Altered Neuronal Activity Patterns of the Prefrontal Cortex in Alzheimer's Disease After Transcranial Alternating Current Stimulation: A Resting-State fMRI Study.

Background: Transcranial alternating current stimulation (tACS) could improve cognition in patients with Alzheimer's disease (AD). However, the effects of tACS on brain activity remain unclear. Objective: The purpose is to investigate the change in regional neuronal activity after tACS in AD patients employing resting-state functional magnetic resonance imaging (rs-fMRI). Methods: A total of 46 patients with mild AD were enrolled. Each patient received 30 one-hour sessions of real or sham tACS for three weeks (clinical trial: NCT03920826). The fractional amplitude of low-frequency fluctuations (fALFF) and the regional homogeneity (ReHo) measured by rs-fMRI were calculated to evaluate the regional brain activity. Results: Compared to baseline, AD patients in the real group exhibited increased fALFF in the left middle frontal gyrus-orbital part and right inferior frontal gyrus-orbital part, as well as increased ReHo in the left precentral gyrus and right middle frontal gyrus at the end of intervention. At the 3-month follow-up, fALFF increased in the left superior parietal lobule and right inferior temporal gyrus, as well as ReHo, in the left middle frontal gyrus and right superior medial frontal gyrus. A higher fALFF in the right lingual gyrus and ReHo in the right parahippocampal gyrus were observed in the response group than in the nonresponse group. Conclusions: The findings demonstrated the beneficial effects of tACS on the neuronal activity of the prefrontal cortex and even more extensive regions and provided a neuroimaging biomarker of treatment response in AD patients.

Closed-Loop Force Control by Biorealistic Hand Prosthesis With Visual and Tactile Sensory Feedback.

The ability of a novel biorealistic hand prosthesis for grasp force control reveals improved neural compatibility between the human-prosthetic interaction. The primary purpose here was to validate a virtual training platform for amputee subjects and evaluate the respective roles of visual and tactile information in fundamental force control tasks. We developed a digital twin of tendon-driven prosthetic hand in the MuJoCo environment. Biorealistic controllers emulated a pair of antagonistic muscles controlling the index finger of the virtual hand by surface electromyographic (sEMG) signals from amputees' residual forearm muscles. Grasp force information was transmitted to amputees through evoked tactile sensation (ETS) feedback. Six forearm amputees participated in force tracking and holding tasks under different feedback conditions or using their intact hands. Test results showed that visual feedback played a predominant role than ETS feedback in force tracking and holding tasks. However, in the absence of visual feedback during the force holding task, ETS feedback significantly enhanced motor performance compared to feedforward control alone. Thus, ETS feedback still supplied reliable sensory information to facilitate amputee's ability of stable grasp force control. The effects of tactile and visual feedback on force control were subject-specific when both types of feedback were provided simultaneously. Amputees were able to integrate visual and tactile information to the biorealistic controllers and achieve a good sensorimotor performance in grasp force regulation. The virtual platform may provide a training paradigm for amputees to adapt the biorealistic hand controller and ETS feedback optimally.

The performance of a combination of heparin-binding protein with other biomarkers for sepsis diagnosis: an observational cohort study.

BACKGROUND: HBP, a novel biomarker released from neutrophils, may induce inflammatory responses and exacerbate vascular permeability, representing the pathophysiological characteristics of sepsis and septic shock. However, it remains uncertain whether the combination of HBP with other biomarkers yields enhanced diagnostic capacity for sepsis. We hypothesized that measurements included IL-6·IL-8·HBP, IL-6·IL-8·HBP/ALB and HBP/ALB which based on HBP will improve its diagnostic efficacy and even better than the traditional infection biomarkers. METHODS: Between July 2021 and June 2022, we carried out a comprehensive, multi-center, observational cohort study spanning six leading tertiary hospitals located in Heilongjiang Province, China. Patients were stratified into three categories based on the severity of infection: non-sepsis, sepsis, and septic shock. We collected clinical and laboratory data, along with infection and inflammation biomarkers, for analysis. RESULTS: A total of 195 patients were enrolled. Among the three groups, patients with septic shock (n = 75, 38.5%) had significantly higher baseline levels of HBP, WBC, Lac, CRP, PCT, IL-6, IL-8, and IL-10 compared to non-sepsis patients (n = 43, 22.0%) and sepsis patients (n = 77, 39.5%), with statistically significant differences (p < 0.05) observed for all parameters. When compared to SOFA score and traditional markers of CRP, PCT, IL-6 and IL-8, the combined indexes of IL-6·IL-8·HBP and IL-6·IL-8·HBP/ALB demonstrated significantly improved diagnostic performance for sepsis and septic shock (AUC 0.911 and 0.902 respectively, p < 0.001). CONCLUSIONS: The combined measurements of IL-6·IL-8·HBP and IL-6·IL-8·HBP/ALB can augment the diagnostic capacity of HBP for sepsis, and offer reliable early supplementary indicators to traditional biomarkers for assessing disease severity in patients with infection.

Characteristics of demersal fish community structure during summer hypoxia in the Pearl River Estuary, China.

In recent decades, hypoxic areas have rapidly expanded worldwide in estuaries and coastal zones. The Pearl River Estuary (PRE), one of China's largest estuaries, experiences frequent seasonal hypoxia due to intense human activities and eutrophication. However, the ecological effects of hypoxia in the PRE, particularly on fish communities, remain unclear. To explore these effects, we collected fish community and environmental data in July 2021 during the summer hypoxia development period. The results revealed that bottom-layer dissolved oxygen (DO) in the PRE ranged from 0.08 to 5.71 mg/L, with extensive hypoxic zones (DO ≤ 2 mg/L) observed. Hypoxia has varied effects on fish community composition, distribution, species, and functional diversity in the PRE. A total of 104 fish species were collected in this study, with approximately 30 species (28.6%) exclusively found in hypoxic areas. Species responses to hypoxia varied: species such as Sardinella zunasi, Coilia mystus, and Nuchequula nuchalis were sensitive, while Decapterus maruadsi, Siganus fuscescens, and Lagocephalus spadiceus showed higher tolerance. Within the hypoxia area, dissolved oxygen was the main limiting factor for fish community diversity. Functional diversity (FDiv) decreased with higher dissolved oxygen levels, indicating a potential shift in the functional traits and ecological roles of fish species in response to changing oxygen conditions. Further analysis demonstrated that dissolved oxygen had a significantly stronger effect on fish community structure at hypoxic sites than in the whole PRE. Moreover, other environmental variables also had significant effects on the fish community structure and interacted with dissolved oxygen in the hypoxia area. These findings suggest that maintaining sufficient dissolved oxygen levels is essential for sustaining fish communities and ecosystem health in the PRE. This study provides novel insights into the effects of hypoxia on fish communities in estuarine ecosystems and has significant implications for the ecological health and management of the PRE.

The Complete Chloroplast Genome Sequence of the Medicinal Moss Rhodobryum giganteum (Bryaceae, Bryophyta): Comparative Genomics and Phylogenetic Analyses.

Rhodobryum giganteum (Bryaceae, Bryophyta), a rare medicinal bryophyte, is valued for its cardiovascular therapeutic properties in traditional Chinese medicine. This study presents the first complete chloroplast genome sequence of R. giganteum, including its assembly and annotation. The circular chloroplast genome of R. giganteum is 124,315 bp in length, displaying a typical quadripartite structure with 128 genes: 83 protein-coding genes, 37 tRNAs, and 8 rRNAs. Analyses of codon usage bias, repetitive sequences, and simple sequence repeats (SSRs) revealed an A/U-ending codon preference, 96 repetitive sequences, and 385 SSRs in the R. giganteum chloroplast genome. Nucleotide diversity analysis identified 10 high mutational hotspots. Ka/Ks ratio analysis suggested potential positive selection in rpl20, rps18, petG, and psbM genes. Phylogenetic analysis of whole chloroplast genomes from 38 moss species positioned R. giganteum within Bryales, closely related to Rhodobryum laxelimbatum. This study augments the chloroplast genomic data for Bryales and provides a foundation for molecular marker development and genetic diversity analyses in medicinal bryophytes.

Cluster analysis as a tool for quantifying structure-transport properties in simulations of superconcentrated electrolyte.

Using molecular dynamics simulations and graph-theory-based cluster analysis, we investigate the structure-transport properties of typical water-in-salt electrolytes. We demonstrate that ions exhibit distinct dynamics across different ionic clusters-namely, solvent-separated ion pairs (SSIPs), contact ion pairs (CIPs), and aggregates (AGGs). We assess the average proportions of various ionic species and their lifetimes. Our method reveals a dynamic decoupling of ion kinetics, with each species independently contributing to the overall molecular motion. This is evidenced by the fact that the total velocity autocorrelation function (VACF) and power spectrum can be expressed as a weighted sum of independent functions for each species. The experimental data on the ionic conductivity of the studied LiTFSI electrolytes align well with our theoretical predictions at various concentrations, based on the proportions and diffusion coefficients of free ions derived from our analysis. The insights gained into the solvation structures and dynamics of different ionic species enable us to elucidate the physical mechanisms driving ion transport in such superconcentrated electrolytes, providing a comprehensive framework for the future design and optimization of electrolytes.

Modeling of Nanomaterials for Supercapacitors: Beyond Carbon Electrodes.

Capacitive storage devices allow for fast charge and discharge cycles, making them the perfect complements to batteries for high power applications. Many materials display interesting capacitive properties when they are put in contact with ionic solutions despite their very different structures and (surface) reactivity. Among them, nanocarbons are the most important for practical applications, but many nanomaterials have recently emerged, such as conductive metal-organic frameworks, 2D materials, and a wide variety of metal oxides. These heterogeneous and complex electrode materials are difficult to model with conventional approaches. However, the development of computational methods, the incorporation of machine learning techniques, and the increasing power in high performance computing now allow us to tackle these types of systems. In this Review, we summarize the current efforts in this direction. We show that depending on the nature of the materials and of the charging mechanisms, different methods, or combinations of them, can provide desirable atomic-scale insight on the interactions at play. We mainly focus on two important aspects: (i) the study of ion adsorption in complex nanoporous materials, which require the extension of constant potential molecular dynamics to multicomponent systems, and (ii) the characterization of Faradaic processes in pseudocapacitors, that involves the use of electronic structure-based methods. We also discuss how recently developed simulation methods will allow bridges to be made between double-layer capacitors and pseudocapacitors for future high power electricity storage devices.

Bioinspired Artificial Visual-Respiratory Synapse as Multimodal Scene Recognition System with Oxidized-Vacancies MXene.

In the pursuit of artificial neural systems, the integration of multimodal plasticity, memory retention, and perceptual functions stands as a paramount objective in achieving neuromorphic perceptual components inspired by the human brain, to emulating the neurological excitability tuning observed in human visual and respiratory collaborations. Here, an artificial visual-respiratory synapse is presented with monolayer oxidized MXene (VRSOM) exhibiting synergistic light and atmospheric plasticity. The VRSOM enables to realize facile modulation of synaptic behaviors, encompassing postsynaptic current, sustained photoconductivity, stable facilitation/depression properties, and "learning-experience" behavior. These performances rely on the privileged photocarrier trapping characteristics and the hydroxyl-preferential selectivity inherent of oxidized vacancies. Moreover, environment recognitions and multimodal neural network image identifications are achieved through multisensory integration, underscoring the potential of the VRSOM in reproducing human-like perceptual attributes. The VRSOM platform holds significant promise for hardware output of human-like mixed-modal interactions and paves the way for perceiving multisensory neural behaviors in artificial interactive devices.

MicroRNA and Gut Microbiota Alter Intergenerational Effects of Paternal Exposure to Polyethylene Nanoplastics.

Nanoplastics (NPs), as emerging contaminants, have been shown to cause testicular disorders in mammals. However, whether paternal inheritance effects on offspring health are involved in NP-induced reproductive toxicity remains unclear. In this study, we developed a mouse model where male mice were administered 200 nm polyethylene nanoparticles (PE-NPs) at a concentration of 2 mg/L through daily gavage for 35 days to evaluate the intergenerational effects of PE-NPs in an exclusive male-lineage transmission paradigm. We observed that paternal exposure to PE-NPs significantly affected growth phenotypes and sex hormone levels and induced histological damage in the testicular tissue of both F0 and F1 generations. In addition, consistent changes in sperm count, motility, abnormalities, and gene expression related to endoplasmic reticulum stress, sex hormone synthesis, and spermatogenesis were observed across paternal generations. The upregulation of microRNA (miR)-1983 and the downregulation of miR-122-5p, miR-5100, and miR-6240 were observed in both F0 and F1 mice, which may have been influenced by reproductive signaling pathways, as indicated by the RNA sequencing of testis tissues and quantitative real-time polymerase chain reaction findings. Furthermore, alterations in the gut microbiota and subsequent Spearman correlation analysis revealed that an increased abundance of Desulfovibrio (C21_c20) and Ruminococcus (gnavus) and a decreased abundance of Allobaculum were positively associated with spermatogenic dysfunction. These findings were validated in a fecal microbiota transplantation trial. Our results demonstrate that changes in miRNAs and the gut microbiota caused by paternal exposure to PE-NPs mediated intergenerational effects, providing deeper insights into mechanisms underlying the impact of paternal inheritance.

Monolayer Vacancy-Induced MXene Memory for Write-Verify-Free Programming.

The fundamental logic states of 1 and 0 in Complementary Metal-Oxide-Semiconductor (CMOS) are essential for modern high-speed non-volatile solid-state memories. However, the accumulated storage signal in conventional physical components often leads to data distortion after multiple write operations. This necessitates a write-verify operation to ensure proper values within the 0/1 threshold ranges. In this work, a non-gradual switching memory with two distinct stable resistance levels is introduced, enabled by the asymmetric vertical structure of monolayer vacancy-induced oxidized Ti3C2Tx MXene for efficient carrier trapping and releasing. This non-cumulative resistance effect allows non-volatile memories to attain valid 0/1 logic levels through direct reprogramming, eliminating the need for a write-verify operation. The device exhibits superior performance characteristics, including short write/erase times (100 ns), a large switching ratio (≈3 × 104), long cyclic endurance (>104 cycles), extended retention (>4 × 106 s), and highly resistive stability (>104 continuous write operations). These findings present promising avenues for next-generation resistive memories, offering faster programming speed, exceptional write performance, and streamlined algorithms.

Anti-OX40 Antibody Combined with HBc VLPs Delays Tumor Growth in a Mouse Colon Cancer Model.

Objective: Combination immunotherapy strategies targeting OX40, a co-stimulatory molecule that can enhance antitumor immunity by modulating the proliferation, differentiation, and effector function of tumor-infiltrating T cells, have attracted much attention for their excellent therapeutic effects. In this study, we aimed to evaluate the antitumor efficacy of combined anti-OX40 and hepatitis B core virus-like particles (HBc VLPs) therapy using a mouse colon cancer model. Methods: Humanized B-hOX40 mice were injected subcutaneously with MC38 colon tumor cells and treated with HBc VLPs+anti-hOX40 antibody. Tumor growth was monitored. Flow cytometric analysis was performed to evaluate the populations of T cell subsets in the tumors. Results: The combination of anti-OX40 with HBc VLPs resulted in a significant delay in tumor growth, suggesting that a potent antitumor immunity was induced by the combination therapy. Further studies revealed that HBc VLPs+anti-OX40 treatment induced a significant increase in effector T cells (Teffs) and a significant decrease in regulatory T cells (Tregs) in the tumor microenvironment (TME), which accounted for the synergistic antitumor effect of anti-OX40 in combination with HBc VLPs. Conclusion: Combination therapy of anti-hOX40 and HBc VLPs provides synergistic antitumor activity in colon cancer-bearing mice, which may represent a potential design strategy for cancer immunotherapy.

Self-interaction corrected SCAN functional for molecules and solids in the numeric atom-center orbital framework.

Semilocal density-functional approximations (DFAs), including the state-of-the-art SCAN functional, are plagued by the self-interaction error (SIE). While this error is explicitly defined only for one-electron systems, it has inspired the self-interaction correction method proposed by Perdew and Zunger (PZ-SIC), which has shown promise in mitigating the many-electron SIE. However, the PZ-SIC method is known for its significant numerical instability. In this study, we introduce a novel constraint that facilitates self-consistent localization of the SIC orbitals in the spirit of Edmiston-Ruedenberg orbitals [Rev. Mod. Phys. 35, 457 (1963)]. Our practical implementation within the all-electron numeric atom-centered orbitals code FHI-aims guarantees efficient and stable convergence of the self-consistent PZ-SIC equations for both molecules and solids. We further demonstrate that our PZ-SIC approach effectively mitigates the SIE in the meta-generalized gradient approximation SCAN functional, significantly improving the accuracy for ionization potentials, charge-transfer energies, and bandgaps for a diverse selection of molecules and solids. However, our PZ-SIC method does have its limitations. It cannot improve the already accurate SCAN results for properties such as cohesive energies, lattice constants, and bulk modulus in our test sets. This highlights the need for new-generation DFAs with more comprehensive applicability.

Zirconium Doping to Enable High-Efficiency and Stable CsPbI2Br All-Inorganic Perovskite Solar Cells.

All-inorganic wide-bandgap perovskite CsPbI2Br has attracted much attention because of its inherent thermal stability and ideal bandgap for the front subcell of tandem solar cells (TSCs). However, the low power conversion efficiency (PCE) and poor moisture stability of CsPbI2Br still restrict its future commercialization. Herein, zirconium tetrachloride (ZrCl4) was doped into CsPbI2Br films to modulate the crystal growth and improve the film quality. The partial substitution of the B-site Pb2+ of CsPbI2Br with Zr4+ suppresses the unwanted phase conversion from the crystallized black α-phase to the δ-phase, resulting in improved phase stability. Consequently, the humidity and thermal stability of the film are greatly improved. Additionally, the incorporation of ZrCl4 suppresses nonradiative recombination and forms a matched energy-level alignment with the hole-transport layer (Spiro-OMeTAD). Benefiting from these features, the ZrCl4-doped CsPbI2Br perovskite solar cell (PSC) shows an outstanding efficiency of 16.60% with a high open-circuit voltage of 1.29 V. The unencapsulated devices simultaneously show excellent humidity and thermal stability, retaining over 91% of PCEinitial after 1000 h of aging in ambient air conditions and 92% PCEinitial after 500 h of continuous heating at 85 °C in a nitrogen environment, respectively. Furthermore, ZrCl4-doped CsPbI2Br was employed as the front subcell of perovskite/organic TSCs and achieved a remarkable PCE of 19.42%, showing great potential for highly efficient and stable TSCs.

Comparison of 18F-FDG PET and arterial spin labeling MRI in evaluating Alzheimer's disease and amnestic mild cognitive impairment using integrated PET/MR.

BACKGROUND: Developing biomarkers for early stage AD patients is crucial. Glucose metabolism measured by 18F-FDG PET is the most common biomarker for evaluating cellular energy metabolism to diagnose AD. Arterial spin labeling (ASL) MRI can potentially provide comparable diagnostic information to 18F-FDG PET in patients with neurodegenerative disorders. However, the conclusions about the diagnostic performance of AD are still controversial between 18F-FDG PET and ASL. This study aims to compare quantitative cerebral blood flow (CBF) and glucose metabolism measured by 18F-FDG PET diagnostic values in patients with Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI) using integrated PET/MR. RESULTS: Analyses revealed overlapping between decreased regional rCBF and 18F-FDG PET SUVR in patients with AD compared with NC participants in the bilateral parietotemporal regions, frontal cortex, and cingulate cortex. Compared with NC participants, patients with aMCI exclusively demonstrated lower 18F-FDG PET SUVR in the bilateral temporal cortex, insula cortex, and inferior frontal cortex. Comparison of the rCBF in patients with aMCI and NC participants revealed no significant difference (P > 0.05). The ROC analysis of rCBF in the meta-ROI could diagnose patients with AD (AUC, 0.87) but not aMCI (AUC, 0.61). The specificity of diagnosing aMCI has been improved to 75.56% when combining rCBF and 18F-FDG PET SUVR. CONCLUSION: ASL could detect similar aberrant patterns of abnormalities compared to 18F-FDG PET in patients with AD compared with NC participants but not in aMCI. The diagnostic efficiency of 18F-FDG-PET for AD and aMCI patients remained higher to ASL. Our findings support that applying 18F-FDG PET may be preferable for diagnosing AD and aMCI.

Multiparametric hippocampal signatures for early diagnosis of Alzheimer's disease using 18F-FDG PET/MRI Radiomics.

PURPOSE: This study aimed to explore the utility of hippocampal radiomics using multiparametric simultaneous positron emission tomography (PET)/magnetic resonance imaging (MRI) for early diagnosis of Alzheimer's disease (AD). METHODS: A total of 53 healthy control (HC) participants, 55 patients with amnestic mild cognitive impairment (aMCI), and 51 patients with AD were included in this study. All participants accepted simultaneous PET/MRI scans, including 18F-fluorodeoxyglucose (18F-FDG) PET, 3D arterial spin labeling (ASL), and high-resolution T1-weighted imaging (3D T1WI). Radiomics features were extracted from the hippocampus region on those three modal images. Logistic regression models were trained to classify AD and HC, AD and aMCI, aMCI and HC respectively. The diagnostic performance and radiomics score (Rad-Score) of logistic regression models were evaluated from 5-fold cross-validation. RESULTS: The hippocampal radiomics features demonstrated favorable diagnostic performance, with the multimodal classifier outperforming the single-modal classifier in the binary classification of HC, aMCI, and AD. Using the multimodal classifier, we achieved an area under the receiver operating characteristic curve (AUC) of 0.98 and accuracy of 96.7% for classifying AD from HC, and an AUC of 0.86 and accuracy of 80.6% for classifying aMCI from HC. The value of Rad-Score differed significantly between the AD and HC (p < 0.001), aMCI and HC (p < 0.001) groups. Decision curve analysis showed superior clinical benefits of multimodal classifiers compared to neuropsychological tests. CONCLUSION: Multiparametric hippocampal radiomics using PET/MRI aids in the identification of early AD, and may provide a potential biomarker for clinical applications.

ZIF-based boronic acid modified molecular imprinted polymers in combination with silver nanoparticles/glutathione coated graphene oxide adsorbent for the selective enrichment of ellagic acid.

This study focuses on the extraction of ellagic acid (EA), a valued phenolic compound, from agricultural waste chestnut shell samples. A novel approach is introduced using a combination of boronic acid-modified molecularly imprinted polymer (ZIF@B@MIP) and a nanocomposite of graphene oxide-coated silver nanoparticles (GO@Ag@GSH) to enhance EA enrichment. ZIF@B@MIP precisely captured EA through boronate affinity-based molecular imprinting recognition. ZIF@B@MIP employs boronate affinity-based molecular imprinting recognition to precisely capture EA, while GO@Ag@GSH provides ample adsorption sites. The synergistic effect of ZIF@B@MIP and GO@Ag@GSH demonstrates excellent enrichment capability and selectivity for EA. High-performance liquid chromatography (HPLC) is employed for sensitive EA detection, achieving a maximum adsorption capacity of 46.25 mg g-1 and an imprinting factor of 3.01. The adsorption capacity to different structural analogue was investigated, and the selectivity coefficient was used to evaluate the selectivity, and its value was 1.16-3.01. The method successfully enriches EA in chestnut shell samples with a recovery rate of 95.6 %-110.1 %. This research presents an innovative approach for effective phenolic components enrichment from natural resources for pharmaceutical and biochemical applications.

Stitching Locally Fitted T-Splines for Fast Fitting of Large-Scale Freeform Point Clouds.

Parametric splines are popular tools for precision optical metrology of complex freeform surfaces. However, as a promising topologically unconstrained solution, existing T-spline fitting techniques, such as improved global fitting, local fitting, and split-connect algorithms, still suffer the problems of low computational efficiency, especially in the case of large data scales and high accuracy requirements. This paper proposes a speed-improved algorithm for fast, large-scale freeform point cloud fitting by stitching locally fitted T-splines through three steps of localized operations. Experiments show that the proposed algorithm produces a three-to-eightfold efficiency improvement from the global and local fitting algorithms, and a two-to-fourfold improvement from the latest split-connect algorithm, in high-accuracy and large-scale fitting scenarios. A classical Lena image study showed that the algorithm is at least twice as fast as the split-connect algorithm using fewer than 80% control points of the latter.

Improving XYG3-type doubly hybrid approximation using self-interaction corrected SCAN density and orbitals via the PZ-SIC framework: The xDH@SCAN(SIC) approach.

XYG3-type doubly hybrid (xDH) approximations have gained widespread recognition for their accuracy in describing a diverse range of chemical and physical interactions. However, a recent study [Song et al., J. Phys. Chem. Lett. 12, 800-807 (2021)] has highlighted the limitation of xDH methods in calculating the dissociation of NaCl molecules. This issue has been related to the density and orbitals used for evaluating the energy in xDH methods, which are obtained from lower-rung hybrid density functional approximations (DFAs) and display substantial density errors in the dissociation limit. In this work, we systematically investigate the influence of density on several challenging datasets and find that xDH methods are less sensitive to density errors compared to semi-local and hybrid DFAs. Furthermore, we demonstrate that the self-interaction corrected SCAN density approach offers superior accuracy compared to the self-consistent SCAN density and Hartree-Fock density approaches, as evidenced by performing charge analysis on the dissociation of heterodimers, such as NaCl and LiF. Building on these insights, we propose a five-parameter xDH method using the SCAN density and orbitals corrected by the PZ-SIC scheme. This new xDH@SCAN(SIC) method provides a balanced and accurate description across a wide range of challenging systems.

A novel mRNA rabies vaccine as a promising candidate for rabies post-exposure prophylaxis protects animals from different rabies viruses.

Rabies, caused by the rabies virus (RABV), is the most fatal zoonotic disease. It is a neglected tropical disease which remains a major public health problem, causing approximately 59,000 deaths worldwide annually. Despite the existence of effective vaccines, the high incidence of human rabies is mainly linked to tedious vaccine immunisation procedures and the overall high cost of post-exposure prophylaxis. Therefore, it is necessary to develop an effective vaccine that has a simple procedure and is affordable to prevent rabies infection in humans. RABV belongs to the genus Lyssavirus and family Rhabdoviridae. Previous phylogenetic analyses have identified seven major clades of RABV in China (China I-VII), confirmed by analysing nucleotide sequences from both the G and N proteins. This study evaluated the immunogenicity and protective capacity of SYS6008, an mRNA rabies vaccine expressing rabies virus glycoprotein, in mice and cynomolgus macaques. We demonstrated that SYS6008 induced sufficient levels of rabies neutralising antibody (RVNA) in mice. In addition, SYS6008 elicited strong and durable RVNA responses in vaccinated cynomolgus macaques. In the pre-exposure prophylaxis murine model, one or two injections of SYS6008 at 1/10 or 1/30 of dosage provided protection against a challenge with a 30-fold LD50 of rabies virus (China I and II clades). We also demonstrated that in the post-exposure prophylaxis murine model, which was exposed to lethal rabies virus (China I-VII clades) before vaccination, one or two injections of SYS6008 at both 1/10 and 1/30 dosages provided better protection against rabies virus challenge than the immunization by five injections of commercial vaccines at the same dosage. In addition, we proved that SYS6008-induced RVNAs could neutralise RABV from the China I-VII clades. Finally, 1/10 of the dosage of SYS6008 was able to stimulate significant RABV-G specificity in the T cell response. Furthermore, we found that SYS6008 induced high cellular immunity, including RABV-G-specific T cell responses and memory B cells. Our results imply that the SYS6008 rabies vaccine, with a much simpler vaccination procedure, better immunogenicity, and enhanced protective capacity, could be a candidate vaccine for post-exposure prophylaxis of rabies infections.

[Targeted muscle reinnervation: a surgical technique of human-machine interface for intelligent prosthesis].

Objective: To review targeted muscle reinnervation (TMR) surgery for the construction of intelligent prosthetic human-machine interface, thus providing a new clinical intervention paradigm for the functional reconstruction of residual limbs in amputees. Methods: Extensively consulted relevant literature domestically and abroad and systematically expounded the surgical requirements of intelligent prosthetics, TMR operation plan, target population, prognosis, as well as the development and future of TMR. Results: TMR facilitates intuitive control of intelligent prostheses in amputees by reconstructing the "brain-spinal cord-peripheral nerve-skeletal muscle" neurotransmission pathway and increasing the surface electromyographic signals required for pattern recognition. TMR surgery for different purposes is suitable for different target populations. Conclusion: TMR surgery has been certified abroad as a transformative technology for improving prosthetic manipulation, and is expected to become a new clinical paradigm for 2 million amputees in China.