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Xian Pan,1,2,* Shao-Jie Wu,1,2,* Yi Tang,1,2,* Yan-Feng Zhou,1,2 Jie-Wei Luo,1,3 Zhu-Ting Fang1,2 1Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, People’s Republic of China; 2Department of Interventional Radiology, Fujian Provincial Hospital, Fuzhou, People’s Republic of China; 3Department of Traditional Chinese Medicine, Fujian Provincial Hospital, Fuzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jie-Wei Luo; Zhu-Ting Fang, Tel +86 59188217540, Email docluo0421@aliyun.com; 470389481@qq.comPurpose: In China, many patients with hepatocellular carcinoma (HCC) are diagnosed at an advanced stage. Several studies have shown that triple therapy [transarterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs)] is beneficial for patient survival. In this study, we aimed to evaluate the efficacy of triple therapy (TACE + TKIs + ICIs) for unresectable HCC (uHCC) and the conversion rate of surgical resection (SR). The primary endpoints were objective response rate (ORR) and disease control rate (DCR) based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST) and RECIST v1.1 and adverse events (AEs), while the secondary endpoint was the conversion rate of patients with uHCC treated with triple therapy followed by SR.Patients and Methods: Forty-nine patients with uHCC who received triple therapy at Fujian Provincial Hospital between January 2020 and June 2022 were retrospectively included. The treatment efficacy, SR conversion rate, and associated AEs were recorded.Results: Among the 49 patients enrolled, the ORRs assessed by mRECIST and RECIST v1.1 were 57.1% (24/42) and 14.3% (6/42), respectively, and the DCRs were 92.9% (39/42) and 88.1% (37/42), respectively. Seventeen (34.7%) patients met the criteria for resectable HCC and underwent resection. The median interval between the start of triple therapy and resection was 113.5 days (range 94.75 to 182 d), and the median number of TACE was 2 (range 1 to 2.5). The patients did not achieve median overall survival or median progression-free survival. Treatment-related AEs occurred in 48 (98%) patients, and 18 (36.7%) patients had grade ≥ 3 AEs.Conclusion: Triple combination therapy resulted in a relatively high ORR and conversion resection rate following uHCC treatment.Keywords: TACE, immune checkpoint inhibitors, tyrosine kinase inhibitor, surgical resection

Bi4I4 belongs to a novel family of quasi-one-dimensional (1D) topological insulators (TIs). While its β phase was demonstrated to be a prototypical weak TI, the α phase, long thought to be a trivial insulator, was recently predicted to be a rare higher order TI. Here, we report the first gate tunable transport together with evidence for unconventional band topology in exfoliated α-Bi4I4 field effect transistors. We observe a Dirac-like longitudinal resistance peak and a sign change in the Hall resistance; their temperature dependences suggest competing transport mechanisms: a hole-doped insulating bulk and one or more gate-tunable ambipolar boundary channels. Our combined transport, photoemission, and theoretical results indicate that the gate-tunable channels likely arise from novel gapped side surface states, two-dimensional (2D) TI in the bottommost layer, and/or helical hinge states of the upper layers. Markedly, a gate-tunable supercurrent is observed in an α-Bi4I4 Josephson junction, underscoring the potential of these boundary channels to mediate topological superconductivity.

The cerebellum is conceptualized as a processor of complex movements and is also endowed with roles in cognitive and emotional behaviors. Although the axons of deep cerebellar nuclei are known to project to primary thalamic nuclei, macroscopic investigation of the characteristics of these projections, such as the spatial distribution of recipient zones, is lacking. Here, we studied the output of the cerebellar interposed nucleus (IpN) to the ventrolateral (VL) and centrolateral (CL) thalamic nuclei using electrophysiological recording in vivo and trans-synaptic viral tracing. We found that IpN stimulation induced mono-synaptic evoked potentials (EPs) in the VL but not the CL region. Furthermore, both the EPs induced by the IpN and the innervation of IpN projections displayed substantial heterogeneity across the VL region in three-dimensional space. These findings indicate that the recipient zones of IpN inputs vary between and within thalamic nuclei and may differentially control thalamo-cortical networks. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12264-021-00780-y.

Quasi-one-dimensional (1D) materials provide a superior platform for characterizing and tuning topological phases for two reasons: i) existence for multiple cleavable surfaces that enables better experimental identification of topological classification, and ii) stronger response to perturbations such as strain for tuning topological phases compared to higher dimensional crystal structures. In this paper, we present experimental evidence for a room-temperature topological phase transition in the quasi-1D material Bi$_4$I$_4$, mediated via a first order structural transition between two distinct stacking orders of the weakly-coupled chains. Using high resolution angle-resolved photoemission spectroscopy on the two natural cleavable surfaces, we identify the high temperature $\beta$ phase to be the first weak topological insulator with gapless Dirac cones on the (100) surface and no Dirac crossing on the (001) surface, while in the low temperature $\alpha$ phase, the topological surface state on the (100) surface opens a gap, consistent with a recent theoretical prediction of a higher-order topological insulator beyond the scope of the established topological materials databases that hosts gapless hinge states. Our results not only identify a rare topological phase transition between first-order and second-order topological insulators but also establish a novel quasi-1D material platform for exploring unprecedented physics., Comment: 9 pages, 4 figures, accepted for publication in Phys. Rev. X

The non-Abelian braiding of Majorana fermions is one of the most promising operations providing a key building block for the realization of topological quantum computation. Recently, the chiral Majorana fermions were observed in a hybrid junction btween a quantum anomalous Hall insulator and an s-wave superconductor. Here we show that if a quantum dot or Majorana zero mode couples to the chiral Majorana fermions, the resulting resonant exchange of chiral Majorana fermions can lead to the non-Abelian braiding. Remarkably, any operation in the braid group can be achieved by this scheme. We further propose electrical transport experiments to observe the braiding of four chiral Majorana fermions and demonstrate the non-Abelian braiding statistics in four-terminal devices of the hybrid junctions. Both a conductance peak due to the braiding and the braiding-order dependent conductance are predicted. These findings pave a way to perform any braiding operation of chiral Majorana fermions by electrically controllable quantum dots., 11 pages, 9 figures

We study the influence of step defect on surface states in three-dimensional topological insulators subject to a perpendicular magnetic field. By calculating the energy spectrum of the surface states, we find that Landau levels (LLs) can form on flat regions of the surface and are distant from the step defect, and several subbands emerge at side surface of the step defect. The subband which connects to the two zeroth LLs is spin-polarized and chiral. In particular, when the electron transports along the side surface, the electron spin direction can be manipulated arbitrarily by gate voltage. And no reflection occurs even if the electron spin direction is changed. This provides a fascinating avenue to control the electron spin easily and coherently. In addition, regarding the subbands with high LL index, there exist spin-momentum locking helical states and the quantum spin Hall effect can appear., 6 pages, 5 figures

A remote control system has been developed to deliver stimuli into the rat brain through a wireless micro-stimulator for animal behavior training. The system consists of the following main components: an integrated PC control program, a transmitter and a receiver based on Bluetooth (BT) modules, a stimulator controlled by C8051 microprocessor, as well as an operant chamber and an eight-arm radial maze. The micro-stimulator is featured with its changeable amplitude of pulse output for both constant-voltage and constant-current mode, which provides an easy way to set the proper suitable stimulation intensity for different training. The system has been used in behavior experiments for monitoring and recording bar-pressing in the operant chamber, contriolling rat roaming in the eight-arm maze, as well as navigating rats through a 3D obstacle route. The results indicated that the system worked stably and that the stimulation was effective for different types of rat behavior controls. In addition, the results showed that stimulation in the whisker barrel region of rat primary somatosensory cortex (SI) acted like a cue. The animals can be trained to take different desired turns upon the association between the SI cue stimulation and the reward stimulation in the medial forebrain bundle (MFB).

Phase-locking is an important encoding mode in the hippocampal region of brain where neuronal firing concentrates on a certain phase of the periodic field potential, especially θ rhythm. It can be observed during many behaviors while the locked-phase varies accordingly. In this study, the changes of neuronal phase-locking induced by somatosensory stimulation of tail-clamping were investigated. The local field potential and spike signals were recorded in hippocampal CA1 region of anesthetized rats with microelectrode array. The phase-locking relationship was analyzed with Raleigh test and spike-phase histogram. The results showed that during spontaneous activity, 3 of 20 examined neurons were phase-locking to the θ rhythm of the field potential. However, during the tail clamping periods, the number of phase-locking neurons increased from 3 to 8, and the mean locked-phase shifted towards the negative peak of the field potential cycle, which became θ rhythm dominated. These findings suggest that the hippocampus may encode somatosensory information with the phase-locking neurons and by shifting their locked-phases.

Objective: To directly examine the effects of carnosine on neuronal excitation and inhibition in rat hippocampus in vivo. Methods: Artificial cerebrospinal fluid with carnosine was directly administrated over the exposed rat hippocampus. The changes of neuron activity in the CA1 region of hippocampus were evaluated by orthodromically- and antidromically-evoked potentials, as well as paired-pulse stimulation paradigm. Results: In both orthodromic and antidromic response potentials, carnosine transformed population spikes (PSs) with single spike into epileptiform multiple spikes. In addition, similar to the effect of γ-aminobutyric acidA (GABAA) antagonist picrotoxin, carnosine decreased paired-pulse stimulating depression significantly. However, no significant change was observed in the spontaneous field potentials during the application of carnosine. Conclusion: The results indicate a disinhibition-induced excitation effect of carnosine on the CA1 pyramidal neurons. It provides important information against the application of carnosine as a potential anticonvulsant in clinical treatment.

The dynamic features of rat EEGs collected during slow wave sleep (SWS) and transition sleep (TS) were investigated in both time and frequency domains using wavelet transform based on multi-resolution signal decomposition. EEGs of freely moving rats were recorded with implanted electrodes and then decomposed into four components of delta, theta, alpha and beta using wavelet transform. The power and power percentage of each component were calculated as functions of time. In SWS EEGs, the results showed that there existed as much as 26.2% +/- 7.7% time duration in which the delta power percentage was less than 50%. In addition, the powers of other three components in small delta EEGs were significantly larger than those in large delta EEGs. This result revealed a reciprocal relationship between delta oscillation and spindle oscillation. Comparatively, the conventional method of FFT based power spectrum could only show a delta power-dominating (70.6% +/- 6.4%) spectrum of SWS EEGs. In the non-stationary TS EEG, spindle and non-spindle segments were distinguished based on the wavelet components of theta and alpha, and then the average duration of the spindles was estimated. In conclusion, the wavelet transform may be useful in developing novel quantitative time-frequency measures of sleep EEGs as valuable complements of conventional FFT method to analyze the transient changes in sleep EEGs induced by physiological, pathological or pharmacological conditions.

OBJECTIVE: To study the sedative effects of Jujuboside A (JuA) on the Central Nervous System of mice. METHODS: Using a novel jiggle-cage test, we compared the sedative effect of JuA with that of Diazepam (DZP) both with a single and cumulative dose of JuA. We also assessed the anticonvulsant effect of JuA on pentylenetetrazol (PTZ)-induced seizures in mice. RESULTS: JuA significantly decreased total activity intensity and increased the quiet state time of mice. The sedative effects of JuA were more stable and more lasting than that of DZP. However, JuA failed to resist and delay the induced seizure activity in mice. CONCLUSION: Though JuA has sedative effects on mice CNS, it has no anticonvulsant effect on PTZ-induced seizures.

Objective. To study the complexity and the power spectrum of cortical EEG and hippocampal potential in rats under waking and sleep states. Method. Cortical EEG and hippocampal potential were collected by implanted electrodes in freely moving rats. Algorithmic complexity (Kc), approximate entropy (ApEn), power spectral density (PSD) and gravity frequency of PSD of the potential waves were calculated. Result. The complexity of hippocampal potential was higher than that of cortical EEG under every state. The complexity of cortical EEG was lowest under the state of non rapid eye movement (NREM) sleep. The complexity of hippocampal potential was highest under waking state. The total power of both potentials in 0.5- 30 Hz frequency band showed their highest values under NREM state. Conclusion. The values of Kc and ApEn are closely related to the distributions of PSD. When there are evident peaks in PSD, the complexities of signals will decrease. The complexities may be used to distinguish the difference between cortical EEG and hippocampal potential, or large differences between the same kind of potentials under different behavioral states.

The hippocampal region of the brain is important for encoding environment inputs and memory formation. However, the underlying mechanisms are unclear. To investigate the behavior of individual neurons in response to somatosensory inputs in the hippocampal CA1 region, we recorded and analyzed changes in local field potentials and the firing rates of individual pyramidal cells and interneurons during tail clamping in urethane-anesthetized rats. We also explored the mechanisms underlying the neuronal responses. Somatosensory stimulation, in the form of tail clamping, chan-ged local field potentials into theta rhythm-dominated waveforms, decreased the spike firing of pyramidal cells, and increased interneuron firing. In addition, somatosensory stimulation attenuated orthodromic-evoked population spikes. These results suggest that somatosensory stimulation suppresses the excitability of pyramidal cells in the hippocampal CA1 region. Increased inhibition by local interneurons might underlie this effect. These findings provide insight into the mechanisms of signal processing in the hippocampus and suggest that sensory stimulation might have therapeutic potential for brain disorders associated with neuronal hyperexcitability.