Direct and indirect treatment effects in the presence of semicompeting risks.

Semicompeting risks refer to the phenomenon that the terminal event (such as death) can censor the nonterminal event (such as disease progression) but not vice versa. The treatment effect on the terminal event can be delivered either directly following the treatment or indirectly through the nonterminal event. We consider 2 strategies to decompose the total effect into a direct effect and an indirect effect under the framework of mediation analysis in completely randomized experiments by adjusting the prevalence and hazard of nonterminal events, respectively. They require slightly different assumptions on cross-world quantities to achieve identifiability. We establish asymptotic properties for the estimated counterfactual cumulative incidences and decomposed treatment effects. We illustrate the subtle difference between these 2 decompositions through simulation studies and two real-data applications in the Supplementary Materials.

Causal inference for time-to-event data with a cured subpopulation.

When studying the treatment effect on time-to-event outcomes, it is common that some individuals never experience failure events, which suggests that they have been cured. However, the cure status may not be observed due to censoring which makes it challenging to define treatment effects. Current methods mainly focus on estimating model parameters in various cure models, ultimately leading to a lack of causal interpretations. To address this issue, we propose 2 causal estimands, the timewise risk difference and mean survival time difference, in the always-uncured based on principal stratification as a complement to the treatment effect on cure rates. These estimands allow us to study the treatment effects on failure times in the always-uncured subpopulation. We show the identifiability using a substitutional variable for the potential cure status under ignorable treatment assignment mechanism, these 2 estimands are identifiable. We also provide estimation methods using mixture cure models. We applied our approach to an observational study that compared the leukemia-free survival rates of different transplantation types to cure acute lymphoblastic leukemia. Our proposed approach yielded insightful results that can be used to inform future treatment decisions.

Profiles of attitudes toward inclusive education among Chinese in-service teachers: their relationships with demographic factors and organizational commitment.

Introduction: The increased diversity of students (e.g., students with special educational needs) has presented teachers with unprecedented challenges. Teachers' attitudes toward inclusive education play a crucial role in teachers' organizational well-being. However, existing studies mostly explored attitudes toward inclusive education based on a variable-centered approach. This study used a person-centered approach to identify teachers' attitude profile membership and explored the relationships of attitude profiles with demographic factors (i.e., gender, years of teaching experience, subject taught, and in-service training) and organizational commitment. Methods: Nine hundred and seventy-two in-service teachers from forty-nine inclusive education schools in Beijing responded to the Revised Multidimensional Attitudes toward Inclusive Education Scale and the Organizational Commitment Inventory. Latent profile analyses, multinomial logistic regression, and univariate analysis of variance were used to analyze data. Results and discussion: The results revealed four attitude profiles: involuntary participation, behavior avoidance, neutral, and proactive involvement. Years of teaching experience and in-service training were significant predictors of teachers' latent profile membership. Teachers belonging to the involuntary participation profile showed the highest levels of maladaptive commitments to inclusive education schools. Teachers belonging to the proactive involvement and the behavior avoidance profiles showed higher levels of adaptive commitments. However, teachers belonging to the neutral profile had the lowest levels of adaptive commitments. The theoretical contributions, practical implications, and limitations are discussed.

Roles and interactions of tumor microenvironment components in medulloblastoma with implications for novel therapeutics.

Medulloblastomas, the most common malignant pediatric brain tumors, can be classified into the wingless, sonic hedgehog (SHH), group 3, and group 4 subgroups. Among them, the SHH subgroup with the TP53 mutation and group 3 generally present with the worst patient outcomes due to their high rates of recurrence and metastasis. A novel and effective treatment for refractory medulloblastomas is urgently needed. To date, the tumor microenvironment (TME) has been shown to influence tumor growth, recurrence, and metastasis through immunosuppression, angiogenesis, and chronic inflammation. Treatments targeting TME components have emerged as promising approaches to the treatment of solid tumors. In this review, we summarize progress in research on medulloblastoma microenvironment components and their interactions. We also discuss challenges and future research directions for TME-targeting medulloblastoma therapy.

Short-Wave Infrared Colloidal QD Photodetector with Nanosecond Response Times Enabled by Ultrathin Absorber Layers.

Ultrafast short-wavelength infrared (SWIR) photodetection is of great interest for emerging automated vision and spatial mapping technologies. Colloidal quantum dots (QDs) stand out for SWIR photodetection compared to epitaxial (In,Ga)As or (Hg,Cd)Te semiconductors by their combining a size-tunable bandgap and a suitability for cost-effective, solution-based processing. However, achieving ultrafast, nanosecond-level response time has remained an outstanding challenge for QD-based SWIR photodiodes (QDPDs). Here, record 4 ns response time in PbS-based QDPDs that operate at SWIR wavelengths is reported, a result reaching the requirement of SWIR light detection and ranging based on colloidal QDs. These ultrafast QDPDs combine a thin active layer to reduce the carrier transport time and a small area to inhibit slow capacitive discharging. By implementing a concentration gradient ligand exchange method, high-quality p-n junctions are fabricated in these ultrathin QDPDs. Moreover, these ultrathin QDPDs attain an external quantum efficiency of 42% at 1330 nm, due to a 2.5-fold enhanced light absorption through the formation of a Fabry-Perot cavity within the QDPD and the highly efficient extraction (98%) of photogenerated charge carriers. Based on these results, it is estimated that a further increase of the charge-carrier mobility can lead to PbS QDPDs with sub-nanosecond response time.

Multilevel Information Encryption Based on Thermochromic Perovskite Microcapsules via Orthogonal Photic and Thermal Stimuli Responses.

Increasing modal variations of stimulus-responsive materials ensure the high capacity and confidentiality of information storage and encryption systems that are crucial to information security. Herein, thermochromic perovskite microcapsules (TPMs) with dual-variable and quadruple-modal reversible properties are designed and prepared on the original oil-in-fluorine (O/F) emulsion system. The TPMs respond to the orthogonal variations of external UV and thermal stimuli in four reversible switchable modes and exhibit excellent thermal, air, and water stability due to the protection of perovskites by the core-shell structure. Benefiting from the high-density information storage TPMs, multiple information encryptions and decryptions are demonstrated. Moreover, a set of devices are assembled for a multilevel information encryption system. By taking advantage of TPMs as a "private key" for decryption, the signal can be identified as the corresponding binary ASCII code and converted to the real message. The results demonstrate a breakthrough in high-density information storage materials as well as a multilevel information encryption system based on switchable quadruple-modal TPMs.

Integrated PbS Colloidal Quantum Dot Photodiodes on Silicon Nitride Waveguides.

Colloidal quantum dots (QDs) have become a versatile optoelectronic material for emitting and detecting light that can overcome the limitations of a range of electronic and photonic technology platforms. Photonic integrated circuits (PICs), for example, face the persistent challenge of combining active materials with passive circuitry ideally suited for guiding light. Here, we demonstrate the integration of photodiodes (PDs) based on PbS QDs on silicon nitride waveguides (WG). Analyzing planar QDPDs first, we argue that the main limitation WG-coupled QDPDs face is detector saturation induced by the high optical power density of the guided light. Using the cladding thickness and waveguide width as design parameters, we mitigate this issue, and we demonstrate WG-QDPDs with an external quantum efficiency of 67.5% at 1275 nm that exhibit a linear photoresponse for input powers up to 400 nW. In the next step, we demonstrate a compact infrared spectrometer by integrating these WG-QDPDs on the output channels of an arrayed waveguide grating demultiplexer. This work provides a path toward a low-cost PD solution for PICs, which are attractive for large-scale production.

Gaussian Boson Sampling with Pseudo-Photon-Number-Resolving Detectors and Quantum Computational Advantage.

We report new Gaussian boson sampling experiments with pseudo-photon-number-resolving detection, which register up to 255 photon-click events. We consider partial photon distinguishability and develop a more complete model for the characterization of the noisy Gaussian boson sampling. In the quantum computational advantage regime, we use Bayesian tests and correlation function analysis to validate the samples against all current classical spoofing mockups. Estimating with the best classical algorithms to date, generating a single ideal sample from the same distribution on the supercomputer Frontier would take ∼600 yr using exact methods, whereas our quantum computer, Jiǔzhang 3.0, takes only 1.27 µs to produce a sample. Generating the hardest sample from the experiment using an exact algorithm would take Frontier∼3.1×10^{10} yr.

Reversible Thermochromic Microcapsules and Their Applications in Anticounterfeiting.

The common, commercial reversible thermochromic (RT) melamine-formaldehyde resin microcapsules containing formaldehyde are very harmful to human health. To address this issue, we successfully prepared a novel formaldehyde-free microcapsule via interfacial polymerization using RT compositions as the core and poly(urethane-urea) (PUU) as the shell. The core material consisted of a color former (crystal violet lactone), a developer (bisphenol AF), and a solvent (methyl stearate). To optimize the synthesis of the microcapsules, an L9 (34) orthogonal design and single-factor experiments were employed to analyze the effects of four factors (N3300-to-L75 shell material mass ratio, core-to-shell material mass ratio, emulsifier concentration, and shear rate during emulsification) on the encapsulation efficiency. The results showed that the optimal parameter values were as follows: a shear rate of 2500 rpm, N3300-to-L75 shell material mass ratio of 1:4, core-to-shell material mass ratio of 11:5, and emulsifier concentration of 3.5%. The influence of the shear rate on the particle size and distribution, surface morphology, dispersibility, and reversible thermochromic properties of the microcapsules was investigated. Furthermore, analyses on the phase-change characteristics, thermal stability, ultraviolet aging, and solvent and acid-base resistances of the microcapsules were conducted systematically. Finally, a reversible thermochromic mark containing the RTPUU microcapsules was designed and fabricated, which could be used against falsification. Moreover, these RTPUU microcapsules can be potentially used for anticounterfeiting applications.

Bridging the Green Gap: Monochromatic InP-Based Quantum-Dot-on-Chip LEDs with over 50% Color Conversion Efficiency.

Solid-state light-emitting diodes (LEDs) emit nearly monochromatic light, yet seamless tuning of emission color throughout the visible region remains elusive. Color-converting powder phosphors are therefore used for making LEDs with a bespoke emission spectrum, yet broad emission lines and low absorption coefficients compromise the formation of small-footprint monochromatic LEDs. Color conversion by quantum dots (QDs) can address these issues, but high-performance monochromatic LEDs made using QDs free of restricted, hazardous elements remain to be demonstrated. Here, we show green, amber, and red LEDs formed using InP-based QDs as on-chip color convertor for blue LEDs. Implementing QDs with near-unity photoluminescence efficiency yields a color conversion efficiency over 50% with little intensity roll-off and nearly complete blue light rejection. Moreover, as the conversion efficiency is mostly limited by package losses, we conclude that on-chip color conversion using InP-based QDs can provide spectrum-on-demand LEDs, including monochromatic LEDs that bridge the green gap.

Solving Graph Problems Using Gaussian Boson Sampling.

Gaussian boson sampling (GBS) is not only a feasible protocol for demonstrating quantum computational advantage, but also mathematically associated with certain graph-related and quantum chemistry problems. In particular, it is proposed that the generated samples from the GBS could be harnessed to enhance the classical stochastic algorithms in searching some graph features. Here, we use Jiǔzhang, a noisy intermediate-scale quantum computer, to solve graph problems. The samples are generated from a 144-mode fully connected photonic processor, with photon click up to 80 in the quantum computational advantage regime. We investigate the open question of whether the GBS enhancement over the classical stochastic algorithms persists-and how it scales-with an increasing system size on noisy quantum devices in the computationally interesting regime. We experimentally observe the presence of GBS enhancement with a large photon-click number and a robustness of the enhancement under certain noise. Our work is a step toward testing real-world problems using the existing noisy intermediate-scale quantum computers and hopes to stimulate the development of more efficient classical and quantum-inspired algorithms.

Eltoprazine modulated gamma oscillations on ameliorating L-dopa-induced dyskinesia in rats.

AIM: Parkinson's disease (PD) is a pervasive neurodegenerative disease, and levodopa (L-dopa) is its preferred treatment. The pathophysiological mechanism of levodopa-induced dyskinesia (LID), the most common complication of long-term L-dopa administration, remains obscure. Accumulated evidence suggests that the dopaminergic as well as non-dopaminergic systems contribute to LID development. As a 5-hydroxytryptamine 1A/1B receptor agonist, eltoprazine ameliorates dyskinesia, although little is known about its electrophysiological mechanism. The aim of this study was to investigate the cumulative effects of chronic L-dopa administration and the potential mechanism of eltoprazine's amelioration of dyskinesia at the electrophysiological level in rats. METHODS: Neural electrophysiological analysis techniques were conducted on the acquired local field potential (LFP) data from primary motor cortex (M1) and dorsolateral striatum (DLS) during different pathological states to obtain the information of power spectrum density, theta-gamma phase-amplitude coupling (PAC), and functional connectivity. Behavior tests and AIMs scoring were performed to verify PD model establishment and evaluate LID severity. RESULTS: We detected exaggerated gamma activities in the dyskinetic state, with different features and impacts in distinct regions. Gamma oscillations in M1 were narrowband manner, whereas that in DLS had a broadband appearance. Striatal exaggerated theta-gamma PAC in the LID state contributed to broadband gamma oscillation, and aperiodic-corrected cortical beta power correlated robustly with aperiodic-corrected gamma power in M1. M1-DLS coherence and phase-locking values (PLVs) in the gamma band were enhanced following L-dopa administration. Eltoprazine intervention reduced gamma oscillations, theta-gamma PAC in the DLS, and coherence and PLVs in the gamma band to alleviate dyskinesia. CONCLUSION: Excessive cortical gamma oscillation is a compelling clinical indicator of dyskinesia. The detection of enhanced PAC and functional connectivity of gamma-band oscillation can be used to guide and optimize deep brain stimulation parameters. Eltoprazine has potential clinical application for dyskinesia.

Unconditional and Robust Quantum Metrological Advantage beyond N00N States.

Quantum metrology employs quantum resources to enhance the measurement sensitivity beyond that can be achieved classically. While multiphoton entangled N00N states can in principle beat the shot-noise limit and reach the Heisenberg limit, high N00N states are difficult to prepare and fragile to photon loss which hinders them from reaching unconditional quantum metrological advantages. Here, we combine the idea of unconventional nonlinear interferometers and stimulated emission of squeezed light, previously developed for the photonic quantum computer Jiuzhang, to propose and realize a new scheme that achieves a scalable, unconditional, and robust quantum metrological advantage. We observe a 5.8(1)-fold enhancement above the shot-noise limit in the Fisher information extracted per photon, without discounting for photon loss and imperfections, which outperforms ideal 5-N00N states. The Heisenberg-limited scaling, the robustness to external photon loss, and the ease-of-use of our method make it applicable in practical quantum metrology at a low photon flux regime.

Maintaining higher grain production with less reactive nitrogen losses in China: A meta-analysis study.

Managing reactive nitrogen (Nr) in agricultural production is crucial for addressing the triple challenges of food security, climate change and environmental degradation. Intensive work has been conducted to investigate the effects of mitigation strategies on reducing Nr losses by ammonia emission (Nr-NH3), nitrous oxide emission (Nr-N2O) and nitrate leaching (Nr-NO3-) separately. This meta-analysis evaluated the efficiency of each strategy in mitigating Nr losses coupled with grain yield responses. The results indicate that producing one Megagram (Mg) of wheat grains caused higher Nr losses, twice that of rice and 17% that of maize. The Nr-NH3 and Nr-NO3- were the dominant sources of Nr losses of the three crops (96%), while Nr-NH3 only presented 86% of the total Nr losses for rice. Reducing the N rate strategy decreased the yield by 33% and the Nr losses by 62% compared with the conventional rate (150-250 kg N ha-1) as an average of the three crops. In contrast, increasing the N rate higher than 250 kg N ha-1 amplified the yield by 15% but also caused a 71% increase in Nr losses compared with the conventional rate. Although subsurface application decreased Nr losses by 5%, this study rejected this approach as an effective strategy due to a 4% yield decline on average of the grain crops. Slow-release fertilizers decreased Nr-NH3 and Nr-N2O losses by 41-58% and 54-89%, respectively, of the highest losses under urea in the three crops, but also led to yield reductions. Organic amendments achieved the highest drop in Nr-NO3- loss by 66% in maize coupled with yield declines. Biochar increased wheat and maize yields by 0.3 and 0.1 Mg, respectively, coupled with 1 kg reduction in Nr losses. On average, inhibitors augmented the grain yields by 0.2 Mg ha-1 for each 1 kg decline in Nr losses. In conclusion, for sustainable agricultural intensification, biochar (for wheat only) and inhibitors (for the three crops) are strongly recommended as mitigation strategies for Nr losses from grain crop production systems in China.

The 532 nm Laser Treatment Promotes the Proliferation of Tendon-Derived Stem Cells and Upregulates Nr4a1 to Stimulate Tenogenic Differentiation.

Objective: This study aimed to verify the effect of photobiomodulation therapy (PBMT) with a wavelength of 532 nm on the proliferation and differentiation of tendon-derived stem cells (TDSCs) of Sprague-Dawley (SD) rats. Background: The combination of PBMT and stem cell transplantation with TDSCs provides a new treatment strategy for tendon injury. Nevertheless, the effect of PBMT on the biological behavior of TDSCs and its internal mechanisms remain unclear. Methods: TDSCs were isolated from Achilles tendons of SD rats and identified by cell morphology and flow cytometric analysis. Energy density gradient experiment was performed to determine the ideal energy. Then, TDSCs were treated with PBMT using a wavelength of 532 nm at a fluence of 15 J/cm2 in 532 nm laser group, and the TDSC in control group were not treated with 532 nm laser. Cell response after irradiation was observed to ascertain cell morphology and cell proliferation in the 532 nm laser group and the control group. The RNA expression levels of the key genes of TDSC differentiation, including scleraxis (Scx), tenomodulin (Tnmd), Mohawk homeobox (Mkx), Decorin (Dcn), peroxisome proliferator-activated receptor gamma (PPARγ), SRY-box transcription factor 9 (Sox9), and RUNX family transcription factor 2 (Runx2), were detected by reverse transcription-polymerase chain reaction. Then, gene chip microarray was used to detect the expression of differential genes after 532 nm laser intervention in TDSCs, and the target genes were screened out to verify the role in this process in vitro and in vivo. Results: When the 532 nm laser energy density was 15 J/cm2, the proliferation capacity of TDSCs was improved (2.73 ± 0.24 vs. 1.81 ± 0.71, p < 0.05), and the expression of genes related to tenogenic differentiation of TDSCs was significantly increased (p < 0.01). After RNA sequencing and bioinformatics analyses, we speculated that nuclear receptor subfamily 4 group A member 1 (Nr4a1) was involved in the tenogenic differentiation process of TDSCs regulated by 532 nm laser treatment. Subsequent experiments confirmed that Nr4a1 regulated the expression of the tenogenic differentiation genes Scx and Tnmd in TDSCs. Conclusions: A 532 nm laser with 15 J/cm2 regulated the process of TDSC proliferation and upregulated Nr4a1 to stimulate tenogenic differentiation.

Identification of PBK as a hub gene and potential therapeutic target for medulloblastoma.

Medulloblastoma (MB) is the most frequent malignant brain tumor in pediatrics. Since the current standard of care for MB consisting of surgery, cranio­spinal irradiation and chemotherapy often leads to a high morbidity rate, a number of patients suffer from long­term sequelae following treatment. Targeted therapies hold the promise of being more effective and less toxic. Therefore, the present study aimed to identify hub genes with an upregulated expression in MB and to search for potential therapeutic targets from these genes. For this purpose, gene expression profile datasets were obtained from the Gene Expression Omnibus database and processed using R 3.6.0 software to screen differentially expressed genes (DEGs) between MB samples and normal brain tissues. A total of 282 upregulated and 436 downregulated DEGs were identified. Functional enrichment analysis revealed that the upregulated DEGs were predominantly enriched in the cell cycle, DNA replication and cell division. The top 10 hub genes were identified from the protein­protein interaction network of upregulated genes, and one identified hub gene [PDZ binding kinase (PBK)] was selected for further investigation due to its possible role in the pathogenesis of MB. The aberrant expression of PBK in MB was verified in additional independent gene expression datasets. Survival analysis demonstrated that a higher expression level of PBK was significantly associated with poorer clinical outcomes in non­Wingless MBs. Furthermore, targeting PBK with its inhibitor, HI­TOPK­032, impaired the proliferation and induced the apoptosis of two MB cell lines, with the diminished phosphorylation of downstream effectors of PBK, including ERK1/2 and Akt, and the activation of caspase­3. Hence, these results suggest that PBK may be a potential prognostic biomarker and a novel candidate of targeted therapy for MB.

Equivalence tests for ratio of means in bioequivalence studies under crossover design.

There are several problems concerning the statistical definition of average bioequivalence provided by the U.S. Food and Drug Administration. We proposed a ratio of means based on the original bioavailability measure as the definition for average bioequivalence. Under the log-normal distribution assumption, we proposed a hypothesis testing-based method and a confidence interval-based method to answer the question of whether the ratio of means falls into a predetermined interval. For the hypothesis testing-based method, we decomposed the null two-sided hypothesis of the ratio of means into two one-sided hypotheses. With the intersection-union theorem for asymptotic tests, we constructed two asymptotic size-α tests for the original null hypothesis. The method of variance estimation recovery was adopted to develop the confidence interval-based method. Simulation studies showed that the proposed methods can maintain the empirical type I error rate closely at the nominal level and is as powerful as the two one-sided t-test for testing the ratio of means under different settings. The application of the proposed methods was illustrated through six datasets in real-world examples.

Colloidal III-V Quantum Dot Photodiodes for Short-Wave Infrared Photodetection.

Short-wave infrared (SWIR) image sensors based on colloidal quantum dots (QDs) are characterized by low cost, small pixel pitch, and spectral tunability. Adoption of QD-SWIR imagers is, however, hampered by a reliance on restricted elements such as Pb and Hg. Here, QD photodiodes, the central element of a QD image sensor, made from non-restricted In(As,P) QDs that operate at wavelengths up to 1400 nm are demonstrated. Three different In(As,P) QD batches that are made using a scalable, one-size-one-batch reaction and feature a band-edge absorption at 1140, 1270, and 1400 nm are implemented. These QDs are post-processed to obtain In(As,P) nanocolloids stabilized by short-chain ligands, from which semiconducting films of n-In(As,P) are formed through spincoating. For all three sizes, sandwiching such films between p-NiO as the hole transport layer and Nb:TiO2 as the electron transport layer yields In(As,P) QD photodiodes that exhibit best internal quantum efficiencies at the QD band gap of 46±5% and are sensitive for SWIR light up to 1400 nm.

Role of Canonical Wnt/ß-Catenin Pathway in Regulating Chondrocytic Hypertrophy in Mesenchymal Stem Cell-Based Cartilage Tissue Engineering.

In the past 3 decades, the cartilage repair potential of mesenchymal stromal cells, or mesenchymal stem cells (MSCs), has been widely examined in animal studies. Unfortunately, the phenotype and physical properties of MSC-derived cartilage tissue are not comparable to native hyaline cartilage. In particular, chondrocytic hypertrophy, a phenotype that is not observed in healthy hyaline cartilage, is concomitant with MSC chondrogenesis. Given that hypertrophic chondrocytes potentially undergo apoptosis or convert into osteoblasts, this undesired phenotype needs to be prevented or minimized before MSCs can be used to repair cartilage injuries in the clinic. In this review, we first provide an overview of chondrocytic hypertrophy and briefly summarize current methods for suppressing hypertrophy in MSC-derived cartilage. We then highlight recent progress on modulating the canonical Wnt/ß-catenin pathway for inhibiting hypertrophy. Specially, we discuss the potential crosstalk between Wnt/ß-catenin with other pathways in regulating hypertrophy. Lastly, we explore future perspectives to further understand the role of Wnt/ß-catenin in chondrocytic hypertrophy.

Teriparatide induces angiogenesis in ischemic cerebral infarction zones of rats through AC/PKA signaling and reduces ischemia-reperfusion injury.

Teriparatide is a commonly used drug indicated for the treatment of osteoporosis in postmenopausal women. Teriparatide can also upregulate Ang-1 expression through the AC/PKA signaling pathway to promote angiogenesis. At present, promoting angiogenesis is a promising but unrealized strategy for the treatment of ischemic cerebral infarction. However, there are few studies on the application of teriparatide in the treatment of cerebral infarction. We used teriparatide to treat ischemic cerebral infarction in rats and obtained three major findings. First, teriparatide can promote angiogenesis, reduce cerebral infarct size, and increase cerebral perfusion by upregulating Ang-1 expression. Second, teriparatide can promote the expression of HO1, SOD2 and inhibit the production of pro-inflammatory cytokines IL-1ß, IL-6 by upregulating Nrf2 expression. Third, we further found that teriparatide can mitigate blood-brain barrier disruption and brain edema by downregulating the expressions of MMP9, Ang-2 and AQP4. Our results indicate that teriparatide is neuroprotective through multiple mechanisms of action that include promoting angiogenesis, inhibiting oxidative stress and neuroinflammation, protecting blood-brain barrier, and reducing brain edema.