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Abstract Background High‐frequency repetitive transcranial magnetic stimulation (HF‐rTMS) has been found to ameliorate cognitive impairment. However, the effects of HF‐rTMS remain unknown in chronic cerebral hypoperfusion (CCH). Aim To investigate the effects of HF‐rTMS on cognitive improvement and its potential mechanisms in CCH mice. Materials and methods Daily HF‐rTMS therapy was delivered after bilateral carotid stenosis (BCAS) and continued for 14 days. The mice were randomly assigned to three groups: the sham group, the model group, and the HF‐rTMS group. The Y maze and the new object recognition test were used to assess cognitive function. The expressions of MAP‐2, synapsis, Myelin basic protein(MBP), and brain‐derived growth factors (BDNF) were analyzed by immunofluorescence staining and western blot to evaluate neuronal plasticity and white matter myelin regeneration. Nissl staining and the expression of caspase‐3, Bax, and Bcl‐2 were used to observe neuronal apoptosis. In addition, the activation of microglia and astrocytes were evaluated by fluorescence staining. The inflammation levels of IL‐1β, IL‐6, and Tumor Necrosis Factor(TNF)‐α were detected by qPCR in the hippocampus of mice in each group. Results Via behavioral tests, the BCAS mice showed reduced a rate of new object preference and decreased a rate of spontaneous alternations, while HF‐rTMS significantly improved hippocampal learning and memory deficits. In addition, the mice in the model group showed decreased levels of MAP‐2, synapsis, MBP, and BDNF, while HF‐rTMS treatment reversed these effects. As expected, activated microglia and astrocytes increased in the model group, but HF‐rTMS treatment suppressed these changes. HF‐rTMS decreased BCAS‐induced neuronal apoptosis and the expression of pro‐apoptotic protein (Caspase‐3 and Bax) and increased the expression of anti‐apoptotic protein (Bcl‐2). In addition, HF‐rTMS inhibited the expression of inflammatory cytokines (IL‐1β, IL‐6, and TNF‐α). Conclusions HF‐rTMS alleviates cognitive impairment in CCH mice by enhancing neuronal plasticity and inhibiting inflammation, thus serving as a potential method for vascular cognitive impairment.

Disturbances in the microbiota-gut-brain axis may contribute to the development of Alzheimer’s disease. Magnesium-L-threonate has recently been found to have protective effects on learning and memory in aged and Alzheimer’s disease model mice. However, the effects of magnesium-L-threonate on the gut microbiota in Alzheimer’s disease remain unknown. Previously, we reported that magnesium-L-threonate treatment improved cognition and reduced oxidative stress and inflammation in a double-transgenic line of Alzheimer’s disease model mice expressing the amyloid-β precursor protein and mutant human presenilin 1 (APP/PS1). Here, we performed 16S rRNA amplicon sequencing and liquid chromatography-mass spectrometry to analyze changes in the microbiome and serum metabolome following magnesium-L-threonate exposure in a similar mouse model. Magnesium-L-threonate modulated the abundance of three genera in the gut microbiota, decreasing Allobaculum and increasing Bifidobacterium and Turicibacter. We also found that differential metabolites in the magnesium-L-threonate-regulated serum were enriched in various pathways associated with neurodegenerative diseases. The western blotting detection on intestinal tight junction proteins (zona occludens 1, occludin, and claudin-5) showed that magnesium-L-threonate repaired the intestinal barrier dysfunction of APP/PS1 mice. These findings suggest that magnesium-L-threonate may reduce the clinical manifestations of Alzheimer’s disease through the microbiota-gut-brain axis in model mice, providing an experimental basis for the clinical treatment of Alzheimer’s disease.

Abstract Li+ insertion and extraction inherently impact the switching dynamics and cycling stability of inorganic electrochromic (EC) electrodes. Herein, the extraction of Li+ out of the TiO2 lattice to release the electron is replaced by the charge recombination of the electron with I3− at the TiO2‐electrolyte interface, which avoids the mechanical breakdown of the electrodes and renders self‐bleaching with no applied voltages. A device design of the same two TiO2 nanocrystal (NC) electrodes combined with the redox lithium salt (LiI) electrolyte confers symmetric electrochromism. By applying a forward or reverse bias, the two TiO2 electrodes alternately serve as the electrochromic electrode and exhibit voltage‐controlled gradient coloration, a maximum optical modulation of 90% at 700 nm, and a doubled cycling performance. The microstructure of the TiO2 NC film is characterized by transmission electron microscopy, X‐ray diffraction, X‐ray photoelectron spectroscopy, and Brunauer–Emmett–Teller methods. The electrochemical and electrochromic properties of the device are investigated using cyclic voltammetry, chronoamperometry, electrochemical impedance spectroscopy, and Mott–Schottky method.

Objective: This study was to investigate the therapeutic effect of high-frequency repetitive magnetic stimulation (HF-rMS) at the sacrum for chronic constipation in Parkinson's patients (PD). Materials and Methods: Eventually 48 PD patients were enrolled from July 2019 to October 2020, and randomly divided into the HF-rMS group (the intervention group, n = 24) and the sham HF-rMS group (the control group, n = 24). The intervention group received HF-rMS at the sacrum, whereas the control group received ineffective magnetic stimulation. We performed clinical evaluation before and after HF-rMS treatment, including constipation score scale (KESS questionnaire), Unified Parkinson's Disease Rating Scale (UPDRS-III exercise examination), Hoehn-Yahr (H-Y) stage of motor function; simple mental status scale (MMSE), anxiety/depression table (HAD-A/HAD-D), the activity of daily living (ADL), and quality of life scale for patients with constipation (PAC-QOL) to evaluate symptoms and satisfaction of PD patients with chronic constipation. Results: There was no significant difference in the clinical characteristics between the two groups. As compared to the control group, the HF-rMS group displayed a larger change (pre and posttreatment) in the KESS scores of PD patients with chronic constipation, suggesting a significant improvement. Moreover, HF-rMS significantly promoted the mood, activity of daily living, and quality of life of PD patients when comparing the alteration of HAD-A/HAD-D scores, ADL scores, and PAC-QOL scores between the two groups. Finally, there was no significant difference in the change of the UPDRS III score and the MMSE score between the two groups. Conclusion: HF-rMS at the sacrum can improve chronic constipation in PD patients.

Optical thermometry has emerged as a promising technology to overcome the limitations of traditional thermometry techniques. Herein, we report an Eu ^3+ -activated tungstate Ba _2 CaWO _6 phosphors for luminescent thermometry with a maximum relative sensitivity of 4.84% based on a single-band ratiometric technique. By monitoring the ^5 D _0 → ^7 F _1 (595 nm) emission of Eu ^3+ , excitation spectrum of the as-prepared sample was measured, showing a dominant broad band ranging from 240 to 345 nm corresponding to the O ^2− -W ^6+ charge transfer band (CTB). The intensity of CTB gradually decreases and the CTB edge shows an appreciable red shift when the temperature increases due to thermal population of the [WO _6 ] ^6− moiety at higher vibrational levels. The opposite temperature dependences of the two specific excitations, one at the peak of CTB and the other from the edge of CTB, were employed to design a luminescence intensity ratio thermometry scheme in the tungstate. When compared to other related schemes, our scheme showed a higher relative sensitivity.

Abstract Introduction Schizophrenia's heritability and familial transmission have been known for several decades. The male‐specific Y chromosome plays an important role in schizophrenia. Short tandem repeats (STRs)have been recognized as risk genes in the development of schizophrenia. Here, we investigated the association between male schizophrenia and Y‐chromosomal STRs loci. Methods We recruited 355 patients with schizophrenia and 473 healthy males for physical examination and amplified them with a PowerPlex 21 System fluorescence‐labeled composite amplification System. Then, the resultant products were separated by electrophoresis and further detected. Finally, differences in allele and genotype frequency distributions of STR loci were observed. Results Our results showed that all 20 STR loci were in accordance with Hardy–Weinberg's law (p > .05). There were statistically significant differences in alleles of D13S317 and D5S818 loci and genotype frequency distribution between the two groups (alleles: p = .039, p = .022, respectively; genotype: p = .0004, p = .011, respectively). However, there was no difference in the other autosomal 18 STR loci between the two groups (p > .05). Univariate analysis showed that the frequency distribution differences of allele 11 and genotype 10‐11 at the D13S317 locus between the two groups were significant (compared to the controls, p = 0.005, odds ratio (OR) = 1.37, 95%b confidence interval (CI) = 1.10–1.71, compared to the controls, p = .0000002, OR = 3.92, 95% CI = 2.27–6.77, respectively). The frequency distribution differences of allele 7 and genotype 7‐10 at D5S818 between the two groups were significant (compared to the controls, p = .0006, OR = 3.42, 95% CI = 1.63–7.16, compared to the controls, p = .0011, OR = 8.24, 95% CI = 1.83–37.05, respectively). Conclusion Polymorphisms of the D13S317 and D5S818 loci may be predisposing factors for schizophrenia.

This work reports on ratiometric optical thermometers consisting of luminescent lanthanide complexes, namely Ln-PDC (Ln = Nd, Nd1.43Yb0.57, Gd1.45Nd0.40Yb0.15, PDC = pyridine-3,5-dicarboxylate). The fluorescence intensity ratio techniques based on emissions of Stark sublevels of 4F3/2 (Nd3+) excited state for Nd3+-single doped sample, and the intensity ratio of Stark sublevels emissions which is severally from Nd3+ and Yb3+ ions for co-doped samples are employed for the thermometric characterizations in the physiological range (298–318 K).The results show that all three complexes can be employed as luminescent thermometers with comparable temperature sensing performance and operating in biological range under 808-nm excitation. Gd1.45Nd0.40Yb0.15-PDC demonstrates to be the best one with the relative sensitivity varying from 0.482 to 0.439% K−1in the physiological range, and the minimum temperature uncertainty is less than 0.08 K. The results may provide a new approach for lanthanide organic complexes based optical thermometer working in the second biological window.

Objective This study aimed to explore the therapeutic effect of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) with two different inter-train intervals (ITIs) on upper limb motor function in the early period of stroke. Methods We recruited 48 post-stroke patients in the early period and randomly divided them into three cohorts: the sham group, the short ITI (8 s) group, and the long ITI (28 s) group. HF-rTMS was delivered at 20 Hz. The amplitude of motor evoked potentials at the affected cortical region, representing the abductor pollicis brevis muscle, reflected cortical excitability. At baseline, immediately after treatment, and 1 month after treatment, we evaluated the recovery of upper limb motor function using Brunnstrom recovery stages (BRSs) and the Fugl–Meyer Assessment for upper extremity (FMA-UE), and assessed functional independence using the Barthel Index (BI). Results HF-rTMS with two different ITIs significantly improved upper limb functional recovery relative to the sham group, but there was no significant difference in cortical excitability changes or BRS, FMA-UE, or BI scores between the different ITI groups. Conclusions At the early post-stroke stage, HF-rTMS with short ITIs generates a similar therapeutic effect to HF-rTMS with long ITIs, suggesting that treatment times can be decreased.

Objective: To examine the variability and safety of serum trough concentrations of vancomycin in patients admitted to the intensive care unit (ICU) and to analyze the factors influencing the trough concentration. Methods: Data were collected retrospectively from ICU patients receiving vancomycin treatment at a fixed dose of 2 g/day due to unobtainable weight data, at Changzhou No. 2 People’s Hospital, between 2012 and 2015. Vancomycin trough concentrations were compared between groups stratified by sex, age, and estimated glomerular filtration rate (eGFR). Results: The vancomycin trough concentration varied significantly among ICU patients on a fixed dose of 2 g/day. Only 16.9% of ICU patients met the concentration target of 15–20 mg/l, while 25% of patients showed supratherapeutic concentrations. A higher proportion of female patients than male patients showed supratherapeutic concentrations (40.4% vs. 15.5%). The trough concentration was positively correlated with age (y = 0.279 x − 2.085; R2 = 0.186) and negatively correlated with eGFR (y = −0.2 x + 33.776; R2 = 0.366). Vancomycin-related nephrotoxicity occurred at an incidence of 5.9%. Conclusions: These results suggest that the fixed-dose regimen is not appropriate for ICU patients in view of the low incidence of target trough concentrations and the high incidence of supratherapeutic concentrations. The dose should be individualized based on weight, age, and renal function to improve outcomes and patient safety.

Recently, repetitive transcranial magnetic stimulation (rTMS) has been widely used for treating neurological and psychiatric diseases. Low-frequency rTMS is used to effectively control the occurrence of seizures, including medication-refractory epilepsy and cortical dysplasia or neocortical epilepsy. However, there have been no reports on the effects of long-term rTMS on epilepsy. We observed the clinical effects of long-term rTMS in two drug-free adolescent epileptic patients with a preference for non-drug therapy. The two drug-free adolescent patients, who underwent intermittent low-frequency rTMS treatment for 36 weeks, obtained effective control of seizures (including episode and severity). However, a systematic study is required to confirm our observations.

Abstract Introduction Repetitive transcranial magnetic stimulation has been widely used for the treatment of neurological and psychiatric diseases. Rodent animals including mice and rats are often used to investigate the potential cellular and molecular mechanisms for the therapeutic effects of repetitive transcranial magnetic stimulation. So far there is no report about an easy‐to‐use device to restrain rodent animals for repetitive transcranial magnetic stimulation. Methods and Results We introduced the design and use of the restraint device for mice or rats. In the mouse device, western blot and real‐time PCR analysis showed that，in stimulated mouse frontal cortex, 10 Hz high frequency stimulation for 10 sessions resulted in enhanced expression of NR2B‐containing N‐methyl‐D‐aspartic acid receptors and reduced α1 subunit of inhibitory GABAA receptors, whereas 0.5 Hz low frequency stimulation for 10 sessions caused decreased expression of NR2B subunit and increased α1 subunit of GABAA receptors. In the rat device, measures of motor evoke potentials indicated that 10 Hz stimulation for 10 sessions increased the excitability of stimulated cortex, whereas 0.5 Hz for 10 sessions reduced it. Conclusions These results suggested the effectiveness of the devices. Thus, the two devices are practical and easy‐to‐use to investigate the mechanisms of repetitive transcranial magnetic stimulation.

Objective This study was performed to determine whether repetitive transcranial magnetic stimulation (rTMS) combined with neuromuscular electrical stimulation (NMES) effectively ameliorates dysphagia and how rTMS protocols (bilateral vs. unilateral) combined with NMES can be optimized. Methods Sixty-four patients were randomly divided into four groups using a random distribution table: the sham rTMS plus NMES (Sham-rTMS/NMES), ipsilesional 10-Hz rTMS plus NMES (Ipsi-rTMS/NMES), contralesional 1-Hz rTMS plus NMES (Contra-rTMS/NMES), and bilateral rTMS plus NMES (Bi-rTMS/NMES) groups. Cortical excitability as measured by the amplitude of the motor evoked potential at the mylohyoid muscle cortical representative area, swallowing function as measured by the Standardized Swallowing Assessment, and the degree of dysphagia were evaluated at baseline, after the stimulation course, and at the 1-month follow-up. Results Bi-rTMS/NMES produced higher cortical excitability and better swallowing function recovery. Compared with NMES alone, unilateral rTMS plus NMES had additional effects on cortical excitability and rehabilitation of dysphagia, but there were no differences between the Contra-rTMS/NMES and Ipsi-rTMS/NMES groups. No adverse events occurred. Conclusion The combination of rTMS with NMES was superior to NMES alone in improving the recovery of post-stroke dysphagia, and the combination of bilateral rTMS with NMES was more effective than unilateral rTMS combined with NMES.

Levodopa (L-DOPA) is still the most effective drug for the treatment of Parkinson’s disease (PD). However, the long-term therapy often triggers L-DOPA-induced dyskinesia (LID). Metabotropic glutamate receptor type 5 (mGluR5) is abundant in the basal ganglia, and its inhibition is thought to modulate postsynaptic excitatory synaptic transmission and glutamate hyperactivity in PD and LID. In this report, we examined the effects of mGluR5-specific antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP) on LID and synaptic components in the PD model rat. We found the selective mGluR5 antagonist MPEP attenuated abnormal involuntary movements, prolonged the duration of rotational response, reversed the decrease of left forepaw adjusting steps, and reduced overexpression of striatal mGluR5 in the LID rats. Moreover, our results showed much thicker postsynaptic densities, narrower synapse cleft, as well as the increased ratio of perforated synapses induced by L-DOPA treatment, while coadministration of L-DOPA and MPEP reversed these postsynaptic effects. Finally, MPEP reduced overexpression of the two postsynaptic proteins (PSD-95 and SAP102) induced by L-DOPA treatment. Hence, these results provide evidence that aberrant neural plasticity at corticostriatal synapses in the striatum is closely correlated with the occurrence of LID, and targeted inhibition of mGluR5 by MPEP alleviates LID in the PD rat model.

Objectives The serum concentration of brain-derived neurotrophic factor (BDNF) was compared among patients with Parkinson’s disease (PD), patients with essential tremor (ET), and healthy participants, and its association with clinical features of PD and ET was assessed. Methods Demographic and clinical data were collected from 60 patients with PD at different clinical stages, 60 patients with ET, and 60 controls. All participants’ serum BDNF concentrations were measured. Their motor abilities and activity were assessed by the Unified PD Rating Scale and the Hoehn and Yahr (H-Y) staging scale. Results Serum BDNF was significantly lower in patients with PD than in patients with ET and controls. BDNF decreased only in the early disease stages (H-Y stages I and II), but increased markedly in the advanced stages (H-Y stages III–V). There was no significant difference between patients with ET and controls. The BDNF concentration was negatively correlated with age at PD onset and positively associated with disease duration, severity of PD symptoms, and treatment with L-DOPA. Conclusions A low serum BDNF concentration may serve as a biomarker in the early stages of PD, whereas a high concentration with PD progression may be due to treatment with L-DOPA in the advanced stages.

Aim: The study aims to describe a less invasive technique for displaced tibial intercondylar eminence fractures, using only one bone tunnel with suture anchor and EndoButton system. Methods: Seventeen patients were followed up after arthroscopic fixation for tibial eminence fractures using suture anchor and EndoButton. The patients were followed with clinical examinations such as Lysholm, Tegner, and International Knee Documentation Committee (IKDC) rating scales. Radiographic assessments were also performed during the follow-up for evaluating the healing of the fracture. Results: There were 14 male patients and 3 female patients with 10 right knees, and 7 left knees included. All the fractures healed anatomically at final follow-up. Also, no clinical signs of anterior cruciate ligament deficiency were detected. The mean Lysholm score improved significantly from 74.72 ± 3.24 (range from 70 to 79) to 96.2 ± 2.54 (range from 89 to 98) ( p < 0.001). The IKDC category was abnormal or severely abnormal preoperatively and all the patients improved to normal or nearly normal at final follow-up. The Tegner score also improved significantly postoperatively from 3.45 ± 1.02 to 6.34 ± 1.22 ( p < 0.001). Conclusion: The study demonstrated that the procedure is safe and effective, which can be another option for tibial intercondylar eminence fractures.

We carry out ab initio calculations, based on finite-field scheme, of the longitudinal polarizabilities (αL) and second hyperpolarizabilities (γL) of conjugated polyenes, and study the effects of electron correlation, with second-order Moller-Plesset perturbation theory and coupled cluster with singles and doubles method. Calculations with density functional theory are also made to compare with wave-function based methods. Our study shows that electron correlation reduces linear longitudinal polarizability and enhances longitudinal second hyperpolarizability for short polyenes, but the effects decrease as the chain increases; choosing appropriate basis sets is important when quantitative results are required.

The title dimeric complex, [Eu2(C7H5O2)6(C3H7NO)2(H2O)2], is centrosymmetric, implying that pairs of equivalent Eu3+ ions and ligands lie trans to each other and that the two Eu3+ ions have exactly the same coordination environment. Each Eu3+ ion is nine-coordinated by two bidentate benzoate ligands, two bridging tridentate chelating benzoate ligands, and one dimethylformamide and one water molecule. The coordination polyhedron of each Eu3+ ion can be described with a distorted monocapped square-antiprismatic geometry. The molecular structure is stabilized by intra- and intermolecular hydrogen bonds between the water molecules and benzoate O atoms.

Activity-dependent transcription of brain-derived neurotrophic factor (BDNF) has been studied as an important model to elucidate the mechanisms underlying numerous aspects of neuroplasticity. It has been extensively emphasized that Ca(2+) influx through different routes may have significantly different effects on BDNF transcription. Here, we examined the regulatory property of the major calcium responsive elements (CaRE) in BDNF promoter IV in cultured rat cortical neurons. BDNF promoter IV, as well as CaRE1 and CaRE3, was significantly activated by Ca(2+) influx through L-type voltage-gated calcium channel (L-VGCC) or NMDA receptor (NMDAR). However, the L-VGCC- and NMDAR-mediated activation of CaRE was differentially regulated by different Ca(2+)-stimulated protein kinases. Specifically, PKA, CaMKI, and CaMKIV activity were required for L-VGCC-, but not NMDAR-mediated CaRE1 activation. CaMKI activity was required for NMDAR- but not L-VGCC-mediated CaRE3 activation. Surprisingly, the activation of CaRF, a previously identified transcription factor for CaRE1, was stimulated via L-VGCC but not NMDAR, and required MEK, PI3K and CaMKII activity. These results suggest a new working model that activity-dependent BDNF IV up-regulation may be coordinately mediated by CaRE1 and CaRE3 activity, which show different responses to Ca(2+)-stimulated kinases. Our data also explain how the individual cis-element in BDNF promoter is distinctively coupled to different Ca(2+) routes.

The near-infrared (NIR) phosphor-converted light-emitting diode (pc-LED) is heavily reliant upon the performance of NIR phosphors. However, the current NIR pc-LEDs suffer from low photoelectric efficiency and insufficient near-infrared output power. In this study, Cr3+-doped Ca3MgZrGe3O12 phosphors leading to high-performance NIR pc-LEDs were developed for the first time. They feature robust and wide NIR emission that extends over the spectrum from 650 to 1100 nm with a full width at half maximum of 120 nm, a high quantum yield of 82% and excellent thermal stability of T50% = 250 °C and I150°C = 80% when excited at 460 nm. The NIR pc-LED was constructed by combining the Ca3MgZrGe3O12:0.04Cr3+ phosphor with a blue LED chip, resulting in a device that exhibits a photoelectric conversion efficiency of 20% and a near-infrared output power of 54.19 mW when operated at a current of 100 mA. The obtained luminous efficacy is superior to that of the vast majority of current broadband near-infrared pc-LEDs. In addition, this NIR pc-LED exhibits strong penetration and its applications in bio-imaging are demonstrated. The results indicate that Ca3MgZrGe3O12:Cr3+ NIR broadband phosphors are efficient for NIR pc-LEDs. [ABSTRACT FROM AUTHOR]