Manganese deficiency alters photosynthetic electron transport in Marchantia polymorpha.

Manganese (Mn) is considered as an essential element for plant growth. Mn starvation has been shown to affect photosystem II, the site of the Mn4CaO5 cluster responsible for water oxidation. Less is known on the effect of Mn starvation on photosystem I. Here we studied the effects of Mn deficiency in vivo on redox changes of P700 and plastocyanin (Pc) in the liverwort Marchantia polymorpha using the KLAS-NIR spectrophotometer. Far-red illumination is used to excite preferentially photosystem I, thus facilitating cyclic electron transport. Under Mn starvation, we observed slower oxidation of P700 and a decrease in the Pc signal relative to P700. The lower Pc content under Mn deficiency was confirmed by western blots. Re-reduction kinetics of P700+ and Pc+ were faster in Mn deficient thalli than in the control. The above findings show that the kinetics studied under Mn deficiency not only depend on the number of available reductants but also on how quickly electrons are transferred from stromal donors via the intersystem chain to Pc+ and P700+. We suggest that under Mn deficiency a structural reorganization of the thylakoid membrane takes place favoring the formation of supercomplexes between ferredoxin, cytochrome b6f complex, Pc and photosystem I, and thus an enhanced cyclic electron transport.

109Pd/109mAg in-vivo generator in the form of nanoparticles for combined ß- - Auger electron therapy of hepatocellular carcinoma.

BACKGROUND: Convenient therapeutic protocols for hepatocellular carcinoma (HCC) are often ineffective due to late diagnosis and high tumor heterogeneity, leading to poor long-term outcomes. However, recently performed studies suggest that using nanostructures in liver cancer treatment may improve therapeutic effects. Inorganic nanoparticles represent a unique material that tend to accumulate in the liver when introduced in-vivo. Typically, this is a major drawback that prevents the therapeutic use of nanoparticles in medicine. However, in HCC tumours, this may be advantageous because nanoparticles may accumulate in the target organ, where the leaky vasculature of HCC causes their accumulation in tumour cells via the EPR effect. On the other hand, recent studies have shown that combining low- and high-LET radiation emitted from the same radionuclide, such as 161Tb, can increase the effectiveness of radionuclide therapy. Therefore, to improve the efficacy of radionuclide therapy for hepatocellular carcinoma, we suggest utilizing radioactive palladium nanoparticles in the form of 109Pd/109mAg in-vivo generator that simultaneously emits ß- particles and Auger electrons. RESULTS: Palladium nanoparticles with a size of 5 nm were synthesized using 109Pd produced through neutron irradiation of natural palladium or enriched 108Pd. Unlike the 109Pd-cyclam complex, where the daughter radionuclide diffuses away from the molecules, 109mAg remains within the nanoparticles after the decay of 109Pd. In vitro cell studies using radioactive 109Pd nanoparticles revealed that the nanoparticles accumulated inside cells, reaching around 50% total uptake. The 109Pd-PEG nanoparticles exhibited high cytotoxicity, even at low levels of radioactivity (6.25 MBq/mL), resulting in almost complete cell death at 25 MBq/mL. This cytotoxic effect was significantly greater than that of PdNPs labeled with ß- (131I) and Auger electron emitters (125I). The metabolic viability of HCC cells was found to be correlated with cell DNA DSBs. Also, successful radioconjugate anticancer activity was observed in three-dimensional tumor spheroids, resulting in a significant treatment response. CONCLUSION: The results indicate that nanoparticles labeled with 109Pd can be effectively used for combined ß- - Auger electron-targeted radionuclide therapy of HCC. Due to the decay of both components (ß- and Auger electrons), the 109Pd/109mAg in-vivo generator presents a unique potential in this field.

Advances in hepatocellular carcinoma drug resistance models.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Surgery has been the major treatment method for HCC owing to HCC's poor sensitivity to radiotherapy and chemotherapy. However, its effectiveness is limited by postoperative tumour recurrence and metastasis. Systemic therapy is applied to eliminate postoperative residual tumour cells and improve the survival of patients with advanced HCC. Recently, the emergence of various novel targeted and immunotherapeutic drugs has significantly improved the prognosis of advanced HCC. However, targeted and immunological therapies may not always produce complete and long-lasting anti-tumour responses because of tumour heterogeneity and drug resistance. Traditional and patient-derived cell lines or animal models are used to investigate the drug resistance mechanisms of HCC and identify drugs that could reverse the resistance. This study comprehensively reviewed the established methods and applications of in-vivo and in-vitro HCC drug resistance models to further understand the resistance mechanisms in HCC treatment and provide a model basis for possible individualised therapy.

Guided wave elastography of human skins with a layered model incorporating the effect of muscle state.

In vivo mechanical characterization of skin finds broad applications in understanding skin aging, diagnosis of some skin diseases and assessing the effectiveness of diverse skin care strategies. Skin has a layered structure consisting of the epidermis, dermis and subcutaneous layers. Although much effort has been made towards mechanical characterization of skin, it remains a challenging issue to measure the mechanical properties of an individual layer in vivo. To address this issue, we here report a guided wave elastography method for layered human skin which incorporates the effect of muscle states. Both finite element simulations and phantom experiments have been performed to validate the method. For skin-mimicking phantoms with different fat layer thicknesses, the errors in the identified shear modulus of the skin layers are no more than 11 %. In vivo experiments have been carried out on 6 healthy subjects to demonstrate the potential use of the method in clinics. A statistical analysis indicates the muscle contraction contributes to the stiffening of the skin (p < 0.001). Finally, a phase diagram has been constructed to reveal the extent to which muscle sates (including both passive and active states) affect the measurement of elastic modulus of a skin layer, which may guide the application of the method in practice.

Light-Driven Microrobots for Targeted Drug Delivery.

As a new micromanipulation tool with the advantages of small size, flexible movement and easy manipulation, light-driven microrobots have a wide range of prospects in biomedical fields such as drug targeting and cell manipulation. Recently, microrobots have been controlled in various ways, and light field has become a research hotspot by its advantages of noncontact manipulation, precise localization, fast response, and biocompatibility. It utilizes the force or deformation generated by the light field to precisely control the microrobot, and combines with the drug release technology to realize the targeted drug application. Therefore, this paper provides an overview of light-driven microrobots with drug targeting to provide new ideas for the manipulation of microrobots. Here, this paper briefly categorizes the driving mechanisms and materials of light-driven microrobots, which mainly include photothermal, photochemical, and biological. Then, typical designs of light-driven microrobots with different driving mechanisms and control strategies for multiple physical fields are summarized. Finally, the applications of microrobots in the fields of drug targeting and bioimaging are presented as well as the future prospects of light-driven microrobots in the biomedical field are demonstrated.

Lead-212/Bismuth-212 In Vivo Generator Based on Ultrasmall Silver Telluride Nanoparticles.

Radionuclide therapy employing alpha emitters holds great potential for personalized cancer treatment. However, certain challenges remain when designing alpha radiopharmaceuticals, including the lack of stability of used radioconjugates due to nuclear decay events. In this work, ultrasmall silver telluride nanoparticles with a core diameter of 2.1 nm were prepared and radiolabeled with lead-212 using a chelator-free method with a radiolabeling efficiency of 75%. The results from the in vitro radiochemical stability assay indicated a very high retention of bismuth-212 despite the internal conversion effects originating from the decay of 212Pb. To further evaluate the potential of the nanoparticles, they were radiolabeled with indium-111, and their cell uptake and subcellular distribution were determined in 2D U87 cells, showing accumulation in the nucleus. Although not intentional, it was observed that the indium-111-radiolabeled nanoparticles induced efficient tumor cell killing, which was attributed to the Auger electrons emitted by indium-111. Combining the results obtained in this work with other favorable properties such as fast renal clearance and the possibility to attach targeting vectors on the surface of the nanoparticles, all well-known from the literature, these ultra-small silver telluride nanoparticles provide exciting opportunities for the design of theragnostic radiopharmaceuticals.

Effects of Latilactobacillus sakei LZ217 on Gastric Mucosal Colonization, Metabolic Interference, and Urease Expression in Helicobacter pylori Infection.

Emerging evidence suggests differential antagonism of lactic acid-producing bacteria (LAB) to Helicobacter pylori, posing challenges to human health and food safety due to unclear mechanisms. This study assessed 21 LAB strains from various sources on H. pylori growth, urease activity, and coaggregation. Composite scoring revealed that Latilactobacillus sakei LZ217, derived from fresh milk, demonstrates strong inhibitory effects on both H. pylori growth and urease activity. L. sakei LZ217 significantly reduced H. pylori adherence of gastric cells in vitro, with inhibition ratios of 47.62%. Furthermore, in vivo results showed that L. sakei LZ217 alleviated H. pylori-induced gastric mucosa damage and inflammation in mice. Metabolomic exploration revealed metabolic perturbations in H. pylori induced by L. sakei LZ217, including reduced amino acid levels (e.g., isoleucine, leucine, glutamate, aspartate, and phenylalanine) and impaired carbohydrate and nucleotide synthesis, contributing to the suppression of ureA (28.30%), ureE (84.88%), and ureF (59.59%) expressions in H. pylori. This study underscores the efficacy of LAB against H. pylori and highlights metabolic pathways as promising targets for future interventions against H. pylori growth and colonization.

Current advances in the development of bioluminescent probes toward spatiotemporal trans-scale imaging.

Bioluminescence imaging has recently attracted great attention as a highly sensitive and non-invasive analytical method. However, weak signal and low chemical stability of the luciferin are conventional drawbacks of bioluminescence imaging. In this review article, we describe the recent progress on the development and applications of bioluminescent probes for overcoming the aforementioned limitations, thereby enabling spatiotemporal trans-scale imaging. The detailed molecular design for manipulation of their luminescent properties and functions enabled a variety of applications, including in vivo deep tissue imaging, long-term imaging, and chemical sensor.

Unveiling the Therapeutic Potentials of Water Hyacinth (Eichhornia crassipes (Mart.) Solms) Flower against Oxidative Stress, Inflammation and Depressive Disorders: GC-MS/MS, In Vitro, In Vivo and In Silico Approaches.

Water hyacinth (Eichhornia crassipes (Mart.) Solms) is a highly invasive aquatic weed native to the Amazonia basin, known for its rapid propagation, adaptability and utilization in traditional medicine. The study aims to unveil the therapeutic potential of water hyacinth flowers methanolic extract (EC-CME) and its four kupchan fractions (EC-PESF, EC-DCMSF, EC-EASF, EC-ASF) through diversified chemical-pharmacological approaches. GC-MS/MS of EC-CME uncovered a rich tapestry of 72 phytochemical components. In vitro DPPH scavenging assay and total phenolic content determination assay deciphered promising antioxidant assays with remarkably low IC50 values of 0.353 and 0.485 µg/mL, respectively for EC-ESF and EC-ASF. Besides, different in vivo tests, including tail emersion, acetic acid-induced writhing, and thiopental-induced sleeping test of EC-CME, yielded a remarkable 8.61 ± 0.29 minutes of tail immersion time compared to the control's 2.05 ± 0.11 minutes at the highest dose (600 mg/kg). The best % inhibition of writhing was recorded as 47.96% accrued in 400 mg/kg dose, indicating robust pain-relieving properties. The onset and duration of sleep are significantly ameliorated for EC-CME, unveiling its antidepressant potential. Besides, molecular docking studies along with ADME/T analysis also validated the wet lab findings as well as their safety, efficacy and drug-likeliness profile.

Cortical Acetylcholine Response to Deep Brain Stimulation of the Basal Forebrain.

Background: Deep brain stimulation (DBS), the direct electrical stimulation of neuronal tissue in the basal forebrain to enhance release of the neurotransmitter acetylcholine, is under consideration as a method to improve executive function in patients with dementia. While some small studies indicate a positive response in the clinical setting, the relationship between DBS and acetylcholine pharmacokinetics is incompletely understood. Objective: We examined the cortical acetylcholine response to different stimulation parameters of the basal forebrain. Methods: 2-photon imaging was combined with deep brain stimulation. Stimulating electrodes were implanted in the subpallidal basal forebrain, and the ipsilateral somatosensory cortex was imaged. Acetylcholine activity was determined using the GRABACh-3.0 muscarinic acetylcholine receptor sensor, and blood vessels were imaged with Texas red. Results: Experiments manipulating pulse train frequency demonstrated that integrated acetylcholine induced fluorescence was insensitive to frequency, and that peak levels were achieved with frequencies from 60 to 130 Hz. Altering pulse train length indicated that longer stimulation resulted in higher peaks and more activation with sublinear summation. The acetylcholinesterase inhibitor donepezil increased the peak response to 10s of stimulation at 60Hz, and the integrated response increased 57% with the 2 mg/kg dose, and 126% with the 4 mg/kg dose. Acetylcholine levels returned to baseline with a time constant of 14 to 18 seconds in all experiments. Conclusions: These data demonstrate that acetylcholine receptor activation is insensitive to frequency between 60 and 130 Hz. High peak responses are achieved with up to 900 pulses. Donepezil increases total acetylcholine receptor activation associated with DBS but did not change temporal kinetics. The long time constants observed in the cerebral cortex add to the evidence supporting volume in addition to synaptic transmission.

Dietary incorporation of magnetic bentonite nanocomposite: impacts on in vitro fermentation pattern, nutrient digestibility, and growth performance of Baluchi male lambs.

Background: Incorporation of bentonite into the diets of ruminants can be helpful to maximize their performance. Modifying the structure of bentonite to nano and nanocomposite has improved their chemical stability and physicochemical properties, enhancing adsorption, absorption, and cation exchange capacity. Aims: This study aimed to assess the effect of magnetic bentonite nanocomposite (MBNC) on in vivo and in vitro fermentation process patterns, nutrient digestibility, and growth performance of Baluchi male lambs. Methods: Effects of control (basal diet), natural bentonite (NB) (10 g/kg dry matter (DM)), processed bentonite (PB) (5 and 10 g/kg DM basal diet), and MBNC (5 and 10 g/kg DM basal diet) on gas production (GP), and the fermentation process were determined using in vitro GP technique. For the in vivo experiment, 20 Baluchi male lambs were used with 4 experimental treatments: control, NB (5 g/kg DM), PB (5 g/kg DM), and MBNC (5 g/kg DM) and 5 replications in a completely randomized design for 60 consecutive days. Results: The potential for GP and its fractional rates were significantly decreased and increased in MBNC, respectively (P<0.01). The lowest cumulative GP, and CH4 yield were observed in MBNC (P<0.05). In vitro, DM and organic matter (OM) digestibility and all fermentation parameters increased with the addition of two levels of MBNC to the culture medium (P<0.01). Except for feed conversion ratio (FCR), other growth performance parameters increased with the addition of MBNC to the diet (P<0.01). The ruminal pH, total volatile fatty acids (TVFA), acetate, and propionate significantly increased when MBNC incorporated to the diet (P<0.01). The NH3-N (P<0.001) was significantly decreased in MBNC. The bentonite supplementation decreased acetate to propionate (P=0.001) compared to the control. Conclusion: Adding MBNC at the 5 g/kg diet DM level can be used as a useful supplement to optimize rumen fermentation pattern, reduce methane production, and increase lamb performance.

Transdermal Drug Delivery of Rizatriptan Using Microneedles Array Patch: Preparation, Characterization and Ex-vivo/In-Vivo Study.

Given the extensive first pass metabolism of rizatriptan in oral administration and its delayed absorption during a migraine attack as a result of gastric stasis, focus has been on transdermal delivery. The main purpose of this study is to prepare and assess transdermal formulation of rizatriptan, loaded on hydrogel microneedles delivery system, to avoid first pass metabolism and also improve its percutaneous permeation rate. Rizatriptan hydrogel microneedles were prepared using micromolding method and evaluated in terms of mechanical strength, encapsulation efficiency, permeation and in-vivo skin absorption. Different formulations of rizatriptan microneedles (F1-F5) were successfully prepared using different concentrations of carboxymethyl cellulose and gelatin type A. Rizatriptan hydrogel microneedles demonstrated favorable mechanical properties, demonstrating its mechanical strength to withstand insertion forces, thereby enhancing its skin insertion ability. In permeation study the percent cumulative drug released after 24 hours ranged between 93.1-100% which means that microneedles were able to deliver the drug effectively. For in-vivo study, F3 formulation was selected due to its superior characteristics over other formulations as it exhibited the highest swelling capacity, demonstrated favorable mechanical properties. Furthermore, F3 showcased the most controlled drug release over a 24-hour period. Relative bioavailability of F3 microneedles was 179.59% compared to oral administration based on the AUC0-24. The observed AUC0-24 in F3 microneedles was statistically significant and 1.80 times greater than that in oral administration. The higher rizatriptan level in the microneedle demonstrated adequate drug permeability through the rat skin, suggesting the potential of microneedles for enhanced therapeutic effectiveness.

Upconversion nanoparticles-CuMnO2 nanoassemblies for NIR-excited imaging of reactive oxygen species in vivo.

Here, we designed a ratiometric luminescent nanoprobe based on lanthanide-doped upconversion nanoparticles-CuMnO2 nanoassemblies for rapid and sensitive detection of reactive oxygen species (ROS) levels in living cells and mouse. CuMnO2 nanosheets exhibit a wide absorption range of 300-700 nm, overlapping with the visible-light emission of upconversion nanoparticles (UCNPs), resulting in a significant upconversion luminescence quenching. In an acidic environment, H2O2 can promote the redox reaction of CuMnO2, leading to its dissociation from the surface of UCNPs and the restoration of upconversion luminescence. The variation in luminescence intensity ratio (UCL475/UCL450) were monitored to detect ROS levels. The H2O2 nanoprobe exhibited a linear response in the range of 0.314-10 µM with a detection limit of 11.3 nM. The biological tests proved the excellent biocompatibility and low toxicity of obtained UCNPs-CuMnO2 nanoassemblies. This ratiometric luminescent nanoprobe was successfully applied for the detection of exogenous and endogenous ROS in live cells as well as in vivo ROS quantitation. The dual transition metal ions endow this probe efficient catalytic decomposition capabilities, and this sensing strategy broadens the application of UCNPs-based nanomaterials in the field of biological analysis and diagnosis.

In vivo antibody labeling route and fluorophore dictate labeling efficiency, sensitivity, and longevity.

Leukocytes migrate through the blood and extravasate into organs to surveil the host for infection or cancer. Recently, we demonstrated that intravenous (IV) anti-CD45.2 antibody labeling allowed for precise tracking of leukocyte migration. However, the narrow labeling window can make this approach challenging for tracking rare migration events. Here, we show that altering antibody administration route and fluorophore can significantly extend the antibody active labeling time. We found that while both IV and intraperitoneal (IP) anti-CD45.2 antibody labeled circulating leukocytes after injection, they had different kinetic properties that impacted labeling time and intensity. Quantification of circulating antibody revealed that while unbound IV anti-CD45.2 antibody rapidly decreased, unbound IP anti-CD45.2 antibody increased over one hour. Using in vitro and in vivo serial dilution assays, we found that Alexa Fluor 647 (AF647) and Brilliant Blue 700 (BB700) dyes had the greatest labeling sensitivity compared to other fluorophores. However, IP antibody injection with anti-CD45.2 BB700, but not AF647, resulted in continuous blood leukocyte labeling for over 6 hours. Finally, we leveraged IP anti-CD45.2 BB700 antibody to track slower migrating leukocytes into tumors. We found that IP anti-CD45.2 antibody injection allowed for the identification of ~seven times as many tumor-specific CD8+ T cells that had recently migrated from blood into tumors. Our results demonstrate how different injection routes and fluorophores affect anti-CD45.2 antibody leukocyte labeling and highlight the utility of this approach for defining leukocyte migration in the context of homeostasis and cancer.

Antisense Oligonucleotide Embedded Context Responsive Nanoparticles Derived from Synthetic Ionizable Lipids for lncRNA Targeted Therapy of Breast Cancer.

The long noncoding RNAs (lncRNA) are primarily associated with several essential gene regulations but are also connected to cancer metabolism and progression. HOTAIR and MALAT1 are two such lncRNAs that are detected in malignancies of various origins and are responsible for the poor prognosis of cancer patients. Due to these factors, the lncRNAs have emerged as prime targets for the development of anticancer therapeutics. However, nonviral delivery of lncRNA-targeted antisense oligonucleotides (ASOs) still remains a critical challenge while maintaining their structural and functional integrity. Herein, we have designed and synthesized a new series of ionizable lipids with variations in their head groups to prepare lipid nanoparticle (LNP) formulation along with cholesterol-based twin cationic lipid and amphiphilic zwitterionic lipid. The context responsiveness of these formulations in delivering the ASOs has been thoroughly investigated by various bioanalytical techniques, and an optimum formulation has been identified. The LNPs are utilized to deliver the ASOs targeting HOTAIR lncRNA in human cancer cell lines and MALAT1 lncRNA in mouse models. This study thus standardizes an advanced nanomaterial system for nonviral gene delivery that has been validated by a considerable reduction in the target lncRNA level under in vitro and a significant reduction in tumor volume under in vivo settings.

Discovery of novel 2-substituted 2, 3-dihydroquinazolin-4(1H)-one derivatives as tubulin polymerization inhibitors for anticancer therapy: The in vitro and in vivo biological evaluation.

A series of novel 2-substituted 2, 3-dihydroquinazolin-4(1H)-one derivatives were designed, synthesized and estimated for their in vitro antiproliferative activities against HepG2, U251, PANC-1, A549 and A375 cell lines. Among them, compound 32 was the most promising candidate, and displayed strong broad-spectrum anticancer activity. The mechanism studies revealed that compound 32 inhibited tubulin polymerization in vitro, disrupted cell microtubule networks, arrested the cell cycle at G2/M phase, and induced apoptosis by up-regulating the expression of cleaved PARP-1 and caspase-3. Furthermore, molecular docking analysis suggested that compound 32 well occupied the binding site of tubulin. In addition, compound 32 exhibited no significant activity against 30 different kinases respectively, indicating considerable selectivity. Moreover, compound 32 significantly inhibited the tumour growth of the HepG2 xenograft in a nude mouse model by oral gavage without apparent toxicity. These results demonstrated that some 2-substituted 2, 3- dihydroquinazolin-4(1H)-one derivatives bearing phenyl, biphenyl, naphthyl or indolyl side chain at C2-position might be potentially novel antitumor agents as tubulin polymerization inhibitors.

Mechanical and Thermal Stimulation for Studying the Somatosensory System: a Review on Devices and Methods.

The somatosensory system is widely studied to understand its functioning mechanisms. Multiple tests, based on different devices and methods, have been performed not only on humans but also on animals and ex-vivo models. Depending on the nature of the sample under analysis and on the scientific aims of interest, several solutions for experimental stimulation and for investigations on sensation or pain have been adopted. In this review paper, an overview of the available devices and methods has been reported, also analyzing the representative values adopted during literature experiments. Among the various physical stimulations used to study the somatosensory system, we focused only on mechanical and thermal ones. Based on the analysis of their main features and on literature studies, we pointed out the most suitable solution for humans, rodents, and ex-vivo models and investigation aims (sensation and pain).

Research Progress on Detection of New Psychoactive Substance Piperazines in vivo.

Piperazines are a class of new psychoactive substances with hallucinogenic effects that affect the central nervous system by affecting the level of monoamine neurotransmitters. Abuse of piperazines will produce stimulating and hallucinogenic effects, accompanied by headache, dizziness, anxiety, insomnia, vomiting, chest pain, tachycardia, hypertension and other adverse reactions, and may even cause cardiovascular diseases and multiple organ failure and lead to death, seriously affecting human physical and mental health and public safety. The abuse of new psychoactive substance piperazines has attracted extensive attention from the international community. The study of its pharmacological toxicology and analytical methods has become a research hotspot in the field of forensic medicine. This paper reviews the in vivo processes, sample treatment and analytical methods of existing piperazines, in order to provide reference for forensic identification.

Repetitive mild closed-head injury induced synapse loss and increased local BOLD-fMRI signal homogeneity.

Repeated mild head injuries due to sports, or domestic violence and military service are increasingly linked to debilitating symptoms in the long term. Although symptoms may take decades to manifest, potentially treatable neurobiological alterations must begin shortly after injury. Better means to diagnose and treat traumatic brain injuries, requires an improved understanding of the mechanisms underlying progression and means through which they can be measured. Here, we employ a repetitive mild closed-head injury (rmTBI) and chronic variable stress (CVS) mouse model to investigate emergent structural and functional brain abnormalities. Brain imaging is achieved with [18F]SynVesT-1 positron emission tomography, with the synaptic vesicle glycoprotein 2A ligand marking synapse density and BOLD (blood-oxygen-level-dependent) functional magnetic resonance imaging (fMRI). Animals were scanned six weeks after concluding rmTBI/Stress procedures. Injured mice showed widespread decreases in synaptic density coupled with an increase in local BOLD-fMRI synchrony detected as regional homogeneity. Injury-affected regions with higher synapse density showed a greater increase in fMRI regional homogeneity. Taken together, these observations may reflect compensatory mechanisms following injury. Multimodal studies are needed to provide deeper insights into these observations.