Non-Clinical Safety Evaluation of Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells in Cynomolgus Monkeys.

Purpose: In recent years, exosomes have been proved to be used to treat many diseases. However, due to the lack of uniform quality control standards for exosomes, the safety of exosomes is still a problem to be solved, especially now more and more exosomes are used in clinical trials, and its non-clinical safety evaluation is particularly important. However, there is no safety evaluation standard for exosomes at present. Therefore, this study will refer to the evaluation criteria of therapeutic biological products, adopt non-human primates to evaluate the non-clinical safety of human umbilical cord mesenchymal stem cell exosomes from the general pharmacology and immunotoxicity, aiming at establishing a safety evaluation system of exosomes and providing reference for the clinical application of exosomes in the future. Methods: 3.85 × 1012 exosomes derived from human umbilical cord mesenchymal stem cells were injected into cynomolgus monkeys intravenously. The changes of general clinical conditions, hematology, immunoglobulin, Th1/Th2 cytokines, T lymphocytes and B lymphocytes, and immune organs were observed before and within 14 days after injection. Results: The results showed that exosomes did not have obvious pathological effects on the general clinical conditions, blood, coagulation function, organ coefficient, immunoglobulin, Th1/Th2 cytokines, lymphocytes, major organs, and major immune organs (spleen, thymus, bone marrow) of cynomolgus monkeys. However, the number of granulocyte-macrophage colonies in exosomes group was significantly higher than that in control group. Conclusion: To sum up, the general pharmacological results and immunotoxicity results showed that the injection of 3.85 × 1012 exosomes may have no obvious adverse reactions to cynomolgus monkeys. This dose of exosomes is relatively safe for treatment, which provides basis research for non-clinical safety evaluation of exosomes and provides reliable research basis for future clinical application of exosomes.

Controlled NiOx Defect Engineering to Harnessing Redox Reactions in Perovskite Photovoltaic Cells via Atomic Layer Deposition.

Albeit the undesirable attributes of NiOx, such as low conductivity, unmanageable defects, and redox reactions occurring at the perovskite/NiOx interface, which impede the progress in inverted perovskite solar cells (i-PSCs), it is the most favorable choice of technology for industrialization of PSCs. In this study, we propose a novel Ni vacancy defect modulate approach to leverage the conformal growth and surface self-limiting reaction characteristics of the atomic layer deposition (ALD)-fabricated NiOx by varying the O2 plasma injection time (tOE) to induce self-doping. Consequently, NiOx thin films with enhanced conductivity, an appropriate Ni3+/Ni2+ ratio, stable surface states, and ultrathinness are realized as hole-transporting layers (HTLs) in p-i-n PSCs. As a result of these improvements, ALD-NiOx-based devices exhibit the highest power conversion efficiency (PCE) of 19.86% and a fill factor (FF) of 81.86%. Notably, the optimal interfacial defects effectively suppressed the severe reaction between the perovskite and NiOx. This suppression is evidenced by the lowest decay rate observed in a harsh environment, lasting for 500 consecutive hours. The proposed approach introduces the possibility of a hierarchical distribution of defects and offers feasibility for the fabrication of large-area, uniform, and high-quality films.

Zanubrutinib delays selinexor resistance evolution in biopsy sample-derived primary central nervous system lymphoma models.

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive lymphoma of the brain with poor prognosis. The scarcity of cell lines established using PCNSL makes it difficult to conduct preclinical studies on new drugs. We aimed to explore the effect of selinexor combined with zanubrutinib in PCNSL using established PCNSL cells and an orthotopic PCNSL model. Primary PCNSL cells were successfully cultured. Selinexor inhibited proliferation, induced G1 phase arrest, and promoted apoptosis, however, induced drug resistance in PCNSL. Selinexor combined with zanubrutinib had a synergistic effect on PCNSL and prevented the onset of selinexor resistance in PCNSL by inhibiting AKT signaling. Moreover, selinexor combined with zanubrutinib notably slowed tumor growth and prolonged survival compared to that of the control. Overall, the addition of zanubrutinib to selinexor monotreatment had a synergistic effect in vitro and prolonged survival in vivo.

Cel-CS1K: A Celastrol-Chitosan Conjugate for Treating Diet-Induced Obesity.

Celastrol (Cel), extracted from Tripterygium wilfordii Hook, is a potential antiobesity drug, except for its adverse reactions in clinic. In the present study, we synthesized a promising celastrol-chitosan conjugate (Cel-CS1K) and evaluated its antiobesity effect and biological safety in diet-induced obese mice. Cel-CS1K showed higher drug loading (over 10 wt %), good solubility (18-19 mg/mL) in water, slower peak time (Tmax = 4 h), and clearance (T1/2 = 8.97 h) in rats. Cel-CS1K effectively attenuated the cytotoxicity, celastrol-induced apoptosis, and fat accumulation of hepatocytes. Cel-CS1K reduced body weight and dietary amount same as the free Cel but with lower toxicity in blood, liver, and testis. Cel-CS1K improved the glucose homeostasis, HDL-C level, insulin sensitivity, and leptin sensitivity, while it significantly reduced the gene expression levels of LDL-C, TG, and TC in obese mice. Furthermore, the adipose-related gene expression levels provided evidence in support of a role for Cel-CS1K in losing weight by the multimode regulation. Overall, Cel-CS1K provides a translatable therapeutic strategy for the treatment of diet-induced obese humans.

Realization of fractional quantum Hall state with interacting photons.

Fractional quantum Hall (FQH) states are known for their robust topological order and possess properties that are appealing for applications in fault-tolerant quantum computing. An engineered quantum platform would provide opportunities to operate FQH states without an external magnetic field and enhance local and coherent manipulation of these exotic states. We demonstrate a lattice version of photon FQH states using a programmable on-chip platform based on photon blockade and engineering gauge fields on a two-dimensional circuit quantum electrodynamics system. We observe the effective photon Lorentz force and butterfly spectrum in the artificial gauge field, a prerequisite for FQH states. After adiabatic assembly of Laughlin FQH wave function of 1/2 filling factor from localized photons, we observe strong density correlation and chiral topological flow among the FQH photons. We then verify the unique features of FQH states in response to external fields, including the incompressibility of generating quasiparticles and the smoking-gun signature of fractional quantum Hall conductivity. Our work illustrates a route to the creation and manipulation of novel strongly correlated topological quantum matter composed of photons and opens up possibilities for fault-tolerant quantum information devices.

Coenzyme Q10 prevents RANKL-induced osteoclastogenesis by promoting autophagy via inactivation of the PI3K/AKT/mTOR and MAPK pathways.

Coenzyme Q10 (CoQ10) is a potent antioxidant that is implicated in the inhibition of osteoclastogenesis, but the underlying mechanism has not been determined. We explored the underlying molecular mechanisms involved in this process. RAW264.7 cells received receptor activator of NF-κB ligand (RANKL) and CoQ10, after which the differentiation and viability of osteoclasts were assessed. After the cells were treated with CoQ10 and/or H2O2 and RANKL, the levels of reactive oxygen species (ROS) and proteins involved in the PI3K/AKT/mTOR and MAPK pathways and autophagy were tested. Moreover, after the cells were pretreated with or without inhibitors of the two pathways or with the mitophagy agonist, the levels of autophagy-related proteins and osteoclast markers were measured. CoQ10 significantly decreased the number of TRAP-positive cells and the level of ROS but had no significant impact on cell viability. The relative phosphorylation levels of PI3K, AKT, mTOR, ERK, and p38 were significantly reduced, but the levels of FOXO3/LC3/Beclin1 were significantly augmented. Moreover, the levels of FOXO3/LC3/Beclin1 were significantly increased by the inhibitors and mitophagy agonist, while the levels of osteoclast markers showed the opposite results. Our data showed that CoQ10 prevented RANKL-induced osteoclastogenesis by promoting autophagy via inactivation of the PI3K/AKT/mTOR and MAPK pathways in RAW264.7 cells.

Prediction of hypoattenuating leaflet thickening in patients underwent transcatheter aortic valves replacement based on clinical factors and 4D-computed tomography morphological characteristics: A retrospective cross-sectional study.

BACKGROUND: The rapid increase in the number of transcatheter aortic valve replacement (TAVR) procedures in China and worldwide has led to growing attention to hypoattenuating leaflet thickening (HALT) detected during follow-up by 4D-CT. It's reported that HALT may impact the durability of prosthetic valve. Early identification of these patients and timely deployment of anticoagulant therapy are therefore particularly important. METHODS: We retrospectively recruited 234 consecutive patients who underwent TAVR procedure in Fuwai Hospital. We collected clinical information and extracted morphological characteristics parameters of the transcatheter heart valve (THV) post TAVR procedure from 4D-CT. LASSO analysis was conducted to select important features. Three models were constructed, encapsulating clinical factors (Model 1), morphological characteristics parameters (Model 2), and all together (Model 3), to identify patients with HALT. Receiver operating characteristic (ROC) curves and decision curve analysis (DCA) were plotted to evaluate the discriminatory ability of models. A nomogram for HALT was developed and verified by bootstrap resampling. RESULTS: In our study patients, Model 3 (AUC = 0.738) showed higher recognition effectiveness compared to Model 1 (AUC = 0.674, p = 0.032) and Model 2 (AUC = 0.675, p = 0.021). Internal bootstrap validation also showed that Model 3 had a statistical power similar to that of the initial stepwise model (AUC = 0.723 95%CI: 0.661-0.786). Overall, Model 3 was rated best for the identification of HALT in TAVR patients. CONCLUSION: A comprehensive predictive model combining patient clinical factors with CT-based morphology parameters has superior efficacy in predicting the occurrence of HALT in TAVR patients.

Twist angle-dependent valley polarization switching in heterostructures.

The twist engineering of moiré superlattice in van der Waals heterostructures of transition metal dichalcogenides can manipulate valley physics of interlayer excitons (IXs), paving the way for next-generation valleytronic devices. However, the twist angle-dependent control of excitonic potential on valley polarization is not investigated so far in electrically controlled heterostructures and the physical mechanism underneath needs to be explored. Here, we demonstrate the dependence of both polarization switching and degree of valley polarization on the moiré period. We also find the mechanisms to reveal the modulation of twist angle on the exciton potential and the electron-hole exchange interaction, which elucidate the experimentally observed twist angle-dependent valley polarization of IXs. Furthermore, we realize the valley-addressable devices based on polarization switch. Our work demonstrates the manipulation of the valley polarization of IXs by tunning twist angle in electrically controlled heterostructures, which opens an avenue for electrically controlling the valley degrees of freedom in twistronic devices.

Timing Matters: Time of Day Impacts the Ergogenic Effects of Caffeine-A Narrative Review.

Caffeine has attracted significant attention from researchers in the sports field due to its well-documented ergogenic effects across various athletic disciplines. As research on caffeine continues to progress, there has been a growing emphasis on evaluating caffeine dosage and administration methods. However, investigations into the optimal timing of caffeine intake remain limited. Therefore, this narrative review aimed to assess the ergogenic effects of caffeine administration at different times during the morning (06:00 to 10:00) and evening (16:00 to 21:00). The review findings suggest that circadian rhythms play a substantial role in influencing sports performance, potentially contributing to a decline in morning performance. Caffeine administration has demonstrated effectiveness in mitigating this phenomenon, resulting in ergogenic effects and performance enhancement, even comparable to nighttime levels. While the specific mechanisms by which caffeine regulates circadian rhythms and influences sports performance remain unclear, this review also explores the mechanisms underlying caffeine's ergogenic effects, including the adenosine receptor blockade, increased muscle calcium release, and modulation of catecholamines. Additionally, the narrative review underscores caffeine's indirect impact on circadian rhythms by enhancing responsiveness to light-induced phase shifts. Although the precise mechanisms through which caffeine improves morning performance declines via circadian rhythm regulation necessitate further investigations, it is noteworthy that the timing of caffeine administration significantly affects its ergogenic effects during exercise. This emphasizes the importance of considering caffeine intake timing in future research endeavors to optimize its ergogenic potential and elucidate its mechanisms.

Tantalum-doped tin oxide thin films using hollow cathode gas flow sputtering technology.

SnO2 and tantalum doped SnO2 (TTO) thin films were prepared using reactive hollow cathode gas flow sputtering (GFS) on glass substrates. An in-situ heating process under vacuum preceded the sputtering. The resistivity of the tin oxide films was reduced to a remarkable low of 2.02 × 10-3 Ω cm, with a carrier concentration of 2.55 × 1020 cm-3 and a mobility of 12.11 cm2V-1s-1. As the substrate temperature increased, the film resistivity decreased. Notably, at a substrate temperature of 270 °C, the effect of Ta doping on the film resistivity and carrier concentration was significantly stronger compared to higher temperatures. Elevating the substrate temperature and Ta doping resulted in a lower refractive index (n). This effect was consistently strong at higher temperatures, attributed to the higher film-free carrier concentration (4.54 × 1020 cm-3) compared to lower temperatures (2.35 × 1020 cm-3). The film's structure was characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD) and atomic force microscope (AFM). The preferred direction of film growth was discussed. The successful and reproducible fabrication of tin oxide films underscores the advantages of gas flow sputtering (GFS) technology. GFS offers stable operating conditions across various oxygen flow levels without requiring target oxidization control, as is required in magnetron sputtering when managing gas status and film quality.

Factors Influencing Social Isolation among Cancer Patients: A Systematic Review.

(1) Background: Social isolation, which has numerous adverse effects on health status, is prevalent among cancer patients. This review proposes to identify the influencing factors of social isolation among cancer patients. (2) Methods: Articles published in English or Chinese from six electronic databases before December 2023 were identified via a systematic search. A manual search was also performed. (3) Results: Twenty-eight studies were identified in this systematic review. The factors associated with social isolation can be summarized into the following categories: demographic characteristics, having cancer, health status, coping, social support and social interaction. Despite the heterogeneity, 20 factors were significantly associated with social isolation, including age, gender, comorbidity burden, education level, residence, medical insurance, occupation status, personality, race, smoking status, having children, not living alone, household income level, marital status, the role of primary caregiver, physical health status, mental health status, social health status, coping styles, and the level of social support and social interaction. (4) Conclusions: The systematic review showed that cancer patients' social isolation was influenced by their demographic characteristics, cancer-related factors, physical condition, psychological status, social health status, coping styles, and level of social support and social interaction. In addition, future group intervention could be considered to improve social isolation.

Stochastic processes shape microbial community assembly in biofilters: Hidden role of rare taxa.

Stochastic and deterministic processes are the major themes governing microbial community assembly; however, their roles in bioreactors are poorly understood. Herein, the mechanisms underlying microbial assembly and the effect of rare taxa were studied in biofilters. Phylogenetic tree analysis revealed differences in microbial communities at various stages. Null model analysis showed that stochastic processes shaped the community assembly, and deterministic processes emerged only in the inoculated activated sludge after domestication. This finding indicates the dominant role of stochastic factors (biofilm formation, accumulation, and aging). The Sloan neutral model corroborated the advantages of stochastic processes and mainly attributed these advantages to rare taxa. Cooccurrence networks revealed the importance of rare taxa, which accounted for more than 85% of the keystones. Overall, these results provide good foundations for understanding community assembly, especially the role of rare taxa, and offer theoretical support for future community design and reactor regulation.

SnO2 Interacted with Sodium Thiosulfate for Perovskite Solar Cells over 25% Efficiency.

Tin oxide (SnO2) as electron transportation layer (ETL) has demonstrated remarkable performance applied in perovskite solar cells but still accommodated a host of defects such as oxygen vacancies, uncoordinated Sn4+ , and absorbed hydroxyl groups. Here, we use inorganic sodium thiosulfate Na2S2O3 to modify SnO2 nanoparticles in a bulk blending manner. Strong interaction between Na2S2O3 and SnO2 occurs, as reflected from the elemental chemical state change. The interaction has endowed the SnO2 film with better uniformity, increased conductivity, and more matched energy level with perovskite. Moreover, the modified SnO2 film as a substrate could promote the crystallization of perovskite by suppressing unreacted residual PbI2. The trap density from perovskite bulk to the SnO2 film across their interface has been effectively reduced, thus inhibiting the nonradiative recombination and promoting the transportation and extraction of charge carriers. Finally, the solar cell based on modified SnO2 has achieved a champion efficiency of 25.2%, demonstrating the effectiveness and potential of sulfur-containing molecules on optimizing the SnO2 property.

Investigation of the Shared Biomarkers in Heterotopic Ossification Between Ossification of the Ligamentum Flavum and Ankylosing Spondylitis.

STUDY DESIGN: Bioinformatics analysis of Gene Expression Omnibus (GEO). OBJECTIVE: Ossification of the ligamentum flavum (OLF) and ankylosing spondylitis (AS) represent intricate conditions marked by the gradual progression of endochondral ossification. This investigation endeavors to unveil common biomarkers associated with heterotopic ossification and explore the potential molecular regulatory mechanisms. METHODS: Microarray and RNA-sequencing datasets retrieved from the Gene Expression Omnibus (GEO) repository were harnessed to discern differentially expressed genes (DEGs) within the OLF and AS datasets. Subsequently, Weighted Gene Co-expression Network Analysis (WGCNA) was implemented to pinpoint co-expression modules linked to OLF and AS. Common genes were further subjected to an examination of functional pathway enrichment. Moreover, hub intersection genes were identified using the Least Absolute Shrinkage and Selection Operator (LASSO) regression, followed by an evaluation of diagnostic performance in external OLF and AS cohorts. Lastly, an analysis of immune cell infiltration was conducted to scrutinize the correlation of immune cell presence with shared biomarkers in OLF and AS. RESULTS: A total of 1353 and 91 Differentially Expressed Genes (DEGs) were identified in OLF and AS, respectively. Using the Weighted Gene Co-expression Network Analysis (WGCNA), 2 modules were found to be notably significant for OLF and AS. The integrative bioinformatic analysis revealed 3 hub genes (MAB21L2, MEGF10, ISLR) as shared risk biomarkers, with MAB21L2 being the central focus. Receiver Operating Characteristic (ROC) analysis exhibited a strong diagnostic potential for these hub genes. Gene Ontology (GO) analysis indicated their involvement in the positive regulation of myoblast proliferation. Notably, MAB21L2 was singled out as the optimal common biomarker for OLF and AS. Furthermore, an analysis of immune infiltration demonstrated a correlation between MAB21L2 expression and changes in immune cells. Activated CD8 T cells were identified as shared differential immune infiltrating cells significantly linked to MAB21L2 in both OLF and AS. CONCLUSION: This study represents the first instance of identifying MAB21L2 as a prospective diagnostic marker for patients contending with OLF associated with AS. The research results indicate that the ECM-receptor interaction and the cell-cell adhesion may play a role in both disease processes. This newfound knowledge not only enhances our understanding of the pathogenesis behind spinal ligament ossification but also uncovers potential targets for therapeutic interventions.

Development of an Automated Morphometric Approach to Assess Vascular Outcomes following Exposure to Environmental Chemicals in Zebrafish.

BACKGROUND: Disruptions in vascular formation attributable to chemical insults is a pivotal risk factor or potential etiology of developmental defects and various disease settings. Among the thousands of chemicals threatening human health, the highly concerning groups prevalent in the environment and detected in biological monitoring in the general population ought to be prioritized because of their high exposure risks. However, the impacts of a large number of environmental chemicals on vasculature are far from understood. The angioarchitecture complexity and technical limitations make it challenging to analyze the entire vasculature efficiently and identify subtle changes through a high-throughput in vivo assay. OBJECTIVES: We aimed to develop an automated morphometric approach for the vascular profile and assess the vascular morphology of health-concerning environmental chemicals. METHODS: High-resolution images of the entire vasculature in Tg(fli1a:eGFP) zebrafish were collected using a high-content imaging platform. We established a deep learning-based quantitative framework, ECA-ResXUnet, combined with MATLAB to segment the vascular networks and extract features. Vessel scores based on the rates of morphological changes were calculated to rank vascular toxicity. Potential biomarkers were identified by vessel-endothelium-gene-disease integrative analysis. RESULTS: Whole-trunk blood vessels and the cerebral vasculature in larvae exposed to 150 representative chemicals were automatically segmented as comparable to human-level accuracy, with sensitivity and specificity of 95.56% and 95.81%, respectively. Chemical treatments led to heterogeneous vascular patterns manifested by 31 architecture indexes, and the common cardinal vein (CCV) was the most affected vessel. The antipsychotic medicine haloperidol, flame retardant 2,2-bis(chloromethyl)trimethylenebis[bis(2-chloroethyl) phosphate], and tert-butylphenyl diphenyl phosphate ranked as the top three in vessel scores. Pesticides accounted for the largest group, with a vessel score of ≥1, characterized by a remarkable inhibition of subintestinal venous plexus and delayed development of CCV. Multiple-concentration evaluation of nine per- and polyfluoroalkyl substances (PFAS) indicated a low-concentration effect on vascular impairment and a positive association between carbon chain length and benchmark concentration. Target vessel-directed single-cell RNA sequencing of fli1a+ cells from larvae treated with λ-cyhalothrin, perfluorohexanesulfonic acid, or benzylbutyl phthalate, along with vessel-endothelium-gene-disease integrative analysis, uncovered potential associations with vascular disorders and identified biomarker candidates. DISCUSSION: This study provides a novel paradigm for phenotype-driven screenings of vascular-disrupting chemicals by converging morphological and transcriptomic profiles at a high-resolution level, serving as a powerful tool for large-scale toxicity tests. Our approach and the high-quality morphometric data facilitate the precise evaluation of vascular effects caused by environmental chemicals. https://doi.org/10.1289/EHP13214.

Predictors of Inadequate Serum Urate Response to Low-Dose Febuxostat in Male Patients with Gout.

Objective: This study aimed to understand predictors of inadequate response (IR) to low-dose febuxostat treatment based on clinical variables. Methods: We pooled data from 340 patients of an observational cohort and two clinical trials who received febuxostat 20 mg/day for at least 3 months. IR was defined as failure to reach the target serum urate level (sUA<6 mg/dL) at any time point during 3 months treatment. The potential predictors associated with short- or mid-term febuxostat IR after pooling the three cohorts were explored using mixed-effect logistic analysis. Machine learning models were performed to evaluate the predictors for IR using the pooled data as the discovery set and validated in an external test set. Results: Of the 340 patients, 68.9% and 51.8% were non-responders to low-dose febuxostat during short- and mid-term follow-up, respectively. Serum urate and triglyceride (TG) levels were significantly associated with febuxostat IR, but were also selected as significant features by LASSO analysis combined with age, BMI, and C-reactive protein (CRP). These five features in combination, using the best-performing stochastic gradient descent classifier, achieved an area under the receiver operating characteristic curve of 0.873 (95% CI [0.763, 0.942]) and 0.706 (95% CI [0.636, 0.727]) in the internal and external test sets, respectively, to predict febuxostat IR. Conclusion: Response to low-dose febuxostat is associated with early sUA improvement in individual patients, as well as patient age, BMI, and levels of TG and CRP.

Regulating Spin Density using TEMPOL Molecules for Enhanced CO2-to-Ethylene Conversion by HKUST-1 Framework Derived Electrocatalysts.

The selectivity of multicarbon products in the CO2 reduction reaction (CO2RR) depends on the spin alignment of neighboring active sites, which requires a spin catalyst that facilitates electron transfer with antiparallel spins for enhanced C-C coupling. Here, we design a radical-contained spin catalyst (TEMPOL@HKUST-1) to enhance CO2-to-ethylene conversion, in which spin-disordered (SDO) and spin-ordered (SO) phases co-exist to construct an asymmetric spin configuration of neighboring active sites. The replacement of axially coordinated H2O molecules with TEMPOL radicals introduces spin-spin interactions among the Cu(II) centers to form localized SO phases within the original H2O-mediated SDO phases. Therefore, TEMPOL@HKUST-1 derived catalyst exhibited an approximately two-fold enhancement in ethylene selectivity during the CO2RR at -1.8 V versus Ag/AgCl compared to pristine HKUST-1. In situ ATR-SEIRAS spectra indicate that the spin configuration at asymmetric SO/SDO sites significantly reduces the kinetic barrier for *CO intermediate dimerization toward the ethylene product. The performance of the spin catalyst is further improved by spin alignment under a magnetic field, resulting in a maximum ethylene selectivity of more than 50%. The exploration of the spin-polarized kinetics of the CO2RR provides a promising path for the development of novel spin electrocatalysts with superior performance.

Enhanced Electron Transport and Mitigated Voltage Loss in Perovskite Photovoltaics Using Sb2O5@SnO2 Composite Electron Transport Layer.

The efficacy of electron transport layers (ETLs) is pivotal for optimizing the device performance of perovskite photovoltaic applications. However, colloidal dispersions of SnO2 are prone to aggregation and possess structural defects, such as terminal-hydroxyls (OHT) and oxygen vacancies (VOs), which can degrade the quality of ETLs, impede charge extraction and transport, and affect the nucleation and growth processes of the perovskite layer. In this study, the Sb(OH)4 - ions hydrolyzed from SbCl3 in colloidal dispersion can bind to defect sites and effectively stabilize the SnO2 nanocrystals are demonstrated. Upon oxidative annealing, a Sb2O5@SnO2 composite film is formed, in which the Sb2O5 not only mitigates the aforementioned defects but also broadens the energy range of unoccupied states through its dispersed conduction band. The increased electron affinity (EA) facilitates more efficient capture of photoexcited electrons from the perovskite layer, thus augmenting electron extraction and minimizing electron-hole recombination. As a result, a significant improvement in power conversion efficiency (PCE) from 22.60% to 24.54% is achieved, with an open circuit voltage (VOC) of up to 1.195 V, along with excellent stability of unsealed devices under various conditions. This study provides valuable insights for the understanding and design of ETLs in perovskite photovoltaic applications.

Mobilizing endogenous neuroprotection: the mechanism of the protective effect of acupuncture on the brain after stroke.

Given its high morbidity, disability, and mortality rates, ischemic stroke (IS) is a severe disease posing a substantial public health threat. Although early thrombolytic therapy is effective in IS treatment, the limited time frame for its administration presents a formidable challenge. Upon occurrence, IS triggers an ischemic cascade response, inducing the brain to generate endogenous protective mechanisms against excitotoxicity and inflammation, among other pathological processes. Stroke patients often experience limited recovery stages. As a result, activating their innate self-protective capacity [endogenous brain protection (EBP)] is essential for neurological function recovery. Acupuncture has exhibited clinical efficacy in cerebral ischemic stroke (CIS) treatment by promoting the human body's self-preservation and "Zheng Qi" (a term in traditional Chinese medicine (TCM) describing positive capabilities such as self-immunity, self-recovery, and disease prevention). According to research, acupuncture can modulate astrocyte activity, decrease oxidative stress (OS), and protect neurons by inhibiting excitotoxicity, inflammation, and apoptosis via activating endogenous protective mechanisms within the brain. Furthermore, acupuncture was found to modulate microglia transformation, thereby reducing inflammation and autoimmune responses, as well as promoting blood flow restoration by regulating the vasculature or the blood-brain barrier (BBB). However, the precise mechanism underlying these processes remains unclear. Consequently, this review aims to shed light on the potential acupuncture-induced endogenous neuroprotective mechanisms by critically examining experimental evidence on the preventive and therapeutic effects exerted by acupuncture on CIS. This review offers a theoretical foundation for acupuncture-based stroke treatment.