Change of function and brain activity in patients of right spastic arm paralysis combined with aphasia after contralateral cervical seventh nerve transfer surgery.

Left hemisphere injury can cause right spastic arm paralysis and aphasia, and recovery of both motor and language functions shares similar compensatory mechanisms and processes. Contralateral cervical seventh cross transfer (CC7) surgery can provide motor recovery for spastic arm paralysis by triggering interhemispheric plasticity, and self-reports from patients indicate spontaneous improvement in language function but still need to be verified. To explore the improvements in motor and language function after CC7 surgery, we performed this prospective observational cohort study. The Upper Extremity part of Fugl-Meyer scale (UEFM) and Modified Ashworth Scale were used to evaluate motor function, and Aphasia Quotient calculated by Mandarin version of the Western Aphasia Battery (WAB-AQ, larger score indicates better language function) was assessed for language function. In 20 patients included, the average scores of UEFM increased by .40 and 3.70 points from baseline to 1-week and 6-month post-surgery, respectively. The spasticity of the elbow and fingers decreased significantly at 1-week post-surgery, although partially recurred at 6-month follow-up. The average scores of WAB-AQ were increased by 9.14 and 10.69 points at 1-week and 6-month post-surgery (P < .001 for both), respectively. Post-surgical fMRI scans revealed increased activity in the bilateral hemispheres related to language centrals, including the right precentral cortex and right gyrus rectus. These findings suggest that CC7 surgery not only enhances motor function but may also improve the aphasia quotient in patients with right arm paralysis and aphasia due to left hemisphere injuries.

Rapid cancer diagnosis by highly fluorescent carbon nanodots-based imaging.

Carbon dots (Cdots) with bright green fluorescence were applied to the rapid and selective cell imaging for a variety of cell lines. Different labeling distributions of hepatoma cells (HepG2) and normal human liver cells (LO2) were achieved using Cdots as imaging agents. For HepG2 cells, the Cdots could rapidly permeate the cell membrane and diffuse into the cytoplasm and nucleus within 3 min, and retained their location in the targets for 24 h. However, the Cdots exhibited bright fluorescence only in the cytoplasm of LO2 cell lines. Moreover, the Cdots were almost non-cytotoxic and exhibited superior photostability over a wide range of pH. Therefore, these Cdots have great potential for rapid, luminous and selective bioimaging applications, and are expected to be used as a nucleus-staining agent in cancer diagnosis. Graphical abstract ᅟ.

Comparative Assessment of In Vitro Xanthine Oxidase and α-Glucosidase Inhibitory Activities of Cultured Cambial Meristematic Cells, Adventitious Roots, and Field-Cultivated Ginseng.

Panax ginseng, a traditional Chinese medicine with a history spanning thousands of years, faces overexploitation and challenges related to extended growth periods. Tissue-cultured adventitious roots and stem cells are alternatives to wild and field-cultivated ginseng. In this study, we assessed the in vitro xanthine oxidase and α-glucosidase inhibitory activities of saponin extracts among cultured cambial meristematic cells (CMC), adventitious ginseng roots (AGR), and field-cultivated ginseng roots (CGR). The xanthine oxidase (XO) and α-glucosidase inhibitory activities were determined by uric acid estimation and the p-NPG method, respectively. Spectrophotometry and the Folin-Ciocalteu, aluminum nitrate, and Bradford methods were employed to ascertain the total saponins and phenolic, flavonoid, and protein contents. The calculated IC50 values for total saponin extracts against XO and α-glucosidase were 0.665, 0.844, and >1.6 mg/mL and 0.332, 0.745, and 0.042 mg/mL for AGR, CMC, CGR, respectively. Comparing the total saponin, crude protein, and total phenolic contents revealed that AGR > CMC > CGR. To the best of our knowledge, this study presents the first report on the in vitro comparison of xanthine oxidase and α-glucosidase inhibitory activities among AGR, CMC, and CGR. The findings offer valuable insights into the development of hypoglycemic and antihyperuricemic medicinal, nutraceutical, and functional products utilizing AGR and CMC.

Unveiling the role of dorsal root ganglia in spasticity reduction: Insights from contralateral seventh cervical nerve cross transfer surgery.

BACKGROUND: Central nervous system (CNS) disorders, such as stroke, often lead to spasticity, which result in limb deformities and significant reduction in quality of life. Spasticity arises from disruptions in the normal functioning of cortical and descending inhibitory pathways in the brainstem, leading to abnormal muscle contractions. Contralateral seventh cervical nerve cross transfer (CC7) surgery has been proven to effectively reduce spasticity, but the specific mechanism for its effectiveness is unclear. METHODS: This study aimed to investigate the changes in the dorsal root ganglia (DRG) following CC7 surgery. A comprehensive anatomical analysis was conducted through cadaveric study and magnetic resonance imaging (MRI) study, to accurately measure the regional anatomy of the C7 DRG. DRG perfusion changes were quantitatively assessed by comparing pre- and postoperative dynamic contrast-enhanced (DCE) MRI. RESULTS: In CC7 surgery, the C7 nerve root on the affected side is cut close to the DRG (3.6 ± 1.0 mm), while the C7 nerve root on the healthy side is cut further away from the DRG (65.0 ± 10.0 mm). MRI studies revealed that after C7 proximal neurotomy on the affected side, there was an increase in DRG volume, vascular permeability, and perfusion; after C7 distal neurotomy on the healthy side, there was a decrease in DRG volume, with no significant changes in vascular permeability and perfusion. CONCLUSION: This study provides preliminary insights into the mechanisms of spasticity reduction following CC7 surgery, indicating that changes in the DRG, such as increased vascular permeability and perfusion, could disrupt abnormal spinal γ-circuits. The resulting high-perfusion state of DRG, possibly due to heightened neuronal activity and metabolic demands, necessitating further research to verify this hypothesis.

Distinct plasma phosphorylated-tau proteins profiling for the differential diagnosis of mild cognitive impairment and Alzheimer's disease by plasmonic asymmetric nanobridge-based biosensor.

The differential diagnosis between mild cognitive impairment (MCI) and Alzheimer's disease (AD) has been highly demanded for its effectiveness in preventing and contributing to early diagnosis of AD. To this end, we developed a single plasmonic asymmetric nanobridge (PAN)-based biosensor to differentially diagnose MCI and AD by quantitative profiling of phosphorylated tau proteins (p-tau) in clinical plasma samples, which revealed a significant correlation with AD development and progression. The PAN was designed to have a conductive junction and asymmetric structure, which was unable to be synthesized by the traditional thermodynamical methods. For its unique morphological characteristics, PAN features high electromagnetic field enhancement, enabling the biosensor to achieve high sensitivity, with a limit of detection in the attomolar regime for quantitative analysis of p-tau. By introducing support vector machine (SVM)-based machine learning algorithm, the improved diagnostic system was achieved for prediction of healthy controls, MCI, and AD groups with an accuracy of 94.47 % by detecting various p-tau species levels in human plasma. Thus, our proposed PAN-based plasmonic biosensor has a powerful potential in clinical utility for predicting the onset of AD progression in the asymptomatic phase.

Femtomolar detection of single mismatches by discriminant analysis of DNA hybridization events using gold nanoparticles.

Even though DNA-based nanosensors have been demonstrated for quantitative detection of analytes and diseases, hybridization events have never been numerically investigated for further understanding of DNA mediated interactions. Here, we developed a nanoscale platform with well-designed capture and detection gold nanoprobes to precisely evaluate the hybridization events. The capture gold nanoprobes were mono-laid on glass and the detection probes were fabricated via a novel competitive conjugation method. The two kinds of probes combined in a suitable orientation following the hybridization with the target. We found that hybridization efficiency was markedly dependent on electrostatic interactions between DNA strands, which can be tailored by adjusting the salt concentration of the incubation solution. Due to the much lower stability of the double helix formed by mismatches, the hybridization efficiencies of single mismatched (MMT) and perfectly matched DNA (PMT) were different. Therefore, we obtained an optimized salt concentration that allowed for discrimination of MMT from PMT without stringent control of temperature or pH. The results indicated this to be an ultrasensitive and precise nanosensor for the diagnosis of genetic diseases.

Nanoplasmonic biosensors for precision medicine.

Nanoplasmonic biosensors have a huge boost for precision medicine, which allows doctors to better understand diseases at the molecular level and to improve the earlier diagnosis and develop treatment programs. Unlike traditional biosensors, nanoplasmonic biosensors meet the global health industry's need for low-cost, rapid and portable aspects, while offering multiplexing, high sensitivity and real-time detection. In this review, we describe the common detection schemes used based on localized plasmon resonance (LSPR) and highlight three sensing classes based on LSPR. Then, we present the recent applications of nanoplasmonic in other sensing methods such as isothermal amplification, CRISPR/Cas systems, lab on a chip and enzyme-linked immunosorbent assay. The advantages of nanoplasmonic-based integrated sensing for multiple methods are discussed. Finally, we review the current applications of nanoplasmonic biosensors in precision medicine, such as DNA mutation, vaccine evaluation and drug delivery. The obstacles faced by nanoplasmonic biosensors and the current countermeasures are discussed.

Longitudinal optogenetic mapping reveals enhanced motor control by the contralesional cortex after traumatic brain injury in mice.

Traumatic brain injury (TBI) is a significant cause of human disability, and understanding its spontaneous recovery pattern after injury is critical for potential treatments. However, studies on the function of the contralesional cortex after TBI have mostly focused on acute-phase changes, and long-term dynamic changes in the control of the affected limb by the contralesional cortex are less understood. To unravel long-term adaptations in the contralesional cortex, we developed a mouse model of TBI and used longitudinal optogenetic motor mapping to observe the function of contralesional corticospinal neurons (CSNs) projecting to the unilateral seventh cervical (C7) segment of the spinal cord. We injected a retrograde adeno-associated virus (AAV) expressing channelrhodopsin-2 to optogenetically stimulate and map the functional connections of the motor-sensory cortex. We validated the effectiveness of transcranial optogenetic stimulation for functional mapping and observed a general increase in the control of the affected limb by the contralesional cortex over time. Using retrograde labeling techniques, we showed that TBI does not affect the distribution of C7-CSNs but alters their function, and the labeled CSNs are concentrated in the caudal and rostral forelimb areas. Our findings provide new insights into harnessing contralesional cortical plasticity to improve treatment for affected limbs. This study sheds light on the long-term adaptations in the contralesional cortex after TBI, paving the way for potential clinical applications of optogenetic stimulation to improve motor control and rehabilitation outcomes.

Effect and safety of C7 neurotomy at the intervertebral foramen in patients with chronic poststroke aphasia: a multicentre, randomised, controlled study protocol.

INTRODUCTION: Aphasia affects many stroke survivors; therefore, effective treatments are urgently needed. Preliminary clinical findings have suggested an association between contralateral C7-C7 cross nerve transfer and recovery from chronic aphasia. Randomised controlled trials supporting the efficacy of C7 neurotomy (NC7) are lacking. This study will explore the efficacy of NC7 at the intervertebral foramen for improving chronic poststroke aphasia. METHODS AND ANALYSIS: This study protocol reports a multicentre, randomised, assessor-blinded active-controlled trial. A total of 50 patients with chronic poststroke aphasia for over 1 year and with a aphasia quotient calculated by Western Aphasia Battery Aphasia Quotient (WAB-AQ) score below 93.8 will be recruited. Participants will be randomly assigned to 1 of 2 groups (25 individuals each) to receive NC7 plus intensive speech and language therapy (iSLT), or iSLT alone programme. The primary outcome is the change in Boston Naming Test score from baseline to the first follow-up after NC7 plus 3 weeks of iSLT or iSLT alone. The secondary outcomes include the changes in the WAB-AQ, Communication Activities of Daily Living-3, International Classification of Functioning, Disability and Health (ICF) speech language function, Barthel Index, Stroke Aphasic Depression Questionnaire-hospital version and sensorimotor assessments. The study will also collect functional imaging outcomes of naming and semantic violation tasks through functional MRI and electroencephalogram to evaluate the intervention-induced neuroplasticity. ETHICS AND DISSEMINATION: This study was approved by the institutional review boards of Huashan Hospital, Fudan University, and all participating institutions. The study findings will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: ChiCTR2200057180.

A cost-effective smartphone-based device for rapid C-reaction protein (CRP) detection using magnetoelastic immunosensor.

C-Reaction protein (CRP) is a marker of nonspecific immunity for vital signs and wound assessment, and it can be used to diagnose infections in clinical medicine. However, measuring CRP level currently requires hospital-based instruments, high-cost reagents, and a complex process, all of which have limited its full capabilities for self-detection, a growing trend in modern medicine. In this study, we developed a novel smartphone-based device using advanced methods of magnetoelastic immunosensing to mitigate these limitations. We combined a system-on-chip (SoC) hardware architecture with smartphone apps to realize the sampling of resonance frequency shift on magnetoelastic chips, which can determine the ultra-sensitivity to mass change caused by the binding of anti-CRP antibody and CRP. Through detecting a multi-group of samples, we found that the resonance frequency shift was linearly proportional to the CRP concentration in the range from 0.1 to 100 µg mL-1, with a sensitivity of 12.90 Hz µg-1 mL-1 and a detection limit of 2.349 × 10-4 µg mL-1. Meanwhile, compared with the large-scale instrument used in clinical settings, the performance of our device was stable and significantly more portable, rapid and cost-effective, offering excellent potential for modern home-based diagnosis.

Ultrasensitive detection of the reduced form of nicotinamide adenine dinucleotide based on carbon nanotube field effect transistor.

We developed a simple, ultrasensitive, and quantitative detection method for the reduced form of nicotinamide adenine dinucleotide (NADH), based on carbon nanotube field effect transistors (CNTFETs). Following the injection of NADH at different concentrations, we obtained different electrical signals from a semiconductor characterization system mimicking biological catalysis of NADH dehydrogenase (CoI). Here, FET was fabricated via photolithography, attaching silicon wells, as the detection chamber, on the channel area of the single wall carbon nanotube (SWCNT). SWCNTs were functionalized with phenazine derivant, a counterpart of the key functional prosthetic group of CoI enzyme. In the presence of NADH, electrons transferred to phenazine derivant through SWCNT, by analogous means of the electron transport chain formed by a series of iron-sulfur (FeS) clusters in CoI. Using this method, the limit of detection was as low as 1 pM, and the range of linear response was 10 pM to 500 nM. Significantly, this approach possesses great potential for applications in real-time detection of NADH at extremely low concentrations, and rigorous analysis for NADH in electrochemical fields.

[Effect of methylation modification on the expression of Cosmc gene in peripheral B lymphocyte of IgA nephropathy patients].

OBJECTIVE: To investigate the effect of methylation modification on the mRNA expression of Cosmc gene in peripheral B lymphocytes from IgA nephropathy (IgAN). METHODS: Biopsy identified 22 cases of IgAN patients and 20 cases of normal control were included. Peripheral B lymphocytes were isolated and were cultured with RPMI1640 medium, with LPS (12.5 microg/mL) as well as demethylation agent (5-AZA 0.1 micromol/L, 0.5 micromol/ L and 1.0 micromol/L) for 72 hours, respectively. Expression level of Cosmc gene was measured using real-time PCR. RESULTS: The mRNA expression level of Cosmc gene in IgAN patients was significantly lower than that of control (P<0.05). The Cosmc gene expression level increased dramatically after RPMI1640 treatment (P<0.05), however, LPS could apparently reverse this effect (P<0.05). De-methylation modification up regulated the Cosmc gene expression significantly (P<0.05). CONCLUSION: De-methylation modification could effectively reverse the repressed Comsc gene mRNA expression caused by external suppressors.

Single plasmonic nanostructures for biomedical diagnosis.

The field of single nanoparticle plasmonics has grown enormously. There is no doubt that a wide diversity of the nanoplasmonic techniques and nanostructures represents a tremendous opportunity for fundamental biomedical studies as well as sensing and imaging applications. Single nanoparticle plasmonic biosensors are efficient in label-free single-molecule detection, as well as in monitoring real-time binding events of even several biomolecules. In the present review, we have discussed the prominent advantages and advances in single particle characterization and synthesis as well as new insight into and information on biomedical diagnosis uniquely obtained using single particle approaches. The approaches include the fundamental studies of nanoplasmonic behavior, two typical methods based on refractive index change and characteristic light intensity change, exciting innovations of synthetic strategies for new plasmonic nanostructures, and practical applications using single particle sensing, imaging, and tracking. The basic sphere and rod nanostructures are the focus of extensive investigations in biomedicine, while they can be programmed into algorithmic assemblies for novel plasmonic diagnosis. Design of single nanoparticles for the detection of single biomolecules will have far-reaching consequences in biomedical diagnosis.

Real-time and label-free detection of VKORC1 genes based on a magnetoelastic biosensor for warfarin therapy.

Various thrombotic disorders have been treated with the anticoagulant warfarin. However, a small change in warfarin concentration may lead to drug adverse reactions or therapeutic failure due to its narrow therapeutic index. Therefore, the dose of warfarin must be monitored for each patient during therapy in real-time and in a sensitive and stable manner. In this work, we designed a magnetoelastic (ME) biosensor using Metglas alloy 2826 to detect VKORC1 genotypes, which is one of the most important known genetic determinants of warfarin dosing. The sensor enabled both fast responses to DNA binding and wireless transmission of signals. Specifically in the target recognition layer, the sensor introduced an avidin-biotin interaction system for signal amplification by increasing the surface load mass. The resonance frequency shift of the signal was linear to the concentration of the target in the range of 0.1 fM to 10 pM, with a detection limit (LOD) of 0.00389 fM (S/N = 3) and a sensitivity of 45.7 Hz pM-1. Importantly, this ME-based biosensor was small and portable without the use of any optical labels, which has high potential to be applied in advanced biomedical diagnosis of nucleic acids and proteins.

[Effects of Artesunate on MCP-1 and MCP-1 mRNA expression of renal tissue in the rat IgA nephropathy model].

OBJECTIVE: To investigate the effects of Artesunate on expression of MCP-1 and MCP-1 mRNA in renal tissue of the rat experimental IgA nephropathy model. METHODS: 40 rats were divided randomly into 4 groups with 10 rats in normal control group while the other 30 in model control group, low dose Artesunate group and high dose Artesunate group after the establishment of IgA nephropathy model. MCP-1 and MCP-1 mRNA in renal tissue were tested by immunohistochemical and RT-PCR methods. RESULTS: The expression of MCP-1 mRNA in model control group was significantly increased (0.4726+/-0.086 vs 0.1445+/-0.095, P<0.05, compared with normal control group), which was suppressed in low dose Artesunate group (0.2844+/-0.065) and high dose Artesunate group (0.2184+/-0.058) (both P<0.05, compared with model control group). In addition, hemouria, proteinuria and pathological changes in renal tissue were improved in the Artesunate groups. CONCLUSION: Artesunate shows the ability of downregulating the expression of MCP-1 in renal tissue, which may explain one of the mechanisms of Artesunate effectiveness in clinical treatment of IgA nephropathy.

Wrinkle Structured Network of Silver-Coated Carbon Nanotubes for Wearable Sensors.

Soft-strain-based sensors are being increasingly used across various fields, including wearable sensing, behavior monitoring, and electrophysiological diagnostics. However, throughout all applications, the function of these sensors is limited because of high sensitivity, high-dynamic range, and low-power consumption. In this paper, we focus on improving the sensitivity and strain range of the soft-strain-based sensor through structure, surface, and sensitive unit treatment. Nanosilver (Ag)-coated hydroxyl-functionalized multi-walled carbon nanotubes (OH-f MWCNTs) were explored for highly acute sensing. With stretching and depositing methods, Ag@OH-f MWCNTs and polydimethylsiloxane (PDMS) are fabricated into a wrinkled and sandwich structure for a soft-strain-based sensor. The electronic properties were characterized in that the gauge factor (GF) = ΔR/R0 was 412.32, and the strain range was 42.2%. Moreover, our soft-strain-based sensor exhibits features including flexibility, ultra-lightweight and a highly comfortable experience in terms of wearability. Finally, some physiological and behavioral features can be sampled by testing the exceptional resistance change, including the detection of breath, as well as facial and hand movement recognition. The experiment exhibits its superiority in terms of being highly sensitive and having an extensive range of sensing.

Single gold-bridged nanoprobes for identification of single point DNA mutations.

Consensus ranking of protein affinity to identify point mutations has not been established. Therefore, analytical techniques that can detect subtle variations without interfering with native biomolecular interactions are required. Here we report a rapid method to identify point mutations by a single nanoparticle sensing system. DNA-directed gold crystallization forms rod-like nanoparticles with bridges based on structural design. The nanoparticles enhance Rayleigh light scattering, achieving high refractive-index sensitivity, and enable the system to monitor even a small number of protein-DNA binding events without interference. Analysis of the binding affinity can compile an atlas to distinguish the potential of various point mutations recognized by MutS protein. We use the atlas to analyze the presence and type of single point mutations in BRCA1 from samples of human breast and ovarian cancer cell lines. The strategy of synthesis-by-design of plasmonic nanoparticles for sensors enables direct identification of subtle biomolecular binding distortions and genetic alterations.

Gold nanocrystals with DNA-directed morphologies.

Precise control over the structure of metal nanomaterials is important for developing advanced nanobiotechnology. Assembly methods of nanoparticles into structured blocks have been widely demonstrated recently. However, synthesis of nanocrystals with controlled, three-dimensional structures remains challenging. Here we show a directed crystallization of gold by a single DNA molecular regulator in a sequence-independent manner and its applications in three-dimensional topological controls of crystalline nanostructures. We anchor DNA onto gold nanoseed with various alignments to form gold nanocrystals with defined topologies. Some topologies are asymmetric including pushpin-, star- and biconcave disk-like structures, as well as more complex jellyfish- and flower-like structures. The approach of employing DNA enables the solution-based synthesis of nanocrystals with controlled, three-dimensional structures in a desired direction, and expands the current tools available for designing and synthesizing feature-rich nanomaterials for future translational biotechnology.

[Effects of hepatocyte growth factor on TGF-beta1 triggered tubular epithelial-myofibroblast transdifferentiation by CTGF in vitro].

OBJECTIVE: To observe the effects of hepatocyte growth factor (HGF) on TGF-beta1 triggered tubular epithelial-myofibroblast transdifferentiation (TEMT) and on the expression of connective tissue growth factor (CTGF). METHODS: The morphology of transdifferentiate tubular cells was observed using phase-contrast microscopy and scanning electron microscopy. alpha-SMA was assessed by immunohistochemistry and semiquantified by mean intergrated opitical density (IOD). The level of fibronectin (FN) in the culture supernatant was measured by ELISA. CTGF mRNA expression was examined by RT-PCR. RESULTS: The TGF-beta1-induced TEMT characterized by expression of alpha-SMA was shown by immunohistochemistry. TGF-beta1 was also shown to stimulate the secretion of FN in cultured supernatant and the CTGF mRNA expression of NRK52E cells. There was no statistically significant difference between HGF-treated groups and control group in the result of alpha-SMA immunostaining and the level of FN, except that CTGF mRNA expression was slightly increased in the HGF-treated groups. The addition of HGF inhibited the TGF-beta1-induced TEMT, the secretion of FN, and the CTGF expression of NRK52E cells, there was a significant correlation between the expression of CTGF and the expression of alpha-SMA. CONCLUSION: HGF could block TEMT and FN secretion triggered by TGF-beta1, which implies that HGF could participate in renal interstitial fibrosis as a negative regulator. The negative regulation of transdifferentiation of HGF may be partially achieved by attenuation of CTGF expression.

Gold nanostar based biosensor detects epigenetic alterations on promoter of real cells.

Epigenetic changes, particularly in cancer suppressor genes, are novel biomarkers for cancer diagnostics and therapeutics. However, epigenetic studies should not only provide an estimation of the amount of 5-methylcytosine, but also examine the presence of epigenetic proteins to reveal the complete epigenetic alterations for downstream molecular process. The challenge of natural epigenetics is to unveil key factors of epigenetics in one assay, containing low concentrations. This would be valuable for the monitoring of early-stage cancer. On the basic of the nanoplasmonic biosensor, here we report a sensitive sensor to study epigenetics of DNA promoter. The results show detection limit for dual epigenetic biomarkers methyl-CpG group and methyl-CpG binding domain protein 2 (MBD2) are one 5-methylcytosine molecule and 125fM MBD2. Moreover, DNA structure bending, steric competition under interaction of epigenetic proteins and transcription factors; and epigenetics-mediated suppression of transcription are observed during epigenetic alterations. This study provides a platform for full story of epigenetics, as compared with that of methylcytosine-based techniques only.