Brain-body mechanisms contribute to sexual dimorphism in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is the most common form of human motor neuron disease. It is characterized by the progressive degeneration of upper and lower motor neurons, leading to generalized motor weakness and, ultimately, respiratory paralysis and death within 3-5 years. The disease is shaped by genetics, age, sex and environmental stressors, but no cure or routine biomarkers exist for the disease. Male individuals have a higher propensity to develop ALS, and a different manifestation of the disease phenotype, than female individuals. However, the mechanisms underlying these sex differences remain a mystery. In this Review, we summarize the epidemiology of ALS, examine the sexually dimorphic presentation of the disease and highlight the genetic variants and molecular pathways that might contribute to sex differences in humans and animal models of ALS. We advance the idea that sexual dimorphism in ALS arises from the interactions between the CNS and peripheral organs, involving vascular, metabolic, endocrine, musculoskeletal and immune systems, which are strikingly different between male and female individuals. Finally, we review the response to treatments in ALS and discuss the potential to implement future personalized therapeutic strategies for the disease.

Peripheral mast cells derive the effects of acupuncture in Parkinson's disease.

This research investigates the peripheral mechanisms of acupuncture in treating Parkinson's disease (PD), a progressive neurodegenerative disorder marked by motor impairments. While the central mechanisms of acupuncture have been extensively studied, our focus lies in the peripheral mechanisms at the acupoints, the sites of acupuncture signal initiation. Employing a PD model, we analyzed the local responses to acupuncture stimulation at these points. Our key finding was a significant elevation in both the number and activity of mast cells (MCs) in the peripheral tissues following acupuncture. Intriguingly, pre-treatment with an MC stabilizer diminished the acupuncture's therapeutic effects on PD symptoms. Similarly, local anesthesia with lidocaine at the acupoints attenuated the symptom improvement typically observed with acupuncture. Meanwhile, the augmentation of MC activity induced by acupuncture was significantly impeded by cromolyn, an MC stabilizer, but remained unaffected by lidocaine. This finding suggests that MC activity is a more upstream regulator of acupuncture effects compared to nerve conduction. This study provides groundbreaking insights into the initiation and transmission of acupuncture signals, highlighting the significant role of peripheral MC modulation in PD treatment.

TULIPs decorate the three-dimensional genome of PFA ependymoma.

Posterior fossa group A (PFA) ependymoma is a lethal brain cancer diagnosed in infants and young children. The lack of driver events in the PFA linear genome led us to search its 3D genome for characteristic features. Here, we reconstructed 3D genomes from diverse childhood tumor types and uncovered a global topology in PFA that is highly reminiscent of stem and progenitor cells in a variety of human tissues. A remarkable feature exclusively present in PFA are type B ultra long-range interactions in PFAs (TULIPs), regions separated by great distances along the linear genome that interact with each other in the 3D nuclear space with surprising strength. TULIPs occur in all PFA samples and recur at predictable genomic coordinates, and their formation is induced by expression of EZHIP. The universality of TULIPs across PFA samples suggests a conservation of molecular principles that could be exploited therapeutically.

Clinical outcomes of neoadjuvant chemoradiotherapy followed by total mesorectal excision in locally advanced rectal cancer with mesorectal fascia involvement.

PURPOSE: For the treatment of locally advanced rectal cancer (LARC), research on primary lesions with mesorectal fascia (MRF) involvement is lacking. This study analyzed the clinical outcomes and efficacy of dose-escalated neoadjuvant concurrent chemoradiotherapy (NCRT) to patients with LARC involving MRF. MATERIALS AND METHODS: We retrospectively reviewed 301 patients who were diagnosed with LARC involving MRF and underwent NCRT followed by total mesorectal excision (TME). Patients who received radiotherapy (RT) doses of ≤50.4 Gy were defined as the non-boost group, while ≥54.0 Gy as the boost group. Pathological tumor response and survival outcomes, including intrapelvic recurrence-free survival (IPRFS), distant metastases-free survival (DMFS) and overall survival (OS), were analyzed. RESULTS: A total of 269 patients (89.4%) achieved a negative pathological circumferential resection margin and 104 (34.6%) had good pathological tumor regression grades. With a median follow-up of 32.4 months, IPRFS, DMFS, and OS rates at 5-years were 88.6%, 78.0%, and 91.2%, respectively. In the subgroup analysis by RT dose, the boost group included more advanced clinical stages of patients. For the non-boost group and boost group, 5-year IPRFS rates were 90.3% and 87.0% (p = 0.242), 5-year DMFS rates were 82.0% and 71.3% (p = 0.105), and 5-year OS rates were 93.0% and 80.6% (p = 0.439), respectively. Treatment related toxicity was comparable between the two groups (p = 0.211). CONCLUSION: Although this retrospective study failed to confirm the efficacy of dose-escalated NCRT, favorable IPRFS and pathological complete response was achieved with NCRT followed by TME. Further studies combining patient customized RT dose with systemic therapies are needed.

Oxidized LDL Accelerates Cartilage Destruction and Inflammatory Chondrocyte Death in Osteoarthritis by Disrupting the TFEB-Regulated Autophagy-Lysosome Pathway.

Osteoarthritis (OA) involves cartilage degeneration, thereby causing inflammation and pain. Cardiovascular diseases, such as dyslipidemia, are risk factors for OA; however, the mechanism is unclear. We investigated the effect of dyslipidemia on the development of OA. Treatment of cartilage cells with low-density lipoprotein (LDL) enhanced abnormal autophagy but suppressed normal autophagy and reduced the activity of transcription factor EB (TFEB), which is important for the function of lysosomes. Treatment of LDL-exposed chondrocytes with rapamycin, which activates TFEB, restored normal autophagy. Also, LDL enhanced the inflammatory death of chondrocytes, an effect reversed by rapamycin. In an animal model of hyperlipidemia-associated OA, dyslipidemia accelerated the development of OA, an effect reversed by treatment with a statin, an anti-dyslipidemia drug, or rapamycin, which activates TFEB. Dyslipidemia reduced the autophagic flux and induced necroptosis in the cartilage tissue of patients with OA. The levels of triglycerides, LDL, and total cholesterol were increased in patients with OA compared to those without OA. The C-reactive protein level of patients with dyslipidemia was higher than that of those without dyslipidemia after total knee replacement arthroplasty. In conclusion, oxidized LDL, an important risk factor of dyslipidemia, inhibited the activity of TFEB and reduced the autophagic flux, thereby inducing necroptosis in chondrocytes.

Comparative study for metabolomics, antioxidant activity, and molecular docking simulation of the newly bred Korean red rice accessions.

This study analyzed the metabolite profiles and antioxidant capacities of two waxy and non-waxy Korean red rice accessions newly bred. Fifteen phenolic compounds were detected in the rice samples. Accession1 had high fatty acids, phytosterols, and vitamin E; accession3 had high vitamin E and phytosterol; and accession4 had a high total flavonoid. The correlation analysis findings from this study validated the positive association between all the metabolites and antioxidant activity. in silico results revealed that protocatechuic acid had a docking score of -9.541, followed by luteolin, quercetin, and caffeic acid, all of which had significant docking scores and a significant number of contacts. Similarly, molecular dynamics simulations showed that phytochemicals had root mean square deviation values of <2.8 Å with Keap 1, indicating better stability. This study provides valuable insights into potential directions for future investigations and improvements in the functional qualities of other colored rice varieties.

Effect of Isoscopoletin on Cytokine Expression in HaCaT Keratinocytes and RBL-2H3 Basophils: Preliminary Study.

Isoscopoletin is a compound derived from various plants traditionally used for the treatment of skin diseases. However, there have been no reported therapeutic effects of isoscopoletin on atopic dermatitis (AD). AD is a chronic inflammatory skin disease, and commonly used treatments have side effects; thus, there is a need to identify potential natural candidate substances. In this study, we aimed to investigate whether isoscopoletin regulates the inflammatory mediators associated with AD in TNF-α/IFN-γ-treated HaCaT cells and PMA/ionomycin treated RBL-2H3 cells. We determined the influence of isoscopoletin on cell viability through an MTT assay and investigated the production of inflammatory mediators using ELISA and RT-qPCR. Moreover, we analyzed the transcription factors that regulate inflammatory mediators using Western blots and ICC. The results showed that isoscopoletin did not affect cell viability below 40 µM in either HaCaT or RBL-2H3 cells. Isoscopoletin suppressed the production of TARC/CCL17, MDC/CCL22, MCP-1/CCL2, IL-8/CXCL8, and IL-1ß in TNF-α/IFN-γ-treated HaCaT cells and IL-4 in PMA/ionomycin-treated RBL-2H3 cells. Furthermore, in TNF-α/IFN-γ-treated HaCaT cells, the phosphorylation of signaling pathways, including MAPK, NF-κB, STAT, and AKT/PKB, increased but was decreased by isoscopoletin. In PMA/ionomycin-treated RBL-2H3 cells, the activation of signaling pathways including PKC, MAPK, and AP-1 increased but was decreased by isoscopoletin. In summary, isoscopoletin reduced the production of inflammatory mediators by regulating upstream transcription factors in TNF-α/IFN-γ-treated HaCaT cells and PMA/ionomycin-treated RBL-2H3 cells. Therefore, we suggest that isoscopoletin has the potential for a therapeutic effect, particularly in skin inflammatory diseases such as AD, by targeting keratinocytes and basophils.

CD39 delineates chimeric antigen receptor regulatory T cell subsets with distinct cytotoxic & regulatory functions against human islets.

Human regulatory T cells (Treg) suppress other immune cells. Their dysfunction contributes to the pathophysiology of autoimmune diseases, including type 1 diabetes (T1D). Infusion of Tregs is being clinically evaluated as a novel way to prevent or treat T1D. Genetic modification of Tregs, most notably through the introduction of a chimeric antigen receptor (CAR) targeting Tregs to pancreatic islets, may improve their efficacy. We evaluated CAR targeting of human Tregs to monocytes, a human ß cell line and human islet ß cells in vitro. Targeting of HLA-A2-CAR (A2-CAR) bulk Tregs to HLA-A2+ cells resulted in dichotomous cytotoxic killing of human monocytes and islet ß cells. In exploring subsets and mechanisms that may explain this pattern, we found that CD39 expression segregated CAR Treg cytotoxicity. CAR Tregs from individuals with more CD39low/- Tregs and from individuals with genetic polymorphism associated with lower CD39 expression (rs10748643) had more cytotoxicity. Isolated CD39- CAR Tregs had elevated granzyme B expression and cytotoxicity compared to the CD39+ CAR Treg subset. Genetic overexpression of CD39 in CD39low CAR Tregs reduced their cytotoxicity. Importantly, ß cells upregulated protein surface expression of PD-L1 and PD-L2 in response to A2-CAR Tregs. Blockade of PD-L1/PD-L2 increased ß cell death in A2-CAR Treg co-cultures suggesting that the PD-1/PD-L1 pathway is important in protecting islet ß cells in the setting of CAR immunotherapy. In summary, introduction of CAR can enhance biological differences in subsets of Tregs. CD39+ Tregs represent a safer choice for CAR Treg therapies targeting tissues for tolerance induction.

Centimeter-Scale Tellurium Oxide Films for Artificial Optoelectronic Synapses with Broadband Responsiveness and Mechanical Flexibility.

Prevailing over the bottleneck of von Neumann computing has been significant attention due to the inevitableness of proceeding through enormous data volumes in current digital technologies. Inspired by the human brain's operational principle, the artificial synapse of neuromorphic computing has been explored as an emerging solution. Especially, the optoelectronic synapse is of growing interest as vision is an essential source of information in which dealing with optical stimuli is vital. Herein, flexible optoelectronic synaptic devices composed of centimeter-scale tellurium dioxide (TeO2) films detecting and exhibiting synaptic characteristics to broadband wavelengths are presented. The TeO2-based flexible devices demonstrate a comprehensive set of emulating basic optoelectronic synaptic characteristics; i.e., excitatory postsynaptic current (EPSC), paired-pulse facilitation (PPF), conversion of short-term to long-term memory, and learning/forgetting. Furthermore, they feature linear and symmetric conductance synaptic weight updates at various wavelengths, which are applicable to broadband neuromorphic computations. Based on this large set of synaptic attributes, a variety of applications such as logistic functions or deep learning and image recognition as well as learning simulations are demonstrated. This work proposes a significant milestone of wafer-scale metal oxide semiconductor-based artificial synapses solely utilizing their optoelectronic features and mechanical flexibility, which is attractive toward scaled-up neuromorphic architectures.

Ultrathin, High-Aspect-Ratio Bismuth Sulfohalide Nanowire Bundles for Solution-Processed Flexible Photodetectors.

In this study, a novel synthesis of ultrathin, highly uniform colloidal bismuth sulfohalide (BiSX where X = Cl, Br, I) nanowires (NWs) and NW bundles (NBs) for room-temperature and solution-processed flexible photodetectors are presented. High-aspect-ratio bismuth sulfobromide (BiSBr) NWs are synthesized via a heat-up method using bismuth bromide and elemental S as precursors and 1-dodecanethiol as a solvent. Bundling of the BiSBr NWs occurs upon the addition of 1-octadecene as a co-solvent. The morphologies of the BiSBr NBs are easily tailored from sheaf-like structures to spherulite nanostructures by changing the solvent ratio. The optical bandgaps are modulated from 1.91 (BiSCl) and 1.88 eV (BiSBr) to 1.53 eV (BiSI) by changing the halide compositions. The optical bandgap of the ultrathin BiSBr NWs and NBs exhibits blueshift, whose origin is investigated through density functional theory-based first-principles calculations. Visible-light photodetectors are fabricated using BiSBr NWs and NBs via solution-based deposition followed by solid-state ligand exchanges. High photo-responsivities and external quantum efficiencies (EQE) are obtained for BiSBr NW and NB films even under strain, which offer a unique opportunity for the application of the novel BiSX NWs and NBs in flexible and environmentally friendly optoelectronic devices.

Efficient generation of recombinant anti-HER2 scFv with high yield and purity using a simple method.

We developed a method to produce a soluble form of a single-chain fragment variable (scFv) targeting human epithelial growth factor receptor 2 (HER2) in Escherichia coli. By optimizing the orientations of the variable heavy (VH) and variable light (VL) domains and the His-tag, we identified the HL-His type antibody with the highest HER2-binding activity. Purification of HL-His yielded 40.7 mg from a 1 L culture, achieving >99% purity. The limit of detection was determined to be 2.9 ng, demonstrating high production yield, purity, and sensitivity. Moreover, we successfully labeled HER2+ cell lines with fluorescent dye-conjugated scFv, resulting in a significantly higher observed signal-to-background ratio, compared to that of HER2- cell lines. This highlights the potential of these fluorescent scFvs as valuable probes for HER2+ breast cancer diagnostics. Notably, the process for the complete scFv production was streamlined and required only 4-5 days. Additionally, the product maintained its activity after freeze storage, allowing for large-scale production and a wide range of practical applications.

Lack of association between early on-treatment HBeAg seroclearance and development of hepatocellular carcinoma or decompensated cirrhosis.

Background & Aims: The association between hepatitis B envelope antigen (HBeAg) seroclearance during long-term nucleos(t)ide analogue (NA) treatment and the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB) remains unclear. Here, we aimed to investigate the association of HBeAg seroclearance during potent NA treatment with the development of HCC and decompensated cirrhosis. Methods: Using a multicenter historical cohort including 2,392 non-cirrhotic adult patients with HBeAg-positive CHB who initiated NA treatment with tenofovir or entecavir, the risk of HCC and decompensated cirrhosis was compared between patients who achieved HBeAg seroclearance within 36 months of NA treatment (the HBeAg-loss group) and those who did not (the HBeAg-maintained group), using inverse probability of treatment weighting. Results: Over a median of 6.6 years of NA treatment, 1,077 patients achieved HBeAg seroclearance (HBeAg loss rate = 6.0 per 100 person-years), 64 patients developed HCC (HCC incidence rate = 0.39 per 100 person-years), and 46 patients developed decompensated cirrhosis (decompensation incidence rate = 0.28 per 100 person-years). The HBeAg-loss and HBeAg-maintained groups had a similar risk of developing HCC (hazard ratio 0.89; 95% CI 0.47-1.68; p = 0.72) and decompensated cirrhosis (hazard ratio 0.98; 95% CI 0.48-1.81; p = 0.91). Compared with delayed HBeAg seroclearance beyond 10 years of NA treatment, the risk of HCC was comparable in those who achieved earlier HBeAg seroclearance at any time point within 10 years, regardless of baseline age and fibrotic burden. Conclusions: Early HBeAg seroclearance during NA treatment was not associated with a reduced risk of development of HCC or decompensated cirrhosis in non-cirrhotic HBeAg-positive patients with CHB. Impact and implications: The association between hepatitis B envelope antigen (HBeAg) seroclearance during long-term nucleos(t)ide analogue treatment and the risk of hepatocellular carcinoma in patients with chronic hepatitis B remains unclear. Our findings indicate that early on-treatment HBeAg seroclearance within 3 years was not associated with the development of hepatocellular carcinoma or decompensated cirrhosis. Achieving HBeAg seroclearance may not be an appropriate surrogate endpoint for preventing the development of liver-related outcomes in non-cirrhotic patients with HBeAg-positive chronic hepatitis B treated with nucleos(t)ide analogues.

One-Pot Direct Mechanochemical Silicon Replacement of Sodium Fluorosilicate into Sodium Fluorozirconate and Functionalization of Graphite for Enhanced Sodium-Ion Storage.

Efficient sodium ion storage in graphite is as yet unattainable, because of the thermodynamic instability of sodium ion intercalates-graphite compounds. In this work, sodium fluorozirconate (Na3ZrF7, SFZ) functionalized graphite (SFZ-G) is designed and prepared by the in situ mechanochemical silicon (Si) replacement of sodium fluorosilicate (Na2SiF6, SFS) and functionalization of graphite at the same time. During the mechanochemical process, the atomic Si in SFS is directly replaced by atomic zirconium (Zr) from the zirconium oxide (ZrO2) balls and container in the presence of graphite, forming SFZ-G. The resulting SFZ-G, working as an anode material for sodium ion storage, shows a significantly enhanced capacity of 418.7 mAh g-1 at 0.1 C-rate, compared to pristine graphite (35 mAh g-1) and simply ball-milled graphite (BM-G, 200 mAh g-1). In addition, the SFZ-G exhibits stable sodium-ion storage performance with 86% of its initial capacity retention after 1000 cycles at 2.0 C-rate.

NTRK-fused central nervous system tumours: clinicopathological and genetic insights and response to TRK inhibitors.

Background Neurotrophic tropomyosin receptor kinase (NTRK) gene fusions are found in 1% of gliomas across children and adults. TRK inhibitors are promising therapeutic agents for NTRK-fused gliomas because they are tissue agnostic and cross the blood-brain barrier (BBB). Methods We investigated twelve NGS-verified NTRK-fused gliomas from a single institute, Seoul National University Hospital. Results The patient cohort included six children (aged 1-15 years) and six adults (aged 27-72 years). NTRK2 fusions were found in ten cerebral diffuse low-grade and high-grade gliomas (DLGGs and DHGGs, respectively), and NTRK1 fusions were found in one cerebral desmoplastic infantile ganglioglioma and one spinal DHGG. In this series, the fusion partners of NTRK2 were HOOK3, KIF5A, GKAP1, LHFPL3, SLMAP, ZBTB43, SPECC1L, FKBP15, KANK1, and BCR, while the NTRK1 fusion partners were TPR and TPM3. DLGGs tended to harbour only an NTRK fusion, while DHGGs exhibited further genetic alterations, such as TERT promoter/TP53/PTEN mutation, CDKN2A/2B homozygous deletion, PDGFRA/KIT/MDM4/AKT3 amplification, or multiple chromosomal copy number aberrations. Four patients received adjuvant TRK inhibitor therapy (larotrectinib, repotrectinib, or entrectinib), among which three also received chemotherapy (n = 2) or proton therapy (n = 1). The treatment outcomes for patients receiving TRK inhibitors varied: one child who received larotrectinib for residual DLGG maintained stable disease. In contrast, another child with DHGG in the spinal cord experienced multiple instances of tumour recurrence. Despite treatment with larotrectinib, ultimately, the child died as a result of tumour progression. An adult patient with glioblastoma (GBM) treated with entrectinib also experienced tumour progression and eventually died. However, there was a successful outcome for a paediatric patient with DHGG who, after a second gross total tumour removal followed by repotrectinib treatment, showed no evidence of disease. This patient had previously experienced relapse after the initial surgery and underwent autologous peripheral blood stem cell therapy with carboplatin/thiotepa and proton therapy. Conclusions Our study clarifies the distinct differences in the pathology and TRK inhibitor response between LGG and HGG with NTRK fusions.

Phylogenetic relationships and genetic diversity of the Korean endemic Phedimus latiovalifolius (Crassulaceae) and its close relatives.

Phedimus latiovalifolius (Y.N.Lee) D.C.Son & H.J.Kim is exclusively distributed in the high mountains in the Korean Peninsula, mainly along the Baekdudaegan mountain range. Despite its morphological and distributional distinction from other Phedimus Raf. species, its taxonomic identity and phylogenetic relationship with congeneric species remain unclear. This study employs genotyping-by-sequencing-derived genome-wide single nucleotide polymorphisms to establish the monophyly of P. latiovalifolius and its relationship with closely related species. Genetic diversity and population differentiation of P. latiovalifolius are also assessed to provide baseline genetic information for future conservation and management strategies. Our phylogenetic analyses robustly demonstrate the monophyletic nature of P. latiovalifolius, with P. aizoon (L.) 't Hart identified as its closest sister lineage. There is no genetic evidence supporting a hybrid origin of P. latiovalifolius from P. aizoon involving either P. ellacombeanus (Praeger) 't Hart or P. kamtschaticus (Fisch.) 't Hart. Population genetic analyses reveal two major groups within P. latiovalifolius. A higher genetic variation is observed in P. ellacombeanus than in the congeneric species. Notably, most of the genetic variation exists within P. latiovalifolius populations. Given its distribution and the potential role of Baekdudaegan as an East Asian Pleistocene refugia, P. latiovalifolius could be considered rare and endemic, persisting in the refugium across glacial/interglacial cycles.

Mediation Effect of Social Distancing on Neonatal Vitamin D Status and Related Clinical Outcomes during the Coronavirus Disease-19 Pandemic.

BACKGROUND: We analyzed the impact of social distancing (SD) on vitamin D status and associated morbidity in neonates during the coronavirus disease (COVID-19) pandemic. METHODS: Serum levels of 25-hydroxy vitamin D (25OHD) and clinical characteristics of newborn infants before (2019) and during SD (2021) were compared. RESULTS: A total of 526 neonates (263 in 2019 and 263 in 2021) were included. The rate of vitamin D deficiency in neonates (47.1% vs. 35.4 %, p = 0.008) decreased and the rate of maternal vitamin D intake increased (6.8% vs. 37.6%, p < 0.001), respectively, during SD compared to those in 2019. The rates of hypocalcemia (12.5% vs. 3.8%, p < 0.001) and respiratory illness (57.0% vs. 43.0%, p = 0.002) decreased during SD. Neonatal vitamin D deficiency during SD was associated with maternal vitamin D supplementation (odds ratio [OR] = 0.463, p = 0.003) but was not associated with SD (OR = 0.772, p = 0.189). The mediation effect of SD on neonatal morbidity by neonatal vitamin D status was statistically insignificant. CONCLUSIONS: SD might affect the increased maternal vitamin D intake and decreased neonatal vitamin D deficiency. However, neonatal morbidity was not affected by SD, even with neonatal vitamin D status changes.

ARHGEF5 binds Drebrin and affects α-tubulin acetylation to direct neuronal morphogenesis and migration during mouse brain development.

Rho guanine nucleotide exchange factors (Rho GEFs) activate Rho GTPases, which act as molecular switches regulating various essential cellular functions. This study investigated the role of ARHGEF5, a Rho GEF known for its involvement in cell migration and invasion processes, in the context of brain development. We found that ARHGEF5 is essential for dendrite development during the early stages of neuronal growth. We also discovered that ARHGEF5 binds to Drebrin E, which is vital for coordinating actin and microtubule dynamics, and facilitates the interaction between Drebrin E and Cyclin-dependent kinase 5, which phosphorylates Drebrin E. Notably, ARHGEF5 deficiency resulted in a decrease in acetylated α-tubulin levels, and the expression of an α-tubulin acetylation mimetic mutant (K40Q) rescued the defects in dendrite development and neuronal migration, suggesting ARHGEF5's role in modulating microtubule stability. Additionally, ARHGEF5 was shown to influence Golgi positioning in the leading processes of migrating cortical neurons during brain development. Our study suggests that ARHGEF5 plays a crucial role in integrating cytoskeletal dynamics with neuronal morphogenesis and migration processes during brain development.

Demonstration of a low power and high-speed graphene/silicon heterojunction near-infrared photodetector.

The structure and process of the graphene/Si heterojunction near-infrared photodetector were optimized to enhance the operating speed limit. The introduction of a well-designed structure improved the rise time from 12.6 µs to 115 ns, albeit at the expense of the responsivity, which decreased from 1.25 A W-1 to 0.56 A W-1. Similarly, the falling time was improved from 38 µs to 288 ns with a sacrifice in responsivity from 1.25 A W-1 to 0.29 A W-1, achieved through the introduction of Ge-induced defect-recombination centers within the well. Through a judicious well design and the introduction of recombination defect centers, the minimum pulse width could be improved from 50.6 µs to 435 ns, facilitating 2 MHz operation. This represents more than 100 times increase compared to previously reported graphene and graphene/Si hybrid photodetectors.