In Paguroidea, the chelae of the first thoracopods (chelipeds) encompass heterochelate (unequal), homoiochelate (subequal, weakly differentiated), and homochelate (equal, mirrored) conditions, reflecting functional differentiation and evolutionary adaptation across taxa. For 30 species from seven hermit crab families detailed 3D models of chelae were generated using microCT imaging. For these, 3D shape analysis identified six distinct shape types (I-compact, II- sturdy, III-elongate, IV-scutiform, V-discoid, VI-semidiscoid) across the investigated taxa. These shape types correspond closely with key biological roles. Paired semidiscoid chelae enable symmetrical shelter closure, while scutiform and discoid chelae function in one-sided shelter closure and defense and are associated with the utilization of gastropod shells. Compact and elongate chelae serve in food manipulation and grooming. Sturdy chelae, which include most homoiochelate forms, are associated with intermediate conditions related to alternative defensive strategies, such as complete (deep) withdrawal into shells, preference for shells with narrow apertures, or symbiotic relationships with anthozoans. Phylogenetic patterns might indicate that potentially basal taxa like Pylochelidae retain plesiomorphic, symmetrical semidiscoid chelae, but it cannot be excluded that these homochelate chelae represent an apomorphic condition for the taxon. In any case, the asymmetric hermit crabs (Parapaguridae, Paguridae, Diogenidae, Coenobitidae, Lithodidae) evolved pronounced heterochely, with the dominant chela adapted (primarily) for shelter closure and the subdominant one for feeding and grooming. Homoiochelate forms occur repeatedly across Diogenidae, suggesting multiple evolutionary transitions related to shifts in defensive strategy. The association between chela shape, biological role, and phylogeny highlights the dynamic interplay of evolutionary history, functional demands, and ecological adaptation in shaping hermit crab morphology.

This study explores the role of the src homology-2domain-containing protein tyrosine phosphatase-2 (SHP2)-discoid domain receptor 1 (DDR1)-extracellular signal-regulated kinase (ERK) signaling axis in neuropathic pain following spinal cord injury (SCI). Rats were transfected with LV-shSHP2 before SCI modeling. Hind limb function and paw withdrawal threshold were assessed using the Basso-Beattie-Bresnahan (BBB) scale, and Von Frey filaments, respectively. The effects of SHP2 knockdown on microglial activation and DDR1/SHP2/ERK pathway were examined by Western blotting and immunofluorescence. To further validate the regulatory mechanism of SHP2 in SCI, lipopolysaccharide (LPS)-activated BV-2 microglial cells were subjected to SHP2/DDR1 knockdown, or DDR1 overexpression. Results showed that SCI induced motor deficits, mechanical allodynia, and upregulation of spinal SHP2, DDR1, and p-ERK/ERK ratio, alongside microglial activation. These changes were reversed by LV-shSHP2 treatment. In LPS treated BV-2 cells, DDR1 overexpression promoted cell activation and ERK phosphorylation, while counteracting the effects of LV-shSHP2; however, DDR1 knockdown produced the opposite effects. A direct interaction between SHP2 and DDR1 was confirmed. In conclusion, SHP2 knockdown suppresses microglial hyperactivation and alleviates SCI-induced neuropathic pain by downregulating the DDR1-ERK signaling pathway, during which SHP2-DDR1 interaction has been confirmed as a key regulatory mechanism. Targeting this specific interaction axis may offer a novel therapeutic strategy for neuropathic pain management by selectively disrupting microglial activation.

CetZs are archaeal tubulin superfamily cytoskeletal proteins implicated in the control of cell shape and motility. In the pleomorphic archaeon Haloferax volcanii, CetZ1 is required for the transformation of a discoid, or plate-like, cell morphology to the rod shape in early log-phase cultures, and for the development of swimming motility. In this study, we found that the paralog CetZ2 is not required for rod development or reversion to plates in log phase but was strongly upregulated later in stationary phase, where it participates in the maintenance of plate cell shape. Overproduction of CetZ2 or a functional fluorescently tagged CetZ2 promoted maintenance of plate cell shape specifically in the stationary phase. The tagged CetZ2 localized in patchy subcellular assemblies at the cell edges that were most dynamic in mid-stationary phase, where they showed directional movement around the cell edge and other complex behaviors. The stationary phase dynamics of CetZ1 and CetZ2 localization patterns were dependent on their individual GTPase activities and on the presence of one another, despite the much higher cellular concentration of CetZ1 over CetZ2 (ratios of over 40:1 in log and 5:1 in stationary phase). Together, the results suggest that CetZ2 counteracts the CetZ1-based rod development pathway to maintain plate shape in the stationary phase and imply that additional stationary-phase factors are required. CetZ1 and CetZ2 are co-conserved in many haloarchaea, suggesting that their coordinated functions at different stages of the growth cycle may be widely utilized to control cell shapeshifting.

In apparently idiopathic syndrome of inappropriate antidiuretic hormone secretion (SIADH), chilblain-like hand plaques may reveal autoimmune connective tissue disease. Skin examination, biopsy, and serology can uncover discoid lupus erythematosus with Sjögren's syndrome overlap. Serum sodium improvement after skin treatment requires caution because spontaneous stabilization cannot be excluded.

Apolipoprotein A-II, the second most abundant protein in HDL, plays a key role in the HDL maturation and reverse cholesterol transport. It has a stronger affinity for lipids than apolipoprotein A-I (APOA1), which forms HDL's structural scaffold. Like APOA1, APOA2 mainly consists of amphipathic alpha helices that help it interact with lipid surfaces. Using computer modeling and mutagenesis, we developed a structural model for lipid-bound human APOA2. The protein's single disulfide bond restricts it to a belt-like configuration in discoidal HDL particles. Our model shows several key features: i) most basic residues of APOA2 are in the hairpin loop; ii) salt bridges and π-π interactions stabilize the structure; iii) two high-lipid affinity helical regions are in each APOA2 monomer; and iv) the hairpin structure facilitates interactions with other proteins like APOA1 or APOA2. Chemical crosslinking and MS/MS analysis identified 16 crosslinks; Fifteen of the 16 crosslinks are consistent with the double hairpin belt model, strongly supporting the proposal that the disulfide-dimer double hairpin belt is the primary structure of APOA2 in humans.

Background/Objectives: Facial discoid dermatosis is a rare inflammatory dermatosis presenting with round, superficial erythematous lesions located on the face. Diagnosis may be challenging and often requires careful clinicopathological correlation due to overlapping clinical and histopathological features. Skin lesions are typically resistant to a wide range of topical and systemic treatments. From the perspective of personalized medicine, improved phenotyping of rare inflammatory dermatoses may support more precise diagnosis, individualized therapeutic decisions, and non-invasive disease monitoring. This study aimed to characterize facial discoid dermatosis using line-field confocal optical coherence tomography and reflectance confocal microscopy and to discuss its differential diagnosis and therapeutic implications. Methods: We report a case of facial discoid dermatosis in a 35-year-old patient examined with line-field confocal optical coherence tomography and reflectance confocal microscopy. The imaging findings were interpreted in correlation with clinical and histopathological features. A literature review was performed to summarize differential diagnoses, therapeutic perspectives, and the proposed relationship between facial discoid dermatosis and pityriasis rubra pilaris. Results: Non-invasive imaging revealed morphological features consistent with a psoriasiform inflammatory dermatosis and provided additional in vivo information supporting the diagnosis. The literature review showed limited evidence for a direct association between facial discoid dermatosis and pityriasis rubra pilaris, with only isolated reports suggesting possible overlap or progression. Conclusions: Facial discoid dermatosis appears to represent a distinct psoriasiform dermatosis. Line-field confocal optical coherence tomography and reflectance confocal microscopy may contribute to a personalized diagnostic approach by supporting differential diagnosis and potentially guiding individualized monitoring in rare inflammatory facial dermatoses.

Hydroxychloroquine, which is closely related to chloroquine, can be used for the prevention and treatment of some forms of malaria and rheumatic conditions such as systemic lupus erythematosus (SLE) and rheumatoid arthritis. Malaria is an infection caused by the Plasmodium parasite, transmitted via mosquito bites. Hydroxychloroquine sulfate is indicated for the prevention and treatment of uncomplicated malaria due to sensitive strains of Plasmodium falciparum (P. falciparum), Plasmodium vivax (P. vivax), Plasmodium malariae (P. malariae), Plasmodium ovale (P. ovale), and Plasmodium knowlesi (P. knowlesi) by both the US Centers for Disease Control (CDC) and World Health Organization (WHO) (1, 2). Resistance to chloroquine and hydroxychloroquine has been reported in Plasmodium species, thus hydroxychloroquine therapy is not recommended if the infection arose in a region with known resistance. Most P. falciparum infections are resistant to the 4-aminoquinolines (chloroquine and hydroxychloroquine), and as such these drugs are no longer used widely for these infections. Hydroxychloroquine must be co-administered with an 8-aminoquinoline compound for the radical cure of P. vivax or P. ovale infection to eliminate the hypnozoite forms of these parasites. (3) Additionally, hydroxychloroquine is indicated for the treatment of many rheumatoid conditions in adults, including chronic discoid lupus erythematosus, systemic lupus erythematosus, as well as acute and chronic rheumatoid arthritis. Hydroxychloroquine has also been used in an off-label capacity for the management of Sjögren syndrome (4). Hydroxychloroquine accumulates in cellular acidic compartments such as the parasitic food vacuole and mammalian lysosomes, leading to alkalinization of these structures. Among antimalarial medications, hydroxychloroquine is less likely than other medicines to cause hemolysis in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals; however, the U.S. FDA-approved drug label states there is still a risk of acute hemolytic anemia (AHA) (Table 1) (3). In contrast, the Clinical Pharmacogenetics Implementation Consortium (CPIC) performed a systematic review of the available clinical literature and found low-to-no risk of AHA for individuals with G6PD deficiency who take hydroxychloroquine (5). It should be noted that G6PD deficiency has a range of severity; CPIC advises caution for all medications when used by an individual with a severe G6PD deficiency with chronic non-spherocytic hemolytic anemia (CNSHA) (Table 2) (5). Regardless of G6PD phenotype, chronic use of hydroxychloroquine can cause irreversible retinal damage and regular visual exams are recommended by the FDA (3).

Ferromanganese (Fe-Mn) concretions are porous accumulations of iron and manganese (hydr)oxides. While recent studies suggest that microbes contribute to metal accumulation in Baltic Sea concretions, the detailed composition of microbial communities and their impact on metal enrichment across different concretion morphotypes remain unexplored. We investigated how microbes influence the accumulation and release of trace metals and rare-earth elements in Fe-Mn concretions from the Gulf of Finland through 15-week microcosm incubation experiments with biotic and abiotic treatments, focusing on three main concretion morphotypes: crust, discoidal, and spheroidal. Elemental analysis showed that microbes enhanced metal incorporation in discoidal and spheroidal morphotypes. Characterisation of microbial composition revealed that all three morphologies host distinct communities. Discoidal and spheroidal morphotypes had a higher relative abundance of Gammaproteobacteria and sulfate-reducing bacteria, and a lower abundance of Entotheonellaeota, compared to crusts. In all morphotypes, the bacterial phylum Pseudomonadota dominated, with several genera of Fe- and Mn-oxidisers and reducers. Fe-Mn concretions also host communities involved in methane oxidation and nitrogen cycling, consistent with decreased methane and increased nitrous oxide, nitrite, and nitrate concentrations in the microcosms. Our findings underscore that distinct microbial communities are associated with different concretion morphotypes, potentially influencing nutrient and metal cycling on the seafloor.

A 12-year-old boy presented with bilateral knee pain, and magnetic resonance imaging (MRI) revealed bilateral complete discoid lateral meniscus (DLM) tears. He underwent single-stage bilateral saucerization and was able to return to sports. Within four years, he sustained new tears in both knees during sports participation and underwent repeat arthroscopy. At the last follow-up, he had returned to unrestricted activity with improved symptoms. Single-stage bilateral saucerization may be a feasible and well-tolerated option for select pediatric patients with DLM tears, potentially minimizing cumulative recovery time. Further research is warranted to evaluate long-term outcomes and guide patient selection.