TIP60 acetylation of Bub1 regulates centromeric H2AT120 phosphorylation for faithful chromosome segregation.

Proper function of the centromeres ensures correct attachment of kinetochores to spindle microtubules and faithful chromosome segregation in mitosis. Defects in the integrity and function of centromeres can result in chromosome missegregation and genomic instability. Bub1 is essential for the mitotic centromere dynamics, yet the underlying molecular mechanisms remain largely unclear. Here, we demonstrate that TIP60 acetylates Bub1 at K424 and K431 on kinetochores in early mitosis. This acetylation increases the kinase activity of Bub1 to phosphorylate centromeric histone H2A at T120 (H2ApT120), which recruits Aurora B and Shugoshin 1 (Sgo1) to regulate centromere integrity, protect centromeric cohesion, and ensure the subsequent faithful chromosome segregation. Expression of the non-acetylated Bub1 mutant reduces its kinase activity, decreases the level of H2ApT120, and disrupts the recruitment of centromere proteins and chromosome congression, leading to genomic instability of daughter cells. When cells exit mitosis, HDAC1-regulated deacetylation of Bub1 decreases H2ApT120 levels and thereby promotes the departure of centromeric CPC and Sgo1, ensuring timely centromeres disassembly. Collectively, our results reveal a molecular mechanism by which the acetylation and deacetylation cycle of Bub1 modulates the phosphorylation of H2A at T120 for recruitment of Aurora B and Sgo1 to the centromeres, ensuring faithful chromosome segregation during mitosis.

Bergapten attenuates human papillary thyroid cancer cell proliferation by triggering apoptosis and the GSK-3ß, P13K and AKT pathways.

BACKGROUND: Over the past few decades, thyroid cancer (TC) incidence has steadily increased globally. The most common TC is human papillary thyroid carcinoma (PTC), which is poorly responsive to the current treatments. Hence, finding a successful therapeutic is urgently required. OBJECTIVES: Bergapten (BG) is a furanocoumarin, a natural psoralen derivative isolated from numerous species of citrus and bergamot oil that has demonstrated anti-tumor activity. However, there are no reports available on the efficacy of BG on PTC cells. MATERIAL AND METHODS: The current research investigated the anti-cancer activity of BG on human BCPAP cells, with cytotoxicity and apoptosis evaluated using MTT assay, AO/EB, DAPI, PI, ELISA, mRNA, and western blot. RESULTS: Bergapten (control group, 10 µM/mL and 15 µM/mL) inhibited PTC cell proliferation and stimulated apoptosis by enhancing Bax and caspase and reducing Bcl-2, cyclin-D1, c-myc, and survivin in a dose-dependent manner. Furthermore, BG expressively attenuated PI3K/AKT/GSK-3ß signaling, creating an uneven Bax/Bcl-2 ratio that triggered Cyt-c, caspase cascade and apoptosis in human PTC cells. CONCLUSIONS: Our findings emphasize that BG has the potential to be used as a protective natural remedy for human PTC cells.

Enhancing Persistent Luminescence through Synergy between Optimal Electron Traps and Dye Sensitization.

Due to their unique afterglow ability, long-wavelength-light rechargeable persistent luminescence (PersL) nanoparticles (PLNPs) have been emerging as an important category of imaging probes. Among them, ZnGa2O4:0.6% Cr3+ (ZGC) PLNPs have gained widespread recognition due to the ease of synthesis and uniform morphology. Unfortunately, the limited absorption arising from the low molar extinction coefficient of Cr3+ results in relatively low afterglow intensity and rapid decay after long-wavelength LED light irradiation. Herein, we discovered a strategy that boosting dye-sensitization performance was able to effectively amplify the PersL signal under white LED light. Specifically, Dil served as a highly efficient sensitizer for Cr3+, promoting the absorption of the excitation light. By adjusting the Pr dopant concentrations, ZGCP0.5 PLNPs with optimal trap densities were obtained, which showed the highest PersL intensity and dye-sensitized performance. Strikingly, ZGCP0.5-Dil PLNPs exhibited a 24.3-fold enhancement in intensity and a 2-fold prolongation of decay time over bare ZGC PLNPs through the synergy effect of optimal electron traps and dye sensitization. Photostable ZGCP0.5-Dil PLNPs enabled imaging of the HepG2 tumor and effectively guided tumor surgical resection verified by the H&E staining analysis. This strategy could be a significant reference in other dye-sensitization PLNPs to enhance longer-wavelength rechargeable PersL.

Size-induced d band center upshift of copper for efficient nitrate reduction to ammonia.

Electrocatalytic nitrate reduction (NO3RR) technique has emerged as a hotspot in NH3 production, for its practicability, and a series of advanced electrocatalysts with high activity and robust stability needed to be constructed in today's era. In this work, size-tunable Cu nanoparticles on porous nitrogen-doped hexagonal carbon nanorods (Cu@NHC) were reasonably designed and served for catalyzing NO3RR in neutral media. Especially, Cu30%@NHC demonstrated a remarkable electroactivity for NH3 production as it showed a suitable grain size with massive catalytic centers and favorable d band structure with faster *NO3--to-*NO2- catalytic dynamics. As expected, Cu30%@NHC (3628.28 µg h-1 mgcat.-1) had a much higher NH3 yield than those for Cu20%@NHC (1268.42 µg h-1 mgcat.-1) and Cu40%@NHC (725.03 µg h-1 mgcat.-1). And those collected NH3 products indeed derived from NO3RR process revealed by 15N isotope-labeling and systemic control tests. Moreover, Cu30%@NHC was also durable for NO3RR bulk electrolysis with minor loss in activity. This work offered an effective modifying tactics to boost NO3RR catalysis and could guide the design of other advanced electrocatalysts via size-induced surface engineering.

NuSAP regulates microtubule flux and Kif2A localization to ensure accurate chromosome congression.

Precise chromosome congression and segregation requires the proper assembly of a steady-state metaphase spindle, which is dynamic and maintained by continuous microtubule flux. NuSAP is a microtubule-stabilizing and -bundling protein that promotes chromosome-dependent spindle assembly. However, its function in spindle dynamics remains unclear. Here, we demonstrate that NuSAP regulates the metaphase spindle length control. Mechanistically, NuSAP facilitates kinetochore capture and spindle assembly by promoting Eg5 binding to microtubules. It also prevents excessive microtubule depolymerization through interaction with Kif2A, which reduces Kif2A spindle-pole localization. NuSAP is phosphorylated by Aurora A at Ser-240 during mitosis, and this phosphorylation promotes its interaction with Kif2A on the spindle body and reduces its localization with the spindle poles, thus maintaining proper spindle microtubule flux. NuSAP knockout resulted in the formation of shorter spindles with faster microtubule flux and chromosome misalignment. Taken together, we uncover that NuSAP participates in spindle assembly, dynamics, and metaphase spindle length control through the regulation of microtubule flux and Kif2A localization.

pH-Responsive Plasmon-Enhanced Persistent Luminescent ZnGa2O4:Cr3+ Nanopomegranate for Tumor Imaging.

Noble metal compositing is a promising method to enhance radiance intensity of persistent luminescent (PersL) nanoparticles (NPs) via surface plasmon resonance (SPR) for better tumor imaging, but it rarely unites with the pH-response strategy due to the challenge of realizing rigorous pH-responsive spatial distance control as a "button switch" of SPR. Here, ZnGa2O4:Cr3+ (ZGC) NPs as "pomegranate seeds" are cladded with sodium alginate to form nanoclusters (ZGC-SA), subsequently coated with carboxyl-rich polymers to acquire "pomegranate rind" (ZSPB) and finally decorated with 10 nm gold NPs (AuNPs) on the surface to obtain nanopomegranate structure (ZSPB@AuNPs). Though without deliberate distance control, there are plenty of "seeds" inside ZSPB@AuNPs fortunately at appropriate positions, which could be plasmon-enhanced by AuNPs. Furthermore, triggered by carboxyl protonation in subacid tumor, ZSPB@AuNPs aggregate and subsequently facilitate such plasmon enhancement effect, resulting in 4.4-fold PersL promotion at pH 5.5 (tumor microenvironment, TME) over pH 7.4 and in a maximum "tumor to normal tissue ratio" of PersL imaging signals of 125.9. Under surgical navigation of ZSPB@AuNPs, intramuscular tumors of mice could be resected without residue signals left. This nanopomegranate achieves TME pH-responsive plasmon-enhanced PersL for the first time and broadens the way for designing plasmon-enhanced PersL nanosystems.

Transition of care from hospital to home for older people with chronic diseases: a qualitative study of older patients' and health care providers' perspectives.

Background: Transitional care is a critical area of care delivery for older adults with chronic illnesses and complex health conditions. Older adults have high, ongoing care needs during the transition from hospital to home due to certain physical, psychological, social, and caregiving burdens, and in practice, patients' needs are not being met or are receiving transitional care services that are unequal and inconsistent with their actual needs, hindering their safe, healthy transition. The purpose of this study was to explore the perceptions of older adults and health care providers, including older adults, about the transition of care from hospital to home for older patients in one region of China. Objective: To explore barriers and facilitators in the transition of care from hospital to home for older adults in China from the perspectives of older patients with chronic diseases and healthcare professionals. Methods: This was a qualitative study based on a semi-structured approach. Participants were recruited from November 2021 to October 2022 from a tertiary and community hospital. Data were analyzed using thematic analysis. Results: A total of 20 interviews were conducted with 10 patients and 9 medical caregivers, including two interviews with one patient. The older adult/adults patients included 4 men and 6 women with an age range of 63 to 89 years and a mean age of 74.3 ± 10.1 years. The medical caregivers included two general practitioners and seven nurses age range was 26 to 40 years with a mean age of 32.8 ± 4.6 years. Five themes were identified: (1) attitude and attributes; (2) better interpersonal relationships and communication between HCPs and patients; (3) improved Coordination of Healthcare Services Is Needed; (4) availability of resources and accessibility of services; and (5) policy and environment fit. These themes often serve as both barriers and facilitators to older adults' access to transitional care. Conclusions: Given the fragmentation of the health care system and the complexity of care needs, patient and family-centered care should be implemented. Establish interconnected electronic information support systems; develop navigator roles; and develop competent organizational leaders and appropriate reforms to better support patient transitions.

Assessing the agreement between the partners at care transitions measure and the care transitions measure for elderly patients with chronic diseases.

BACKGROUND: Elderly patients with chronic diseases are very vulnerable during the transition from hospital to home and have a high need for transitional care. The quality of transitional care is closely related to patient health outcomes. Using appropriate scales to evaluate the quality of transitional care is important for efforts aimed at improving it. The study aimed to analyze the consistency between the Chinese version of the Partners at Care Transitions Measure (PACT-M) and the Care Transition Measure (CTM) in assessing the quality of transition care in elderly patients with chronic diseases. METHODS: This is a cross-sectional study, we used a convenience sampling method to investigate patients with chronic diseases aged ≧ 65 years who were about to be discharged from the three affiliated hospitals of Zhengzhou University in Henan Province, from August 2021 to May 2022. The sample consisted of 196 elderly patients with chronic diseases. Data were collected using a demographic survey, PACT-M, and CTM. We used EpiData 3.1 software for systematic logical error checking, SPSS 21.0 to analyze the data, and the Bland-Altman analysis to analyze the consistency of the two scales. RESULTS: The mean total scores for PACT-M and CTM were 65.52 ± 6.23 and 52.07 ± 7.26, respectively. The 95% confidence interval (CI) for the mean difference and ratios were (-31.52, 4.61) and (0.85, 1.72), with 3.57% and 5.10% of the points outside the 95% CI limits, separately. CONCLUSIONS: The difference analysis of Bland-Altman showed a good consistency of the two scales, while the rate analysis did not meet the a priori definition of good consistency, but it is very close to 5%. Therefore, the consistency of the two scales in assessing the quality of transitional care for elderly patients with chronic diseases needs to be further validated.

A novel removable template method for the preparation of persistent luminescence nanoparticles with biocompatible size and high intensity.

NIR persistent luminescence nanoparticles (PLNPs) are appealing for bio-imaging because of the properties of extremely low autofluorescence interference and deep tissue penetrating ability. However, current preparation methods can hardly simultaneously endow PLNPs with nano-scale size, long persistent luminescence (PersL) life, and high luminescence intensity, which can hardly meet the requirements of bio-imaging. Herein, we report a new synthetic route to nano-sized chromium-doped zinc gallate (ZGC) via a removable MOF template, i.e., one-pot hydrothermal synthesis of an intermediate followed by its calcination at 1100 °C in air. By exploiting the regulatory effect of the intermediate on Zn and Ga, the depth of traps in 170 nm-sized ZGC nanoparticles was enhanced to above 0.8 eV, and the PersL duration to more than 24 h, with an average lifetime of up to 216 s. An in vivo experiment shows that tumors can be accurately delineated for more than 3 hours. This strategy largely resolves the conflict between the particle size and PersL properties of PLNPs, and expands the application of PLNPs in bio-imaging.

Facilitators and inhibitors in hospital-to-home transitional care for elderly patients with chronic diseases: A meta-synthesis of qualitative studies.

Background: Chronic diseases are long-term, recurring and prolonged, requiring frequent travel to and from the hospital, community, and home settings to access different levels of care. Hospital-to-home transition is challenging travel for elderly patients with chronic diseases. Unhealthy care transition practices may be associated with an increased risk of adverse outcomes and readmission rates. The safety and quality of care transitions have gained global attention, and healthcare providers have a responsibility to help older adults make a smooth, safe, and healthy transition. Objective: This study aims to provide a more comprehensive understanding of what may shape health transitions in older adults from multiple perspectives, including older chronic patients, caregivers, and healthcare providers. Methods: Six databases were searched during January 2022, including Pubmed, web of science, Cochrane, Embase, CINAHL (EBSCO), and PsycINFO (Ovid). The qualitative meta-synthesis was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. The quality of included studies was appraised using the Critical Appraisal Skills Programme (CASP) qualitative research appraisal tool. A narrative synthesis was conducted informed by Meleis's Theory of Transition. Results: Seventeen studies identified individual and community-focused facilitators and inhibitors mapped to three themes, older adult resilience, relationships and connections, and uninterrupted care transfer supply chain. Conclusion: This study identified potential transition facilitators and inhibitors for incoming older adults transitioning from hospital to home, and these findings may inform the development of interventions to target resilience in adapting to a new home environment, and human relations and connections for building partnerships, as well as an uninterrupted supply chain of care transfer at hospital-home delivery. Systematic review registration: www.crd.york.ac.uk/prospero/, identifier: CRD42022350478.

M1 polarization enhances the antitumor activity of chimeric antigen receptor macrophages in solid tumors.

BACKGROUND: Chimeric antigen receptor macrophage (CAR-M) therapy is a novel cancer immunotherapy approach that integrates CAR structure and macrophage functions. CAR-M therapy has shown unique and impressive antitumor effects in immunotherapy for solid tumors. However, the polarization state of macrophages can affect the antitumor effect of CAR-M. We hypothesized that the antitumor activity of CAR-Ms may be further improved after inducing M1-type polarization. METHODS: In this report, we constructed a novel HER2-targeting CAR-M, which was composed of humanized anti-HER2 scFv, CD28 hinge region and FcγRI transmembrane domain and intracellular domain. Phagocytosis, tumor-killing capacities, and cytokine release of CAR-Ms were detected with or without M1-polarization pretreatment. Several syngeneic tumor models were used to monitor the in vivo antitumor activity of M1-polarized CAR-Ms. RESULTS: After polarization with LPS combined with interferon-γ in vitro, we found that the phagocytic and tumor-killing capacities of CAR-Ms against target cells were significantly enhanced. The expression of costimulatory molecules and proinflammatory cytokines was also significantly increased after polarization. By establishing several syngeneic tumor models in vivo, we also demonstrated that infusing polarized M1-type CAR-Ms could effectively suppress tumor progression and prolong the survival of tumor-bearing mice with enhanced cytotoxicity. CONCLUSIONS: We demonstrated that our novel CAR-M can effectively eliminate HER2-positive tumor cells both in vitro and in vivo, and M1 polarization significantly enhanced the antitumor ability of CAR-M, resulting in a stronger therapeutic effect in solid cancer immunotherapy.

Basal Plane-Activated Boron-Doped MoS2 Nanosheets for Efficient Electrochemical Ammonia Synthesis.

Under the dual pressure of energy crisis and environmental pollution, ammonia (NH3 ) is an indispensable chemical product in the global economy. The electrocatalytic synthesis of NH3 directly from nitrogen and water using renewable electricity has become one of the most attractive and important topics. Basal plane-activated boron-doped MoS2 nanosheets (B-MoS2 ) as a non-noble metal catalyst with excellent performance for N2 electroreduction are synthesized by a facile one-step hydrothermal method. In 0.1 m Na2 SO4 solution, MoS2 nanosheets doped with 300 mg boric acid (B-MoS2 -300) give rise to a good ammonia yield rate of 75.77 µg h-1 mg-1 cat. at -0.75 V vs. RHE, and an excellent Faradaic efficiency of 40.11 % at -0.60 V vs. RHE. In addition, the B-MoS2 -300 nanosheets show good selectivity and chemical stability, and no hydrazine (N2 H4 ) by-product is generated during the reaction. 15 N isotopic labeling confirms that nitrogen in produced ammonia originates from N2 in the electrolyte. On the one hand, the high conductivity of MoS2 guarantees guarantees a high electron transfer rate from nitrogen to ammonia; on the other hand, the successful incorporation of heteroatom B enlarges the interlayer spacing of MoS2 , and the B atom can act as an active site for basal plane activation, providing more active sites for the nitrogen reduction reaction (NRR). Density functional theory calculations show that the doping of B activates the base plane of 1T-MoS2 , which makes the adsorption of N2 on the base plane easier and promotes the NRR.

Experiences of family caregivers of patients with post-traumatic hydrocephalus from hospital to home: a qualitative study.

BACKGROUND: Post-traumatic hydrocephalus (PTH) is a complication of traumatic brain injury (TBI) that requires treatment and postoperative care. The shunt is one of the main treatments for PTH, which presents with dysfunction and infection. Considering brain injury, hydrocephalus shunt malfunction, and infection, family caregivers need to be responsible for caring for PTH patients, recognizing shunt malfunction and infection, and managing those patients accordingly from hospital to home. Understanding the experiences and needs of caregivers is beneficial for knowing their competency and quality of health care, ameliorating and ensuring future transition care. The study aimed to explore the feelings, experiences, and needs of family caregivers when caring for patients with TBI, PTH and shunts. METHODS: This was exploratory research of a purposive sample of 12 family caregivers of adult patients with TBI, PTH and shunts in five neurosurgery departments at a general hospital in Zhengzhou, Henan Province, China, using a semi-structured interview method. Data were collected from October 2021 to March 2022 before being analyzed by content analysis methods. RESULTS: Caregivers required professional and social knowledge and support in the areas of TBI, PTH and shunts, caregiving interventions, psychological care needs, and health insurance, just as caregivers do, but unlike other general caregivers, care for patients with TBI, PTH, and shunt is fraught with uncertainty and the need to manage shunt setting, and caregivers often experience 'complex emotional reaction' during the transitional period, where care needs and complex emotions may lead to a lack of caregiver confidence, which in turn may affect caregiving behaviors, and experiences that affect care may be mediated through caregiving confidence. The perceived availability of resources, particularly those that are still available to them when they return home, has a significant impact on participants' emotional response and sense of confidence. CONCLUSIONS: The emotional response and the impact of stressor caregivers after TBI, PTH, and shunt was important, and sometimes confidence in care appeared to be an intermediate and useful factor that needed to be considered as health professionals prepared to develop care resources on how to manage and empower patients with TBI, PTH, and shunt. Meanwhile, there may be gaps and inequities in supportive care for patients diagnosed with TBI, PTH, and shunt in China.

Low-intensity-low-temperature stability assessment of perovskite solar cells operating on simulated Martian surface conditions.

Immigration to Mars, which is expected to be powered mainly by photovoltaics, is one of the greatest dreams of humanity. However, the extreme temperature difference and high-energy cosmic radiation on the surface of Mars make it difficult for conventional photovoltaics to operate steadily over time. With their advantages of being lightweight, having a high irradiation tolerance, and an outstanding power conversion efficiency (PCE), perovskite solar cells (PSCs) have shown themselves to be a promising candidate for Martian applications. In this study, we simulated the low-intensity-low-temperature (LILT) environment of the Mars surface, and monitored the in situ device performance of PSCs. Surprisingly, the device PCE was not only maintained at a high level but was even improved slightly. Further investigation revealed that the self-healing effect of perovskites under LILT conditions could be attributed to the light-induced decomposition of the perovskite film and the ß-phase perovskite recrystallization process at the perovskite/hole transport layer interface. Interfacial ß-phase perovskites are stable at low temperatures, which can facilitate charge extraction and protect the perovskite bulk from long-term light damage. This study demonstrated the feasibility of PSCs and provides a reference for Martian applications.

Association between olfactory pathway gene variants and obesity in Chinese Han population: A case-control study based on genetic score.

BACKGROUND: Our previous bivariate genome-wide association study in dizygotic twins suggested that the olfactory transduction pathway genes were associated with obesity in Northern Han Chinese adults. In this study, we attempted to verify the associations of the olfactory transduction pathway genes score with obesity in population with the same genetic background, and to estimate the interaction between gene variants and potential environment factors. METHODS: A case-control study was conducted in Qingdao, China in 2019-2021, which enrolled 301 obesity cases and 307 controls. Based on the candidate gene selection method, 29 single nucleotide polymorphisms (SNPs) in 7 olfactory pathway genes were selected. Genomic deoxyribonucleic acid (DNA) was isolated and purified from the peripheral blood leukocytes by using DNA extraction kits and was genotyped by the MassArray system. The weighted genetic score of each gene was calculated to analyze the effect of whole gene. The effect of gene scores on obesity and the gene-environment interaction were estimated by logistic regression. RESULTS: After adjusting for age, sex, smoking, alcohol drinking, physical activity, we observed positive associations of OR4D1 (OR = 1.531, 95% CI = 1.083-2.164, P = 0.016) and OR52K1 (OR = 1.437, 95% CI = 1.055-1.957, P = 0.022) gene scores with obesity, as well as negative associations of OR2L8 (OR = 0.708, 95% CI = 0.504-0.995, P = 0.046) and CALML3 (OR = 0.601, 95% CI = 0.410-0.881, P = 0.009) gene scores with obesity. Significant multiplicative model interaction between OR4D1 and smoking (Pinteraction = 0.041) as well as CALML3 and smoking (Pinteraction = 0.026) on obesity were identified. Stratified analysis showed that in smokers, OR4D1 gene score was positively associated with obesity (OR = 2.673, 95% CI = 1.348-5.299, P = 0.005) and CALML3 gene score was negatively correlated with obesity (OR = 0.252, 95% CI = 0.103-0.618, P = 0.003). The relationships were not statistically significant in non-smokers (OR4D1: OR = 1.216, 95% CI = 0.806-1.836, P = 0.351; CALML3: OR = 0.764, 95% CI = 0.492-1.188, P = 0.232). CONCLUSIONS: Genetic variations in the olfactory pathway were associated with obesity in Northern Han Chinese adults. Smoking modified the effect of OR4D1 and CALML3 gene variants on obesity.

Improving the Performance of Perovskite Solar Cells with Insulating Additive-Modified Hole Transport Layers.

Invert perovskite solar cells (PSCs) present a great potential for next-generation photovoltaics for their flexibility and tandem adaptability. In order to improve the conductivity of the hole transport layer (HTL), such as poly(triarylamine), highly conductive additives (e.g., F4TCNQ, Li-TFSI) were generally applied to achieve a power conversion efficiency (PCE) exceeding 21%. However, these additives significantly affect the long-term stability of the devices due to their humidity sensitivity. In this work, the HTL was counterintuitively optimized with insulating additives, such as polyphenylene sulfide, which enhanced PCE from 19.1 to 21.5% along with a noticeable improvement in device stability with T50 of 574 h under double 85 aging conditions. The performance enhancement is attributed to larger grain sizes in perovskite films on the HTL and better energy-level alignment between the HTL and perovskite after introducing the insulating additives, which compensate negative influence caused by additive-induced reduction in conductivity. Our work demonstrates that low-conductivity additives, rather than the commonly used high-conductivity counterparts, can also contribute to improving the photovoltaic performance in PSCs.

Dynapenic abdominal obesity and the effect on long-term gait speed and falls in older adults.

BACKGROUND: Although both dynapenia and abdominal obesity have negative impact on physical function and health, few prospective studies evaluate the association of dynapenic abdominal obesity (D/AO) with gait speed and falls. Our aim was to examine the combined effect of low muscle strength and abdominal obesity on long-term gait speed and falls in older adults. METHODS: We used longitudinal data from the English Longitudinal Study of Ageing (ELSA), including 4987 individuals aged 60 years and over. Grip strength and waist circumference were measured at baseline. Gait speed and fall events (falls, recurrent falls, and fall-related injury) were evaluated during a 14-year follow-up. The study population were divided into nondynapenic nonabdominal obesity (ND/NAO), nondynapenic abdominal obesity (ND/AO), dynapenic nonabdominal obesity (D/NAO), and D/AO, according to the sex-specific grip strength (<16 kg for women and <26 kg for men) and waist circumference (>88 cm for women and >102 cm for men). We used generalized estimating equation (GEE) model with gait speed as the outcome and cox proportional hazards models with fall events as the outcome. RESULTS: GEE model showed that gait speed decreased during the 14-year follow-up in all groups (all Ptime < 0.001). Participants with ND/AO, D/NAO, and D/AO at baseline exhibited a worse gait speed than those with ND/NAO (all Pgroup < 0.001). No significant difference in the rate of gait speed decline between four groups was found (Pgroup×time = 0.062). Cox regression analysis showed that D/NAO and D/AO highly predicted falls, and the hazard ratio (HR) was 1.181 (95% CI: 1.002, 1.392) for D/NAO and 1.195 (95% CI: 1.006, 1.421) for D/AO. D/AO was the unique condition associated with recurrent falls and fall-related injury, and the HRs were 1.276 (95% CI: 1.018, 1.599) and 1.348 (95% CI: 1.066, 1.704), respectively. CONCLUSION: Dynapenia abdominal obesity, determined by low grip strength and high waist circumference, exhibits worse gait speed and increases the risk of fall events in older adults. Effort to maintain the mobility should focus on improving muscle strength and reducing excess body fat.

Bridging micro/nano-platform and airway allergy intervention.

Allergic airway diseases, with incidence augmenting visibly as industrial development and environmental degradation, are characterized by sneezing, itching, wheezing, chest tightness, airway obstruction, and hyperresponsiveness. Current medical modalities attempt to combat these symptoms mostly by small molecule chemotherapeutants, such as corticosteroids, antihistamines, etc., via intranasal approach which is one of the most noninvasive, rapid-absorbed, and patient-friendly routes. Nevertheless, inherent defects for irritation to respiratory mucosa, drug inactivation and degradation, and rapid drug dispersal to off-target sites are inevitable. Lately, intratracheal micro/nano therapeutic systems are emerging as innovative alternatives for airway allergy interventions. This overview introduces several potential application directions of mic/nano-platform in the treatment of airway allergic diseases, including carriers, therapeutic agents, and immunomodulators. The improvement of the existing drug therapy of respiratory allergy management by micro/nano-platform is described in detail. The challenges of the micro/nano-platform nasal approach in the treatment of airway allergy are summarized and the development of micro/nano-platform is also prospected. Although still a burgeoning area, micro/nano therapeutic systems are gradually turning to be realistic orientations as crucial future alternative therapeutic options in allergic airway inflammation interventions.

Tumor acid microenvironment-activated self-targeting & splitting gold nanoassembly for tumor chemo-radiotherapy.

Low accumulation and penetration of nanomedicines in tumor severely reduce therapeutic efficacy. Herein, a pH-responsive gold nanoassembly is designed to overcome these problems. Polyethylene glycol linked raltitrexed (RTX, target ligand and chemotherapy drug) and two tertiary amine molecules (1-(2-aminoethyl) pyrrolidine and N, N-dibutylethylenediamine) are modified on the surface of the 6-nm gold nanoparticles by lipoic acid to form gold nanoassembly defined as Au-NNP(RTX). The Au-NNP (RTX) nanoassembly could remain at about 160 nm at the blood circulation (pH 7.4), while split into 6-nm gold nanoparticles due to tertiary amine protonation at tumor extracellular pH (pH 6.8). This pH-responsive disassembly behavior endows Au-NNP(RTX) better tumor tissue permeability through the better diffusion brought by the size reduction. Meanwhile, after disassembly, more RTXs on the surface of gold nanoparticles are exposed from the shielded state of assembly along with 2.25-fold augment of cellular uptake capability. Most importantly, the results show that Au-NNP(RTX) possesses of high tumor accumulation and effective tumor penetration, thereby enhancing the tumor chemo-radiotherapy efficiency.

NuMA regulates mitotic spindle assembly, structural dynamics and function via phase separation.

A functional mitotic spindle is essential for accurate chromosome congression and segregation during cell proliferation; however, the underlying mechanisms of its assembly remain unclear. Here we show that NuMA regulates this assembly process via phase separation regulated by Aurora A. NuMA undergoes liquid-liquid phase separation during mitotic entry and KifC1 facilitates NuMA condensates concentrating on spindle poles. Phase separation of NuMA is mediated by its C-terminus, whereas its dynein-dynactin binding motif also facilitates this process. Phase-separated NuMA droplets concentrate tubulins, bind microtubules, and enrich crucial regulators, including Kif2A, at the spindle poles, which then depolymerizes spindle microtubules and promotes poleward spindle microtubule flux for spindle assembly and structural dynamics. In this work, we show that NuMA orchestrates mitotic spindle assembly, structural dynamics and function via liquid-liquid phase separation regulated by Aurora A phosphorylation.