Galectin-8 is a small soluble lectin with two carbohydrate recognition domains (CRDs). N- and C-terminal CRDs of Gal-8 differ in their specificity for glycan ligands. Here, we wanted to find out whether oligomerization of individual CRDs of galectin-8 affects its biological activity. Using green fluorescent protein polygons (GFPp) as an oligomerization scaffold, we generated intrinsically fluorescent CRDs with altered valency. We show that oligomers of C-CRD are characterized by significant cell surface affinity. Furthermore, the multivalency of the resulting variants has an impact on cellular activities such as cell signaling, heparin binding and proliferation. Our data indicates that tunable valence is a useful tool for modifying the biological activity of CRDs of galectins.

BACKGROUND: Chronic respiratory diseases (CRDs) contribute significantly to morbidity and mortality worldwide and in India. Access to nonpharmacological options, such as pulmonary rehabilitation (PR), are, however, limited. Given the difference between need and availability, exploring PR, specifically remotely delivered PR, in a resource-poor setting, will help inform future work.
OBJECTIVE: This study explored the perceptions, experiences, needs, and challenges of patients with CRDs and the potential of and the need for PR from the perspective of patients as well as medical professionals involved in the referral (doctors) and delivery (physiotherapists) of PR.
METHODS: In-depth qualitative semistructured interviews were conducted among 20 individuals diagnosed with CRDs and 9 medical professionals. An inductive thematic analysis approach was used as we sought to identify the meanings shared both within and across the 2 participant groups.
RESULTS: The 20 patients considered lifestyle choices (smoking and drinking), a lack of physical activity, mental stress, and heredity as the triggering factors for their CRDs. All of them equated the disease with breathlessness and a lack of physical strength, consulting multiple doctors about their physical symptoms. The most commonly cited treatment choice was an inhaler. Most of them believed that yoga and exercise are good self-management strategies, and some were performing yoga postures and breathing exercises, as advised by friends or family members or learned from a televised program or YouTube videos. None of them identified with the term \"pulmonary rehabilitation,\" but many were aware of the exercise component and its benefits. Despite being naive to smartphone technology or having difficulty in reading, most of them were enthusiastic about enrolling in an application-based remotely delivered digital PR program. The 9 medical professionals were, however, reluctant to depend on a PR program delivered entirely online. They recommended that patients with CRDs be supported by their family to use technology, with some time spent with a medical professional during the program.
CONCLUSIONS: Patients with CRDs in India currently manage their disease with nonguided strategies but are eager to improve and would benefit from a guided PR program to feel better. A home-based PR program, with delivery facilitated by digital solutions, would be welcomed by patients and health care professionals involved in their care, as it would reduce the need for travel, specialist equipment, and setup. However, low digital literacy, low resource availability, and a lack of expertise are of concern to health care professionals. For India, including yoga could be a way of making PR \"culturally congruent\" and more successful. The digital PR intervention should be flexible to individual patient needs and should be complemented with physical sessions and a feedback mechanism for both practitioners as well as patients for better uptake and adherence.

Both iodine concentration and protein intake are important nutritional factors that may influence the development of depressive symptoms. However, there are no studies on the effect of protein intake on the relationship between iodine concentration and the risk of depression. The study aimed to explore the relationship between iodine and the risk of clinically relevant depression (CRD) according to protein intake. This study analyzed the adults (≥18 years) who participated in the 2007-2018 National Health and Nutrition Cross-sectional Survey (N = 10,462). CRD was assessed using the Patient Health Questionnaire (PHQ-9). Protein intake was assessed using two 24-h dietary recalls and urinary iodine concentration (UIC) was measured using inductively coupled plasma dynamic response cell mass spectrometry. Weighted multivariate logistic regression and restrictive cubic splines were performed to assess the relationship between UIC and CRD according to protein category (low protein intake <0.8 g/kg/day; high protein intake: ≥0.8 g/kg/day). After controlling for sociodemographic, behavioral, chronic diseases, and dietary factors, a positive correlation was observed between UIC (log10) and CRD (OR: 1.36, 95% CI: 1.026, 1.795). Low UIC (<100 μg/L) was associated with a lower prevalence of CRD (OR: 0.73, 95% CI: 0.533, 0.995) in high protein intake individuals, whereas this relationship did not exist in those with low protein intake. Moreover, restrictive cubic splines confirmed a near L-shaped relationship between UIC and CRD in the low-protein group (nonlinear p = .042) and a linear relationship between them in the high-protein group (nonlinear p = .392). This study illustrates that protein intake affects the relationship between UIC and CRD. Combining lower UIC and high protein intake may help reduce the prevalence of CRD, which would have significant implications for managing patients with depressive CRD in the clinical setting.

BACKGROUND: Chronic respiratory diseases (CRDs) may cause reduced oxygen availability to organs and body tissues, leading to an increased risk for ischemic damage, which can result in brain tissue injury. This damage can lead to a myriad of neurological symptoms contributing to cognitive decline. Cognitive interventions may attenuate cognitive deficits in people with CRDs; however, the effects have not yet been systematically summarized in the literature.
OBJECTIVE: The purpose of this systematic review is to assess the effects of cognitive interventions (including cognitive behavioral therapy and transcranial brain stimulation) on cognitive function (primary outcome), HRQL, self-management, symptoms, physical activity, physical function, ability to complete activities of daily living (ADLs), hospital admissions, functional capacity, functional performance, psychological and social outcomes, exacerbations, healthcare utilization, and survival in individuals with CRDs.
METHODS: This review will be conducted in accordance with the Cochrane handbook for systematic reviews of interventions and reported following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Searches will be performed in MEDLINE, Embase, Emcare, PsycINFO, Scopus, and CINAHL. Articles will be included if they focus on the effects of cognitive interventions on adults with CRDs, are published in peer-reviewed journals, and are written in English, French, or Portuguese. Risk of bias will be evaluated with the Cochrane Risk of Bias 2 tool for randomized controlled trials, and the Risk of Bias in Non-randomized Studies of Interventions tool for nonrandomized studies. Meta-analyses will be performed if at least 2 studies provided sufficient data for a specific outcome. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) assessment will be used to evaluate the overall quality of the evidence.
RESULTS: This systematic review was initiated in November 2022 and registered with PROSPERO in February 2023, prior to title and abstract screening. Full-text screening of articles will be completed in June 2023. Data extraction and drafting of the manuscript will occur from July 2023 to August 2023, with expected publication in February 2024.
CONCLUSIONS: This systematic review will summarize the effects of cognitive interventions on cognitive function in people with CRDs. It will guide health care professionals in selecting evidence-based strategies to enhance cognitive well-being and overall health outcomes for individuals with CRDs. Additionally, it will identify research gaps and highlight areas for future exploration, supporting researchers in advancing knowledge in this field.
BACKGROUND: PROSPERO CRD42023396234; https://tinyurl.com/mwjrfbxv.
UNASSIGNED: PRR1-10.2196/48235.

Background: Cone-rod dystrophies (CRDs) are a heterogeneous group of inherited retinal diseases (IRDs) characterized by cone photoreceptor loss, that is followed by subsequent rod photoreceptor impairment. Case presentation: A 49-year-old man complaining of diminution of vision in both eyes (OU) was referred to our outpatient clinic. He reported visual loss for 5 years, but it was most progressive during the last few months. The best-corrected visual acuity (BCVA) at presentation was 0.4 in the right eye (RE) and 1.0 in the left eye (LE). Fundus fluorescein angiography (FFA) revealed granular hyperfluorescence in the macula and concomitant areas of capillary atrophy. Flash full-field electroretinography (ffERG) showed lowering of a and b waves as well as prolonged peak time in light-adapted conditions. However, outcomes of dark-adapted ERGs were within normal limits. Based on the constellation of clinical, angiographic, and electrophysiological tests findings, a diagnosis of IRD was suspected. Genetic testing showed a homozygous, pathogenic c.783G>A mutation in the cadherin-related family member 1 (CDHR1) gene, which confirmed CRD type 15 (CRD15). Conclusions: We demonstrate the clinical characteristics, retinal imaging outcomes, and genetic test results of a patient with CRD15. Our case contributes to expanding our knowledge of the clinical involvement of the pathogenic mutation c.783G>A in CDHR1 variants.

Clubroot, caused by Plasmodiophora brassicae, is an economically important soil-borne disease that threatens Brassicaceae crops worldwide. In recent years, the incidence area of Chinese cabbage (Brassica rapa ssp. pekinensis) clubroot disease has increased, which severely affects the yield and quality of Chinese cabbage. The resistance of varieties harboring the single clubroot-resistance (CR) gene is easily broken through by P. brassicae pathotypes. CRa and CRd, genetically identified in B. rapa, are CR genes known to be highly resistant to different P. brassicaea pathotypes. In our study, we perform the gene pyramiding of CRa and CRd in Chinese cabbages through marker-assisted selection (MAS), and develop homozygous pyramided lines. The newly generated pyramided lines exhibit greater resistance to six different pathotypes than that of two parental lines carrying a single CR gene. This study provides new CR-gene-pyramided lines for the development of clubroot-resistant Brassica varieties for future breeding programs.

OBJECTIVE: Complex repetitive discharges (CRDs) are spontaneous electromyography (EMG) waveforms often associated with chronic neurogenic or myopathic diseases, but incidentally identified CRDs have also been described. In this study we describe the distribution and possible significance of incidentally seen CRDs in otherwise normal electrodiagnostic studies.
METHODS: A retrospective chart review was performed of all patients with CRDs incidentally documented on otherwise normal electrodiagnostic studies at Mayo Clinic from January 2013 through December 2020. Each patient\'s clinical symptoms, referral reason, electrodiagnostic report, and imaging studies were analyzed using descriptive statistics.
RESULTS: Ninety-four patients (86 females; mean age, 62 years; range, 20 to 86 years) and 107 CRDs were studied. The most common neuromuscular reasons for electrodiagnostic referrals included radiculopathy, peripheral neuropathy, and myopathy. Mean symptom duration was 43 months (range, 1 to 312 months). Eighty-five patients had a CRD identified in one muscle (range, in all patients, one to five muscles). CRDs were identified most frequently in tensor fasciae latae (n = 21), biceps brachii (n = 16), and gluteus maximus (n = 9). Of the 58 patients in whom imaging was available, 46 (79%) had abnormalities that corresponded to the myotome in which the CRDs were visualized, most commonly L5 (n = 19) and C6 (n = 12). Of these 46 patients, 28 (61%) were referred for radicular or limb pain.
CONCLUSIONS: CRDs can be incidentally noted on otherwise normal electrodiagnostic studies, most commonly in L5 and C6 myotomes. The mechanism of CRDs in the absence of electrodiagnostic features of axon loss or remodeling is unknown.

BRAF is frequently mutated in human cancer and the RASopathy syndromes, with RASopathy mutations often observed in the cysteine-rich domain (CRD). Although the CRD participates in phosphatidylserine (PS) binding, the RAS-RAF interaction, and RAF autoinhibition, the impact of these activities on RAF function in normal and disease states is not well characterized. Here, we analyze a panel of CRD mutations and show that they increase BRAF activity by relieving autoinhibition and/or enhancing PS binding, with relief of autoinhibition being the major factor determining mutation severity. Further, we show that CRD-mediated autoinhibition prevents the constitutive plasma membrane localization of BRAF that causes increased RAS-dependent and RAS-independent function. Comparison of the BRAF- and CRAF-CRDs also indicates that the BRAF-CRD is a stronger mediator of autoinhibition and PS binding, and given the increased catalytic activity of BRAF, our studies reveal a more critical role for CRD-mediated autoinhibition in BRAF regulation.

UNASSIGNED: Bermuda grass pollen is a common inhaled allergen. The aim of this study was to investigate the molecular sensitization patterns to major pollen allergens (Bermuda grass, Mugwort and Timothy grass) and cross-reactive carbohydrate determinants (CCD) in Bermuda grass sensitized patients in southern China.
UNASSIGNED: Serum specific IgE (sIgE) levels of Bermuda grass allergen components (Cyn d 1 and Cyn d 12), Timothy grass allergen components (Phl p 1, Phl p 4, Phl p 5, Phl p 7 and Phl p 12), Mugwort allergen components (Art v 1, Art v 3 and Art v 4) and CCD were detected in 78 patients sensitized to Bermuda grass via EUROBlotMaster system.
UNASSIGNED: Compared with CCD-positive patients, those with negative CCD results had significant higher positive rates of Cyn d 1 (47.8% vs 14.5%), Phl p 1 (26.1% vs 7.3%), Phl p 12 (21.7% vs 3.6%) and Art v 4 (26.1% vs 3.6%) (all p < 0.05). Patients <18 years old had the highest positive rate of Cyn d 1 (40.7%). Additionally, rhinitis patients had the highest positive rate of Cyn d 1 (60.0%), and all patients with Cyn d 12 sensitization (17.2%) were asthmatic patients. Optimal scale analysis showed that Phl p 1 and Cyn d 1 were closely related (Cronbach\'s alpha = 85.1%).
UNASSIGNED: The highest positive rate of pollen allergen components was Cyn d 1 in Bermuda grass sensitized patients in southern China. Most patients were sensitized to CCD alone, and CCD may have less interference in the detection of Cyn d 1, Art v 4, Phl p 1 and Phl p 12. The sensitization patterns of pollen allergen components varied in different ages and diseases, and the diagnostic strategy of pollen allergen needs to be considered in the future.

C-type lectin receptors (CLRs), pattern recognition receptors (PRRs) with a characteristic carbohydrate recognition domain (CRD) in the extracellular portion, mediate crucial cellular functions upon recognition of glycosylated pathogens and self-glycoproteins. CLEC4A is the only classical CLR that possesses an intracellular immunoreceptor tyrosine-based inhibitory motif (ITIM), which possibly transduces negative signals. However, how CLEC4A exerts cellular inhibition remains unclear. Here, we report that the self-interaction of CLEC4A through the CRD is required for the ITIM-mediated suppressive function in conventional dendritic cells (cDCs). Human type 2 cDCs (cDC2) and monocytes display a higher expression of CLEC4A than cDC1 and plasmacytoid DCs (pDCs) as well as B cells. The extracellular portion of CLEC4A specifically binds to a murine cDC cell line expressing CLEC4A, while its extracellular portion lacking the N-glycosylation site or the EPS motif within the CRD reduces their association. Furthermore, the deletion of the EPS motif within the CRD or ITIM in CLEC4A almost completely impairs its suppressive effect on the activation of the murine cDC cell line, whereas the absence of the N-glycosylation site within the CRD exhibits partial inhibition on their activation. On the other hand, antagonistic monoclonal antibody (mAb) to CLEC4A, which inhibits the self-interaction of CLEC4A and its downstream signaling in murine transfectants, enhances the activation of monocytes and monocyte-derived immature DCs upon stimulation with a Toll-like receptor (TLR) ligand. Thus, our findings suggest a pivotal role of the CRD in self-interaction of CLEC4A to elicit the ITIM-mediated inhibitory signal for the control of the function of cDCs.