Improved Protein Removal Performance of PES Hollow-Fiber Ultrafiltration Membrane with Sponge-like Structure.

The research used polyethersulfone (PES) as a membrane material, polyvinylpyrrolidone (PVP) k30 and polyethylene glycol 400 (PEG 400) as water-soluble additives, and dimethylacetamide (DMAc) as a solvent to prepare hollow-fiber ultrafiltration membranes through a nonsolvent-induced phase separation (NIPS) process. The hydrophilic nature of PVP-k30 and PEG caused them to accumulate on the membrane surface during phase separation. The morphology, chemical composition, surface charge, and pore size of the PES membranes were evaluated by SEM, FTIR, zeta potential, and dextran filtration experiments. The paper also investigated how different spinning solution compositions affected membrane morphology and performance. The separation efficiency of membranes with four different morphologies was tested in single-protein and double-protein mixed solutions. The protein separation effectiveness of the membrane was studied through molecular weight cutoff, zeta potential, and static protein adsorption tests. In addition, the operating pressure and pH value were adjusted to improve ultrafiltration process conditions. The PES membrane with an intact sponge-like structure showed the highest separation factor of 11, making it a prime candidate membrane for the separation of bovine serum albumin (BSA) and lysozyme (LYS). The membrane had a minimal static protein adsorption capacity of 48 mg/cm2 and had excellent anti-fouling properties. When pH = 4, the BSA retention rate was 93% and the LYS retention rate was 23%. Furthermore, it exhibited excellent stability over a pH range of 1-13, confirming its suitability for protein separation applications.

Salivary metabolites are promising noninvasive biomarkers of drug-induced liver injury.

BACKGROUND: Drug-induced liver injury (DILI) is one of the most common adverse events of medication use, and its incidence is increasing. However, early detection of DILI is a crucial challenge due to a lack of biomarkers and noninvasive tests. AIM: To identify salivary metabolic biomarkers of DILI for the future development of noninvasive diagnostic tools. METHODS: Saliva samples from 31 DILI patients and 35 healthy controls (HCs) were subjected to untargeted metabolomics using ultrahigh-pressure liquid chromatography coupled with tandem mass spectrometry. Subsequent analyses, including partial least squares-discriminant analysis modeling, t tests and weighted metabolite coexpression network analysis (WMCNA), were conducted to identify key differentially expressed metabolites (DEMs) and metabolite sets. Furthermore, we utilized least absolute shrinkage and selection operato and random fores analyses for biomarker prediction. The use of each metabolite and metabolite set to detect DILI was evaluated with area under the receiver operating characteristic curves. RESULTS: We found 247 differentially expressed salivary metabolites between the DILI group and the HC group. Using WMCNA, we identified a set of 8 DEMs closely related to liver injury for further prediction testing. Interestingly, the distinct separation of DILI patients and HCs was achieved with five metabolites, namely, 12-hydroxydodecanoic acid, 3-hydroxydecanoic acid, tetradecanedioic acid, hypoxanthine, and inosine (area under the curve: 0.733-1). CONCLUSION: Salivary metabolomics revealed previously unreported metabolic alterations and diagnostic biomarkers in the saliva of DILI patients. Our study may provide a potentially feasible and noninvasive diagnostic method for DILI, but further validation is needed.

The EPRS-ATF4-COLI pathway axis is a potential target for anaplastic thyroid carcinoma therapy.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is recognized as the most aggressive and malignant form of thyroid cancer, underscoring the critical need for effective therapeutic strategies to curb its progression and improve patient prognosis. Halofuginone (HF), a derivative of febrifugine, has displayed antitumor properties across various cancer types. However, there is a paucity of published research focused on the potential of HF to enhance the clinical efficacy of treating ATC. OBJECTIVE: In this study, we thoroughly investigated the antitumor effects and mechanisms of HF in ATC, aiming to discover lead compounds for treating ATC and reveal novel therapeutic targets for ATC tumors. METHODS: A series of assays, including CCK8, colony formation, tumor xenograft models, and ATC tumor organoid experiments, were conducted to evaluate the anticancer properties of HF both in vitro and in vivo. Techniques such as drug affinity responsive target stability (DARTS), western blot, immunofluorescence, and immunohistochemistry were employed to pinpoint HF target proteins within ATC. Furthermore, we harnessed the GEPIA and GEO databases and performed immunohistochemistry to validate the therapeutic potential of the glutamyl-prolyl-tRNA-synthetase (EPRS)- activating transcription factor 4 (ATF4)- type I collagen (COLI) pathway axis in the context of ATC. The study also incorporated RNA sequencing analysis, confocal imaging, and flow cytometry to delve into the molecular mechanisms of HF in ATC. RESULTS: HF exhibited a substantial inhibitory impact on cell proliferation in vitro and on tumor growth in vivo. The DARTS results highlighted HF's influence on EPRS within ATC cells, triggering an amino acid starvation response (AASR) by suppressing EPRS expression, consequently leading to a reduction in COLI expression in ATC cells. The introduction of proline mitigated the effect of HF on ATF4 and COLI expression, indicating that the EPRS-ATF4-COLI pathway axis was a focal target of HF in ATC. Analysis of the expression levels of the EPRS, ATF4, and COLI proteins in thyroid tumors, along with an examination of the relationship between COLI expression and thyroid tumor stage, revealed that HF significantly inhibited the growth of ATC tumor organoids, demonstrating the therapeutic potential of targeting the EPRS-ATF4-COLI pathway axis in ATC. RNA sequencing analysis revealed significant differences in the pathways associated with metastasis and apoptosis between control and HF-treated cells. Transwell assays and flow cytometry experiments provided evidence of the capacity of HF to impede cell migration and induce apoptosis in ATC cells. Furthermore, HF hindered cell metastasis by suppressing the epithelial-mesenchymal transition (EMT) pathway, acting through the inhibition of FAK-AKT-NF-κB/Wnt-ß-catenin signaling and restraining angiogenesis via the VEGF pathway. HF also promoted apoptosis through the mitochondrial apoptotic pathway. CONCLUSION: This study provided inaugural evidence suggesting that HF could emerge as a promising therapeutic agent for the treatment of ATC. The EPRS-ATF4-COLI pathway axis stood out as a prospective biomarker and therapeutic target for ATC.

Grandmother-grandchild physiological synchrony in Chinese three-generation families: Links with child emotion regulation.

The current study examined the characteristics of physiological synchrony between grandmothers and grandchildren in Chinese three-generation families, and the associations between physiological synchrony and child emotion regulation. The participants included 92 children (age 8-10-year old) and their grandmothers. Respiratory sinus arrhythmia (RSA) was collected from both grandmothers and their grandchildren throughout a collaborative drawing task and a conflict discussion task. Child emotion regulation was measured using the Children's Emotional Management Scale. We found no evidence for an overall pattern of concordant or discordant synchrony within dyads. Instead, there was great variability in patterns of synchrony across dyads. During the collaborative drawing task, concordance in grandmother's RSA and grandchildren's subsequent RSA was linked with better emotion regulation. During the conflict discussion, concordance in grandmother's RSA and grandchildren's simultaneous RSA was linked with poorer emotion regulation. These results suggest that grandmother-grandchild synchrony in different directions, time lags, and contexts has different influences on children's emotion regulation. The findings of this study highlight the importance of contextual physiological co-regulation between Chinese children and their grandmothers for children's social-emotional development.

Recent progress of UCNPs-MoS2 nanocomposites as a platform for biological applications.

Composite materials can take advantages of the functional benefits of multiple pure nanomaterials to a greater degree than single nanomaterials alone. The UCNPs-MoS2 composite is a nano-application platform that combines upconversion luminescence and photothermal properties. Upconversion nanoparticles (UCNPs) are inorganic nanomaterials with long-wavelength excitation and short-wavelength tunable emission capabilities, and are able to effectively convert near-infrared (NIR) light into visible light for increased photostability. However, UCNPs have a low capacity for absorbing visible light, whereas MoS2 shows better absorption in the ultraviolet and visible regions. By integrating the benefits of UCNPs and MoS2, UCNPs-MoS2 nanocomposites can convert NIR light with a higher depth of detection into visible light for application with MoS2 through fluorescence resonance energy transfer (FRET), which compensates for the issues of MoS2's low tissue penetration light-absorbing wavelengths and expands its potential biological applications. Therefore, starting from the construction of UCNPs-MoS2 nanoplatforms, herein, we review the research progress in biological applications, including biosensing, phototherapy, bioimaging, and targeted drug delivery. Additionally, the current challenges and future development trends of UCNPs-MoS2 nanocomposites for biological applications are also discussed.

Bilateral Focal Choroidal Excavation and Central Serous Chorioretinopathy Coexisting in a Male Patient.

Background: Here, we report a case of a male patient with bilateral focal choroidal excavation (FCE) and central serous chorioretinopathy (CSC). A 33-year-old man complained of mild blurring of vision in the right eye. Optical coherence tomography (OCT) revealed FCE in both eyes, with subretinal fluid in both eyes and serous pigment epithelial detachment in the right eye. Standard laser fluence (50 J/cm2) was used in the right eye, and a subthreshold micropulse laser (SML) was simultaneously used in the left eye. Follow-up visits were recommended. At his last visit (5 months after treatment), the visual acuity was 16/20 in the right eye and 20/20 in the left eye and OCT showed a completed resolution of SRF. Conclusion: FCE is defined as a localized depression of the choroid detected by OCT. It may be congenital or acquired secondarily. We present a case of uncommon focal choroidal excavation and central serous chorioretinopathy (CSC) coexisting in both eyes at a relatively young age in which visual acuity was improved and subretinal fluid (SRF) completely resolved with laser treatment. Timely treatment can promote SRF absorption and improve vision.

Clinical Features and Prognostic Analysis of MuSK-Antibody-Positive Myasthenia Gravis versus Double-Seropositive Myasthenia Gravis: A Single-Center Study from Central South China.

Purpose: To decipher the discrepancies between muscle-specific kinase antibody-positive myasthenia gravis (MuSK-MG) and double-seropositive myasthenia gravis (DSP-MG), and to determine prognostic factors for minimal manifestation status (MMS) achievement in MG patients with MuSK autoantibodies (MuSK-Ab). Patients and Methods: A total of 34 MG patients seropositive for MuSK-Ab were enrolled in this study. The demographic and clinical features were compared between MuSK-MG (n = 28) and DSP-MG (n = 6) patients, and factors affecting MMS induction in all patients with MuSK-Ab were identified using Cox regression analysis. Results: Compared to MuSK-MG patients, those with DSP-MG had similar clinical characteristics, except that they had a lower frequency of bulbar muscle involvement at nadir (50% vs 92.9%; P = 0.029) and higher proportions of comorbidities with diabetes mellitus (33.3% vs 0%; P = 0.027) and thymic abnormalities (33.3% vs 0%; P = 0.027). Higher MG Activities of Daily Living (MG-ADL) scores (HR = 0.16, 95% CI: 0.037-0.7, P = 0.015) and axial muscle involvement at nadir (HR = 0.39, 95% CI: 0.16-0.94, P = 0.035) were negative prognostic factors for MMS achievement in patients with MuSK-Ab regardless of acetylcholine receptor antibody (AChR-Ab) positivity. Multivariable Cox regression analysis further established higher MG-ADL scores at the nadir (HR = 0.19, 95% CI: 0.04-0.94; P = 0.042) as an independent risk factor for MMS achievement. Conclusion: DSP-MG was comparable to MuSK-MG and could be considered a single entity in our cohort. In all MG patients with MuSK-Ab, a higher MG-ADL score at nadir may herald a lower chance of MMS achievement, with no observed potential effect of AChR-Ab presence.

[Research progress in surgical treatment of avascular necrosis of talus].

Objective: To summarize the surgical treatment methods for avascular necrosis of the talus. Methods: The recent domestic and international literature related to avascular necrosis of the talus was extensively conducted. The pathogenesis, surgical treatment methods, and prognosis were summarized. Results: The clinical symptoms of avascular necrosis of the talus at early stage are not obvious, and most patients have progressed to Ficat-Arlet stages Ⅲ-Ⅳ and require surgical treatment. Currently, surgical treatments for this disease include core decompression, vascularized bone flap transplantation, arthroplasty, and arthrodesis, etc. Early avascular necrosis of the talus can be treated conservatively, and if treatment fails, core decompression can be considered. Arthrodesis is a remedial surgery for patients with end-stage arthritis and collapse, and in cases of severe bone loss, tibiotalocalcaneal arthrodesis and bone grafting are required. Vascularized bone flap transplantation is effective and plays a role in all stages of avascular necrosis of the talus, but the appropriate donor area for the flap still needs further to be studied. Conclusion: The surgical treatment and the system of treatment for different stages of avascular necrosis of the talus still need to be refined.

Distribution and correlation of refractive parameters in children with different corneal curvatures in southeast China.

AIM: To analyze the distribution of refractive status in school-age children with different corneal curvatures (CC) and the correlation between CC and refractive status. METHODS: A total of 2214 school-aged children of grade 4 in Hangzhou who were screened for school myopia were included. Uncorrected distance visual acuity (UCDVA), non-cycloplegic refraction, axial length (AL), horizontal and vertical corneal curvature (K1, K2) were measured and spherical equivalent (SE), corneal curvature radius (CCR) and axial length/corneal radius of curvature ratio (AL/CR) were calculated. UCDVA<5.0 and SE≤-0.50 D were classified as school-screening myopia. According to the different CCRs, the patients were divided into the lower corneal curvature (LCC) group (CCR≥7.92) and the higher corneal curvature (HCC) group (CCR<7.92). Each group was further divided into the normal AL subgroup and the long AL subgroup. The refractive parameters were compared to identify any differences between the two groups. RESULTS: Both SE and AL were greater in the LCC group (P=0.013, P<0.001). The prevalence of myopia was 38% in the LCC group and 44% in the HCC group (P<0.001). The proportion of children without screening myopia was higher in the LCC group (62%) than in the HCC group (56%). Among these children without screening myopia, the proportion of long AL in the LCC group (24%) was significantly higher than that in the HCC group (0.012%; P<0.001). The change of SE in the LCC group was less affected by the increase of AL than that in the HCC group. CONCLUSION: School-aged children in the LCC group have a lower incidence of screening myopia and longer AL. Low CC can mask SE reduction and AL growth to some extent, and the change of AL growth change more in children with low CC than high CC. Before the onset of myopia, its growth rate is even faster than that after the onset of myopia.

Clinical diagnostic value of contrast-enhanced ultrasound combined with microflow imaging in benign and malignant renal tumors: A retrospective cohort study.

This study aims to evaluate the clinical diagnostic value of contrast-enhanced ultrasound combined with microflow imaging (CEUS-MFI) in the differential diagnosis of benign and malignant renal tumors. All patients underwent CEUS, MFI, color doppler flow imaging (CDFI), and CEUS-MFI. The efficacies of these different diagnostic modalities in diagnosing benign and malignant renal tumors were evaluated by Kappa consistency test and the receiver operating characteristic (ROC) curve, with pathological findings serving as the gold standard. CDFI, MFI and CEUS-MFI all demonstrated higher blood flow in malignant tumors compared with benign tumors. Compared with benign tumors, CDFI detected a higher rate of punctate and linear Adler grade 2 and 3 blood flows in malignant tumors, as well as peripheral semicircular or annular blood flow. MFI identified a high rate of peripheral circumferential blood flow and irregular vascular morphology in malignant tumors, with most exhibiting Adler grade 3 blood flow. In addition, CEUS-MFI showed more dendritic or irregular Adler grade 2 or 3 blood flows in malignant renal tumors than MFI alone. Further analysis showed that CEUS-MFI had the highest consistency with pathological diagnosis (Kappa = 0.808). The ROC curve showed that the area under the curve (AUC) for CEUS-MFI in differentiating between benign and malignant lesions was 0.898, significantly outperforming other single diagnostic methods. With its capability to display microvascular information and assess overall pathological characteristics, MFI can accurately predict the nature of renal tumors and assist in surgical planning.

Triclocarban and triclosan promote breast cancer progression in vitro and in vivo via activating G protein-coupled estrogen receptor signaling pathways.

Triclocarban (TCC) and triclosan (TCS) have been detected ubiquitously in human body and evoked increasing concerns. This study aimed to reveal the induction risks of TCC and TCS on triple negative breast cancer through non-genomic GPER-mediated signaling pathways. Molecular simulation indicated that TCC exhibited higher GPER binding affinity than TCS theoretically. Calcium mobilization assay displayed that TCC/TCS activated GPER signaling pathway with the lowest observed effective concentrations (LOEC) of 10 nM/100 nM. TCC and TCS also upregulated MMP-2/9, EGFR, MAPK3 but downregulated MAPK8 via GPER-mediated signaling pathway. Proliferation assay showed that TCC/TCS induced 4 T1 breast cancer cells proliferation with the LOEC of 100 nM/1000 nM. Wound-healing and transwell assays showed that TCC/TCS promoted 4 T1 cells migration in a concentration-dependent manner with the LOEC of 10 nM. The effects of TCC on breast cancer cells proliferation and migration were stronger than TCS and both were regulated by GPER. TCC/TCS induced migratory effects were more significantly than proliferative effect. Mechanism study showed that TCC/TCS downregulated the expression of epithelial marker (E-cadherin) but upregulated mesenchymal markers (snail and N-cadherin), which was reversed by GPER inhibitor G15. These biomarkers results indicated that TCC/TCS-induced 4 T1 cells migration was a classic epithelial to mesenchymal transition mechanism regulated by GPER signaling pathway. Orthotopic tumor model verified that TCC promoted breast cancer in-situ tumor growth and distal tissue metastasis via GPER-mediated signaling pathway at human-exposure level of 10 mg/kg/d. TCC-induced tissue metastasis of breast cancer was more significantly than in-situ tumor growth. Overall, we demonstrated for the first time that TCC/TCS could activate the GPER signaling pathways to induce breast cancer progression.

Crystalline Olefin-Linked Chiral Covalent Organic Frameworks as a Platform for Asymmetric Catalysis.

The construction of olefin-linked chiral covalent organic frameworks (COFs) with high crystallinity is highly desirable while remains great challenge due to the poor reversibility of the formation reaction for the olefin linkages during the in situ structural self-healing process. Herein, we successfully synthesized two sets of enantiomeric olefin-linked COFs. The chiral catalytic groups are uniformly distributed on the pore walls of COFs, resulting in the full exposure of catalytic sites to the reactants in asymmetric catalysis. The as-prepared (R)/(S)-CCOF8 exhibits excellent catalytic performance with exceeding 99% enantiomeric excess in the enantioselective electrophilic amination reaction. Moreover, the heterogeneous chiral catalysts are conveniently recycled and could maintain the performance after ten catalytic cycles. Our findings expand the scope to construct stable and crystalline chiral COFs for the asymmetric catalysis.

Unveiling the magic of mega-city block environments: investigating the intriguing mechanisms shaping children's spontaneous play preferences.

Introduction: This study delves into the spatial preferences of children for play spaces within high-density urban block environments, specifically targeting the area of Baihua Second Road in Shenzhen, China. Methods: Recognizing the critical role of play in children's development, and the unique challenges posed by dense urban settings, this research employs multiclass logistic regression models and negative binomial regression models to construct a detailed mathematical analysis of neighborhood spatial elements and children's play space preferences. Data was meticulously gathered through both objective observations of 14 different types of spaces within the block, and subjective assessments via children's responses to a series of environment photos, capturing the essence of over 3,000 child participants' interactions and choices. Results: Key findings reveal a pronounced preference among children for soft facility features and visually appealing spatial experiences, suggesting a nuanced understanding of play space needs beyond traditional playground designs. Notably, the study identifies that while cartoon-style designs in play facilities might increase moderate attractiveness, ordinary designs hold broader appeal, indicating a preference for diversity in play space aesthetics. These insights offer profound implications for urban planners and designers, advocating for a child-centered approach in the creation of urban play environments that prioritize aesthetic diversity, and the integration of natural elements. Conclusion: Moreover, the study situates Baihua Second Road as a paradigmatic case, illustrating the methodology and analytical framework applied in addressing the complex interplay between children's play preferences and urban spatial configurations. By incorporating a comprehensive data-driven analysis, this research contributes significantly to the discourse on child-friendly urban design, offering valuable strategies for cultivating inclusive and engaging urban play spaces for children amidst the constraints of high-density city living.

Carbon emissions changes of animal husbandry in China: Trends, attributions, and solutions: A spatial shift-share analysis.

China is a major livestock producer confronting the dual challenges of rising demand for animal-based food consumption and decreasing carbon emissions. To effectively address these issues, it is crucial to understand the trends of carbon emissions from animal husbandry and the competitive advantages of carbon emission reduction in different regions. This study uses panel data from 31 provinces from 2004 to 2020 to investigate the contributing factors to carbon emissions and explore ways to reduce carbon intensity in animal husbandry. The analysis employs spatial shift-share analysis and the spatial Durbin model. Our findings indicate that life-cycle carbon emissions associated with animal husbandry in China decreased from 572.411 Mt CO2eq to 520.413 Mt CO2eq over time, with an average annual decline of 0.568 %. The annual contribution of output value and internal industry-mix adjustment to carbon emission growth is 22.639 MT CO2eq and 6.226 MT CO2eq, respectively. On the other hand, the annual contribution of carbon efficiency improvement to carbon emission reduction is much higher, at 36.316 MT CO2eq. However, there is significant regional heterogeneity in the spatial decomposition of the carbon efficiency change component. The Northeastern region, Northwest and along the Great Wall demonstrate neighborhood advantages in enhancing carbon efficiency. In contrast, the South China and Southwest regions rely more on local carbon efficiency advantages to reduce the carbon intensity of animal husbandry. Furthermore, the carbon intensity in local and neighboring areas can be reduced through environmental regulations and industrial agglomeration. While technical progress significantly negatively impacts carbon intensity in neighboring regions, it does not contribute to reducing the carbon intensity of local animal husbandry. The findings provide valuable insights for local governments, aiding them in recognizing the pros and cons of carbon reduction in animal husbandry and strengthening regional cooperation in emission reduction management.

Case report: A novel PTCH1 frameshift mutation leading to nevoid basal cell carcinoma syndrome.

A patient presenting with several basal cell carcinomas, pigmented nevi, and developmental defects was diagnosed with nevoid basal cell carcinoma syndrome. Gene panel sequencing and Sanger sequencing were used to identify a novel heterozygous frameshift mutation, c.1312dupA:p.Ser438Lysfs, in exon 9 of PTCH1. I-Tasser and PyMol analyses indicated that the mutated protein patched homolog 1 (PTCH1) lacked 12 transmembrane domains and the intracellular and extracellular rings of ECD2 compared with the wild-type protein, resulting in a remarkably different structure from that of the wild-type protein. This case extends our knowledge of the mutation spectrum of NBCCS.

A virtuous cycle between meaning in daily life and state mindfulness as well as the unique role of depression among young adults: A diary study.

The positive association between meaning in life (MIL) and mindfulness has been supported; however, previous research has been limited to the trait level. To explore the dynamics of mindfulness and MIL in the state level, the present study used the experience sampling method (ESM) and conducted a dynamic structural equation model (DSEM). In addition, we examined the moderation of baseline depression in this dynamic relationship and the protective role of the dynamics on depression. We recruited 184 college students (Mage = 21.58, 33.15% male), who reported three times a day for 14 consecutive days, and analyzed the 7726 collected responses. Firstly, a virtuous cycle between mindfulness and MIL was proven. Besides, the baseline depressive symptoms moderated the predictive of mindfulness on MIL, suggesting state mindfulness gave people with more depressive symptoms more meaningful in daily life. Lastly, the result also demonstrated the positive prediction of mindfulness on MIL and alleviated the worsening of depressive symptoms within 2 weeks. The findings extended the relationship between MIL and mindfulness from trait level to state level, enriching the self-determination theory, and examined the unique effect of depressive symptoms in the dynamics.

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.

Transmission of depressive symptoms in the nuclear family: a cross-sectional and cross-lagged network perspective.

Children are more likely to develop depressive symptoms in families where parents have depressive symptoms. By conceptualizing the individual depressive symptom network of each family member as a whole, this study proposes a family symptom network model, and explored the mechanisms of transmission of depression within nuclear families at the symptom level. This study used four waves (2012, 2016, 2018, 2020) of data from the China Family Panel Studies (CFPS), which in wave one contained a representative sample of 1963 children (1038 boys; age = 12.60), 4763 mothers and 4614 fathers from China. Children with their parents completed the Center for Epidemiology Studies Depression Scale at each wave. Individual depressive symptom networks among children, fathers, and mothers were highly similar and stable across time. When considering depressive symptoms of all family members as a whole, there was a wide range of associations between child, father, and mother depressive symptom networks. The results of the cross-lagged network model suggest the bidirectional relationships between couples and parent-child depression. The current study provides preliminary validation of the family symptom network model. The model represents a further integration and extension of network theory of mental disorders and family systems theory, and points out the limitations of studying the intergenerational transmission of depression from a latent variable perspective. Thus, the family symptom network model proposed in this study could provide valuable new insights into understanding the intergenerational transmission of depression.

Different Valence States of Copper Ion Delivery against Triple-Negative Breast Cancer.

Different valence states of copper (Cu) ions are involved in complicated redox reactions in vivo, which are closely related to tumor proliferation and death pathways, such as cuproptosis and chemodynamic therapy (CDT). Cu ion mediated Fenton-like reagents induced tumor cell death which presents compelling attention for the CDT of tumors. However, the superiority of different valence states of Cu ions in the antitumor effect is unknown. In this study, we investigated different valence states of Cu ions in modulating tumor cell death by Cu-chelated cyanine dye against triple-negative breast cancer. The cuprous ion (Cu+) and copper ion (Cu2+) were chelated with four nitrogen atoms of dipicolylethylenediamine-modified cyanine for the construction of Cu+ and Cu2+ chelated cyanine dyes (denoted as CC1 and CC2, respectively). Upon 660 nm laser irradiation, the CC1 or CC2 can generate reactive oxygen species, which could disrupt the cyanine structure, achieving the rapid release of Cu ions and initiating the Fenton-like reaction for CDT. Compared with Cu2+-based Fenton-like reagent, the CC1 with Cu+ exhibited a better therapeutic outcome for the tumor due to there being no need for a reduction by glutathione and a shorter route to generate more hydroxyl radicals. Our findings suggest the precision delivery of Cu+ could achieve highly efficient antitumor therapy.

Association and predictive value of contrast­enhanced ultrasound features with axillary lymph node metastasis in primary breast cancer.

Primary breast cancer is the most common malignant tumor in women worldwide, and axillary lymph node metastasis (ALNM) is an important marker of disease progression in patients with breast cancer. The objective of the present study was to analyze the association between contrast-enhanced ultrasound (CEUS) features and ALNM in primary breast cancer and its predictive value. A total of 120 patients with breast cancer were assigned to the non-metastatic group (n=70) and metastatic group (n=50). The factors influencing ALNM were explored by multivariate logistic regression analysis. The consistency of CEUS, ordinary ultrasonography and pathological examination in the diagnosis of the ALNM of breast cancer was evaluated by consistency testing. The sensitivity, specificity and consistency rate of CEUS features and ordinary ultrasonography were analyzed by receiver operating characteristic curve and four-fold table analyses. High enhancement amplitude, centripetal enhancement sequence, increased maximum cortical thickness, high peak intensity and a larger area under the curve of lymph nodes were more commonly found in the metastatic group than in the non-metastatic group. The lymph node aspect ratio and time to peak were lower in the metastatic group than the non-metastatic group. The time to peak was a protective factor for ALNM in patients with breast cancer. The sensitivity, specificity and coincidence rate with pathological examination of CEUS in the diagnosis of ALNM were 92.00, 90.00 and 90.83%, while these of ordinary ultrasonography were 76.00, 80.00 and 78.33%, respectively. The consistency test indicated that CEUS and pathological examination were consistent in the diagnosis of ALNM in patients with breast cancer, with a κ value of 0.816, indicating a good consistency. The κ value of ordinary ultrasonography and pathological examination was 0.763, also indicating a good consistency. However, these results indicate that CEUS is more valuable than ordinary ultrasonography in the diagnosis of ALNM in cases of breast cancer. In conclusion, the present study indicates that CEUS features were influencing factors associated with ALNM in patients with breast cancer and may serve as an important reference for the preoperative prediction of ALNM in breast cancer.