A Web-Based Resilience-Enhancing Program to Improve Resilience, Physical Activity, and Well-being in Geriatric Population: Randomized Controlled Trial.

BACKGROUND: Resilience is a protective factor in healthy aging, helping to maintain and recover physical and mental functions. The Resilience in Illness Model has proven effective in fostering resilience and well-being. Physical activity is crucial for older adults' independence and well-being, even as aging causes a progressive decline. Additionally, older adults face challenges such as spousal loss and physical disability, making preventive intervention strategies necessary. OBJECTIVE: This study aims to develop and evaluate a web-based program to enhance resilience, physical activity, and well-being among community-dwelling older adults. Additionally, we aim to gather feedback on the program's strengths and limitations. METHODS: A 4-week resilience-enhancing program was created, incorporating role-play and talk-in-interaction and focusing on 3 key skills: coping, control belief, and manageability. The program included scenarios such as becoming widowed and suffering a stroke, designed to engage older adults. A pilot test preceded the intervention. As a result of the COVID-19 pandemic, the program shifted from in-person to web-based sessions. A single-blind, parallel-group, randomized controlled trial was conducted. Participants aged over 65 years were recruited offline and randomly assigned to either an intervention or control group. A certified resilience practitioner delivered the program. Outcomes in resilience, physical activity, and well-being were self-assessed at baseline (T0), 4 weeks (T1), and 12 weeks (T2) after the program. A mixed methods approach was used to evaluate feedback. RESULTS: A web-based participatory program enhancing 3 skills-coping, control belief, and manageability for resilience-was well developed. Among 96 participants, 63 were randomized into the intervention group (n=31) and the control group (n=32). The mean age in the intervention group was 69.27 (SD 3.08) years and 74.84 (SD 6.23) years in the control group. Significant between-group differences at baseline were found in age (t45.6=-4.53, P<.001) and physical activity at baseline (t61=2.92, P=.005). No statistically significant between-group differences over time were observed in resilience (SE 7.49, 95% CI -10.74 to 18.61, P=.60), physical activity (SE 15.18, 95% CI -24.74 to 34.74, P=.74), and well-being (SE 3.74, 95% CI -2.68 to 11.98, P=.21) after controlling for baseline differences. The dropout rate was lower in the intervention group (2/31, 6%) compared with the control group (5/32, 16%). Moreover, 77% (24/31) of participants in the intervention group completed the entire program. Program feedback from the participants indicated high satisfaction with the web-based format and mentorship support. CONCLUSIONS: This study demonstrated that a web-based resilience-enhancing program is appropriate, acceptable, feasible, and engaging for community-dwelling older adults. The program garnered enthusiasm for its potential to optimize resilience, physical activity, and well-being, with mentorship playing a crucial role in its success. Future studies should aim to refine program content, engagement, and delivery methods to effectively promote healthy aging in this population. TRIAL REGISTRATION: ClinicalTrials.gov NCT05808491; https://clinicaltrials.gov/ct2/show/NCT05808491.

Future Goal Aspirations of Students With Extensive Support Needs: Findings From NLTS 2012.

This study used data from the National Longitudinal Transition Study 2012 (NLTS 2012) to explore the future goal aspirations of students with extensive support needs who participate in alternate assessments, compared to other students with extensive support needs and to students with other disabilities. We examined students' individualized education program (IEP)/transition planning meeting experiences and postschool goals in relation to their functional, communication, and self-advocacy skills, as well as their school/community support. Students with other disabilities held higher expectations than all students with extensive support needs for future participation in postsecondary education, employment, independent living, and financial independence. All students had higher postschool goal expectations than their parents. Implications for supporting students with extensive support needs and directions for future research and practice are discussed.

Combatting Antibiotic-Resistant Staphylococcus aureus: Discovery of TST1N-224, a Potent Inhibitor Targeting Response Regulator VraRC, through Pharmacophore-Based Screening and Molecular Characterizations.

Staphylococcus aureus (S. aureus) is a major global health concern, causing various infections and presenting challenges due to antibiotic resistance. In particular, methicillin-resistant S. aureus, vancomycin-intermediate S. aureus (VISA), and vancomycin-resistant S. aureus pose significant obstacles in treating S. aureus infections. Therefore, the critical need for novel drugs to counter these resistant forms is pressing. Two-component systems (TCSs), integral to bacterial regulation, offer promising targets for disruption. In this study, a comprehensive approach, involving pharmacophore-based inhibitor screening, along with biochemical and biophysical analyses were conducted to identify, characterize, and validate potential inhibitors targeting the response regulator VraRC of S. aureus. The constructed pharmacophore model, Phar-VRPR-N3, demonstrated effectiveness in identifying a potent inhibitor, TST1N-224 (IC50 = 60.2 ± 4.0 µM), against the formation of the VraRC-DNA complex. Notably, TST1N-224 exhibited strong binding to VraRC (KD = 23.4 ± 1.2 µM) using a fast-on-fast-off binding mechanism. Additionally, NMR-based molecular modeling revealed that TST1N-224 predominantly interacts with the α9- and α10-helixes of the DNA-binding domain of VraR, where the interactive and functionally essential residues (N165, K180, S184, and R195) act as hotspots for structure-based inhibitor optimization. Furthermore, TST1N-224 evidently enhanced the susceptibility of VISA to both vancomycin and methicillin. Importantly, TST1N-224 distinguished by 1,2,5,6-tetrathiocane with the 3 and 8 positions modified with ethanesulfonates holds significant potential as a lead compound for the development of new antimicrobial agents.

Topology Prediction of Gas-Separating Metal-Organic Frameworks with Low Symmetry Vertices.

Topology serves as a blueprint for the construction of reticular structures such as metal-organic frameworks, especially for those based on building blocks with highly symmetrical shapes. However, it remains a challenge to predict the topology of the frameworks from less symmetrical units, because their corresponding vertex figures are largely deformed from the perfect geometries with no "default" net embedding. Furthermore, vertices involving flexible units may have multiple shape choices, and the competition among their designated topologies makes the structure prediction in large uncertainty. Herein, the deformation index is proposed to characterize the symmetry loss of the vertex figure by comparing it with its ideal geometry. The mathematical index is employed to predict the shapes of two in situ formed Co-based metalloligands (pseudo-tetrahedron and pseudo-square), which further dictate the framework topology (flu and scu) when they are joined with the [Zr6O8]-based cuboid units. The two frameworks with very similar constituents provide an ideal platform to investigate how the pore shapes and interconnectivity influence the gas separation. The net with cylindrical channels outperforms the other with discreate cages in C3H8/C2H6/CH4 separation, benefiting from the facile accessibility of its interaction sites to the guests imposed by the specific framework topology.

Pd(II)-Catalyzed 1,2-Oxyarylation of Alkenes with O-Acylhydroxylamines as the Oxygen Source.

O-Acylhydroxylamine has been widely employed as an electrophilic amination reagent in transition-metal-catalyzed C-N coupling reactions, but its use as an electrophilic oxygen source has not been disclosed. Here, we report a Pd-catalyzed 1,2-oxyarylation of alkenes with O-acylhydroxylamines as an oxidant and an oxygen source for the first time. With simple amide as the monodentate directing group, this method features a broad substrate scope, good functional group tolerance, and mild conditions.

Catalytic Kinetic Resolution of Monohydrosilanes via Rhodium-Catalyzed Enantioselective Intramolecular Hydrosilylation.

The catalytic access of silicon-stereogenic organosilanes remains a big challenge, and largely depends on the desymmetrization of the symmetric precursors with two identical substitutes attached to silicon atom. Here we report the construction of silicon-stereogenic organosilanes via catalytic kinetic resolution of racemic monohydrosilanes with good to excellent selectivity factors. Both Si-stereogenic dihydrobenzosiloles and Si-stereogenic monohydrosilanes could be efficiently accessed in one single operation via Rh-catalyzed enantioselective intramolecular hydrosilylation, employing (R,R)-Et-DuPhos as the optimal ligand. This catalytic protocol features mild conditions, a low catalyst loading (0.1 mol % [Rh(cod)Cl]2), high stereoinduction (S factor up to 152), and excellent scalability. Moreover, further derivatizations led to the efficient synthesis of uncommon middle-size (7- and 8-membered) Si-stereogenic silacycles. Preliminary mechanistic study indicates this reaction might undergo a modified Chalk-Harrod mechanism.

Structure-guided identification and characterization of potent inhibitors targeting PhoP and MtrA to combat mycobacteria.

Mycobacteria are causative agents of tuberculosis (TB), which is a global health concern. Drug-resistant TB strains are rapidly emerging, thereby necessitating the urgent development of new drugs. Two-component signal transduction systems (TCSs) are signaling pathways involved in the regulation of various bacterial behaviors and responses to environmental stimuli. Applying specific inhibitors of TCSs can disrupt bacterial signaling, growth, and virulence, and can help combat drug-resistant TB. We conducted a comprehensive pharmacophore-based inhibitor screening and biochemical and biophysical examinations to identify, characterize, and validate potential inhibitors targeting the response regulators PhoP and MtrA of mycobacteria. The constructed pharmacophore model Phar-PR-n4 identified effective inhibitors of formation of the PhoP-DNA complex: ST132 (IC50 = 29 ± 1.6 µM) and ST166 (IC50 = 18 ± 1.3 µM). ST166 (KD = 18.4 ± 4.3 µM) and ST132 (KD = 14.5 ± 0.1 µM) strongly targeted PhoP in a slow-on, slow-off manner. The inhibitory potency and binding affinity of ST166 and ST132 for MtrAC were comparable to those of PhoP. Structural analyses and molecular dynamics simulations revealed that ST166 and ST132 mainly interact with the α8-helix and C-terminal ß-hairpin of PhoP, with functionally essential residue hotspots for structure-based inhibitor optimization. Moreover, ST166 has in vitro antibacterial activity against Macrobacterium marinum. Thus, ST166, with its characteristic 1,2,5,6-tetrathiocane and terminal sulphonic groups, has excellent potential as a candidate for the development of novel antimicrobial agents to combat pathogenic mycobacteria.

Discovery of a potent inhibitor, D-132, targeting AsfvPolX, via protein-DNA complex-guided pharmacophore screening and in vitro molecular characterizations.

The heightened transmissibility and capacity of African swine fever virus (ASFV) induce fatal diseases in domestic pigs and wild boars, posing significant economic repercussions and global threats. Despite extensive research efforts, the development of potent vaccines or treatments for ASFV remains a persistent challenge. Recently, inhibiting the AsfvPolX, a key DNA repair enzyme, emerges as a feasible strategy to disrupt viral replication and control ASFV infections. In this study, a comprehensive approach involving pharmacophore-based inhibitor screening, coupled with biochemical and biophysical analyses, were implemented to identify, characterize, and validate potential inhibitors targeting AsfvPolX. The constructed pharmacophore model, Phar-PolX-S, demonstrated efficacy in identifying a potent inhibitor, D-132 (IC50 = 2.8 ± 0.2 µM), disrupting the formation of the AsfvPolX-DNA complex. Notably, D-132 exhibited strong binding to AsfvPolX (KD = 6.9 ± 2.2 µM) through a slow-on-fast-off binding mechanism. Employing molecular modeling, it was elucidated that D-132 predominantly binds in-between the palm and finger domains of AsfvPolX, with crucial residues (R42, N48, Q98, E100, F102, and F116) identified as hotspots for structure-based inhibitor optimization. Distinctively characterized by a 1,2,5,6-tetrathiocane with modifications at the 3 and 8 positions involving ethanesulfonates, D-132 holds considerable promise as a lead compound for the development of innovative agents to combat ASFV infections.

Construction of Si-Stereogenic Silanols by Palladium-Catalyzed Enantioselective C-H Alkenylation.

The construction of silicon-stereogenic silanols via Pd-catalyzed intermolecular C-H alkenylation with the assistance of a commercially available L-pyroglutamic acid has been realized for the first time. Employing oxime ether as the directing group, silicon-stereogenic silanol derivatives could be readily prepared with excellent enantioselectivities, featuring a broad substrate scope and good functional group tolerance. Moreover, parallel kinetic resolution with unsymmetric substrates further highlighted the generality of this protocol. Mechanistic studies indicate that L-pyroglutamic acid could stabilize the Pd catalyst and provide excellent chiral induction. Preliminary computational studies unveil the origin of the enantioselectivity in the C-H bond activation step.

Versatile photonic molecule switch in multimode microresonators.

Harnessing optical supermode interaction to construct artificial photonic molecules has uncovered a series of fundamental optical phenomena analogous to atomic physics. Previously, the distinct energy levels and interactions in such two-level systems were provided by coupled microresonators. The reconfigurability is limited, as they often require delicate external field stimuli or mechanically altering the geometric factors. These highly specific approaches also limit potential applications. Here, we propose a versatile on-chip photonic molecule in a multimode microring, utilizing a flexible regulation methodology to dynamically control the existence and interaction strength of spatial modes. The transition between single/multi-mode states enables the "switched-off/on" functionality of the photonic molecule, supporting wider generalized applications scenarios. In particular, "switched-on" state shows flexible and multidimensional mode splitting control in aspects of both coupling strength and phase difference, equivalent to the a.c. and d.c. Stark effect. "Switched-off" state allows for perfect low-loss single-mode transition (Qi ~ 10 million) under an ultra-compact bend size (FSR ~ 115 GHz) in a foundry-based silicon microring. It breaks the stereotyped image of the FSR-Q factor trade-off, enabling ultra-wideband and high-resolution millimeter-wave photonic operations. Our demonstration provides a flexible and portable solution for the integrated photonic molecule system, extending its research scope from fundamental physics to real-world applications such as nonlinear optical signal processing and sixth-generation wireless communication.

Postschool Goal Expectations for Youth With Intellectual and Developmental Disabilities.

Using National Longitudinal Transition Study 2012 data, this study explored parent and youth expectations in the areas of postsecondary education, employment, independent living, and financial independence. Compared to youth with other disabilities, youth with intellectual and developmental disabilities and their parents had much lower expectations for the four postschool goals, and parent expectations were much lower than youth's own expectations. Also, youth's race, along with their daily living skills and functional abilities, were positively associated with parent and youth expectations in several future goal areas. Our discussion highlights implications for improving the transition experiences of youth with intellectual and developmental disabilities.

Recovery mechanism of bio-promoters on Cr(VI) suppressed denitrification: Toxicity remediation and enhanced electron transmission.

Although the biotoxicity of heavy metals has been widely studied, there are few reports on the recovery strategy of the inhibited bio-system. This study proposed a combined promoter-I (Primary promoter: l-cysteine, biotin, and cytokinin + Electron-shuttle: PMo12) to recover the denitrification suppressed by Cr(VI). Compared with self-recovery, combined promoter-I shortened the recovery time of 28 cycles, and the recovered reactor possessed more stable long-term operation performance with >95 % nitrogen removal. The biomass increased by 7.07 mg VSS/(cm3 carrier) than self-recovery due to the promoted bacterial reproduction, thereby reducing the toxicity load of chromium per unit biomass. The combined promoter-I strengthened the toxicity remediation by promoting 92.84 % of the intracellular chromium release and rapidly activating anti-oxidative stress response. During toxicity remediation, ROS content quickly decreased, and the PN/PS value was 2.27 times that of self-recovery. PMo12 relieved Cr(VI) inhibition on NO3--N reduction by increasing NAR activity. The enhanced intracellular and intercellular electron transmission benefited from the stimulated NADH, FMN, and Cyt.c secretion by the primary promoter and the improved transmembrane electron transmission by Mo. PMo12 and the primary promoter synergized in regulating community structure and improving microbial richness. This study provided practical approaches for microbial toxicity remediation and maintaining high-efficiency denitrification.

Stepwise construction of coordinative linkages and dynamic covalent linkages for a porous metal-organic framework.

A cyclic trinuclear complex is synthesized from AgI and 1H-pyrazole-4-carbaldehyde. Reticulation of the complex with 1,3,5-tris(4-aminophenyl)benzene through Schiff-base reaction affords a porous FDM-72 framework. Amine choice is systematically investigated as it may initiate metal reduction. This study proposes a new route and its amine selection criterion to synthesize Ag-based frameworks.

Diphosphine Ligand-Enabled Nickel-Catalyzed Chelate-Assisted Inner-Selective Migratory Hydroarylation of Alkenes.

The precise control of the regioselectivity in the transition metal-catalyzed migratory hydrofunctionalization of alkenes remains a big challenge. With a transient ketimine directing group, the nickel-catalyzed migratory ß-selective hydroarylation and hydroalkenylation of alkenyl ketones has been realized with aryl boronic acids using alkyl halide as the mild hydride source for the first time. The key to this success is the use of a diphosphine ligand, which is capable of the generation of a Ni(II)-H species in the presence of alkyl bromide, and enabling the efficient migratory insertion of alkene into Ni(II)-H species and the sequent rapid chain walking process. The present approach diminishes organosilanes reductant, tolerates a wide array of complex functionalities with excellent regioselective control. Moreover, this catalytic system could also be applied to the migratory hydroarylation of alkenyl azahetereoarenes, thus providing a general approach for the preparation of 1,2-aryl heteroaryl motifs with wide potential applications in pharmaceutical discovery.

Target Design of Multinary Metal-Organic Frameworks for Near-Infrared Imaging and Chemodynamic Therapy.

Imaging-guided chemodynamic therapy is widely considered a promising modality for personalized and precision cancer treatment. Combining both imaging and chemodynamic functions in one system conventionally relies on the hybrid materials approach. However, the heterogeneous, ill-defined, and dissociative/disintegrative nature of the composites tends to complicate their action proceedings in biological environments and thus makes the treatment imprecise and ineffective. Herein, a strategy to employ two kinds of inorganic units with different functions─reactive oxygen species generation and characteristic emission─has achieved two single-crystalline metal-organic frameworks (MOFs), demonstrating the competency of reticular chemistry in creating multifunctional materials with atomic precision. The multinary MOFs could not only catalyze the transformation from H2O2 to hydroxyl radicals by utilizing the redox-active Cu-based units but also emit characteristic tissue-penetrating near-infrared luminescence brought by the Yb4 clusters in the scaffolds. Dual functions of MOF nanoparticles are further evidenced by pronounced cell imaging signals, elevated intracellular reactive oxygen species levels, significant cell apoptosis, and reduced cell viabilities when they are taken up by the HeLa cells. In vivo NIR imaging is demonstrated after the MOF nanoparticles are further functionalized. The independent yet interconnected modules in the intact MOFs could operate concurrently at the same cellular site, achieving a high spatiotemporal consistency. Overall, our work suggests a new method to effectively accommodate both imaging and therapy functions in one well-defined material for precise treatment.

Effects of coach extraversion and educational environment on transformational leadership and athlete outcomes: A moderated mediation model.

The importance of coach leadership to athlete development and performance has been identified in the literature. We respond to the call to investigate antecedents of coach transformational leadership and their indirect effects on athlete outcomes. We propose that coach extraversion as an antecedent of coach transformational leadership can indirectly impact follower cohesion and satisfaction. Building on this mediation model, we assert that educational environment (i.e., high school and university) may serve as a first-stage moderator between coach extraversion and transformational leadership. We used 48 coaches and their 570 athletes from competitive high school and university basketball teams to test this moderated mediation model. Our results indicate that coach extraversion indirectly impacts athlete cohesion and satisfaction via transformational leadership. Moreover, the indirect effects of coach extraversion on athlete outcomes via coach transformational leadership is conditionally significant only when coaches and athletes are in universities but not in high schools. Our findings highlight the importance of educational environment in determining the association between coach personality and leadership perception. Implications for research and practice are discussed.

Comparison of efficacy of non-pharmacological intervention for post-stroke dysphagia: a systematic review and Bayesian network meta-analysis.

Increasingly, non-pharmacological interventions are being identified and applied to post-stroke dysphagia. Nevertheless, there is insufficient evidence to assess which type of interventions are more effective. In this study, the randomized controlled trials of non-pharmacological interventions on post-stroke dysphagia were retrieved from the relevant databases. Including 96 studies and 12 non-drug treatments. Then, and the network meta-analysis is carried out by statistical software. The results show: In the aspects of videofluoroscopic swallowing study (VFSS), Standardized Swallowing Assessment (SSA), swallowing-quality of life (SWAL-QOL), Water swallow test (WST); Acupuncture + electrotherapy + rehabilitation training, acupuncture + rehabilitation training + massage, electrotherapy + rehabilitation training, acupuncture + electrotherapy + rehabilitation training, electrotherapy, acupuncture + rehabilitation training + acupoints sticking application have significant effects in post-stroke dysphagia. Compared with other interventions, they have more advantages in improving the above indicators. A substantial number of high-quality randomized clinical trials are still necessary in the prospective to validate the therapeutic effectiveness of non-pharmacological interventions in post-stroke dysphagia and the results of this Bayesian network meta-analysis.

Polydopamine and calcium functionalized fiber carrier for enhancing microbial attachment and Cr(VI) resistance.

The formation of biofilm determines the performance and stability of biofilm system. Increasing the hydrophilicity of the carrier surface could efficiently accelerate the attachment and growth of microorganisms. Here, the surface of polypropylene (PP) fiber carrier was modified with polydopamine (PDA) and calcium (Ca(II)) to enhance microbial attachment and toxicity resistance. The results of surface characteristic confirmed the self-polymerization of PDA and the chelation mechanism of Ca(II). Subsequently, the biofilm formation experiments were conducted in sequencing batch biofilm reactors using both normal and chromium-containing wastewater. The biofilm on the surface of the modified carrier exhibited better nitrogen removal and Cr(VI) reduction ability. The biomass of the modified carrier was significantly increased, and the maximum microbial attachment amounts in normal wastewater and chrome-containing wastewater were 1153.34 and 511.78 mg/g carrier, respectively. Furthermore, the confocal laser scanning microscope (CLSM) indicated that the modified carrier coated with PDA and Ca(II) were both biocompatible, and the cell activity was significantly increased. 16S rRNA sequencing results showed that the modified carrier efficiently enriched both denitrification bacteria (Thauera and Flavobacterium) and chrome-reducing bacteria (Simplicispira and Arenimonas) to improve system stability and Cr(VI) resistance. Microbial phenotype prediction based on BugBase analysis further verified the enrichment effect of modified carriers on microorganisms responsible for biofilm formation and oxidative stress resistance. Overall, this work proposed a novel functional carrier that could provide references for advancing the application of biofilm systems in wastewater treatment.