Recycling Fe and improving organic pollutant removal via in situ forming magnetic core-shell Fe3O4@CaFe-LDH in Fe(II)-catalyzed oxidative wastewater treatment.

Due to its high efficiency, Fe(II)-based catalytic oxidation has been one of the most popular types of technology for treating growing organic pollutants. A lot of chemical Fe sludge along with various refractory pollutants was concomitantly produced, which may cause secondary environmental problems without proper disposal. We here innovatively proposed an effective method of achieving zero Fe sludge, reusing Fe resources (Fe recovery = 100%) and advancing organics removal (final TOC removal > 70%) simultaneously, based on the in situ formation of magnetic Ca-Fe layered double hydroxide (Fe3O4@CaFe-LDH) nano-material. Cations (Ca2+ and Fe3+) concentration (≥ 30 mmol/L) and their molar ratio (Ca:Fe ≥ 1.75) were crucial to the success of the method. Extrinsic nano Fe3O4 was designed to be involved in the Fe(II)-catalytic wastewater treatment process, and was modified by oxidation intermediates/products (especially those with COO- structure), which promoted the co-precipitation of Ca2+ (originated from Ca(OH)2 added after oxidation process) and by-produced Fe3+ cations on its surface to in situ generate core-shell Fe3O4@CaFe-LDH. The oxidation products were further removed during Fe3O4@CaFe-LDH material formation via intercalation and adsorption. This method was applicable to many kinds of organic wastewater, such as bisphenol A, methyl orange, humics, and biogas slurry. The prepared magnetic and hierarchical CaFe-LDH nanocomposite material showed comparable application performance to the recently reported CaFe-LDHs. This work provides a new strategy for efficiently enhancing the efficiency and economy of Fe(II)-catalyzed oxidative wastewater treatment by producing high value-added LDHs materials.

Highly capacitive MXene film by incorporating poly(3,4-ethylenedioxythiophene) hollow spheres prepared through an interfacial oxidation polymerization.

Sheets stacking of Ti3C2Tx MXene dramatically reduces the ion-accessible sites and brings a sluggish reaction kinetics. While introducing transitional metal oxides or polymers in the MXene films could partially alleviate such issue, their enhanced performances are realized at the expense of electrode conductivity or cycling stability. Herein, we report an alternative spacer of conductive poly(3,4-ethylenedioxythiophene) (PEDOT) hollow spheres (HSs) which are fabricated by a facile template-assisted interfacial polymerization. The Fe3+ ions electrostatically adsorbed on the -SO3H groups of the sulfonated polystyrene spheres (S-PS) initiate the polymerization of uniform PEDOT shell, yielding uniform PEDOT HSs after dissolving the S-PS core. Introducing these PEDOT HSs in the MXene film generates the highly flexible MXene-PEDOT (MP) films featuring hierarchically porous network and high conductivity (283 S cm-1). Consequently, specific capacitance of 218 F g-1 at 3  mV s-1, along with a forty-folds decrease in relaxation time constant (1.0 vs 39.8 s) has been achieved. Moreover, the MP film also exhibits nearly thickness-independent capacitive performances with film thickness in the range of 10-46 µm. A maximal energy density of 21.2 µWh cm-2 at 1015 µW cm-2 together with 92 % capacitance retention over 5000 cycles are achieved for the MP-based solid-state supercapacitor. The intrinsic high conductivity, excellent mechanical flexibility and good structure integrity are responsible for such outstanding electrochemical behaviors.

Comparative analysis of internal limiting membrane peeling versus internal limiting membrane flap insertion for treating idiopathic macular holes.

OBJECTIVE: To evaluate the clinical efficacy of internal limiting membrane (ILM) peeling combined with perimacular hole massage versus ILM flap insertion in the management of patients with idiopathic macular holes was conducted. METHODS: 35 patients (total of 35 eyes) with idiopathic macular holes (with hole diameters ranging from 366 to 1430 µm) were divided into two groups-Group A consisted of 20 eyes that underwent pars plana vitrectomy (PPV) combined with ILM peeling and perimacular hole massage, while Group B comprised 15 eyes that underwent PPV combined with ILM flap insertion. Subsequent follow-up examinations were performed at 1 week, 1 month, and 3 months post-surgery. The study also involved a comparison of best corrected visual acuity (BCVA) and optical coherence tomography (OCT) classifications between both the patient groups. RESULTS: The macular hole closure rates in Group A were 60%, while in Group B, the closure rate was 93%. There was significant difference in hiatus healing rate between the two groups (t = 4.843, p = 0.048). The difference in BCVA at 3 months post-operation between the two groups was statistically significant (t = 3.221, p = 0.003). Three months post-operatively, the BCVA in Group B demonstrated improvement compared to the pre-operative BCVA, with a statistically significant difference (p > 0.05). Three months post-operatively, the BCVA in Group A demonstrated improvement compared to the pre-operative BCVA, but this difference was not statistically significant (p > 0.05). CONCLUSION: The combination of PPV with ILM flap insertion demonstrates favorable therapeutic efficacy in the treatment of idiopathic macular holes, leading to improved visual acuity.

Homoharringtonine synergizes with venetoclax in early T cell progenitor acute lymphoblastic leukemia: Bench and bed.

BACKGROUND: Early T cell precursor acute lymphoblastic leukemia (ETP-ALL) is a distinct subtype of T-ALL with a poor prognosis. To find a cure, we examined the synergistic effect of homoharringtonine (HHT) in combination with the BCL-2 inhibitor venetoclax (VEN) in ETP-ALL. METHODS: Using in vitro cellular assays and ETP-ALL xenograft models, we first investigated the synergistic activity of HHT and VEN in ETP-ALL. Next, to explore the underlying mechanism, we employed single-cell RNA sequencing of primary ETP-ALL cells treated with HHT or VEN alone or in combination and validated the results with western blot assays. Based on the promising preclinical results and given that both drugs have been approved for clinical use, we then assessed this combination in clinical practice. FINDINGS: Our results showed that HHT synergizes strongly with VEN both in vitro and in vivo in ETP-ALL. Mechanistic studies demonstrated that the HHT/VEN combination concurrently downregulated key anti-apoptotic proteins, i.e., MCL1, leading to enhanced apoptosis. Importantly, the clinical results were very promising. Six patients with ETP-ALL with either refractory/relapsed (R/R) or newly diagnosed disease were treated with an HHT/VEN-based regimen. All patients achieved complete remission (CR) after only one cycle of treatment. CONCLUSIONS: Our findings demonstrate that a combination of HHT/VEN is effective on ETP-ALL and represents the "backbone" of a promising and safe regimen for newly diagnosed and R/R patients with ETP-ALL. FUNDING: This work was funded by the National Cancer Institute, Gehr Family Foundation, George Hoag Family Foundation, National Natural Science Foundation of China, and Key Research and Development Program of Zhejiang Province of China.

To nap or not? Evidence from a meta-analysis of cohort studies of habitual daytime napping and health outcomes.

Habitual daytime napping is a common behavioral and lifestyle practice in particular countries and is often considered part of a normal daily routine. However, recent evidence suggests that the health effects of habitual daytime napping are controversial. We systematically searched PubMed, Web of Science, Embase, and Cochrane Library databases from inception to March 9, 2024, to synthesize cohort studies of napping and health outcome risk. A total of 44 cohort studies with 1,864,274 subjects aged 20-86 years (mean age 56.4 years) were included. Overall, habitual napping increased the risk of several adverse health outcomes, including all-cause mortality, cardiovascular disease, metabolic disease, and cancer, and decreased the risk of cognitive impairment and sarcopenia. Individuals with a napping duration of 30 min or longer exhibited a higher risk of all-cause mortality, cardiovascular disease, and metabolic disease, whereas those with napping durations less than 30 min had no significant risks. No significant differences in napping and health risks were observed for napping frequency, percentage of nappers, sample size, sex, age, body mass index, follow-up years, or comorbidity status. These findings indicate that individuals with a long napping duration should consider shortening their daily nap duration to 30 min or less.

Deleting an xylosidase-encoding gene VdxyL3 increases growth and pathogenicity of Verticillium dahlia.

Introduction: Verticillium dahliae causes a devastating Verticillium wilt disease on hundreds of plant species worldwide, including cotton. Understanding the interaction mechanism between V. dahliae and its hosts is the prerequisite for developing effective strategies for disease prevention. Methods: Here, based on the previous observation of an xylosidase-encoding gene (VdxyL3) in V. dahliae being obviously up-regulated after sensing root exudates from a cotton variety susceptible to this pathogen, we investigated the function of VdxyL3 in the growth and pathogenesis of V. dahliae by generating its deletion-mutant strains (ΔVdxyL3). Results: Deleting VdxyL3 led to increased colony expansion rate, conidial production, mycelial growth, carbon and nitrogen utilization capacities, and enhanced stress tolerance and pathogenicity of V. dahliae. VdxyL3 is a secretory protein; however, VdxyL3 failed to induce cell death in N. benthamiana based on transient expression experiment. Transcriptomic analysis identified 1300 genes differentially expressed (DEGs) between wild-type (Vd952) and ΔVdxyL3 during infection, including 348 DEGs encoding secretory proteins, among which contained 122 classical secreted proteins and 226 non-classical secreted proteins. It was notable that of the 122 classical secretory proteins, 50 were carbohydrate-active enzymes (CAZymes) and 58 were small cysteine rich proteins (SCRPs), which were required for the pathogenicity of V. dahliae. Conclusion: The RNA-seq data thus potentially connected the genes encoding these proteins to the pathogenesis of V. dahliae. This study provides an experimental basis for further studies on the interaction between V. dahliae and cotton and the pathogenic mechanism of the fungus.

Anthracite-derived porous carbon@MoS2 heterostructure for elevated lithium storage regulated by the middle TiO2 layer.

The rational design of MoS2/carbon composites have been widely used to improve the lithium storage capability. However, their deep applications remain a big challenge due to the slow electrochemical reaction kinetics of MoS2 and weak bonding between MoS2 and carbon substrates. In this work, anthracite-derived porous carbon (APC) is sequential coated by TiO2 nanoparticles and MoS2 nanosheets via a chemical activation and two-step hydrothermal method, forming the unique APC@TiO2@MoS2 ternary composite. The dynamic analysis, in-situ electrochemical impedance spectroscopy as well as theoretical calculation together demonstrate that this innovative design effectively improves the ion/electron transport behavior and alleviates the large volume expansion during cycles. Furthermore, the introduction of middle TiO2 layer in the composite significantly strengthens the mechanical stability of the entire electrode. As expected, the as-prepared APC@TiO2@MoS2 anode displays a high lithium storage capacity with a reversible capacity of 655.8 mAh g-1 after 150 cycles at 200 mA g-1, and robust cycle stability. Impressively, even at a high current density of 2 A g-1, the electrode maintains a superior reversible capacity of 597.7 mAh g-1 after 1100 cycles. This design highlights a feasibility for the development of low-cost anthracite-derived porous carbon-based electrodes.

An Engineered Cellular Carrier Delivers miR-138-5p to Enhance Mitophagy and Protect Hypoxic-Injured Neurons via the DNMT3A/Rhebl1 Axis.

Mitophagy influences the progression and prognosis of ischemic stroke (IS). However, whether DNA methylation in the brain is associated with altered mitophagy in hypoxia-injured neurons remains unclear. Here, miR-138-5p was found to be highly expressed in exosomes secreted by astrocytes stimulated with oxygen and glucose deprivation/re-oxygenation (OGD/R), which could influence the recovery of OGD/R-injured neurons through autophagy. Mechanistically, miR-138-5p promotes the stable expression of Ras homolog enriched in brain like 1(Rhebl1) through DNA-methyltransferase-3a (DNMT3A), thereby enhancing ubiquitin-dependent mitophagy to maintain mitochondrial homeostasis. Furthermore, we employed glycosylation engineering and bioorthogonal click reactions to load mirna onto the surface of microglia and deliver them to injured region utilising the inflammatory chemotactic properties of microglia to achieve drug-targeted delivery to the central nervous system (CNS). Our findings demonstrate miR-138-5p improves mitochondrial function in neurons through the miR-138-5p/DNMT3A/Rhebl1 axis. Additionally, our engineered cell vector-targeted delivery system could be promising for treating IS. STATEMENT OF SIGNIFICANCE: : In this study, we demonstrated that miR-138-5p in exosomes secreted by astrocytes under hypoxia plays a critical role in the treatment of hypoxia-injured neurons. And we find a new target of miR-138-5p, DNMT3A, which affects neuronal mitophagy and thus exerts a protective effect by regulating the methylation of Rbebl1. Furthermore, we have developed a carrier delivery system by combining miR-138-5p with the cell membrane of microglia and utilized the inflammatory chemotactic properties of microglia to deliver this system to the brain via intravenous injection. This groundbreaking study not only provides a novel therapeutic approach for ischemia-reperfusion treatment but also establishes a solid theoretical foundation for further research on targeted drug delivery for central nervous system diseases with promising clinical applications.

Integrated immuno-transcriptomic analysis of ovarian cancer identifies a four-chemokine-dominated subtype with antitumor immune-active phenotype and favorable prognosis.

BACKGROUND: Ovarian cancer (OV) is a heterogeneous disease but has traditionally been treated as an immunologically cold malignancy. The relationship between the immune-active cancer phenotype typified by a T helper 1 (Th-1) immune response and clinical outcome in OV remains uncertain. METHODS: A cohort-scale compendium of transcriptomic data from 2850 OV samples from 19 individual datasets was compiled for integrative immuno-transcriptomic analysis. The immunological constant of rejection was used as a metric to assess the Th-1/cytotoxic response orientation and investigate the clinical-biological significance of immune polarization towards a Th-1 immune response. Single-cell RNA sequencing data from 39 OV samples were analyzed to elucidate the variability of the immune microenvironment, and immunohistochemical validation was performed on 39 samples from the Harbin Medical University Cancer Hospital. RESULTS: Our results demonstrated the prognostic significance of a Th-1/cytotoxic immune profile within the tumor microenvironment (TME) using the immunological constant of rejection classification to OV samples. Specifically, patients with tumors expressing high levels of ICR markers showed significantly improved survival. A gene panel consisting of four chemokines (CXCL9, CXCL10, CXCL11 and CXCL13) was identified as critical players in mediating the establishment of an active T-cell-inflamed antitumor phenotype. This 4-chemokine signature, which was extensively validated in external multicenter cohorts through transcriptomic profiling and in an independent in-house cohort through immunohistochemistry, introduced a novel immune classification in OV and identified a chemokine-dominated subtype associated with an active antitumor immune phenotype and favorable prognosis. Single-cell transcriptomic analysis revealed that chemokine-dominated tumors increase CXCR3 + NK and T cell recruitment to the TME primarily through the overexpression of macrophage-derived CXCL9/10/11. CONCLUSIONS: This study provides new insights into understanding immune heterogeneity within the TME and paves the way for tailoring appropriate therapeutic interventions for patients with differing immune profiles.

Phospholipid peroxidation in macrophage confers tumor resistance by suppressing phagocytic capability towards ferroptotic cells.

Ferroptosis holds significant potential for application in cancer therapy. However, ferroptosis inducers are not cell-specific and can cause phospholipid peroxidation in both tumor and non-tumor cells. This limitation greatly restricts the use of ferroptosis therapy as a safe and effective anticancer strategy. Our previous study demonstrated that macrophages can engulf ferroptotic cells through Toll-like receptor 2 (TLR2). Despite this advancement, the precise mechanism by which phospholipid peroxidation in macrophages affects their phagocytotic capability during treatment of tumors with ferroptotic agents is still unknown. Here, we utilized flow sorting combined with redox phospholipidomics to determine that phospholipid peroxidation in tumor microenvironment (TME) macrophages impaired the macrophages ability to eliminate ferroptotic tumor cells by phagocytosis, ultimately fostering tumor resistance to ferroptosis therapy. Mechanistically, the accumulation of phospholipid peroxidation in the macrophage endoplasmic reticulum (ER) repressed TLR2 trafficking to the plasma membrane and caused its retention in the ER by disrupting the interaction between TLR2 and its chaperone CNPY3. Subsequently, this ER-retained TLR2 recruited E3 ligase MARCH6 and initiated the proteasome-dependent degradation. Using redox phospholipidomics, we identified 1-steaoryl-2-15-HpETE-sn-glycero-3-phosphatidylethanolamine (SAPE-OOH) as the crucial mediator of these effects. Conclusively, our discovery elucidates a novel molecular mechanism underlying macrophage phospholipid peroxidation-induced tumor resistance to ferroptosis therapy and highlights the TLR2-MARCH6 axis as a potential therapeutic target for cancer therapy.

A nucleoside-modified mRNA vaccine forming rabies virus-like particle elicits strong cellular and humoral immune responses against rabies virus infection in mice.

Rabies is a lethal zoonotic disease that threatens human health. As the only viral surface protein, the rabies virus (RABV) glycoprotein (G) induces main neutralizing antibody (Nab) responses; however, Nab titre is closely correlated with the conformation of G. Virus-like particles (VLP) formed by the co-expression of RABV G and matrix protein (M) improve retention and antigen presentation, inducing broad, durable immune responses. RABV nucleoprotein (N) can elicit humoral and cellular immune responses. Hence, we developed a series of nucleoside-modified RABV mRNA vaccines encoding wild-type G, soluble trimeric RABV G formed by an artificial trimer motif (tG-MTQ), membrane-anchored prefusion-stabilized G (preG). Furthermore, we also developed RABV VLP mRNA vaccine co-expressing preG and M to generate VLPs, and VLP/N mRNA vaccine co-expressing preG, M, and N. The RABV mRNA vaccines induced higher humoral and cellular responses than inactivated rabies vaccine, and completely protected mice against intracerebral challenge. Additionally, the IgG and Nab titres in RABV preG, VLP and VLP/N mRNA groups were significantly higher than those in G and tG-MTQ groups. A single administration of VLP or VLP/N mRNA vaccines elicited protective Nab responses, the Nab titres were significantly higher than that in inactivated rabies vaccine group at day 7. Moreover, RABV VLP and VLP/N mRNA vaccines showed superior capacities to elicit potent germinal centre, long-lived plasma cell and memory B cell responses, which linked to high titre and durable Nab responses. In summary, our data demonstrated that RABV VLP and VLP/N mRNA vaccines could be promising candidates against rabies.

Highly Reversible and Dendrite-Free Zinc Anodes Enabled by PEDOT Nanowire Interfacial Layers for Aqueous Zinc-Ion Batteries.

The aqueous zinc-ion batteries (ZIBs) have gained increasing attention because of their high specific capacity, low cost, and good safety. However, side reactions, hydrogen evolution reaction, and uncontrolled zinc dendrites accompanying the Zn metal anodes have impeded the applications of ZIBs in grid-scale energy storage. Herein, the poly(3,4-ethylenedioxythiophene) (PEDOT) nanowires as an interfacial layer on the Zn anode (Zn-PEDOT) are reported to address the above issues. Our experimental results and density functional theory simulation reveal that the interactions between the Zn2+ and S atoms in thiophene rings of PEDOT not only facilitate the desolvation of hydrated Zn2+ but also can regulate the diffusion of Zn2+ along the thiophene molecular chains and induce the dendrite-free deposition of Zn along the (002) surface. Consequently, the Zn||Cu-PEDOT half-cell exhibits highly reversible plating/stripping behavior with an average Coulombic efficiency of 99.7% over 2500 cycles at 1 mA cm-2 and a capacity of 0.5 mAh cm-2. A symmetric Zn-PEDOT cell can steadily operate over 1100 h at 1 mA cm-2 (1 mAh cm-2) and 470 h at 10 mA cm-2 (2 mAh cm-2), outperforming the counterpart bare Zn anodes. Besides, a Zn-PEDOT||V2O5 full cell could deliver a specific capacity of 280 mAh g-1 at 1 A g-1 and exhibits a decent cycling stability, which are much superior to the bare Zn||V2O5 cell. Our results demonstrate that PEDOT nanowires are one of the promising interfacial layers for dendrite-free aqueous ZIBs.

Facial recognition for disease diagnosis using a deep learning convolutional neural network: a systematic review and meta-analysis.

BACKGROUND: With the rapid advancement of deep learning network technology, the application of facial recognition technology in the medical field has received increasing attention. OBJECTIVE: This study aims to systematically review the literature of the past decade on facial recognition technology based on deep learning networks in the diagnosis of rare dysmorphic diseases and facial paralysis, among other conditions, to determine the effectiveness and applicability of this technology in disease identification. METHODS: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for literature search and retrieved relevant literature from multiple databases, including PubMed, on 31 December 2023. The search keywords included deep learning convolutional neural networks, facial recognition, and disease recognition. A total of 208 articles on facial recognition technology based on deep learning networks in disease diagnosis over the past 10 years were screened, and 22 articles were selected for analysis. The meta-analysis was conducted using Stata 14.0 software. RESULTS: The study collected 22 articles with a total sample size of 57 539 cases, of which 43 301 were samples with various diseases. The meta-analysis results indicated that the accuracy of deep learning in facial recognition for disease diagnosis was 91.0% [95% CI (87.0%, 95.0%)]. CONCLUSION: The study results suggested that facial recognition technology based on deep learning networks has high accuracy in disease diagnosis, providing a reference for further development and application of this technology.

[Synergistic effect and compatibility structure of active anti-inflammatory ingredients from Lamiophlomis rotata based on network pharmacology and component structure theory].

The synergistic effect and compatibility structure of active anti-inflammatory ingredients(iridoid glycosides: shanzhiside methylester and 8-O-acetylshanzhiside methyl ester, flavonoid glycoside: luteoloside, and phenylethanoid glycoside: forsythoside B) from Lamiophlomis rotata were explored based on network pharmacology and component structure theory. In network pharmacology, CTD, SwisseTargetPrediction, and PharmMapper databases were used to collect and screen the targets of all active ingredients. The inflammation-related targets were obtained from CTD and GeneCards databases. The core targets were obtained by Venny 2.1.0, STRING, and Cytoscape 3.9.1. Core targets were annotated by the GO function and enriched by the KEGG pathway based on the DAVID database. In terms of component structure, based on a uniform design method and xylene-induced ear swelling model in mice, tumor necrosis factor-α and interleukin-6 were taken as the dependent variables, and the compatibility relationship among anti-inflammatory ingredients from L. rotata was explored through the quadratic polynomial stepwise regression. In addition, in vivo pharmacological experiments were conducted to verify the results. A network pharmacology study showed that compared with a single ingredient, the combined action of the three ingredients can synergistically exert anti-inflammatory effects through more biological processes, pathways, and targets. Component structure study showed that the optimal structural ratio of shanzhiside methylester and 8-O-acetylshanzhiside methyl ester in the iridoid glycoside ingredient was 1.21∶1. The optimal structural ratio among the three types of ingredients(iridoid glycosides∶phenylethanol glycoside∶flavonoid glycoside) was 4.8∶1.6∶1. In conclusion, each anti-inflammatory ingredient from L. rotata can work synergistically, and there is an optimal compatibility ratio relationship among these ingredients. This work provides a new experimental basis for the intrinsic quality control of L. rotata.

Tumour vasculature at single-cell resolution.

Tumours can obtain nutrients and oxygen required to progress and metastasize through the blood supply1. Inducing angiogenesis involves the sprouting of established vessel beds and their maturation into an organized network2,3. Here we generate a comprehensive atlas of tumour vasculature at single-cell resolution, encompassing approximately 200,000 cells from 372 donors representing 31 cancer types. Trajectory inference suggested that tumour angiogenesis was initiated from venous endothelial cells and extended towards arterial endothelial cells. As neovascularization elongates (through angiogenic stages SI, SII and SIII), APLN+ tip cells at the SI stage (APLN+ TipSI) advanced to TipSIII cells with increased Notch signalling. Meanwhile, stalk cells, following tip cells, transitioned from high chemokine expression to elevated TEK (also known as Tie2) expression. Moreover, APLN+ TipSI cells not only were associated with disease progression and poor prognosis but also hold promise for predicting response to anti-VEGF therapy. Lymphatic endothelial cells demonstrated two distinct differentiation lineages: one responsible for lymphangiogenesis and the other involved in antigen presentation. In pericytes, endoplasmic reticulum stress was associated with the proangiogenic BASP1+ matrix-producing pericytes. Furthermore, intercellular communication analysis showed that neovascular endothelial cells could shape an immunosuppressive microenvironment conducive to angiogenesis. This study depicts the complexity of tumour vasculature and has potential clinical significance for anti-angiogenic therapy.

Juvenile bright light exposure ameliorates adult behavioral abnormalities by enhancing neurogenesis in a N-methyl-D-aspartate receptor dysfunction mouse model relevant for cognitive impairment in schizophrenia.

Exposure to light has been demonstrated to stimulate brain regions associated with cognition; however, investigations into its cognitive-enhancing effects have primarily focused on wild-type rodents. This study seeks to elucidate how bright light exposure mitigates cognitive deficits associated with schizophrenia by examining its impact on hippocampal neurogenesis and its potential to alleviate sub-chronic MK-801-induced cognitive impairments in mice. Following three weeks of juvenile bright light exposure (5-8 weeks old), significant increases in proliferating neurons (BrdU+) and immature neurons (DCX+ cells) were observed in the dentate gyrus (DG) and lateral ventricle of MK-801-treated mice. Long-term bright light treatment further promoted the differentiation of BrdU+ cells into immature neurons (BrdU+ DCX+ cells), mature neurons (BrdU+ NeuN+ cells), or astrocytes (BrdU+ GFAP+ cells) in the hippocampal DG. This augmented neurogenesis correlated with the attenuation of sub-chronic MK- 801-induced cognitive deficits, as evidenced by enhancements in Y-maze, novel object recognition (NOR), novel location recognition (NLR), and Morris water maze (MWM) test performances. These findings suggest a promising noninvasive clinical approach for alleviating cognitive impairments associated with neuropsychiatric disorders.

Comparative single-cell analysis reveals IFN-γ as a driver of respiratory sequelae after acute COVID-19.

Postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) represent an urgent public health challenge and are estimated to affect more than 60 million individuals globally. Although a growing body of evidence suggests that dysregulated immune reactions may be linked with PASC symptoms, most investigations have primarily centered around blood-based studies, with few focusing on samples derived from affected tissues. Furthermore, clinical studies alone often provide correlative insights rather than causal mechanisms. Thus, it is essential to compare clinical samples with relevant animal models and conduct functional experiments to understand the etiology of PASC. In this study, we comprehensively compared bronchoalveolar lavage fluid single-cell RNA sequencing data derived from clinical PASC samples and a mouse model of PASC. This revealed a pro-fibrotic monocyte-derived macrophage response in respiratory PASC, as well as abnormal interactions between pulmonary macrophages and respiratory resident T cells, in both humans and mice. Interferon-γ (IFN-γ) emerged as a key node mediating the immune anomalies in respiratory PASC. Neutralizing IFN-γ after the resolution of acute SARS-CoV-2 infection reduced lung inflammation and tissue fibrosis in mice. Together, our study underscores the importance of performing comparative analysis to understand the cause of PASC and suggests that the IFN-γ signaling axis might represent a therapeutic target.

Dual-modal imaging-guided agent based on NIR-II aggregation-induced emission luminogens with balanced phototheranostic performance.

Phototherapy has garnered considerable interest for its potential to revolutionize conventional cancer treatment. Organic materials with near-infrared II (NIR-II, 1000-1700 nm) fluorescence and photothermal effects are key for precise tumor diagnosis and treatment, yet optimizing their output for higher resolution and reduced photodamage remains a challenge. Herein, a multifunctional NIR-II photosensitizer (LSC) has been developed using the aggregation-induced emission (AIE) technology. The utilization of thieno[3,2-b]thiophene as an electron-rich and bulky donor/acceptor bridge has allowed for the elongation of conjugation length and distortion of the AIE main chain. This strategic modification effectively enhances the electron push-pull effect, endowing the LSC with a Stokes shift of over 400 nm and AIE characteristics. We have successfully built-up stable nanoparticles called FA-LSC NPs using a nano-precipitation method. These nanoparticles exhibit high NIR-II fluorescent brightness (ε × QY = 1064 M-1 cm-1) and photothermal conversion efficiency (41%). Furthermore, the biocompatible FA-LSC NPs demonstrate effective tumor accumulation and exceptional photothermal therapeutic efficacy both in vitro and in vivo. These nanoparticles were applied to fluorescence-photothermal dual-mode imaging-guided photothermal ablation in a HeLa tumor xenograft mouse model, resulting in favorable photothermal clearance outcomes.

Development of a diagnostic model for biliary atresia based on MMP7 and serological tests using machine learning.

OBJECTIVE: To develop a machine learning diagnostic model based on MMP7 and other serological testing indicators for early and efficient diagnosis of biliary atresia (BA). METHODS: A retrospective analysis was conducted on patient information from those hospitalized for pathological jaundice at Beijing Children's Hospital between January 1, 2019, and December 31, 2023. Patients with serum MMP7, liver stiffness measurements, and other routine serological tests were included in the study. Six machine learning models were constructed, including logistic regression (LR), random forest (RF), decision tree (DET), support vector machine classifier (SVC), neural network (MLP), and extreme gradient boosting (XGBoost), to diagnose BA. The area under the receiver operating characteristic curve was used to evaluate the diagnostic efficacy of the various models. RESULTS: A total of 98 patients were included in the study, comprising 64 BA patients and 34 patients with other cholestatic liver diseases. Among the six machine learning models, the XGBoost algorithm model and RF algorithm model achieved the best predictive performance, with an AUROC of nearly 100% in both the training and validation sets. In the training set, these two algorithm models achieved an accuracy, precision, recall, F1 score, and AUROC of 1. Through model interpretation analysis, serum MMP7 levels, serum GGT levels, and acholic stools were identified as the most important indicators for diagnosing BA. The nomogram constructed based on the XGBoost algorithm model also demonstrated convenient and efficient diagnostic efficacy. CONCLUSION: Machine learning models, especially the XGBoost algorithm and RF algorithm models, constructed based on preoperative serum MMP7 and serological tests can diagnose BA more efficiently and accurately. The most important influencing factors for diagnosis are serum MMP7, serum GGT, and acholic stools.

Exceptional Rate Performances of Li-Rich Mn-Based Cathodes Enabled by Boron-Based Additives-Driven Self-Optimized Interface.

Li-rich Mn-based cathode material (LRM), as a promising cathode for high energy density lithium batteries, suffers from severe side reactions in conventional lithium hexafluorophosphate (LiPF6)-based carbonate electrolytes, leading to unstable interfaces and poor rate performances. Herein, a boron-based additives-driven self-optimized interface strategy is presented to dissolve low ionic conductivity LiF nanoparticles at the outer cathode electrolyte interface, leading to the optimized interfacial components, as well as the enhanced Li ion migration rate in electrolytes. Being attributed to these superiorities, the LRM||Li battery delivers a high-capacity retention of 92.19% at 1C after 200 cycles and a low voltage decay of 1.08 mV/cycle. This work provides a new perspective on the rational selection of functional additives with an interfacial self-optimized characteristic to achieve a long lifespan LRM with exceptional rate performances.