-type p53 can partially restore nuclear Maspin expression and decrease the metastatic potential of gastric adenocarcinoma cells. Downregulated Maspin might be induced by mutations in exon 7 of the TP53 gene but wild-type p53 can partially restore nuclear Maspin expression. These findings should be proved in experimental studies.

Over a 1-year period, 502 mycobacterial cultures submitted to the Microbial Diseases Laboratory were identified by high-performance liquid chromatography (HPLC) in parallel with standard biochemical methods. Identification by HPLC using a curvilinear gradient was achieved by comparing the chromatograms of the unknown cultures to chromatograms for known reference strains, together with calculation of peak height or peak area ratios, as necessary. The overall agreement between HPLC and biochemical identification was 97.2%. In addition, 7 of 12 cultures of Mycobacterium bovis were identified by HPLC as the BCG strain. Of 111 cultures biochemically identified as members of the M. avium complex (MAC), 108 were confirmed as MAC by DNA probe and 106 were confirmed by HPLC. Of the latter 106, 58 probe-positive strains were identified as M. avium, 38 were identified as M. intracellulare, and 10 were identified as Mycobacterium sp. strain "X" by HPLC. Of the remaining five nonchromogenic cultures, four had MAC-like chromatograms that did not match any in our library sufficiently to permit definitive identification. Of the latter four, two were confirmed as MAC strains by DNA probe and two were not. The last of the cultures biochemically identified as MAC (1 of 111) was a mixture of MAC and non-MAC strains. Overall, only 2 of 502 cultures yielded results by HPLC that differed from those obtained by standard biochemical methods. The HPLC result was confirmed in both cases by an independent national reference laboratory. In the 12 instances in which HPLC did not provide identification, the chromatograms were either uninterpretable or did not match available reference chromatograms. These findings show that the identification obtained by HPLC concurs well with that obtained by both the standard biochemical methods and the DNA probes. Thus, identification by HPLC provides mycobacteriology laboratories with a reproducible and specific method for accurate and timely identification of most medically important mycobacteria.

Bell&#xb4;s palsy is the most common cause of facial paralysis worldwide and the most common disorder of the cranial nerves. It is a diagnosis of exclusion, accounting for 60-75% of all acquired peripheral facial nerve palsies. Our case shows the first case of a microcystic adnexal carcinoma-like squamous cell carcinoma as a cause of facial nerve palsy. The patient, a 70-year-old Caucasian male, experienced subsequent functional impairment of the trigeminal and the glossopharyngeal nerve about 1&#xbd;&#x2009;years after refractory facial nerve palsy. An extensive clinical work-up and tissue biopsy of the surrounding parotid gland tissue was not able to determine the cause of the paralysis. Primary infiltration of the facial nerve with subsequent spreading to the trigeminal and glossopharyngeal nerve via neuroanastomoses was suspected. After discussing options with the patient, the main stem of the facial nerve was resected to ascertain the diagnosis of MAC-like squamous cell carcinoma, and radiochemotherapy was subsequently started. This case report shows that even rare neoplastic etiologies should be considered as a cause of refractory facial nerve palsy and that it is necessary to perform an extended diagnostic work-up to ascertain the diagnosis. This includes high-resolution MRI imaging and, as perilesional parotid biopsies might be inadequate for rare cases like ours, consideration of a direct nerve biopsy to establish the right diagnosis.

Microcystic adnexal carcinoma (MAC) is a rare, usually solitary, slowly growing, yet aggressive neoplasm with a tendency for local recurrences. Herein, we present two patients who had been histopathologically diagnosed as suffering from MAC on both cheeks since childhood, an unlikely scenario. Both from a clinical and from a histopathological point of view, our two cases showed some similarities with those previously described in patients with Nicolau-Balus syndrome, Rombo syndrome, and so-called eccrine-pilar hamartoma. Common to all these latter disorders are the round aggregations of elastic tissue in the papillary dermis, a histopathological feature which was also found in our patients. However, to our knowledge, the presence of a MAC-like ductal proliferation embedded in sclerotic stroma and extending to the deep dermis has not been previously described. Dermatologists and dermatopathologists should be aware of this disorder to avoid overdiagnosis of and inappropriate treatment for MAC.

Primary clitoral malignancies are rare and most are invasive squamous cell carcinomas. Microcystic adnexal carcinoma (MAC) is an indolent, rare dermatologic carcinoma that typically affects the head and neck region. A 23-year-old nulligravid Hispanic female presented with a 9-month history of an enlarging periclitoral mass. After surgical resection, the mass was diagnosed as a MAC. MAC is a cutaneous carcinoma rarely found on the vulva. It is a slow growing but locally aggressive carcinoma that is best treated with surgical resection. Sclerosing ductal carcinomas may have MAC-like features, and the diagnosis and management of one case is provided here.

The membrane attack complex (MAC) of complement, also known as C5b-9, was localized in Alzheimer's disease (AD) brain by immunoelectron microscopy using a monoclonal antibody to a neoantigenic epitope of soluble C5b-9 (SC5b-9). Immunopositivity was detected in association with lamellated bodies in the neuronal cytoplasm, lipofuscin granules, lysosomes and neurofibrillary tangles (NFTs). Such intracellular localization of MAC-like immunoreactive (MAC-LI) staining suggests that neurons remove membrane-inserted MAC fragments by endocytosis. These endocytosed membrane fragments then proceed by retrograde transport to the perikaryon for lysosomal degradation. Attachment to the abnormal cytoskeletal proteins found in neurofibrillary tangles also occurs. The results provide further evidence that complement-mediated injury of neurons plays a part in the pathophysiology of AD.

Facile chemical synthesis of the natural chiral-pool-derived host 1 and its subsequent crystallization ("supramolecular synthesis") from different solvents yielded crystalline assemblies. Crystal structure determinations of five of the so formed solvent-inclusion compounds (1 a-1 e) reveal hexagonal symmetries in four cases. The structural characteristics of these chiral host-guest ensembles with varying stoichiometries can be best described as assemblies formed through intra-pair hydrogen bridges of host molecules into Piedfort pairs of differing complexity. Hitherto undescribed, these Piedfort pairs also form even larger regular assemblies that we designate "Big Mac"-like shapes. In the only nonhexagonal case, six independent host molecules form a huge supramolecular analogue of [6]benzocyclophane, also known as [6]chochin, extending this giant supermolecule through intermolecular hydrogen bonds into macroscopic (mm-size) dimensions. As all these crystals are inherently chiral, and new model systems for solid-state applications can be envisaged.

Radio relics are diffuse, extended synchrotron sources located at the outskirts of merging galaxy clusters. Their origin has been linked with shock waves injected into the intracluster medium, but the acceleration mechanism at the shock front is still under debate. Some clusters, like MACS J1752.0+4440, host a double relic system, with two relics found on opposite sides with respect to the cluster center. To investigate the acceleration mechanism that generates radio relics, we study the morphological and spectral properties of the double relic system in MACS J1752. We present new wideband radio continuum observations made with uGMRT and JVLA, and LOFAR data. We perform a detailed, high-resolution spectral analysis of the double relic system in MACS J1752, observing and characterizing substructures, particularly for the brighter relic. We find a double-peaked surface brightness and spectral index profile for the NE relic and identify a "bright bar" substructure. Moreover, we observed surprisingly flat integrated spectral indices for both relics, at $α_{\mathrm{int}}^{\mathrm{NE}} = -0.91 \pm 0.06$ and $α_{\mathrm{int}}^{\mathrm{SW}} = -0.83 \pm 0.05$. We study the spatial variation

We present a parametric strong-lensing model for the galaxy cluster MACS J1931.8-2635 ($z_l = 0.35$), accompanying the detection of the spectroscopically confirmed SN Eos at $z = 5.13$ (Coulter et al. 2026). We identify 10 new multiple-image systems in recent VENUS JWST/NIRCam imaging, so that the model is constrained with a total of 19 robust multiple-image systems -- nine of which also have a spectroscopic redshift. For the point-like source corresponding to SN Eos, our model predicts a total of five images, with the observed radial image pair having a similar magnification of $μ\simeq 25 - 30$ and a small time delay of $&lt; 5$ days, in agreement with their simultaneous observation. According to the model, the other three predicted images arrived earlier, with time delays of $3.6 \pm 0.7$, $3.4 \pm 0.7$ and $53.9 \pm 10.8$ years prior to the two observed images, and with magnifications of $14.5 \pm 2.9$, $11.9 \pm 2.4$ and $2.2 \pm 0.4$, respectively. The absence of detections at the predicted positions, where the host galaxy's images are also visible, confirms the transient nature of the source. SN Eos and its host galaxy are studied in separate articles, and we here focus on t

Resource allocation in the multiple-input multiple-output (MIMO) multiple access channel (MAC) is a fundamental problem in multiuser communications, yet it is increasingly treated as non-convex and computationally intractable. This has motivated a large body of heuristic machine learning and successive-approximation methods. Results here show that the MIMO MAC admits canonical convex formulations and present four solvers that together characterize its capacity region. maxRMAC performs weighted sum-rate maximization under per-user energy constraints, minPMAC finds the minimum weighted energy required to support target rates, maxRESMAC performs weighted sum-rate maximization under a total energy constraint, and admMAC tests rate-region feasibility. The solvers exploit the polymatroid structure of the MAC rate region and the separability of the dual Lagrangian across frequency tones, which reduces the problem to parallel per-tone covariance optimizations solved via limited-memory Broyden-Fletcher-Goldfarb-Shanno (L-BFGS) over Cholesky-like covariance factors. Experiments on spatially correlated MIMO orthogonal frequency-division multiplexing (OFDM) channels show that the proposed solv

We present the first detailed numerical modeling of the radio emission from MACS J0018.5+1626 as part of the Improved Constraints on Mergers with SZ, Hydrodynamical simulations, Optical, and X-ray (ICM-SHOX) project. By matching X-ray, thermal and kinetic Sunyaev--Zel'dovich, optical and lensing observables to simulations, the ICM-SHOX pipeline indicates that MACS J0018.5+1626 is undergoing a binary merger close to pericenter passage and is observed along a line of sight nearly aligned with the merger axis. We perform three-dimensional magnetohydrodynamic simulations of binary cluster mergers coupled to tracer particles and a Fokker--Planck solver to model the radio emission. Exploring variations in the most likely initial conditions within the ICM-SHOX parameter space, such as the relative cluster velocity and impact parameter, we find that the resulting merger configuration consistently produces two merger-driven shocks with typical average Mach numbers $\mathcal{M}_s \sim 2$--$3$ with corresponding standard deviations of $σ_{\mathcal{M}} \sim 0.5$--$1.5$. Within this framework, we examine the cluster conditions under which standard diffusive shock acceleration can reproduce LOFA

To address the global health threat of antimicrobial resistance, antimicrobial peptides (AMP) are being explored for their potent and promising ability to fight resistant pathogens. While artificial intelligence (AI) is being employed to advance AMP discovery and design, most AMP design models struggle to balance key goals like activity, toxicity, and novelty, using rigid or unclear scoring methods that make results hard to interpret and optimize. As the capabilities of Large Language Models (LLM) advance and evolve swiftly, we turn to AI multi-agent collaboration based on such models (multi-agent LLMs), which show rapidly rising potential in complex scientific design scenarios. Based on this, we introduce MAC-AMP, a closed-loop multi-agent collaboration (MAC) system for multi-objective AMP design. The system implements a fully autonomous simulated peer review-adaptive reinforcement learning framework that requires only a task description and example dataset to design novel AMPs. The novelty of our work lies in introducing a closed-loop multi-agent system for AMP design, with cross-domain transferability, that supports multi-objective optimization while remaining explainable rather

Texture shapes how we perceive and like food, yet clear links between mechanical measurements and sensory perception of texture remain elusive. Here we combine sensory data from a blind tasting with 101 participants with mechanical texture profile analysis across six burgers to identify the textural features that drive consumer perception and liking. We compare five burgers -- generated with artificial intelligence -- with animal-based, plant-based, mushroom-based, and hybrid animal-mushroom patties, and the classical Big\,Mac. Three main findings emerge: First, animal-based burgers occupy a distinctive and coherent sensory-mechanical region associated with attributes such as firm, fatty, and holds together. Second, mushroom- and plant-based burgers deviate from this region in protein-dependent ways: mushroom-based burgers associate with springy and gummy textures, while plant-based burgers associate with dry, brittle, and crumbly textures. Hybrid animal-mushroom burgers, however, maintain sensory profiles comparable to fully animal-based burgers. Third, resilience emerges as the strongest mechanical correlate of perceived meatiness and sensory texture, while stiffness and hardness