Chlamydomonas reinhardtii is a unicellular green alga long studied as a biological model system but rarely considered from the perspective of its own ecology, thus epitomizing the disconnection between reductionist biology in the laboratory and life in nature. Here we present insights into its ecology understood from field strains. We examined bacterial communities that coenriched with C. reinhardtii from the field, revealing specific associations. We then compared the biology of C. reinhardtii field strains to laboratory strains, illuminating strain level heterogeneity and adaptations to life in the field vs. laboratory. Field strains exhibited more robust photosynthesis, higher abundances of pherophorin proteins, a propensity for pallmeloid formation, and high cell wall permeability. Finally, we phenotyped cocultures of C. reinhardtii with a coenriched bacterial partner, demonstrating how differences between field and laboratory strains manifest in biotic interactions. Although the organisms in question are classically understood as unicellular, our observations of field strains highlighted their participation in multicellular units, challenging the utility of unicellular frameworks in extending our knowledge of model organism biology in the laboratory towards understanding microbial ecology.
Invasive mold diseases (IMDs) are rare, life-threatening infections that primarily affect persons with immunocompromising conditions. The most common molds associated with IMDs are Aspergillus spp., Mucorales (e.g., Mucor spp., Rhizomucor spp., and Rhizopus spp.), Fusarium spp., and Scedosporium spp. IMDs can affect the lungs, sinuses, skin, central nervous system, or multiple body sites. 2020-2024. IMD is not a nationally notifiable condition. CDC conducts active, laboratory-based IMD surveillance through the Georgia Emerging Infections Program at three laboratories that serve four Atlanta, Georgia, hospitals: two academic hospitals and their associated outpatient clinics, one federal hospital, and one community hospital. Identifying and classifying IMD cases is challenging because 1) symptoms often are nonspecific and 2) the presence of mold growth in clinical cultures might indicate infection, colonization, or laboratory contamination.Potential IMD cases were identified through a review of records from laboratories serving the hospitals included in this surveillance system to identify patients who received positive results from mold cultures or Aspergillus galactomannan tests, which detect the presence of galactomannan, a compound found in Aspergillus fungi, in serum or bronchoalveolar lavage fluid specimens. Potential cases in these patients were classified as proven or probable cases using established National Institute of Allergy and Infectious Diseases Mycoses Study Group (MSG) criteria that consider laboratory findings (e.g., histopathologic evidence of angioinvasive mold infection or a fungal culture from a normally sterile body site), clinical or radiologic features supporting IMD classification (e.g., chest computed tomography or bronchoscopy results suggestive of fungal disease, sinonasal signs, or central nervous system imaging results), and host factors that predispose patients to IMD (e.g., recent history of neutropenia, hematologic malignancy, transplantation receipt, and use of certain immunosuppressive medications). Potential cases that did not meet the laboratory, clinical, and host-factor criteria for MSG-proven or MSG-probable cases could be categorized as surveillance cases if treating clinicians diagnosed IMD in a patient and initiated treatment with antifungal therapy effective against mold or if the patient died within 3 days of specimen collection. During 2020-2024, a total of 968 unique patients with potential IMD were identified across four Atlanta hospitals and their associated outpatient clinics. Of those, 449 (46%) were classified as having IMD, including 89 (20%) MSG-proven, 142 (32%) MSG-probable, and 218 (49%) surveillance cases. Among patients with IMD, 58 (13%) had a current or recent COVID-19 diagnosis. Information on bed count was available for three of the four hospitals. At the two academic hospitals, the pooled average annual IMD incidence was 4.8 inpatient cases per 100 inpatient beds and 14.0 intensive care unit (ICU) cases per 100 ICU beds. At the community hospital, the average annual incidence was 2.8 inpatient cases per 100 inpatient beds and 10.2 ICU cases per 100 ICU beds.Among 449 patients with IMD, the largest percentage were aged 45-64 years (43%), followed by ≥65 years (39%), 19-44 years (18%). Patients aged 1-18 years and <1 year each accounted for <1% of IMD cases. Pulmonary infections were most common (68%), followed by cutaneous or deep tissue (nonfacial) infections (11%), sinus or nasal infections (10%), and central nervous system infections (excluding eyes) (9%); less frequent sites of infection included soft tissue (2%), blood (1%), bone (1%), and eye (1%). The most common fungal species identified among IMD cases were Aspergillus spp. (n = 319 [71%]), most commonly Aspergillus fumigatus (n = 94 [21%]). Fusarium spp. were the second most common (n = 20 [4%]), followed by Mucorales (n = 17 [4%]), and Scedosporium spp. (n = 12 [3%]). Aspergillus spp., Scedosporium spp., and Curvularia spp. were most commonly associated with pulmonary infections. Mucorales genera were more commonly associated with sinus, nasal, or facial infections and Fusarium spp. with cutaneous or deep tissue infections. Among patients with IMD, 65% (n = 292) had at least one MSG host factor that predisposes patients to IMD, and 53% (n = 238) had at least one MSG clinical criterion supporting IMD classification, suggesting that surveillance based only on classic host risk factors or typical clinical findings might miss a substantial proportion of IMD cases.A total of 363 (81%) of 449 patients with IMD received antifungal treatment effective against molds, most commonly isavuconazole (n = 178 [40%]), followed by voriconazole (n = 142 [32%]) and amphotericin B (n = 93 [21%]). Overall, 43% of patients with IMD were admitted to an ICU during the 2 weeks preceding specimen collection, and 50% of patients with IMD required intubation and mechanical ventilation; the 90-day all-cause mortality rate, excluding 2024 cases, was 45% (157 of 349). Indicators of severe illness were more common among IMD patients with a current or recent COVID-19 diagnosis than among those without COVID-19, including higher frequency of ICU admission during the 2 weeks preceding specimen collection (66% [38 of 58] versus 39% [154 of 391]; p<0.001) and increased 90-day all-cause mortality (66% [35 of 53] versus 41% [122 of 296]; p<0.001). IMDs are severe infections associated with frequent ICU admission and high mortality rates, especially among patients with a current or recent COVID-19 diagnosis. The findings from this report could serve as benchmark data in establishing baseline IMD rates for future surveillance to detect outbreaks in health care settings. More than one third of IMD cases (35%) occurred in patients without MSG host factors, underscoring the need for clinicians and surveillance efforts to consider the possibility of IMDs among patients without classic host risk factors for infection. Health care providers should be vigilant for IMDs as a life-threatening complication among persons with immunocompromising conditions or critical illness. Continued surveillance could help identify emerging populations at risk for IMD, facilitate earlier recognition and treatment, and support detection of health care-associated outbreaks.
Foodborne botulism is a severe neuroparalytic disease caused by ingestion of foods containing botulinum neurotoxins, produced by Clostridium botulinum. In 2024, a 74-year-old woman from Newfoundland and Labrador with complete bilateral flaccid paralysis and respiratory distress was hospitalized and required intubation. From the broader differential diagnosis list, botulism was favoured prior to laboratory confirmation. Serum and feces samples initially tested negative for botulinum neurotoxins by mouse bioassay, yet viable C. botulinum type A was recovered from the feces. Food history investigation included some diced garlic in a repurposed coffee container that tested negative for botulinum neurotoxins by mouse bioassay, but viable C. botulinum type A was recovered from the sample. Both the fecal and garlic enrichment cultures were positive for bont/A and bont/B genes by real-time PCR. Whole genome sequencing revealed that both fecal and garlic isolates were highly similar with conserved gene synteny, including an intact bont/A1 gene and a disrupted (silent) bont/B5 gene encoded on the chromosome. This single-case foodborne botulism outbreak from Newfoundland and Labrador in 2024 was caused by C. botulinum type A1(B5) in diced garlic.
Kratom (Mitragyna speciosa) is increasingly used by U.S. adults for pain management, mental health symptoms, and substance withdrawal, yet remains minimally regulated and poorly integrated into clinical guidance. This scoping review characterized patterns and motivations for kratom use, associated health outcomes, and regulatory and social factors shaping access and perception among U.S. adults. A scoping review was conducted following Joanna Briggs Institute (JBI) methodology and Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-SCR) guidelines. Searches of PubMed/MEDLINE, Embase, CENTRAL, and the Cochrane Library identified peer-reviewed studies published between 2015 and 2025. Studies involving U.S. adults that examined kratom use patterns, health outcomes, or regulatory and social factors were included. Screening and data extraction were conducted using Covidence, and qualitative content analysis was used to identify key themes and research gaps. Of 1,887 records identified, 43 studies met inclusion criteria. Most studies were cross-sectional, with sample sizes ranging from small laboratory cohorts to nationally representative surveys. Common motivations for kratom use included pain relief, self-treatment of mental health conditions, mitigation of substance withdrawal, and enhancement of energy or mood. Reported outcomes were primarily behavioral and psychological, including polysubstance use, cravings, tolerance, and perceived symptom improvement, alongside physical effects such as gastrointestinal symptoms and withdrawal. Regulatory factors included legal variability, limited federal oversight, inconsistent product labeling, marketing practices, and stigma. Kratom use among U.S. adults reflects unmet healthcare needs within a fragmented regulatory environment. Coordinated regulation, improved clinical education, standardized surveillance, and stigma-reduction efforts are needed to mitigate harm and support informed decision-making.
Delayed-type cutaneous adverse drug reactions (CADRs) are T-cell-mediated hypersensitivity reactions that may present with variable clinical severity in children. They range from mild maculopapular exanthema (MPE) to severe, life-threatening mucocutaneous syndromes such as drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Data on pediatric delayed-type CADRs remain limited. They represent an important cause of morbidity in pediatric patients and require careful diagnostic evaluation. This study aimed to describe the clinical characteristics, etiologic agents, management strategies, and outcomes of pediatric patients with delayed-type CADR followed at a tertiary pediatric center. This retrospective case series included 33 pediatric patients diagnosed with delayed-type CADR between January 2013 and December 2024. Demographic features, suspected culprit drugs, clinical manifestations, laboratory and histopathologic findings, treatment approaches, and outcomes were reviewed. RegiSCAR, EuroSCAR, and SCORTEN criteria were applied for diagnostic classification and severity assessment of DRESS, AGEP, and SJS/TEN, respectively. The median age was 9 years (range: 9 days-16 years); 17 patients were female. The most frequent diagnosis was MPE (n=18, 54.5%), followed by DRESS (n=5, 15.1%), SJS/TEN (n=3, 9.1%), AGEP/ALEP (n=3, 9.1%), erythema multiforme (n=2, 6.0%), and SDRIFE (n=2, 6.0%). Antibiotics and antiepileptic drugs were the most commonly implicated drug classes. Systemic corticosteroids were administered in moderate-to-severe cases, and intravenous immunoglobulin was used in selected patients with DRESS and SJS/TEN. Four patients died due to underlying primary diseases; no CADR-related mortality was observed. This retrospective case series describes the heterogeneous clinical spectrum of delayed-type CADRs in children in a tertiary referral setting. In our cohort, maculopapular exanthema was the most frequent phenotype, while antibiotics and antiepileptic drugs were the most commonly implicated agents. A high burden of comorbidities, including immunosuppression and polypharmacy, was notable and may have influenced the observed clinical spectrum. Severe reactions required multidisciplinary management.
Can a microblade-based self-collection device (Tasso+, Tasso, USA) provide analytically reliable measurements of key reproductive hormones compared with standard venous sampling under controlled conditions, and does it improve patient experience during IVF monitoring? A multicentre, pilot, paired-sample study was conducted in 39 women undergoing IVF treatment. Paired venous and Tasso+ samples were collected during the same clinical visit and anti-Mullerian hormone (AMH), oestradiol and progesterone concentrations were analysed at 0, 24, 48 and 72 h under controlled storage at 4°C. Agreement was assessed using Pearson correlation coefficients, intra-class correlation coefficients (ICC) and Bland-Altman analyses. Patient experience was evaluated using a structured questionnaire. Hormone concentrations obtained via Tasso+ showed excellent agreement with venous sampling across all analytes and time points (Pearson's r = 0.948-0.998, ICC = 0.948-0.998). AMH and oestradiol remained stable for up to 72 h at 4°C, with minimal bias and narrow limits of agreement. Progesterone maintained high agreement at 24 h but showed increasing dispersion at 48 and 72 h. Patient-reported experience was favourable across all domains, with overall mean scores ranging from 7.80 to 8.18 on a 10-point Likert scale. Under controlled clinical and laboratory conditions, Tasso+ provides analytically reliable measurements of AMH, oestradiol and progesterone with favourable patient acceptability. AMH and oestradiol concentrations remained stable for up to 72 h at 4°C, whereas progesterone samples should ideally be analysed within 24 h for clinical decision making. These findings support the further evaluation of self-collection devices as complementary tools in patient-centred IVF monitoring pathways.
Ibogaine is a natural hallucinogen with emerging evidence for treating substance use disorders. However, its cardiovascular effects are not fully known, and most clinical data focus on opioid dependence, with limited data for Alcohol Use Disorder (AUD). This study assessed the feasibility, safety, and preliminary effects of ibogaine in patients with AUD. In this preliminary open-label, pilot, feasibility study, nine adults with moderate to severe AUD received oral ibogaine hydrochloride in a sequential order: volunteer 1 20/40/80 mg; volunteer 2 80/160/240 mg, volunteer 3: 240/320 mg, and the next six received a single 400 mg dose. Participants were hospitalized 24-48 hours before dosing with continuous monitoring. Primary outcome included safety measures (QTc interval, vital signs, laboratory tests, adverse effects, and psychiatric assessments). Secondary outcome included alcohol and substance use. QTc alterations, including transient prolongation and shortening, occurred in five patients. Mild/moderate blood pressure alterations were also observed. Mild/moderate adverse effects were common (drowsiness, nausea, anxiety), particularly at higher doses (240-400 mg). No serious adverse effects were observed, but two patients needed medication for psychomotor agitation, insomnia and hypertension. Most participants reported reductions in alcohol use, but only five completed the study. Moderate doses of ibogaine showed a cardiotoxic potential that demands rigorous cardiovascular screening and continuous monitoring. Patients reported reduced substance use, but motivation and placebo effects could explain these results. Randomized controlled trials are needed to confirm efficacy and establish protocols with safety parameters.
Türkiye has intermediate hepatitis B virus (HBV) infection prevalence and an additional burden of hepatitis D virus (HDV). Large-scale real-world data describing adults with chronic HBV-infection and the completeness of routinely collected electronic health record (EHR) data for HBV monitoring and surveillance is not well characterized. A retrospective, cross-sectional study using EHR data from a multicenter private hospital network, including 18,284 adult patients with chronic HBV infection between 2017 and 2025 was conducted. The primary analysis included 17,927 adults with HBV monoinfection, defined as patients without a recorded ICD-10 B18.0 diagnosis code for chronic HBV with delta agent. We described demographic and clinical characteristics, liver disease outcomes, and the availability and consistency of key EHR variables relevant to HBV care, including ALT, HBV DNA, HBeAg, anti-HDV testing, B18.0 diagnosis coding, and structured treatment documentation. Among adult patients with HBV monoinfection, 60.6% were male and the mean age was 53.5 years (SD 14.5). Cirrhosis and hepatocellular carcinoma (HCC) were recorded in 11.1% and 3.4% of patients, respectively, and were more common among men and older adults. Baseline ALT values were available for 45.5% of HBV monoinfected patients. Among patients without cirrhosis, HCC, or liver failure, both HBV DNA and HBeAg status were available for 1274 of 15,243 patients. Documented anti-HDV testing was available for 2213 of 18,284 patients (12.1%), while 357 patients (2.0%) had recorded B18.0 diagnosis code; only 76 of these 357 patients also had documented anti-HDV testing in available EHR field. In this large private-sector EHR cohort of adults with recorded chronic HBV infection, cirrhosis and HCC were common, particularly among older adults and men. The findings should not be interpreted as national HBV prevalence estimates, but they demonstrate the value of private-sector EHR data for characterizing diagnosed HBV care while highlighting gaps in laboratory monitoring, HDV documentation, and treatment data needed to support HBV surveillance and elimination efforts.
The Hawaiian flower thrips (Thrips hawaiiensis Morgan) is a significant pest of bananas that causes black spotting on the fruit peel. This study investigated the attraction of banana flower-bud color and volatiles on thrips. Results showed that female T. hawaiiensis locate flower buds primarily through volatile organic compounds (VOCs), with bud color having no significant influence. Y-tube olfactometer assays revealed significant attraction to volatiles emitted from bracts, stamens and pistils, and young fruits. HS-SPME/GC-MS identified 7 major VOCs, and laboratory bioassays confirmed significant attraction to 5: α-pinene, β-pinene, D-limonene, DL-limonene, and β-caryophyllene. Field trials utilizing blue sticky traps treated with these individual and blended compounds significantly increased the capture of females. These findings highlight the key role of specific VOCs in T. hawaiiensis host-location behavior, providing a basis for behaviorally guided pest management in banana cultivation.
Bordetella pertussis (BP) infection remains a major public health concern because of its substantial clinical and epidemiological impact. Although nucleic acid amplification tests (NAATs) are widely used for pertussis diagnosis, their real-world performance in routine clinical laboratories has not been systematically evaluated. This study implemented an external quality assessment (EQA) program to assess laboratory proficiency and identify potential sources of analytical variability. An EQA panel comprising five samples (four positive and one negative) was prepared using 10-fold serial dilutions of BP (2.0 × 102-2.0 × 105 copies/mL). The panel was distributed to participating laboratories, and performance was evaluated based on qualitative agreement with the expected results. A total of 69 laboratories participated, including 63 (91.30%) hospital-based laboratories and 6 (8.70%) independent clinical laboratories, generating 345 test results. All laboratories achieved acceptable performance (scores ≥ 80). The overall concordance rate was 98.84% (341/345). Four false-negative results were identified, all of which occurred in the lowest-concentration sample (200 copies/mL). Pertussis NAATs demonstrated generally reliable diagnostic performance among participating laboratories in Chongqing, China. However, challenges remain in detecting low-copy-number specimens near the analytical sensitivity threshold. Continuous quality monitoring, standardized workflows, optimized nucleic acid extraction procedures, and regular performance verification are essential to ensure accurate pertussis diagnosis and support effective public health surveillance and outbreak response.
Autoimmune hepatitis (AIH) is an important indication for liver transplantation (LT), but recurrence affects over 30% of recipients, threatening long-term survival. Current strategies to prevent recurrence and progressive graft fibrosis remain suboptimal, with limited evidence to guide selection of immunosuppressive regimens. We aimed to develop a dynamic, individualized, artificial intelligence-powered model for post-transplant recurrent AIH. We conducted a multicenter, retrospective cohort study of 706 patients who underwent LT for AIH between January 1987 and June 2020 at 33 centers in North America, South America, Europe, and Asia. We trained 4 predictive machine learning models-Logistic Regression, Random Forest, XGBoost, and Gradient Boost-to predict recurrent AIH (rAIH) using 62 clinical and laboratory variables, including demographic, biochemical features, and immunosuppressive drugs up to 1-year post-transplant. Feature importance was assessed using SHapley Additive exPlanations (SHAP) to enable interpretability at both individual and population levels.Results:AIH recurred in 16.5% of patients after LT. SHAP analysis identified younger age at LT, higher necroinflammatory activity in the explanted liver, and elevated MELD score at LT as key predictors of rAIH in the overall population. Tacrolimus-based therapy was associated with a lower risk of recurrence, while cyclosporine use conferred a higher risk. The addition of long-term prednisone to a regimen of tacrolimus and mycophenolate mofetil did not provide additional protective effect against rAIH. Our AI-powered clinical decision model provides personalized prediction of post-transplant rAIH. While it offers insight into modifiable and non-modifiable predictors, prospective validation is required before informing immunosuppressive decisions.
SIRT6 downregulation in atherosclerotic vascular endothelial cells (ECs) is exacerbated under diabetic conditions, and EC-specific Sirt6 knockout aggravates diabetic atherosclerosis progression. EC-specific Sirt6 knockout aggravates atherosclerosis progression through vasculature hyperpermeability and monocyte/macrophage accumulation in vessels. SIRT6 directly interacts with transcription factor zinc finger E-box binding homeobox 1 (ZEB1) for deacetylation/degradation, preserving ZEB1 at a low level for normal expression of tight junction protein claudin-1 in ECs to maintain endothelial barrier function for vascular homeostasis. Naringin, a natural flavonoid ZEB1 inhibitor, reverses the diabetes-exacerbated vascular endothelial dysfunction to attenuate atherosclerosis progression, offering a promising, novel therapeutic strategy for diabetic atherosclerotic cardiovascular diseases.
Solvation structure regulation plays crucial roles in stabilizing the Zn anode by suppressing dendrite and hydrogen evolution, but sluggish ion transport results in poor rate performance of the anode. In this study, we proposed an "anion regulation" strategy by introducing amphiphilic benzyl alcohol (BA) to the Zn(OTf)2 electrolyte, which modulated the electrolyte microstructure and dual solvation structure. BA provided weak solvation ability with Zn2+ and induced the Zn2+-OTf-BA dual solvation structure by anion-solvent interaction, which downsized the solvation clusters with improved microscopic uniformity, improving the Zn2+ diffusion kinetics. Synergistic regulation on the first solvation shell was also achieved, where BA not only reduced the coordinated water but also weakened the Zn2+-OTf- interaction, accelerating the desolvation kinetics. Additionally, an inorganic-rich solid electrolyte interphase was constructed by anion decomposition, favorable for interfacial stability. Consequently, the modulated electrolyte enabled the Zn anode with impressive rate performance (1500 h, 10 mA cm-2/10 mAh cm-2; 294 h, 20 mA cm-2/20 mAh cm-2) and superior stability at 85% utilization (260 h). The 1.2 Ah Zn-NH4V4O10 pouch cell also maintained cyclability (∼85.3% retention) over 200 cycles. This work provides a novel way of regulating the electrolyte microstructure to improve interfacial kinetics toward practical zinc-ion batteries.
Four organotin acridine-9-carboxylate complexes (C1-C4) were successfully synthesized by the reaction of 9-acridinecarboxylic acid (YCOOH) with organotin precursors. The structures of these complexes were systematically characterized using elemental analysis, IR, NMR, X-ray single-crystal diffraction, X-ray powder diffraction and thermogravimetric analysis. Among them, the tributyltin complex C4 exhibited the most potent in vitro antiproliferative activity against HepG2, MCF-7, and NCI-H460 cancer cell lines, with IC50 values as low as 0.08 μM against HepG2 cells. Mechanistic studies identified two functional pathways: (i) DNA intercalation, as evidenced by UV-Vis, fluorescence titrations, viscosity measurements, and molecular docking, which directly disrupts DNA architecture; and (ii) mitochondria-mediated apoptosis, characterized by collapse of mitochondrial membrane potential (ΔΨm), cytochrome c (CytC) release, elevated ROS generation, upregulation of Bax and Cleaved-caspase-3, and downregulation of Bcl-2. Importantly, these two pathways act synergistically: DNA intercalation triggers early nuclear stress, which amplifies mitochondrial dysfunction and ROS burst, thereby lowering the apoptotic threshold and enhancing the overall cytotoxic efficacy. Collectively, the dual DNA-mitochondria targeting and their cooperative action establish acridine-based organotin complexes as promising anticancer candidates.
Fruit acidity, a key quality trait, is primarily determined by malic acid in many fruit crops. However, the molecular machinery governing its accumulation, particularly in response to hormonal cues like auxin, remains a "black box." Here, we systematically deconstruct the regulatory pathway controlling malic acid in litchi (Litchi chinensis). We first identify the tonoplast-localized transporter LcALMT1 as the principal channel for malate sequestration into the vacuole. We then uncover its upstream regulatory module, revealing that the R2R3-MYB transcription factor LcMYB70 directly binds the LcALMT1 promoter but lacks intrinsic transcriptional activity. Instead, LcMYB70 functions as a molecular scaffold to recruit the Auxin Response Factor LcARF10, which confers transcriptional repression upon the complex. This LcMYB70-LcARF10 repressor module is negatively regulated by auxin signaling, providing a direct molecular link between the decline in endogenous auxin during fruit maturation and the attenuation of malate accumulation. Critically, we identified a single-nucleotide polymorphism in the LcARF10 gene that governs the divergence between high- and low-acid cultivars. The functional C allele in low-acid cultivars enables the formation of the repressor complex. In contrast, the T allele in high-acid cultivars contains a premature stop codon that results in a non-functional, truncated protein, preventing complex assembly and causing the high-acid phenotype. Our study defines a complete pathway from hormone to trait and its genetic basis, revealing a novel MYB-ARF scaffold module; a definitive molecular link between auxin withdrawal and metabolic reprogramming; and the functional integrity of a corepressor as a new paradigm for trait diversification.
Parental history of hip fracture is an independent risk factor for fragility fracture, yet the skeletal traits underlying this risk remain poorly defined. We examined whether parental hip fracture is associated with differences in bone microarchitecture and estimated bone strength in a large, ethnically diverse cohort of older adults (n = 950; mean age 76.1 ± 6.2 yr; 71% female; 55.8% Hispanic) using high resolution peripheral quantitative computed tomography (HR-pQCT) with individual trabecula segmentation (ITS) and finite element-based analysis. Ten percent (n = 95) reported a parental hip fracture. Femoral neck aBMD was 3.8% lower in those with versus without parental history (p = .04). At the radius, the parental hip fracture group had lower adjusted trabecular rod bone volume fraction (10.6%), plate and rod number, axial BV/TV (12.2%) and plate connectivity (9.5%; all p < .05). At the tibia, parental hip fracture history was associated with lower adjusted trabecular density (8.8%), trabecular thickness (2.4%), plate and axial BV/TV (14%-15%, all p < .05), and 4%-5% lower estimated stiffness and failure load, differences that persisted after adjustment for aBMD. Patterns were similar regardless of race/ethnicity and whether parental hip fracture was maternal or paternal. Similar patterns were observed in a subset who were matched by propensity score. Individuals with a parental history of hip fracture exhibited significant microarchitectural deterioration, especially in trabecular structure at weight-bearing sites, and reduced estimated bone strength independent of areal BMD. These findings suggest that inherited deficits in trabecular morphology may contribute to familial fracture susceptibility and underscore the utility of HR-pQCT in identifying heritable skeletal fragility beyond DXA indices. History of parental hip fracture has been shown to increase fragility fracture risk. Our study uses high-resolution bone imaging in a diverse population to assess if parental hip fracture is associated with worse bone microstructure and strength in offspring. Trabecular bone structure was worse at both the radius and tibia while bone strength was worse at the tibia, regardless of race/ethnicity and if the hip fracture was maternal or paternal. Familial predisposition to fracture could be associated with inherited trabecular bone weaknesses, highlight the importance of using high-resolution bone imaging to identify potential heritable determinants of bone strength.
The drug-to-antibody ratio (DAR) represents a critical quality attribute for antibody-drug conjugates (ADCs). Conventional site-specific conjugation strategies typically generate ADCs with defined DAR values ranging from 2 to 8. However, for ultrapotent cytotoxic payloads, lower DAR values have been shown to enhance tumor tissue penetration and improve safety profiles. Similarly, in antibody-oligonucleotide conjugates (AOCs), reduced DAR values contribute to optimized pharmacokinetic behavior. Previously, we developed a glycosite-specific ADC construction method, termed DisacLink technology, based on synthetic LacNAc oxazoline derivatives. Building on this platform, we have now designed bis-functionalized drug-linkers that enable the generation of glycosite-specific DAR1 ADCs. This method achieves high conjugation efficiency, demonstrates the applicability to the major human IgG subclasses and commonly used payloads, yielding site-specific conjugates with acceptable homogeneity, favorable thermal and aggregation stability, and potent in vitro and in vivo antitumor activity.
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Asymmetric (transfer) hydrogenation of olefins is an important route to chiral molecules used in pharmaceuticals, agrochemicals, and fine chemicals. Although this transformation is well established with ruthenium-, rhodium-, and iridium-based catalysts, analogous reactions catalyzed by earth-abundant metals remain limited, particularly for acyclic olefins. Here we report a manganese catalytic system that enables highly enantioselective reduction of both cyclic and acyclic olefins, delivering diverse chiral products in up to 99% yield and >99% ee. Density functional theory (DFT) studies indicate that the reaction proceeds predominantly through a concerted hydrogen-transfer pathway involving a six-membered transition state. These results expand the scope of manganese-catalyzed asymmetric olefin transfer hydrogenation and provide mechanistic insight into hydrogen transfer by base-metal catalysts.
The newborn period is a critical phase in the clinical management of patients with ichthyosis. However, there are no clinical guidelines for the care of ichthyosis in newborns. Awareness of ichthyosis among healthcare professionals remains limited, and nurses often assume care responsibilities without specialized training or adequate information support. The preterm female infant presented with generalized gelatinous skin changes accompanied by fissures and bilateral ectropion. Significant clinical findings also included skin breakdown in the major folds (neck, axilla, popliteal fossa, and groin), along with systemic issues such as metabolic acidosis, hyperlactatemia, and the presence of elevated infection indicators. The primary diagnosis was low birth weight, prematurity, congenital ichthyosis, metabolic acidosis, hyperlactatemia, neonatal pathologic jaundice, and newborn thrush. The available evidence was rapidly reviewed to guide individualized management, including skin care and emollient therapy, infection surveillance and prevention, fluid and nutritional management based on intake and output, and multidisciplinary psychosocial support. After 13 days of treatment and nursing care, the infant was discharged in improved condition. This case may provide practical evidence to inform the care of similar newborns with congenital ichthyosis and improve clinical outcomes.