An intranasal attenuated Coxsackievirus B3 vaccine induces strong systemic and mucosal immunity against CVB3 lethal challenge.

Coxsackievirus B3 (CVB3) triggers viral myocarditis, with no effective vaccine yet. This fecal-oral transmitted pathogen has prompted interest in mucosal immunization strategies to impede CVB3 spread. We developed a new attenuated vaccine strain, named CVB3(mu). The potential of CVB3(mu) to stimulate mucosal immune protection remains to be elucidated. This study evaluates the attenuation characteristics of CVB3(mu) via a rapid evolution cellular model and RNA sequencing. Its temperature sensitivity and safety were evaluated through in vitro and in vivo experiments. The mucosal immunity protection of CVB3(mu) was assessed via intranasal immunization in Balb/c mice. The results indicate that CVB3(mu) exhibits temperature sensitivity and forms smaller plaques. It sustains fewer genetic mutations and still possesses certain attenuated traits up to the 25th passage, in comparison to CVB3(WT). Intranasal immunization elicited a significant serum neutralizing antibodies, and a substantial sIgA response in nasal washes. In vivo trials revealed CVB3(mu) protection in adult mice and passive protection in suckling mice against lethal CVB3(WT) challenges. In conclusion, CVB3(mu), a live attenuated intranasal vaccine, provides protection involving humoral and mucosal immunity, making it a promising candidate to control CVB3 spread and infection.

Dual-Level Enhanced Nonradiative Carrier Recombination in Wide-Gap Semiconductors: The Case of Oxygen Vacancy in SiO2.

The conventional single-defect-mediated Shockley-Read-Hall model suggests that the nonradiative carrier recombination rate in wide-band gap (WBG) semiconductors would be negligible because the single-defect level is expected to be either far from valence-band-maximum (VBM) or conduction-band-minimum (CBM), or both. However, this model falls short of elucidating the substantial nonradiative recombination phenomena often observed experimentally across various WBG semiconductors. Owing to more localized nature of defect states inherent to WBG semiconductors, when the defect charge state changes, there is a pronounced structural relaxation around the local defect site. This suggests that a defect at each charge state may exhibit a few distinct local configurations, namely, a stable configuration and a few metastable/transit state configurations. Consequently, a dual-level nonradiative recombination model should more realistically exist in WBG semiconductors. In this model, through the dual-level mechanism, electron and hole trap levels are different from each other and could be closer to the CBM for the electron trap and closer to the VBM for the hole trap, respectively; therefore, this significantly increases the corresponding electron and hole capture rates, enhancing the overall process of nonradiative recombination, and explains the experimental observations. In this work, taking technically important SiO2 as an illustrative example, we introduce the dual-level mechanism to elucidate the mechanism of nonradiative carrier recombination in WBG semiconductors. Our findings demonstrated strong alignment with available experimental data, reinforcing the robustness of our proposed dual-level model. Our fundamental understanding, therefore, provides a clear physical picture of the issue and can also be applied to predict the defect-related nonradiative carrier recombination characteristics in other WBG materials.

Exploring the Metal-Insulator Transition in (Ga,Mn)As by Molecular Absorption.

The metal-insulator transition (MIT) is normally assisted by certain external power input, such as temperature, pressure, strain, or doping. However, these may increase the disorder of the crystal or cause other effects, which makes device fabrication complicated and/or hinders large-scale application. Here, we adopt a new approach to obtain robust modulation of physical properties in magnetic semiconductor (Ga,Mn)As by surface molecular modification. We have probed both sides of the MIT with n- and p-type molecular doping. Density functional theory calculations are carried out to determine the stable absorption configuration and charge transfer mechanism of electron acceptor and donor molecules on the semiconductor surface. Both experimental and theoretical results confirm a remarkable modulation in carrier concentrations without introducing impurities or defects. This work points out the possibility of effectively tuning physical properties of solid-state materials by functional molecules, which is clean, flexible, nondestructive, and easily achieved.

Donor-Acceptor Pair Quantum Emitters in Hexagonal Boron Nitride.

Quantum emitters are needed for a myriad of applications ranging from quantum sensing to quantum computing. Hexagonal boron nitride (hBN) quantum emitters are one of the most promising solid-state platforms to date due to their high brightness and stability and the possibility of a spin-photon interface. However, the understanding of the physical origins of the single-photon emitters (SPEs) is still limited. Here we report dense SPEs in hBN across the entire visible spectrum and present evidence that most of these SPEs can be well explained by donor-acceptor pairs (DAPs). On the basis of the DAP transition generation mechanism, we calculated their wavelength fingerprint, matching well with the experimentally observed photoluminescence spectrum. Our work serves as a step forward for the physical understanding of SPEs in hBN and their applications in quantum technologies.

Spatial learning and memory impaired after infection of non-neurotropic influenza virus in BALB/c male mice.

During the influenza pandemic or seasonal influenza outbreak, influenza infection can cause acute influenza-associated encephalopathy/encephalitis (IAE), even death. Patients with severe IAE will also have severe neurological sequelae. Neurologic disorders have been demonstrated in the mice treated with peripheral influenza viruses infection, whether neurotropic or non-neurotropic viruses. However, previous studies focused on the acute phase of infection, and rarely paid attention to a longer range of observations. Therefore, the long-term effect of non-neurotropic virus infection on the host is not very clear. In this study, adult mice were infected with influenza virus H1N1/PR8. Then, spontaneous behavior, body weight, expression of cytokines in brain, spatial learning ability and spatial memory ability were observed, until the complete recovery period. The results showed that cytokines in the brain were highly expressed in the convalescent phase (14 day post inoculation, dpi), especially BDNF, IBA1, CX3CL1 and CD200 were still highly expressed in the recovery phase (28 dpi). Otherwise the emotional and spatial memory ability of mice were impacted in the convalescent phase (14 dpi) and the recovery phase (28 dpi). In brief, BALB/c mice infected with non-neurotropic influenza virus H1N1, the weight and motor ability decreased in acute stage. During the recovery period, the body weight and activity ability were completely restored, whereas the emotion disordered, and the ability of spatial learning and memory were impacted in the infected mice. This long-term behavior impact may be the lag injury caused by non-neurotropic influenza infection.

Extrinsic Photoconduction Induced Short-Wavelength Infrared Photodetectors Based on Ge-Based Chalcogenides.

2D layered photodetectors have been widely researched for intriguing optoelectronic properties but their application fields are limited by the bandgap. Extending the detection waveband can significantly enrich functionalities and applications of photodetectors. For example, after breaking through bandgap limitation, extrinsic Si photodetectors are used for short-wavelength infrared or even long-wavelength infrared detection. Utilizing extrinsic photoconduction to extend the detection waveband of 2D layered photodetectors is attractive and desirable. However, extrinsic photoconduction has yet not been observed in 2D layered materials. Here, extrinsic photoconduction-induced short-wavelength infrared photodetectors based on Ge-based chalcogenides are reported for the first time and the effectiveness of intrinsic point defects are demonstrated. The detection waveband of room-temperature extrinsic GeSe photodetectors with the assistance of Ge vacancies is broadened to 1.6 µm. Extrinsic GeSe photodetectors have an excellent external quantum efficiency (0.5%) at the communication band of 1.31 µm and polarization-resolved capability to subwaveband radiation. Moreover, room-temperature extrinsic GeS photodetectors with a detection waveband to the communication band of 1.55 µm further verify the versatility of intrinsic point defects. This approach provides design strategies to enrich the functionalities of 2D layered photodetectors.

Symmetry-Reduction Enhanced Polarization-Sensitive Photodetection in Core-Shell SbI3 /Sb2 O3 van der Waals Heterostructure.

Structural symmetry is a simple way to quantify the anisotropic properties of materials toward unique device applications including anisotropic transportation and polarization-sensitive photodetection. The enhancement of anisotropy can be achieved by artificial symmetry-reduction design. A core-shell SbI3 /Sb2 O3 nanowire, a heterostructure bonded by van der Waals forces, is introduced as an example of enhancing the performance of polarization-sensitive photodetectors via symmetry reduction. The structural, vibrational, and optical anisotropies of such core-shell nanostructures are systematically investigated. It is found that the anisotropic absorbance of a core-shell nanowire is obviously higher than that of two single compounds from both theoretical and experimental investigations. Anisotropic photocurrents of the polarization-sensitive photodetectors based on these core-shell SbI3 /Sb2 O3 van der Waals nanowires are measured ranging from ultraviolet (UV) to visible light (360-532 nm). Compared with other van der Waals 1D materials, low anisotropy ratio (Imax /Imin ) is measured based on SbI3 but a device based on this core-shell nanowire possesses a relatively high anisotropy ratio of ≈3.14 under 450 nm polarized light. This work shows that the low-symmetrical core-shell van der Waals heterostructure has large potential to be applied in wide range polarization-sensitive photodetectors.

Anaphase-promoting complex/cyclosome-Cdc-20 promotes Zwint-1 degradation.

ZW10 interactor (Zwint-1) is an important component of the centromere and can recruit the dynamic protein kinase and dynein to promote chromosome movement and regulate the spindle assembly checkpoint (SAC). Zwint-1 activity is tightly regulated during the cell cycle. However, how the stability of Zwint-1 is regulated has not been clarified. Here, we show that the relative levels of Zwint-1 expression gradually decreased with the progression of cell cycling and decline sharply during mitotic exit. Treatment with cycloheximide reduced the levels of Zwint-1 while treatment with MG132 to inhibit endogenous ubiquitin-proteasome elevated the levels of Zwint-1 in HEK293T cells or Hela cells. Such data suggest that Zwint-1 may be degraded by endogenous ubiquitin-proteasome. Furthermore, induction of cell-division cycle protein 20 (Cdc20) overexpression decreased the levels of Zwint-1, which was abrogated by MG132 treatment. In contrast, Cdc20 silencing promoted the accumulation of Zwint-1. in vivo ubiquitination assay revealed that Cdc20 promoted the formation of Zwint-1 and ubiquitin-proteasome conjugates. Cotransfection with Cdc20 and wild-type Zwint-1, but not Zwint-1ΔD-box , reduced the levels of Zwint-1. Immunoprecipitation and western blot analyses showed that Cdc20 interacted with wild-type Zwint-1, but not Zwint-1ΔD-box although both Zwint-1 and Zwint-1ΔD-box overexpression did not induce mitotic arrest. Collectively, our data indicated that Zwint-1 was ubiquitinated by anaphase-promoting complex/cyclosome (APC/C)-Cdc20 in a D-box-dependent manner. Therefore, the APC/C-Cdc20 controls the stability of Zwint-1, ensuring accurate regulation of the spindle assembly during the cell cycling in HEK293T cells.

Highly polarization sensitive photodetectors based on quasi-1D titanium trisulfide (TiS3).

Photodetectors with high polarization sensitivity are in great demand in advanced optical communication. Here, we demonstrate that photodetectors based on titanium trisulfide (TiS3) are extremely sensitive to polarized light (from visible to the infrared), due to its reduced in-plane structural symmetry. By density functional theory calculation, TiS3 has a direct bandgap of 1.13 eV. The highest photoresponsivity reaches 2500 A W-1. What is more, in-plane optical selection caused by strong anisotropy leads to the photoresponsivity ratio for different directions of polarization that can reach 4:1. The angle-dependent photocurrents of TiS3 clearly display strong linear dichroism. Moreover, the Raman peak at 370 cm-1 is also very sensitive to the polarization direction. The theoretical optical absorption of TiS3 is calculated by using the HSE06 hybrid functional method, in qualitative agreement with the observed experimental photoresponsivity.

Oxymatrine Inhibits Influenza A Virus Replication and Inflammation via TLR4, p38 MAPK and NF-κB Pathways.

Oxymatrine (OMT) is a strong immunosuppressive agent that has been used in the clinic for many years. In the present study, by using plaque inhibition, luciferase reporter plasmids, qRT-PCR, western blotting, and ELISA assays, we have investigated the effect and mechanism of OMT on influenza A virus (IAV) replication and IAV-induced inflammation in vitro and in vivo. The results showed that OMT had excellent anti-IAV activity on eight IAV strains in vitro. OMT could significantly decrease the promoter activity of TLR3, TLR4, TLR7, MyD88, and TRAF6 genes, inhibit IAV-induced activations of Akt, ERK1/2, p38 MAPK, and NF-κB pathways, and suppress the expressions of inflammatory cytokines and MMP-2/-9. Activators of TLR4, p38 MAPK and NF-κB pathways could significantly antagonize the anti-IAV activity of OMT in vitro, including IAV replication and IAV-induced cytopathogenic effect (CPE). Furthermore, OMT could reduce the loss of body weight, significantly increase the survival rate of IAV-infected mice, decrease the lung index, pulmonary inflammation and lung viral titter, and improve pulmonary histopathological changes. In conclusion, OMT possesses anti-IAV and anti-inflammatory activities, the mechanism of action may be linked to its ability to inhibit IAV-induced activations of TLR4, p38 MAPK, and NF-κB pathways.

Origin of the Distinct Diffusion Behaviors of Cu and Ag in Covalent and Ionic Semiconductors.

It is well known that Cu diffuses faster than Ag in covalent semiconductors such as Si, which has prevented the replacement of Ag by Cu as a contact material in Si solar cells for reducing the cost. Surprisingly, in more ionic materials such as CdTe, Ag diffuses faster than Cu despite that it is larger than Cu, which has prevented the replacement of Cu by Ag in CdTe solar cells to improve the performance. But, so far, the mechanisms behind these distinct diffusion behaviors of Cu and Ag in covalent and ionic semiconductors have not been addressed. Here we reveal the underlying mechanisms by combining the first-principles calculations and group theory analysis. We find that the symmetry controlled s-d coupling plays a critical role in determining the diffusion behaviors. The s-d coupling is absent in pure covalent semiconductors but increases with the ionicity of the zinc blende semiconductors, and is larger for Cu than for Ag, owing to its higher d orbital energy. In conjunction with Coulomb interaction and strain energy, the s-d coupling is able to explain all the diffusion behaviors from Cu to Ag and from covalent to ionic hosts. This in-depth understanding enables us to engineer the diffusion of impurities in various semiconductors.

Dynamical Symmetry-Reduction-Induced Giant Anharmonicity in IV-VI Compounds: Role of Cation Lone-Pair s Electrons.

The low thermal conductivity of group IV-VI semiconductors is often attributed to the soft phonons and giant anharmonicity observed in these materials. However, there is still no broad consensus on the fundamental origin of this giant anharmonic effect. Utilizing first-principles calculations and group symmetry analysis, we find that the cation lone-pairs s electrons in IV-VI materials cause a significant coupling between occupied cation s orbitals and unoccupied cation p orbitals due to the symmetry reduction when atoms vibrate away from their equilibrium positions under heating. This leads to an electronic energy gain, consequently flattening the potential energy surface and causing soft phonons and strong anharmonic effects. Our findings provide an intrinsic understanding of the low thermal conductivity in IV-VI compounds by connecting the anharmonicity with the dynamical electronic structures, and can also be extended to a large family of hybrid systems with lone-pair electrons, for promising thermoelectric applications and predictive designs.

Transforming growth factor-ß1 protects mechanically injured cortical murine neurons by reducing trauma-induced autophagy and apoptosis.

Transforming growth factor ß1 (TGF-ß1) has a neuroprotective function in traumatic brain injury (TBI) through its anti-inflammatory and immunomodulatory properties. However, the precise mechanisms underlying the neuroprotective actions of TGF-ß1 on the cortex require further investigation. In this study, we were aimed to investigate the regulatory function of TGF-ß1 on neuronal autophagy and apoptosis using an in vitro primary cortical neuron trauma-injury model. LDH activity was assayed to measure cell viability, and intracellular [Ca2+] was measured using Fluo-4-AM in an in vitro primary cortical neuron trauma-injury model. RNA-sequencing (RNAseq), immunofluorescent staining, transmission electron microscopy (TEM), western blot and CTSD activity detection were employed. We observed significant enrichment of DEGs related to autophagy, apoptosis, and the lysosome pathway in trauma-injured cortical neurons. TEM confirmed the presence of autophagosomes as well as autophagolysosomes. Western blot revealed upregulation of autophagy-related protein light chain 3 (LC3-II/LC3-I), sequestosome 1 (SQSTM1/p62), along with apoptosis-related protein cleaved-caspase 3 in trauma-injured primary cortical neurons. Furthermore, trauma-injured cortical neurons showed an upregulation of lysosomal marker protein (LAMP1) and lysosomal enzyme mature cathepsin D (mCTSD), but a decrease in the activity of CTSD enzyme. These results indicated that apoptosis was up-regulated in trauma- injured cortical neurons at 24 h, accompanied by lysosomal dysfunction and impaired autophagic flux. Notably, TGF-ß1 significantly reversed these changes. Our results suggested that TGF-ß1 exerted neuroprotective effects on trauma- injured cortical neurons by reducing lysosomal dysfunction, decreasing the accumulation of autophagosomes and autophagolysosomes, and enhancing autophagic flux.

Blood Stream Microbiota Dysbiosis Establishing New Research Standards in Cardio-Metabolic Diseases, A Meta-Analysis Study.

AIMS: Scientists have recently discovered a link between the circulating microbiome and homeostasis, as well as the pathogenesis of a number of metabolic diseases. It has been demonstrated that low-grade chronic inflammation is one of the primary mechanisms that has long been implicated in the risk of cardio-metabolic disease (CMDs) and its progression. Currently, the dysbiosis of circulating bacteria is considered as a key regulator for chronic inflammation in CMDs, which is why we have conducted this systemic review focused on circulating bacterial dysbiosis. METHODS: A systemic review of clinical and research-based studies was conducted via PubMed, Scopus, Medline, and Web of Science. Literature was considered for risk of bias and patterns of intervention effects. A randomized effect model was used to evaluate the dysbiosis of circulating microbiota and clinical outcomes. We conducted a meta-analysis considering the circulating bacteria in both healthy people and people with cardio-metabolic disorders, in reports published mainly from 2008 to 2022, according to the PRISMA guidelines. RESULTS: We searched 627 studies and, after completing the risk of bias and selection, 31 studies comprising of 11,132 human samples were considered. This meta-analysis found that dysbiosis of phyla Proteobacteria, Firmicutes, and Bacteroidetes was associated with metabolic diseases. CONCLUSIONS: In most instances, metabolic diseases are linked to higher diversity and elevated bacterial DNA levels. Bacteroides abundance was higher in healthy people than with metabolic disorders. However, more rigorous studies are required to determine the role of bacterial dysbiosis in cardio-metabolic diseases. Understanding the relationship between dysbiosis and cardio-metabolic diseases, we can use the bacteria as therapeutics for the reversal of dysbiosis and targets for therapeutics use in cardio-metabolic diseases. In the future, circulating bacterial signatures can be used as biomarkers for the early detection of metabolic diseases.

Low symmetric sub-wavelength array enhanced lensless polarization-sensitivity photodetector of germanium selenium.

Polarization-sensitive photodetectors, with the ability of identifying the texture-, stress-, and roughness-induced light polarization state variation, displace unique advantages in the fields of national security, medical diagnosis, and aerospace. The utilization of in-plane anisotropic two-dimensional (2D) materials has led the polarization photodetector into a polarizer-free regime, and facilitated the miniaturization of optoelectronic device integration. However, the insufficient polarization ratio (usually less than 10) restricts the detection resolution of polarized signals. Here, we designed a sub-wavelength array (SWA) structure of 2D germanium selenium (GeSe) to further improve its anisotropic sensitivity, which boosts the polarized photocurrent ratio from 1.6 to 18. This enhancement comes from the combination of nano-scale arrays with atomic-scale lattice arrangement at the low-symmetric direction, while the polarization-sensitive photoresponse along the high-symmetric direction is strongly suppressed due to the SWA-caused depolarization effect. Our mechanism study revealed that the SWA can improve the asymmetry of charge distribution, attenuate the matrix element in zigzag direction, and the localized surface plasma, which elevates the photo absorption and photoelectric transition probability along the armchair direction, therefore accounts for the enhanced polarization sensitivity. In addition, the photodetector based on GeSe SWA exhibited a broad power range of 40 dB at a near-infrared wavelength of 808 nm and the ability of weak-light detection under 0.1 LUX of white light (two orders of magnitude smaller than pristine 2D GeSe). This work provides a feasible guideline to improve the polarization sensitivity of 2D materials, and will greatly benefit the development of polarized imaging sensors.

Electrical and magnetic anisotropies in van der Waals multiferroic CuCrP2S6.

Multiferroic materials have great potential in non-volatile devices for low-power and ultra-high density information storage, owing to their unique characteristic of coexisting ferroelectric and ferromagnetic orders. The effective manipulation of their intrinsic anisotropy makes it promising to control multiple degrees of the storage "medium". Here, we have discovered intriguing in-plane electrical and magnetic anisotropies in van der Waals (vdW) multiferroic CuCrP2S6. The uniaxial anisotropies of current rectifications, magnetic properties and magnon modes are demonstrated and manipulated by electric direction/polarity, temperature variation and magnetic field. More important, we have discovered the spin-flop transition corresponding to specific resonance modes, and determined the anisotropy parameters by consistent model fittings and theoretical calculations. Our work provides in-depth investigation and quantitative analysis of electrical and magnetic anisotropies with the same easy axis in vdW multiferroics, which will stimulate potential device applications of artificial bionic synapses, multi-terminal spintronic chips and magnetoelectric devices.

Human circulating bacteria and dysbiosis in non-infectious diseases.

Blood microorganisms were once thought to indicate infection. Blood in healthy people appears to be devoid of growing bacteria; nonetheless, intracellular dormant forms of bacteria have been reported previously. With breakthroughs in sequencing and bioinformatics, the presence of bacterial DNA in healthy human blood initiated the controversy of human blood microbiota (HBM). Recently, bacteria-specific DNA and culturable bacteria were found in healthy human blood. Researchers wanted to study the phenomena of a "healthy blood microbiota" by providing a thorough description of bacterially produced nucleic acids using many complementing molecular and traditional microbiological approaches. Because blood is a relatively limited and particular environment, culturability and plate count issues can be overcome using enhanced cultured procedures. However, more evidence is required to confirm that healthy human blood contains normal microbiota. Cavities, mouth and intestinal microbiota, trauma, surgery, and animal/insect bites can introduce bacteria into human blood. All these factors strengthen the concept of transient blood bacteria too. The presence of blood bacteria may be caused by temporary immunological clearance and absorption by dendritic or M cells. This review provides an extensive and comprehensive analysis that suggests that healthy blood bacteria may not be typical microbiota but transient circulatory microorganisms. In this study, we look at how contaminants (Escherichia, Shigella, Pseudomonads, etc.) from the skin, laboratory environments, and reagents can affect the interpretation of blood-derived microbial information and the relationship between the circulating bacteria and non-communicable diseases. Circulating transient bacteria may play a role in the pathogenesis of non-infectious diseases such as diabetes and CVD. Contamination-free hematological studies can aid in understanding the disease mechanisms, therapy, and biomarkers.

Inactive (PbI2)2RbCl stabilizes perovskite films for efficient solar cells.

In halide perovskite solar cells the formation of secondary-phase excess lead iodide (PbI2) has some positive effects on power conversion efficiency (PCE) but can be detrimental to device stability and lead to large hysteresis effects in voltage sweeps. We converted PbI2 into an inactive (PbI2)2RbCl compound by RbCl doping, which effectively stabilizes the perovskite phase. We obtained a certified PCE of 25.6% for FAPbI3 (FA, formamidinium) perovskite solar cells on the basis of this strategy. Devices retained 96% of their original PCE values after 1000 hours of shelf storage and 80% after 500 hours of thermal stability testing at 85°C.

TGF-ß1 Protects Trauma-injured Murine Cortical Neurons by Upregulating L-type Calcium Channel Cav1.2 via the p38 Pathway.

Traumatic brain injury (TBI) is a leading cause of disability and death in adolescents, and there is a lack of effective methods of treatment. The neuroprotective effects exerted by TGF-ß1 can ameliorate a range of neuronal lesions in multiple central nervous system diseases. In this study, we used an in-vitro TBI model of mechanical injury on murine primary cortical neurons and the neuro-2a cell line to investigate the neuroprotective role played by TGF-ß1 in cortical neurons in TBI. Our results showed that TGF-ß1 significantly increased neuronal viability and inhibited apoptosis for 24 h after trauma. The expression of Cav1.2, an L-type calcium channel (LTCC) isoform, decreased significantly after trauma injury, and this change was reversed by TGF-ß1. Nimodipine, a classic LTCC blocker, abolished the protective effect of TGF-ß1 on trauma-induced neuronal apoptosis. The knockdown of Cav1.2 in differentiated neuro-2a cells significantly inhibited the anti-apoptosis effect of TGF-ß1 exerted on injured neuro-2a cells. Moreover, TGF-ß1 rescued and enhanced the trauma-suppressed neuro-2a intracellular Ca2+ concentration, while the effect of TGF-ß1 was partially inhibited by nimodipine. TGF-ß1 significantly upregulated the expression of Cav1.2 by activating the p38 MAPK pathway and by inhibiting trauma-induced neuronal apoptosis. In conclusion, TGF-ß1 increased trauma-injured murine cortical neuronal activity and inhibited apoptosis by upregulating Cav1.2 channels via activating the p38 MAPK pathway. Therefore, the TGF-ß1/p38 MAPK/Cav 1.2 pathway has the potential to be used as a novel therapeutic target for TBI.