Association between household size and risk of incident dementia in the UK Biobank study.

Currently, the relationship between household size and incident dementia, along with the underlying neurobiological mechanisms, remains unclear. This prospective cohort study was based on UK Biobank participants aged ≥ 50 years without a history of dementia. The linear and non-linear longitudinal association was assessed using Cox proportional hazards regression and restricted cubic spline models. Additionally, the potential mechanisms driven by brain structures were investigated by linear regression models. We included 275,629 participants (mean age at baseline 60.45 years [SD 5.39]). Over a mean follow-up of 9.5 years, 6031 individuals developed all-cause dementia. Multivariable analyses revealed that smaller household size was associated with an increased risk of all-cause dementia (HR, 1.06; 95% CI 1.02-1.09), vascular dementia (HR, 1.08; 95% CI 1.01-1.15), and non-Alzheimer's disease non-vascular dementia (HR, 1.09; 95% CI 1.03-1.14). No significant association was observed for Alzheimer's disease. Restricted cubic splines demonstrated a reversed J-shaped relationship between household size and all-cause and cause-specific dementia. Additionally, substantial associations existed between household size and brain structures. Our findings suggest that small household size is a risk factor for dementia. Additionally, brain structural differences related to household size support these associations. Household size may thus be a potential modifiable risk factor for dementia.

Establishment and validation of multiclassification prediction models for pulmonary nodules based on machine learning.

BACKGROUND: Lung cancer is the leading cause of cancer-related death worldwide. This study aimed to establish novel multiclassification prediction models based on machine learning (ML) to predict the probability of malignancy in pulmonary nodules (PNs) and to compare with three published models. METHODS: Nine hundred fourteen patients with PNs were collected from four medical institutions (A, B, C and D), which were organized into tables containing clinical features, radiologic features and laboratory test features. Patients were divided into benign lesion (BL), precursor lesion (PL) and malignant lesion (ML) groups according to pathological diagnosis. Approximately 80% of patients in A (total/male: 632/269, age: 57.73 ± 11.06) were randomly selected as a training set; the remaining 20% were used as an internal test set; and the patients in B (total/male: 94/53, age: 60.04 ± 11.22), C (total/male: 94/47, age: 59.30 ± 9.86) and D (total/male: 94/61, age: 62.0 ± 11.09) were used as an external validation set. Logical regression (LR), decision tree (DT), random forest (RF) and support vector machine (SVM) were used to establish prediction models. Finally, the Mayo model, Peking University People's Hospital (PKUPH) model and Brock model were externally validated in our patients. RESULTS: The AUC values of RF model for MLs, PLs and BLs were 0.80 (95% CI: 0.73-0.88), 0.90 (95% CI: 0.82-0.99) and 0.75 (95% CI: 0.67-0.88), respectively. The weighted average AUC value of the RF model for the external validation set was 0.71 (95% CI: 0.67-0.73), and its AUC values for MLs, PLs and BLs were 0.71 (95% CI: 0.68-0.79), 0.98 (95% CI: 0.88-1.07) and 0.68 (95% CI: 0.61-0.74), respectively. The AUC values of the Mayo model, PKUPH model and Brock model were 0.68 (95% CI: 0.62-0.74), 0.64 (95% CI: 0.58-0.70) and 0.57 (95% CI: 0.49-0.65), respectively. CONCLUSIONS: The RF model performed best, and its predictive performance was better than that of the three published models, which may provide a new noninvasive method for the risk assessment of PNs.

Postoperative pain relief after total knee arthroplasty: A Bayesian network meta-analysis and systematic review of analgesic strategies based on nerve blocks.

STUDY OBJECTIVE: A Bayesian network meta-analysis was performed to compare the analgesic efficacy of the following nerve block techniques: femoral nerve block (FNB), adductor canal block (ACB), infiltration between the popliteal artery and the capsule of the posterior knee (iPACK), and genicular nerve block (GNB) following total knee arthroplasty (TKA). DESIGN: Systematic review and network meta-analysis (NMA). PATIENTS AND MEASUREMENTS: We searched the Web of Science, PubMed, EMBASE, and Cochrane Library databases until September 20, 2022. Patients who were treated by any of the above four nerve block techniques (alone or in combination) after TKA were included. Patients who underwent minimally invasive knee surgery were excluded. The indicators included pain scores during rest and mobilization, opioid consumption after surgery, postsurgical mobilization function (ROM [range of motion], TUG [Timed-Up-and-Go] test) at 24 h and 48 h, and length of hospital stay. The risk of bias was assessed by the Cochrane risk of bias tool. RESULTS: Forty-two studies involving 2857 patients were eligible for this study. This NMA suggested that ACB + iPACK was the most efficacious option for improving ambulation ability and shortening the length of hospital stay. Furthermore, ACB + iPACK was the best regimen for resting-pain and movement-pain relief (78% and 87%, respectively) and for reducing opioid consumption (90%) at 48 h. However, FNB + iPACK was the most efficacious option for relief of resting pain (42%) and reducing opioid consumption (68%) at 24 h; GNB was the most efficacious option for movement pain relief at 24 h (94%). CONCLUSION: Considering both pain control and knee functional recovery, ACB + iPACK may be the optimal analgesic regimen for patients after TKA. At the same time, it significantly reduces pain and opioid consumption at 48 h. However, ACB + iPACK is not the recommended technique for short-term (24 h) pain control. CLINICAL TRIAL REGISTRATION: PROSPERO (CRD42022362322).

Two-dimensional metal-organic framework for post-synthetic immobilization of graphene quantum dots for photoluminescent sensing.

Immobilization of graphene quantum dots (GQDs) on a solid support is crucial to prevent GQDs from aggregation in the form of solid powder and facilitate the separation and recycling of GQDs after use. Herein, spatially dispersed GQDs are post-synthetically coordinated within a two-dimensional (2D) and water-stable zirconium-based metal-organic framework (MOF). Unlike pristine GQDs, the obtained GQDs immobilized on 2D MOF sheets show photoluminescence in both suspension and dry powder. Chemical and photoluminescent stabilities of MOF-immobilized GQDs in water are investigated, and the use of immobilized GQDs in the photoluminescent detection of copper ions is demonstrated. Findings here shed the light on the use of 2D MOFs as a platform to further immobilize GQDs with various sizes and distinct chemical functionalities for a range of applications.

Interaction Pattern Disentangling for Multi-Agent Reinforcement Learning.

Deep cooperative multi-agent reinforcement learning has demonstrated its remarkable success over a wide spectrum of complex control tasks. However, recent advances in multi-agent learning mainly focus on value decomposition while leaving entity interactions still intertwined, which easily leads to over-fitting on noisy interactions between entities. In this work, we introduce a novel interactiOn Pattern disenTangling (OPT) method, to disentangle the entity interactions into interaction prototypes, each of which represents an underlying interaction pattern within a subgroup of the entities. OPT facilitates filtering the noisy interactions between irrelevant entities and thus significantly improves generalizability as well as interpretability. Specifically, OPT introduces a sparse disagreement mechanism to encourage sparsity and diversity among discovered interaction prototypes. Then the model selectively restructures these prototypes into a compact interaction pattern by an aggregator with learnable weights. To alleviate the training instability issue caused by partial observability, we propose to maximize the mutual information between the aggregation weights and the history behaviors of each agent. Experiments on single-task, multi-task and zero-shot benchmarks demonstrate that the proposed method yields results superior to the state-of-the-art counterparts. Our code is available at https://github.com/liushunyu/OPT.

High Performance As-Cast Organic Solar Cells Enabled by a Refined Double-Fibril Network Morphology and Improved Dielectric Constant of Active Layer.

High performance organic solar cells (OSCs) are usually realized by using post-treatment and/or additive, which can induce the formation of metastable morphology, leading to unfavorable device stability. In terms of the industrial production, the development of high efficiency as-cast OSCs is crucially important, but it remains a great challenge to obtain appropriate active layer morphology and high power conversion efficiency (PCE). Here, efficient as-cast OSCs are constructed via introducing a new polymer acceptor PY-TPT with a high dielectric constant into the D18:L8-BO blend to form a double-fibril network morphology. Besides, the incorporation of PY-TPT enables an enhanced dielectric constant and lower exciton binding energy of active layer. Therefore, efficient exciton dissociation and charge transport are realized in D18:L8-BO:PY-TPT-based device, affording a record-high PCE of 18.60% and excellent photostability in absence of post-treatment. Moreover, green solvent-processed devices, thick-film (300 nm) devices, and module (16.60 cm2) are fabricated, which show PCEs of 17.45%, 17.54%, and 13.84%, respectively. This work brings new insight into the construction of efficient as-cast devices, pushing forward the practical application of OSCs.

Rational Design of Ruddlesden-Popper Perovskite Ferrites as Air Electrode for Highly Active and Durable Reversible Protonic Ceramic Cells.

Reversible protonic ceramic cells (RePCCs) hold promise for efficient energy storage, but their practicality is hindered by a lack of high-performance air electrode materials. Ruddlesden-Popper perovskite Sr3Fe2O7-δ (SF) exhibits superior proton uptake and rapid ionic conduction, boosting activity. However, excessive proton uptake during RePCC operation degrades SF's crystal structure, impacting durability. This study introduces a novel A/B-sites co-substitution strategy for modifying air electrodes, incorporating Sr-deficiency and Nb-substitution to create Sr2.8Fe1.8Nb0.2O7-δ (D-SFN). Nb stabilizes SF's crystal, curbing excessive phase formation, and Sr-deficiency boosts oxygen vacancy concentration, optimizing oxygen transport. The D-SFN electrode demonstrates outstanding activity and durability, achieving a peak power density of 596 mW cm-2 in fuel cell mode and a current density of - 1.19 A cm-2 in electrolysis mode at 1.3 V, 650 °C, with excellent cycling durability. This approach holds the potential for advancing robust and efficient air electrodes in RePCCs for renewable energy storage.

Photosynthetic response of Chlamydomonas reinhardtii and Chlamydomonas sp. 1710 to zinc toxicity.

Zinc (Zn) is an essential trace element but can lead to water contamination and ecological deterioration when present in excessive amounts. Therefore, investigating the photosynthetic response of microalgae to Zn stress is of great significance. In this study, we assessed the photosynthetic responses of neutrophilic Chlamydomonas reinhardtii and acidophilic Chlamydomonas sp. 1710 to Zn exposure for 96 h. The specific growth rate (µ), chlorophyll-a (Chl-a) content, and chlorophyll fluorescence parameters were determined. The results demonstrated that Chlamydomonas sp. 1710 was much more tolerant to Zn than C. reinhardtii, with the half-maximal inhibitory concentration (IC50) values of 225.4 mg/L and 23.4 mg/L, respectively. The µ and Chl-a content of C. reinhardtii decreased in the presence of 15 mg/L Zn, whereas those of Chlamydomonas sp. 1710 were unaffected by as high as 100 mg/L Zn. Chlorophyll fluorescence parameters indicated that the regulation of energy dissipation, including non-photochemical quenching, played a crucial role in Zn stress resistance for both Chlamydomonas strains. However, in the case of C. reinhardtii, non-photochemical quenching was inhibited by 5 mg/L Zn in the first 48 h, whereas for Chlamydomonas sp. 1710, it remained unaffected under 100 mg/L Zn. Chlamydomonas sp. 1710 also exhibited a 20 times stronger capacity for regulating the electron transfer rate than C. reinhardtii under Zn stress. The light energy utilization efficiency (α) of Chlamydomonas sp. 1710 had the most highly non-linear correlation with µ, indicating the energy utilization and regulation process of Chlamydomonas sp. 1710 was well protected under Zn stress. Collectively, our findings demonstrate that the photosystem of Chlamydomonas sp. 1710 is much more resilient and tolerant than that of C. reinhardtii under Zn stress.

Disorder-Broadened Phase Boundary with Enhanced Amorphous Superconductivity in Pressurized In2Te5.

As an empirical tool in materials science and engineering, the iconic phase diagram owes its robustness and practicality to the topological characteristics rooted in the celebrated Gibbs phase law free variables (F) = components (C) - phases (P) + 2. When crossing the phase diagram boundary, the structure transition occurs abruptly, bringing about an instantaneous change in physical properties and limited controllability on the boundaries (F = 1). Here, the sharp phase boundary is expanded to an amorphous transition region (F = 2) by partially disrupting the long-range translational symmetry, leading to a sequential crystalline-amorphous-crystalline (CAC) transition in a pressurized In2Te5 single crystal. Through detailed in situ synchrotron diffraction, it is elucidated that the phase transition stems from the rotation of immobile blocks [In2Te2]2+, linked by hinge-like [Te3]2- trimers. Remarkably, within the amorphous region, the amorphous phase demonstrates a notable 25% increase of the superconducting transition temperature (Tc), while the carrier concentration remains relatively constant. Furthermore, a theoretical framework is proposed revealing that the unconventional boost in amorphous superconductivity might be attributed to an intensified electron correlation, triggered by a disorder-augmented multifractal behavior. These findings underscore the potential of disorder and prompt further exploration of unforeseen phenomena on the phase boundaries.

Correlations between developmental trajectories of brain functional connectivity, neurocognitive functions, and clinical symptoms in patients with attention-deficit hyperactivity disorder.

Several studies on attention-deficit hyperactivity disorder (ADHD) have suggested a developmental sequence of brain changes: subcortico-subcortical connectivity in children, evolving to subcortico-cortical in adolescence, and culminating in cortico-cortical connectivity in young adulthood. This study hypothesized that children with ADHD would exhibit decreased functional connectivity (FC) between the cortex and striatum compared to adults with ADHD, who may show increased FC in these regions. Seventy-six patients with ADHD (26 children, 26 adolescents, and 24 adults) and 74 healthy controls (25 children, 24 adolescents, and 25 adults) participated in the study. Resting state magnetic resonance images were acquired using a 3.0 T Philips Achieva scanner. The results indicated a gradual decrease in the number of subcategories representing intelligence quotient deficits in the ADHD group with age. In adulthood, the ADHD group exhibited lower working memory compared to the healthy control group. The number of regions showing decreased FC from the cortex to striatum between the ADHD and control groups reduced with age, while regions with increased FC from the default mode network and attention network in the ADHD group increased with age. In adolescents and adults, working memory was positively associated with brain activity in the postcentral gyrus and negatively correlated with ADHD clinical symptoms. In conclusion, the findings suggest that intelligence deficits in certain IQ subcategories may diminish as individuals with ADHD age. Additionally, the study indicates an increasing anticorrelation between cortical and subcortical regions with age in individuals with ADHD.

Tumor-penetrating iRGD facilitates penetration of poly(floxuridine-ketal)-based nanomedicine for enhanced pancreatic cancer therapy.

Efficient intratumoral penetration is essential for nanomedicine to eradicate pancreatic tumors. Although nanomedicine can enter the perivascular space of pancreatic tumors, their access to distal tumor cells, aloof from the vessels, remains a formidable challenge. Here, we synthesized an acid-activatable macromolecular prodrug of floxuridine (FUDR)-poly(FUDR-ketal), engineered a micellar nanomedicine of FUDR, and intravenously co-administered the nanomedicine with the tumor-penetrating peptide iRGD for enhanced treatment of pancreatic tumor. A FUDR-derived mono-isopropenyl ether was synthesized and underwent self-addition polymerization to afford the hydrophobic poly(FUDR-ketal), which was subsequently co-assembled with amphiphilic DSPE-mPEG into the micellar nanomedicine with size of 12 nm and drug content of 56.8 wt% using nanoprecipitation technique. The acetone-based ketal-linked poly(FUDR-ketal) was triggered by acid to release FUDR to inhibit cell proliferation. In an orthotopic pancreatic tumor model derived from KPC (KrasLSL-G12D/+; Trp53LSL-R172H/+; Pdx1-Cre) cells that overexpress neuropilin-1 (NRP-1) receptor, iRGD improved penetration of FUDR nanomedicine into tumor parenchyma and potentiated the therapeutic efficacy. Our nanoplatform, along with iRGD, thus appears to be promising for efficient penetration and activation of acid-responsive nanomedicines for enhanced pancreatic cancer therapy.

Insecticidal activity of the spider neurotoxin PPTX-04 through modulating insect voltage-gated sodium channel.

Ion channels on cell membrane are molecular targets of more than half peptide neurotoxins from spiders. From Pardosa pseudoannulata, a predatory spider on a range of insect pests, we characterized a peptide neurotoxin PPTX-04 with an insecticidal activity. PPTX-04 showed high toxicity to Nilaparvata lugens, a main prey of P. pseudoannulata, and the toxicity was not affected by the resistance to etofenprox (IUPAC chemical name:1-ethoxy-4-[2-methyl-1-[(3-phenoxyphenyl)methoxy]propan-2-yl]benzene, purity: 99%). On N. lugens voltage-gated sodium channel NlNav1 expressed in Xenopus oocytes, PPTX-04 prolonged the channel opening and induced tail currents, which is similar to pyrethroid insecticides. However, PPTX-04 potency on NlNav1 was not affected by mutations conferring pyrethroid resistance in insects, which revealed that PPTX-04 and pyrethroids should act on different receptors in NlNav1. In contrast, two mutations at the extracellular site 4 significantly reduced PPTX-04 potency, which indicated that PPTX-04 would act on a potential receptor containing the site 4 in NlNav1. The result from the molecular docking supported the conclusion that the binding pocket of PPTX-04 in NlNav1 should contain the site 4. In summary, PPTX-04 had high insecticidal activity through acting on a distinct receptor site in insect Nav, and was a potential resource to control insect pests and manage resistance to pyrethroids.

Efficacy of a Virtual 3D Simulation-Based Digital Training Module for Building Dental Technology Students' Long-Term Competency in Removable Partial Denture Design: Prospective Cohort Study.

Background: Removable partial denture (RPD) design is crucial to long-term success in dental treatment, but shortcomings in RPD design training and competency acquisition among dental students have persisted for decades. Digital production is increasing in prevalence in stomatology, and a digital RPD (D-RPD) module, under the framework of the certified Objective Manipulative Skill Examination of Dental Technicians (OMEDT) system reported in our previous work, may improve on existing RPD training models for students. Objective: We aimed to determine the efficacy of a virtual 3D simulation-based progressive digital training module for RPD design compared to traditional training. Methods: We developed a prospective cohort study including dental technology students at the Stomatology College of Chongqing Medical University. Cohort 1 received traditional RPD design training (7 wk). Cohort 2 received D-RPD module training based on text and 2D sketches (7 wk). Cohort 3 received D-RPD module pilot training based on text and 2D sketches (4 wk) and continued to receive training based on 3D virtual casts of real patients (3 wk). RPD design tests based on virtual casts were conducted at 1 month and 1 year after training. We collected RPD design scores and the time spent to perform each assessment. Results: We collected the RPD design scores and the time spent to perform each assessment at 1 month and 1 year after training. The study recruited 109 students, including 58 (53.2%) female and 51 male (56.8%) students. Cohort 1 scored the lowest and cohort 3 scored the highest in both tests (cohorts 1-3 at 1 mo: mean score 65.8, SD 21.5; mean score 81.9, SD 6.88; and mean score 85.3, SD 8.55, respectively; P<.001; cohorts 1-3 at 1 y: mean score 60.3, SD 16.7; mean score 75.5, SD 3.90; and mean score 90.9, SD 4.3, respectively; P<.001). The difference between cohorts in the time spent was not statistically significant at 1 month (cohorts 1-3: mean 2407.8, SD 1370.3 s; mean 1835.0, SD 1329.2 s; and mean 1790.3, SD 1195.5 s, respectively; P=.06) but was statistically significant at 1 year (cohorts 1-3: mean 2049.16, SD 1099.0 s; mean 1857.33, SD 587.39 s; and mean 2524.3, SD 566.37 s, respectively; P<.001). Intracohort comparisons indicated that the differences in scores at 1 month and 1 year were not statistically significant for cohort 1 (95% CI -2.1 to 13.0; P=.16), while cohort 3 obtained significantly higher scores 1 year later (95% CI 2.5-8.7; P=.001), and cohort 2 obtained significantly lower scores 1 year later (95% CI -8.8 to -3.9; P<.001). Conclusions: Cohort 3 obtained the highest score at both time points with retention of competency at 1 year, indicating that progressive D-RPD training including virtual 3D simulation facilitated improved competency in RPD design. The adoption of D-RPD training may benefit learning outcomes.

Pharmacokinetics and relative bioavailability study of two cefquinome sulfate intramammary infusions in cow milk.

In this study, two intramammary infusions of cefquinome sulfate were investigated for pharmacokinetics and bioavailability. Twelve lactating cows for each group were administered an effective dose of 75 mg/gland for cefquinome, with milk samples collected at various time intervals. The concentrations of cefquinome in milk at different times were determined by the UPLC-MS/MS method. Analyses of noncompartmental pharmacokinetics were conducted on the concentration of cefquinome in milk. Mean pharmacokinetic parameters of group A and group B following intramammary administration were as follows: AUClast 300558.57 ± 25052.78 ng/mL and 266551.3 ± 50654.85 ng/mL, Cmax 51786.35 ± 11948.4 ng/mL and 59763.7 ± 8403.2 ng/mL, T1/2 5.69 ± 0.62 h and 5.25 ± 1.62 h, MRT 7.43 ± 0.79 h and 4.8 ± 0.78 h, respectively. Pharmacokinetic experiments showed that the relative bioavailability of group B was 88.69% that of group A. From our findings, group B (3 g: 75 mg) shows a quicker drug elimination process than group A (8 g: 75 mg), which suggests that the withdrawal period for the new formulation may be shorter.

Quantitative evaluation of morphological and functional changes in meibomian glands and lipid layer thickness in patients with and without keratoconus.

PURPOSE: To quantitatively evaluate the morphological parameters of meibomian glands (MGs) and lipid layer thickness (LLT) in patients with keratoconus (KC). METHODS: In this prospective, cross-sectional study, 164 eyes of 164 keratoconus patients and 64 eyes of 64 age-matched control subjects were included. An advanced automatic MG analyzer was used to quantitatively measure the morphological and functional parameters of MGs. Morphological and functional parameters of MGs, LLT, and other ocular surface parameters were compared between the control and KC groups. RESULTS: The mean meibomian gland diameter, length, square, and gland area ratio (GA) were all significantly decreased in the KC group (all P < 0.05), while no significant difference was observed in the gland tortuosity index (TI) and gland signal index (SI) between the KC and control groups (all P > 0.05). There was no significant difference in the number of total and incomplete blinking among patients with different stages of keratoconus (all P > 0.05). The gland diameter, square, and TI were all negatively associated with KC severity (all P < 0.05), while no significant difference was observed among all stages of KC in gland length, GA, and SI (all P > 0.05). Moreover, the LLTs were positively correlated with the gland diameter, square, GA, and TI and negatively correlated with anterior corneal curvature or KC severity (all P < 0.05). CONCLUSIONS: Atrophic morphological changes in the meibomian glands were closely correlated with the severity of keratoconus. Gland diameter may be a sensitive functional morphology metric of meibomian glands in patients with keratoconus.

Aberrant phenotypes of circulating γδ-T cells may be involved in the onset of systemic lupus erythematosus.

OBJECTIVE: Human gamma-delta T cells (γδ-T cells) play crucial roles in both innate and adaptive immune responses. However, much less is known about the immune status of γδT cells in systemic lupus erythematosus (SLE) patients. The objective of this study was to explore potential relationships between the frequency of γδ-T-cell subpopulations and disease activity, autoantibody titres and renal involvement in patients with SLE. METHODS: Circulating γδ-T cells and their subsets (Vδ1+ T cells, Vδ2+ T cells and γδ-T-cell subpopulations defined by expression of surface receptors, including NKG2D, NKp30, NKp46 and PD-1), were identified via flow cytometry. Sixty active SLE patients were selected, including 41 new-onset and 19 relapsing cases. One hundred healthy controls (HCs) were enrolled as the control group. Percentages of these cell subsets in SLE patients and HCs and their relationships with disease activity were analysed. Twenty-two of the 41 new-onset SLE patients were assessed before and after treatment. Changes in the frequencies of these cell subsets and their relationships with renal involvement were also analysed. RESULTS: Compared with that in HCs, the percentage of total γδ-T cells among CD3+ T cells in SLE patients was significantly lower. An imbalance in the proportions of Vδ1+ and Vδ2+ T cells among γδ-T cells was observed. The proportion of Vδ1+ T cells among γδ-T cells was significantly greater in SLE patients than in HCs, while the proportion of Vδ2+ T cells was significantly lower. Expression levels of PD-1, NKG2D, NKp30 and NKp46 in Vδ1+ T cells and Vδ2+ T cells from SLE patients were generally significantly increased, except for expression of NKG2D in Vδ2+ T cells. Moreover, Vδ2+ T cells, Vδ1+ T cells and Vδ1+PD-1+ T cells were associated with disease activity, and an increase in Vδ2+ T-cell frequency and a decrease in PD-1 expression by γδ-T cells might be associated with effective treatment. Interestingly, our results indicated that Vδ2+ T cells and their Vδ2+NKp30+ T-cell subpopulation might be associated with renal involvement in SLE. CONCLUSION: A broad range of anomalies in the proportions of γδ-T-cell subsets and γδ-T cells in SLE patients may be involved in the pathogenesis of SLE. There is a strong association between Vδ2+ T cells and their Vδ2+NKp30+ T-cell subpopulation and LN occurrence. Our results indicate that γδ-T cells and their subpopulations might be key players in disease immunopathology and renal involvement in SLE.

Supramolecular Switch for the Regulation of Antibacterial Efficacy of Near-Infrared Photosensitizer.

The global antibiotic resistance crisis has drawn attention to the development of treatment methods less prone to inducing drug resistance, such as antimicrobial photodynamic therapy (aPDT). However, there is an increasing demand for new photosensitizers capable of efficiently absorbing in the near-infrared (NIR) region, enabling antibacterial treatment in deeper sites. Additionally, advanced strategies need to be developed to avert drug resistance stemming from prolonged exposure. Herein, we have designed a conjugated oligoelectrolyte, namely TTQAd, with a donor-acceptor-donor (D-A-D) backbone, enabling the generation of reactive oxygen species (ROS) under NIR light irradiation, and cationic adamantaneammonium groups on the side chains, enabling the host-guest interaction with curcubit[7]uril (CB7). Due to the amphiphilic nature of TTQAd, it could spontaneously form nanoassemblies in aqueous solution. Upon CB7 treatment, the positive charge of the cationic adamantaneammonium group was largely shielded by CB7, leading to a further aggregation of the nanoassemblies and a reduced antibacterial efficacy of TTQAd. Subsequent treatment with competitor guests enables the release of TTQAd and restores its antibacterial effect. The reversible supramolecular switch for regulating the antibacterial effect offers the potential for the controlled release of active photosensitizers, thereby showing promise in preventing the emergence of drug-resistant bacteria.

Targeting vulnerable microcircuits in the ventral hippocampus of male transgenic mice to rescue Alzheimer-like social memory loss.

BACKGROUND: Episodic memory loss is a prominent clinical manifestation of Alzheimer's disease (AD), which is closely related to tau pathology and hippocampal impairment. Due to the heterogeneity of brain neurons, the specific roles of different brain neurons in terms of their sensitivity to tau accumulation and their contribution to AD-like social memory loss remain unclear. Therefore, further investigation is necessary. METHODS: We investigated the effects of AD-like tau pathology by Tandem mass tag proteomic and phosphoproteomic analysis, social behavioural tests, hippocampal electrophysiology, immunofluorescence staining and in vivo optical fibre recording of GCaMP6f and iGABASnFR. Additionally, we utilized optogenetics and administered ursolic acid (UA) via oral gavage to examine the effects of these agents on social memory in mice. RESULTS: The results of proteomic and phosphoproteomic analyses revealed the characteristics of ventral hippocampal CA1 (vCA1) under both physiological conditions and AD-like tau pathology. As tau progressively accumulated, vCA1, especially its excitatory and parvalbumin (PV) neurons, were fully filled with mislocated and phosphorylated tau (p-Tau). This finding was not observed for dorsal hippocampal CA1 (dCA1). The overexpression of human tau (hTau) in excitatory and PV neurons mimicked AD-like tau accumulation, significantly inhibited neuronal excitability and suppressed distinct discrimination-associated firings of these neurons within vCA1. Photoactivating excitatory and PV neurons in vCA1 at specific rhythms and time windows efficiently ameliorated tau-impaired social memory. Notably, 1 month of UA administration efficiently decreased tau accumulation via autophagy in a transcription factor EB (TFEB)-dependent manner and restored the vCA1 microcircuit to ameliorate tau-impaired social memory. CONCLUSION: This study elucidated distinct protein and phosphoprotein networks between dCA1 and vCA1 and highlighted the susceptibility of the vCA1 microcircuit to AD-like tau accumulation. Notably, our novel findings regarding the efficacy of UA in reducing tau load and targeting the vCA1 microcircuit may provide a promising strategy for treating AD in the future.

Noise-induced synchrony of two-neuron motifs with asymmetric noise and uneven coupling.

Synchronous dynamics play a pivotal role in various cognitive processes. Previous studies extensively investigate noise-induced synchrony in coupled neural oscillators, with a focus on scenarios featuring uniform noise and equal coupling strengths between neurons. However, real-world or experimental settings frequently exhibit heterogeneity, including deviations from uniformity in coupling and noise patterns. This study investigates noise-induced synchrony in a pair of coupled excitable neurons operating in a heterogeneous environment, where both noise intensity and coupling strength can vary independently. Each neuron is an excitable oscillator, represented by the normal form of Hopf bifurcation (HB). In the absence of stimulus, these neurons remain quiescent but can be triggered by perturbations, such as noise. Typically, noise and coupling exert opposing influences on neural dynamics, with noise diminishing coherence and coupling promoting synchrony. Our results illustrate the ability of asymmetric noise to induce synchronization in such coupled neural oscillators, with synchronization becoming increasingly pronounced as the system approaches the excitation threshold (i.e., HB). Additionally, we find that uneven coupling strengths and noise asymmetries are factors that can promote in-phase synchrony. Notably, we identify an optimal synchronization state when the absolute difference in coupling strengths is maximized, regardless of the specific coupling strengths chosen. Furthermore, we establish a robust relationship between coupling asymmetry and the noise intensity required to maximize synchronization. Specifically, when one oscillator (receiver neuron) receives a strong input from the other oscillator (source neuron) and the source neuron receives significantly weaker or no input from the receiver neuron, synchrony is maximized when the noise applied to the receiver neuron is much weaker than that applied to the source neuron. These findings reveal the significant connection between uneven coupling and asymmetric noise in coupled neuronal oscillators, shedding light on the enhanced propensity for in-phase synchronization in two-neuron motifs with one-way connections compared to those with two-way connections. This research contributes to a deeper understanding of the functional roles of network motifs that may serve within neuronal dynamics.

Traditional Chinese medicine polysaccharide in nano-drug delivery systems: Current progress and future perspectives.

Traditional Chinese medicine polysaccharides (TCMPs) have gained increasing attention in the field of nanomedicine due to their diverse biological activities and favorable characteristics as drug carriers, including biocompatibility, biodegradability, safety, and ease of modification. TCMPs-based nano-drug delivery systems (NDDSs) offer several advantages, such as evasion of reticuloendothelial system (RES) phagocytosis, protection against biomolecule degradation, enhanced drug bioavailability, and potent therapeutic effects. Therefore, a comprehensive review of the latest developments in TCMPs-based NDDSs and their applications in disease therapy is of great significance. This review provides an overview of the structural characteristics and biological activities of TCMPs relevant to carrier design, the strategies employed for constructing TCMPs-based NDDSs, and the versatile role of TCMPs in these systems. Additionally, current challenges and future prospects of TCMPs in NDDSs are discussed, aiming to provide valuable insights for future research and clinical translation.