Formation and Dynamics of Imidazole Supramolecular Chains Investigated by Deep Potential Molecular Dynamics Simulation.

Imidazole-based materials have attracted considerable attention due to their promising potential for facilitating anhydrous proton transport at high temperatures. Herein, a machine learning-based deep potential (DP) model for bulk imidazole with first-principles accuracy is developed. The trained model exhibits remarkable accuracy in predicting energies and forces, with minor errors of 4.71 × 10-4 eV/atom and 3.23 × 10-2 eV/Å, respectively. Utilizing DP molecular dynamics simulations, we have systematically investigated the temperature-dependent formation and dynamics of imidazole supramolecular chains through the partial radial distribution function, quantification of hydrogen bond numbers, incoherent intermediate scattering function, and diffusion coefficient. The findings reveal the influence of temperature on the proton transport path following either the "Grotthuss" and "vehicle" mechanism.

A Gluconeogenesis-Related Genes Model for Predicting Prognosis, Tumor Microenvironment Infiltration, and Drug Sensitivity in Hepatocellular Carcinoma.

Background: Hepatocellular carcinoma (HCC) is a prevalent malignancy within the digestive system, known for its poor prognosis. Gluconeogenesis, a critical metabolic pathway, is responsible for the synthesis of glucose in the normal liver. This study aimed to examine the role of gluconeogenesis-related genes (GRGs) in HCC and evaluate their impact on the tumor microenvironment infiltration and drug sensitivity in HCC. Methods: We retrieved gene expression and clinical pathological data of HCC from The Cancer Genome Atlas (TCGA) database. This dataset was utilized to develop a prognosis model. The data from The International Cancer Genome Consortium (ICGC) served as an independent validation cohort. A least absolute shrinkage and selection operator (LASSO) regression analysis was applied to a curated panel of GRGs to construct and validate the predictive model. Furthermore, unsupervised consensus clustering, based on the expression levels of GRGs, categorized HCC patients into distinct subgroups. Results: A four-gene prognostic model, referred to as GRGs, has been successfully developed with high accuracy and stability for the prediction of HCC patient prognosis. This model enables the stratification of patients into high or low risk groups based on individual risk scores, revealing significant differences in immune infiltration patterns and anti-tumor drug responses. Unsupervised consensus clustering analysis delineated four distinct subgroups of patients, each characterized by a unique prognosis and tumor immune microenvironment (TIME). Conclusion: This study is the first to develop a prognostic model incorporating 4-GRGs that effectively predicts the prognosis, tumor microenvironment infiltration, and drug sensitivity in HCC patients. The model based on 4 GRGs may contribute to predict the prognosis, immunotherapy and chemotherapy response of HCC patients.

[Simulating Changes in Ecosystem Carbon Storage and Analyzing Influencing Factors in the Central Zhejiang under the Background of LUCC].

Central Zhejiang is the key ecological function area of Zhejiang Province and an important part of the Qiantang River ecological corridor. Conducting simulations of ecosystem carbon storage changes and analyzing influencing factors under land-use changes in this region is of significant importance for achieving the goals of "peak carbon" and "carbon neutrality" at an early stage. This study, based on the land use data of five periods from 1980 to 2020 in central Zhejiang, coupled the GeoSOS-FLUS and the InVEST model to analyze the spatiotemporal changes in carbon storage in the region over time and project for the year 2030. The study also explored the impact of socio-economic and natural factors on changes in carbon storage. The results showed that： ① Between 1980 and 2020, urban construction land in the Zhejiang Central Region increased by 289.91%, with cultivated land and forest land being the main sources, leading to a 3% decrease in ecosystem carbon storage, amounting to 588.88×104 tons. ② High-value areas of carbon storage in the Zhejiang Central Region were concentrated in P'an-an County, Jinyun County, Wuyi County, and other areas. ③ Under the two different scenarios of natural development and ecological protection, carbon storage in the research area was projected to decrease by 1.05% and 0.05%, respectively, by 2030 compared to that in 2020. ④ Natural factors dominated the distribution of carbon storage, but their influence was gradually decreasing over time. The impact of socio-economic factors was increasing, and the combined effect of socio-economic and natural factors far outweighed the influence of a single factor on carbon storage distribution. These findings can serve as a scientific reference and guide for mitigating carbon loss in ecosystems, promoting ecosystem protection, facilitating sustainable social development, and achieving the "dual carbon" goals in Zhejiang and other regions nationwide.

The efficacy of partial versus total splenectomy in the treatment of hereditary spherocytosis in children: a systematic review and meta-analysis.

OBJECTIVE: To explore the comparative postoperative efficacy of partial splenectomy (PS) and total splenectomy (TS) in the treatment of children with hereditary spherocytosis (HS). METHODS: The relevant HS studies from databases were searched and screened, comparing the differences in hemoglobin concentration, reticulocyte percentage, bilirubin concentration before and after TS and PS surgery, and during the follow-up period, as well as the incidence of postoperative adverse events. Statistical analysis was performed using Review Manager 5.4. RESULTS: A total of 5 studies were included in this meta-analysis, with a cumulative enrollment of 312 children, 130 in the PS group and 182 in the TS group. The meta-analysis results showed that both PS and TS groups had statistically significant differences in postoperative hematological outcomes compared to before surgery, with TS showing better improvement than PS. In the postoperative follow-up, the changes in hematological outcomes between PS and TS were statistically significant for hemoglobin concentration: within 1 year [MD = 1.85, 95%CI(1.09,2.60)], 1-2 years [MD = 1.74, 95%CI(0.25,3.24)], not statistically significant for 4-6 years [MD = 1.28, 95%CI(-1.75,4.32)]; for reticulocyte percentage: within 1 year [MD = 2.23, 95%CI(0.80,3.66)] was statistically significant, not statistically significant for 4-6 years [MD = 1.77, 95%CI(-2.04,5.59)]; for serum bilirubin concentration: within 1 year [MD = 1.55, 95%CI(0.91,2.18)] was statistically significant, not statistically significant for 1-2 years [MD = 1.77, 95%CI(-2.04,5.99)]. In the incidence of postoperative adverse events, the incidence of cholelithiasis [MD = 1.77, 95%CI(-2.04,5.99)] showed a statistically significant difference between PS and TS, while there were no statistically significant differences in other included events, such as postoperative infection rate, secondary surgery rate, thrombosis rate, postoperative hemorrhage rate, and transfusion therapy rate. CONCLUSION: Splenectomy is a beneficial surgical strategy for children with moderate-to-severe HS, reducing; early hematological outcomes of TS are more robust than PS in the follow-up period, and there is no difference between the two in the later period; for postoperative adverse events, the incidence of cholelithiasis in children after PS is higher than after TS, and there is a risk of requiring a second surgery for total splenectomy due to hemolytic recurrences.

Identification of the fructose 1,6-bisphosphate aldolase (FBA) family genes in maize and analysis of the phosphorylation regulation of ZmFBA8.

Fructose 1,6-bisphosphate aldolase (FBA) is a class of aldolase that functions as enzyme participating in carbohydrate metabolism of the Calvin-Benson cycle, gluconeogenesis, and glycolysis, and also as non-enzymatic protein involving in protein binding, gene transcription, signal transduction. FBAs have been identified in a few plant species, however, limited information is known regarding FBA family genes, their biological functions and posttranslational regulations in maize (Zea mays). In this study, nine class I FBAs (ZmFBA1 to ZmFBA9) and one class II FBA (ZmFBA10) in maize were identified. Phosphoproteomic analysis further revealed that multiple ZmFBAs were phosphorylated. We showed that phosphorylation at Ser32 in ZmFBA8 inhibited its FBP binding and enzyme activity. Loss of ZmFBA8 function reduced the growth of maize seedlings. Our results suggest that the phosphorylation is an important regulatory mechanism of ZmFBA8 function.

Ultrasensitive Rapid Antigen Test by Geometric Lateral Flow Assays and Highly Doped Upconversion Nanoparticles.

The paper-based lateral flow assay (LFA) testing strips are currently the most widely used for point-of-care testing (POCT), valued for their rapid result turnaround times in a few minutes. However, their sensitivity has been limited. Upconversion nanoparticles (UCNPs), especially highly doped ones, have emerged as promising luminescent reporters to enhance the LFA sensitivity. These UCNPs exhibit a nonlinear enhancement in luminescence with excitation power density, necessitating higher power densities for higher brightness. In this study, we utilized a geometric paper strip design to minimize the immune reaction area and maximize the excitation power density, enabling ultrasensitive detection of the SARS-CoV-2 nucleoprotein antigen. This design also slowed the antigen flow on the paper strip, extending the reaction time between antigen and antibody, thereby enhancing the efficiency of the immune reaction. Through this design, our approach achieved over a 100-fold enhancement in the limit of detection (LOD) compared with the widely used LFAs, based on gold colloidal nanoparticles and europium nanoparticles. This innovation expands the scope of LFA applications that require a low LOD.

Nitrogen removal performance of bioretention cells under freeze-thaw cycles: Effects of filler structure and microbial community.

Cold climates have an adverse effect on the nitrogen-removal capacity of bioretention cells, especially during freeze-thaw cycles (FTCs). To explore the effects of FTCs on the nitrogen removal performance of bioretention cells, this research compared the effects of FTCs on the pore structure and microbial community composition of the filler, and analyzed the nitrogen removal performance of the bioretention cell before (RT), during (FTC) and after (RRT) FTCs. The results demonstrated that RRT filler had a much greater number of pores with equivalent diameter <500 µm than RT filler, and that RRT had a higher pore volume and pore density than RT. Microbial community analysis revealed that the diversity and richness of the microbial community in FTC were lower than in RT, and the relative abundance of Lacunisphaera, Pseudomonas, and Dokdonella decreased significantly. There was no significant difference in microbial community richness between RRT and RT, however RRT diversity was lower. RRT has a higher relative abundance of nitrifying bacteria (Subgroup_10, Bryobacter, etc.) than RT, but a lower relative abundance of denitrifying bacteria (Pseudomonas, Dokdonella, Arenimonas, etc.). The nitrogen removal efficiency of FTC was inhibited, resulting in a decrease of 13.0 ± 4.86%, 19.7 ± 9.17%, and 26.6 ± 1.74% in the removal rates of ammonia nitrogen(NH4+-N), nitrate nitrogen(NO3--N), and total nitrogen(TN) when compared to RT, respectively. RRT improved nitrification and increased NH4+-N removal rate by 10.3 ± 2.69% compared to RT. However, because of denitrification inhibition, the nitrogen removal performance of RRT was not able to reach RT levels, and its NO3--N and TN removal rates decreased by 100 ± 4.70% and 58.3 ± 3.71%, respectively. This study has demonstrated that FTCs can permanently harm the bioretention cell's filler structure and microbial community, resulting in a significant decrease in the nitrogen removal performance of the bioretention cell designed according to warm climate conditions after experiencing FTCs.

Causal Effect of Immunocytes, Plasma Metabolites, and Hepatocellular Carcinoma: A Bidirectional Two-Sample Mendelian Randomization Study and Mediation Analysis in East Asian Populations.

Background: Hepatocellular carcinoma (HCC) is a primary malignant liver tumor characterized by a low survival rate and high mortality. This study aimed to investigate the causal effect of immune cell phenotypes, plasma metabolites, and HCC in East Asian populations. Methods: The summary results for 731 immunocytes, 1400 plasma metabolites, and HCCs were acquired from publicly available genome-wide association studies (GWASs). This study utilized two-sample Mendelian randomization (MR) analysis to establish causal relationships, which was achieved by employing various statistical methods including inverse variance-weighted, simple mode, MR-Egger, weighted median, and weighted mode. Multiple sensitivity analyses were conducted to confirm the reliability of the MR data. Ultimately, mediation analysis was employed to ascertain the path that leads from immunocytes to plasma metabolites. Results: Among the 20 immune cells and HCC for East Asians, causal links were found, with one showing an inverse correlation. In addition, 36 metabolites were significantly associated with HCC for East Asians. Through analysis of established causative metabolites, we identified a strong correlation between the glycerophospholipid metabolic pathway and HCC for East Asians. By employing a two-step MR analysis, we identified 11 immunocytes that are causally linked to HCC for East Asians through the mediation of 14 plasma metabolites, with Linolenate [α or γ; (18:3n3 or 6)] levels showing the highest mediation proportion (19.3%). Conclusions: Our findings affirm the causal links among immunocytes, plasma metabolites, and HCC in eastern Asia populations by calculating the percentage of the impact that is influenced by plasma metabolites. This study offers innovative perspectives on the early detection, diagnosis, and therapy of HCC.

Polarized Upconversion of sub-100 nm Single Nanoparticles.

Upconversion nanoparticles are popular as imaging probes due to their advantages in photostability and controllable emission dimensions. However, upconversion polarization remains largely uncharted with previous reports limited to microstructures. In this work, we report the observation of polarized upconversion emissions from ß-NaYF4 single nanostructures below 100 nm. At the sub-100 nm scale, nanorods, nanodiscs, and nanoplates exhibit distinctive polarization degrees despite the same doping concentrations of lanthanides. We find this varied polarization degree results from the crystallographic orientation of nanostructure in relation to the light field and can be linked to the distinctive emission spectrum profile with varied Stark splitting transition ratios from Er3+. Our findings provide a comprehensive understanding of the polarization properties of upconversion nanoparticles, revealing a previously unexplored aspect of light emission. This discovery expands our knowledge of upconversion nanoparticles and also opens new possibilities for their use in future imaging and sensing applications, where polarization sensitivity is crucial.

Biomimetic design and integrated biofabrication of an in-vitro three-dimensional multi-scale multilayer cortical model.

The lack of accurate and reliable in vitro brain models hinders the development of brain science and research on brain diseases. Owing to the complex structure of the brain tissue and its highly nonlinear characteristics, the construction of brain-like in vitro tissue models remains one of the most challenging research fields in the construction of living tissues. This study proposes a multi-scale design of a brain-like model with a biomimetic cortical structure, which includes the macroscopic structural features of six layers of different cellular components, as well as micrometer-scale continuous fiber structures running through all layers vertically. To achieve integrated biomanufacturing of such a complex multi-scale brain-like model, a multi-material composite printing/culturing integrated bioprinting platform was developed in-house by integrating cell-laden hydrogel ink direct writing printing and electrohydrodynamic fiber 3D printing technologies. Through integrated bioprinting, multi-scale models with different cellular components and fiber structural parameters were prepared to study the effects of macroscopic and microscopic structural features on the directionality of neural cells, as well as the interaction between glial cells and neurons within the tissue model in a three-dimensional manner. The results revealed that the manufactured in vitro biomimetic cortical model achieved morphological connections between the layers of neurons, reflecting the structure and cellular morphology of the natural cortex. Micrometer-scale (10 µm) cross-layer fibers effectively guided and controlled the extension length and direction of the neurites of surrounding neural cells but had no significant effect on the migration of neurons. In contrast, glial cells significantly promoted the migration of surrounding PC12 cells towards the glial layer but did not contribute to the extension of neurites. This study provides a basis for the design and manufacture of accurate brain-like models for the functionalization of neuronal tissues.

Full-scale polymer relaxation induced by single-chain confinement enhances mechanical stability of nanocomposites.

Polymer nanocomposites with tuning functions are exciting candidates for various applications, and most current research has focused on static mechanical reinforcement. Actually, under service conditions of complex dynamic interference, stable dynamic mechanical properties with high energy dissipation become more critical. However, nanocomposites often exhibit a trade-off between static and dynamic mechanics, because of their contradictory underlying physics between chain crosslinking and chain relaxation. Here, we report a general strategy for constructing ultra-stable dynamic mechanical complex fluid nanocomposites with high energy dissipation by infusing complex fluids into the nanoconfined space. The key is to tailor full-scale polymer dynamics across an exceptionally broad timescale by single-chain confinement. These materials exhibit stable storage modulus (100 ~ 102 MPa) with high energy dissipation (loss factor > 0.4) over a broad frequency range (10-1 ~ 107 Hz)/temperature range (-35 ~ 85°C). In the loss factor > 0.4 region, their dynamic mechanical stability (rate of modulus change versus temperature (k)) is 10 times higher than that of conventional polymer nanocomposites.

Sulfoaluminate cement-modified loess as bioretention cell filler for nutrient removal from stormwater runoff.

In order to reduce the consumption of sand and gravel resources, the use of loess can reduce transportation costs and realize the in-situ construction of spongy in areas with rich loess resources. But the collapsibility and low permeability of loess make it unable to be directly used as the filler of bioretention cells. In this study, sulfoaluminate cement (SAC) mixed with a small amount of basalt fiber was considered to be used for loess modification, and the physicochemical properties and nutrient removal effect of SAC-modified loess as filler in bioretention cells were comprehensively evaluated. The results showed that when the SAC dosage was 15% and the basalt fiber addition was 0% (S15B0) and 0.6% (S15B6) and the curing time was 14 days, the stability and appropriate permeability can be exhibited, which can preliminarily satisfy the requirements of bioretention cell. SAC made the maximum adsorption capacity of S15B0 and S15B6 for ammonia nitrogen (NH4+-N) and phosphate higher than that of sand by 10.96%-31.51% and 45.92%-76.72%, respectively. The hydration products in SAC modified loess can fill the internal pores of loess particles and provide structural support, and ultimately reduce the accumulated pores, mesoporous pore size (20%) and surface homogeneity. Both S15B0 and S15B6 showed good removal effects of NH4+-N and COD. The TP removal efficiency was stable at 95.43%∼99.95%. Both the antecedent drying days and the submerged zone have an effect on the nitrogen removal in the bioretention cells, where a longer antecedent drying days is detrimental to the nitrogen removal, and the installation of a submerged zone improves the nitrogen removal. The basalt fiber can enhance the transformation process from nitrate-nitrogen to nitrite-nitrogen in the bioretention cell. Therefore, the modification of SAC can provide a certain idea for the in-situ use of loess as the filler of the bioretention cell.

Safety, Immunogenicity, and Effectiveness of Chinese-Made COVID-19 Vaccines in the Real World: An Interim Report of a Living Systematic Review.

Background: Several COVID-19 vaccines were developed and approved in China. Of these, the BIBB-CorV and CoronaVac inactivated whole-virion vaccines were widely distributed in China and developing countries. However, the performance of the two vaccines in the real world has not been summarized. Methods: A living systematic review based on findings from ongoing post-licensure studies was conducted, applying standardized algorithms. Articles published between 1 May 2020 and 31 May 2022 in English and Chinese were searched for in Medline, Embase, WanFang Data, medRxiv, bioRxiv, arXiv, SSRN, and Research Square, using SARS-CoV-2, COVID-19, and vaccine as the MeSH terms. Studies with estimates of safety, immunogenicity, and effectiveness from receiving the BIBB-CorV or CoronaVac vaccine that met the predefined screening criteria underwent a full-text review. The Joanna Briggs Institute's Critical Appraisal Checklist and the Cochrane risk of bias were used for assessment of the quality. A random-effects meta-regression model was applied to identify the potential impact factors on the vaccines' effectiveness. Results: In total, 32578 articles were identified, of these, 770 studies underwent a full-text review. Eventually, 213 studies were included. The pooled occurrence of solicited and unsolicited adverse events after any dose of either vaccine varied between 10% and 40%. The top five commonly reported rare adverse events were immunization stress-related responses (211 cases, 50.0%), cutaneous responses (43 cases, 10.2%), acute neurological syndrome (39 cases, 9.2%), anaphylaxis (17 cases, 4.0%), and acute stroke (16 cases, 3.8%). The majority (83.3%) recovered or were relieved within several days. The peak neutralization titers against the ancestral strain was found within 1 month after the completion of the primary series of either vaccine, with a GMT (geometric mean titer) of 43.7 (95% CI: 23.2-82.4), followed by a dramatic decrease within 3 months. At Month 12, the GMT was 4.1 (95% CI: 3.8-4.4). Homologous boosting could restore humoral immunity, while heterologous boosting elicited around sixfold higher neutralization titers in comparison with homologous boosting. The effectiveness of receiving either vaccine against death and severe disease was around 85% for both shortly after the primary series. At Month 12, the protection against death did not decline, while the protection against severe disease decreased to ~75%. Conclusions: Both the BIBP-CorV and CoronaVac inactivated vaccines are safe. Sustained vaccine effectiveness against death was determined 12 months after the primary series, although protection against severe disease decreased slightly over time. A booster dose could strengthen the waning effectiveness; however, the duration of the incremental effectiveness and the additional benefit provided by a heterologous booster need to be studied.

Study of the Epidemiological and Mechanistic Differences Between Carbapenem-Resistant Klebsiella pneumoniae Infections in Children and Adults.

Background: The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) has garnered international concern due to its significant antibiotic resistance. Notably, children exhibit distinct resistance mechanisms compared to adults, necessitating a differential approach to antibiotic selection. A thorough analysis of CRKP's epidemiology and drug resistance mechanisms is essential for establishing a robust foundation for clinical anti-infection strategies and precise prevention and control measures. Methods: This study involved the collection of 31 non-repetitive strains from pediatric and adult patients at a tertiary hospital in China, spanning from July 2016 to July 2022, testing for resistance genes, antimicrobial susceptibility, and homology analysis. Results: Infants (0-1 year) were the largest pediatric CRKP group, with 61.3% of cases. The neonatal intensive care unit (NICU) and pediatrics were the main departments affected. Adults with CRKP had a mean age of 67 years, with the highest prevalence in neurology and emergency ICU. Antimicrobial susceptibility testing revealed that adult CRKP strains exhibited higher resistance to amikacin, ciprofloxacin, cotrimoxazole, and aztreonam compared to pediatric strains. Conversely, pediatric strains showed a higher rate of resistance to ceftazidime/avibactam. The predominant resistance genes identified were bla NDM-5 in children (58.1%) and bla KPC-2 in adults (87.1%), with over 93% of both groups testing positive for extended-spectrum beta-lactamase (ESBL) genes. Multilocus Sequence Typing (MLST) indicated ST2735 and ST11 as the predominant types in children and adults, respectively. Pulsed-field gel electrophoresis (PFGE) identified clonal transmission patterns of ST11 bla KPC-2 and ST15 bla OXA-232 across both age groups. Notably, this study reports the first instance of ST1114-type CRKP co-producing bla NDM-5 and bla OXA-181 in the NICU. Conclusion: This study reveals distinct resistance mechanisms and epidemiology in CRKP from children and adults. The identified clonal transmission patterns emphasize the need for improved infection control to prevent the spread of resistant strains.

Progestogen-driven B7-H4 contributes to onco-fetal immune tolerance.

Immune tolerance mechanisms are shared in cancer and pregnancy. Through cross-analyzing single-cell RNA-sequencing data from multiple human cancer types and the maternal-fetal interface, we found B7-H4 (VTCN1) is an onco-fetal immune tolerance checkpoint. We showed that genetic deficiency of B7-H4 resulted in immune activation and fetal resorption in allogeneic pregnancy models. Analogously, B7-H4 contributed to MPA/DMBA-induced breast cancer progression, accompanied by CD8+ T cell exhaustion. Female hormone screening revealed that progesterone stimulated B7-H4 expression in placental and breast cancer cells. Mechanistically, progesterone receptor (PR) bound to a newly identified -58 kb enhancer, thereby mediating B7-H4 transcription via the PR-P300-BRD4 axis. PR antagonist or BRD4 degrader potentiated immunotherapy in a murine B7-H4+ breast cancer model. Thus, our work unravels a mechanistic and biological connection of a female sex hormone (progesterone) to onco-fetal immune tolerance via B7-H4 and suggests that the PR-P300-BRD4 axis is targetable for treating B7-H4+ cancer.

PIKfyve, expressed by CD11c-positive cells, controls tumor immunity.

Cancer treatment continues to shift from utilizing traditional therapies to targeted ones, such as protein kinase inhibitors and immunotherapy. Mobilizing dendritic cells (DC) and other myeloid cells with antigen presenting and cancer cell killing capacities is an attractive but not fully exploited approach. Here, we show that PIKFYVE is a shared gene target of clinically relevant protein kinase inhibitors and high expression of this gene in DCs is associated with poor patient response to immune checkpoint blockade (ICB) therapy. Genetic and pharmacological studies demonstrate that PIKfyve ablation enhances the function of CD11c+ cells (predominantly dendritic cells) via selectively altering the non-canonical NF-κB pathway. Both loss of Pikfyve in CD11c+ cells and treatment with apilimod, a potent and specific PIKfyve inhibitor, restrained tumor growth, enhanced DC-dependent T cell immunity, and potentiated ICB efficacy in tumor-bearing mouse models. Furthermore, the combination of a vaccine adjuvant and apilimod reduced tumor progression in vivo. Thus, PIKfyve negatively regulates the function of CD11c+ cells, and PIKfyve inhibition has promise for cancer immunotherapy and vaccine treatment strategies.

COVID-19 infection, resilience, and depressive symptoms: the protective role of family functioning for aging Chinese adults in Hong Kong.

OBJECTIVES: Older adults are at an elevated risk of experiencing long COVID, with post-COVID-19 depressive symptoms being prevalent. However, the protective factors against this remain understudied. This study examined (a) the role of resilience in the association between COVID-19 infection and depressive symptoms in aging adults; (b) the moderating role of family functioning in the relationships between COVID-19 and resilience and between resilience and depressive symptoms; and (c) potential gender differences in the moderation. METHOD: Data were drawn from the first wave of the Panel Study of Active Ageing and Society, a representative survey of Hong Kong adults aged 50 or above. Mediation and moderated mediation analyses were conducted. RESULTS: Approximately 35% of the participants had tested positive for COVID-19. Resilience significantly mediated the association between COVID-19 infection and post-COVID-19 depressive symptoms (p < 0.001). Family functioning was a significant moderator: the COVID-19-resilience association was stronger, and the resilience-depressive symptoms association was weaker among participants with higher family functioning. The moderating role of family functioning was more salient in women than in men. CONCLUSION: Resilience can protect aging adults from post-COVID-19 depressive symptoms. Interventions for enhancing family functioning may promote the formation of resilience, especially among older women.

Bioinspired Adaptive Microdrugs Enhance the Chemotherapy of Malignant Glioma: Beyond Their Nanodrugs.

Solid nanoparticle-mediated drug delivery systems are usually confined to nanoscale due to the enhanced permeability and retention effect. However, they remain a great challenge for malignant glioma chemotherapy because of poor drug delivery efficiency and insufficient tumor penetration resulting from the blood-brain barrier/blood-brain tumor barrier (BBB/BBTB). Inspired by biological microparticles (e.g., cells) with excellent adaptive deformation, it is demonstrated that the adaptive microdrugs (even up to 3.0 µm in size) are more efficient than their nanodrugs (less than 200 nm in size) to cross BBB/BBTB and penetrate into tumor tissues, achieving highly efficient chemotherapy of malignant glioma. The distinct delivery of the adaptive microdrugs is mainly attributed to the enhanced interfacial binding and endocytosis via adaptive deformation. As expected, the obtained adaptive microdrugs exhibit enhanced accumulation, deep penetration, and cellular internalization into tumor tissues in comparison with nanodrugs, significantly improving the survival rate of glioblastoma mice. It is believed that the bioinspired adaptive microdrugs enable them to efficiently cross physiological barriers and deeply penetrate tumor tissues for drug delivery, providing an avenue for the treatment of solid tumors.

Suppression of cracking in drying colloidal suspensions with chain-like particles.

The prevention of drying-induced cracking is crucial in maintaining the mechanical integrity and functionality of colloidal deposits and coatings. Despite exploring various approaches, controlling drying-induced cracking remains a subject of great scientific interest and practical importance. By introducing chain-like particles composed of the same material and with comparable size into commonly used colloidal suspensions of spherical silica nanoparticles, we can significantly reduce the cracks formed in dried particle deposits and achieve a fivefold increase in the critical cracking thickness of colloidal silica coatings. The mechanism underlying the crack suppression is attributed to the increased porosity and pore sizes in dried particle deposits containing chain-like particle, which essentially leads to reduction in internal stresses developed during the drying process. Meanwhile, the nanoindentation measurements reveal that colloidal deposits with chain-like particles exhibit a smaller reduction in hardness compared to those reported using other cracking suppression approaches. This work demonstrates a promising technique for preparing colloidal coatings with enhanced crack resistance while maintaining desirable mechanical properties.

[Progressive myoclonic epilepsy: a retrospective study of newly-diagnosed adult patients from a single center].

OBJECTIVE: To retrospectively analyze the clinical phenotype and pathogenic variants in patients with Progressive myoclonus epilepsy (PME). METHODS: Clinical data and results of genetic testing for 11 patients diagnosed with PME at the Department of Neurology, the First Affiliated Hospital of Zhejiang University School of Medicine from June 2017 to December 2022 were collected and analyzed. RESULTS: All of the patients, including 4 males and 7 females, had predominant action myoclonus. Three patients had myoclonus as the initial manifestation, whilst eight were diagnosed through genetic testing, including three cases with NEU1 gene variants, two with EPM2A gene variants (1 was novel), one with MT-TK gene variant, one with ATN1 gene variant, and one with CSTB gene variant. No pathogenic variant was identified in the remaining three cases. Among the eight patients with a genetic diagnosis, three were diagnosed with sialidosis, two with Lafora disease, one with Dentatorubral-pallidoluysian atrophy (DRPLA), one with Unverricht-Lundborg disease (ULD), and one with Myoclonic epilepsy with ragging red fibers (MERRF). CONCLUSION: Compared with pediatric patients, adult patients with PME represent a distinct subtype with slower progression and milder cognitive impairment.