Systemic immune-inflammation index and all-cause and cause-specific mortality in sarcopenia: a study from National Health and Nutrition Examination Survey 1999-2018.

Background: Sarcopenia, common in the elderly, often linked to chronic diseases, correlates with inflammation.The association between SII and mortality in sarcopenia patients is underexplored, this study investigates this relationship in a U.S. adult cohort. Methods: We analyzed 1999-2018 NHANES data, focusing on 2,974 adults with sarcopenia. Mortality outcomes were determined by linking to National Death Index (NDI) records up to December 31, 2019. Using a weighted sampling design, participants were grouped into three groups by the Systemic Immune-Inflammation Index (SII). We used Cox regression models, adjusting for demographic and clinical variables, to explore SII's association with all-cause and cause-specific mortality in sarcopenia, performing sensitivity analyses for robustness. Results: Over a median follow-up of 9.2 years, 829 deaths occurred. Kaplan-Meier analysis showed significant survival differences across SII groups. The highest SII group showed higher hazard ratios (HRs) for all-cause and cause-specific mortality in both crude and adjusted models. The highest SII group had a higher HR for all-cause(1.57, 1.25-1.98), cardiovascular(1.61, 1.00-2.58), cancer(2.13, 1.32-3.44), and respiratory disease mortality(3.21, 1.66-6.19) in fully adjusted models. Subgroup analyses revealed SII's association with all-cause mortality across various demographics, including age, gender, and presence of diabetes or cardiovascular disease. Sensitivity analyses, excluding participants with cardiovascular diseases, those who died within two years of follow-up, or those under 45 years of age, largely reflected these results, with the highest SII group consistently demonstrating higher HRs for all types of mortality in both unadjusted and adjusted models. Conclusion: Our study is the first to demonstrate a significant relationship between SII and increased mortality risks in a sarcopenia population.

A tonically active master neuron modulates mutually exclusive motor states at two timescales.

Continuity of behaviors requires animals to make smooth transitions between mutually exclusive behavioral states. Neural principles that govern these transitions are not well understood. Caenorhabditis elegans spontaneously switch between two opposite motor states, forward and backward movement, a phenomenon thought to reflect the reciprocal inhibition between interneurons AVB and AVA. Here, we report that spontaneous locomotion and their corresponding motor circuits are not separately controlled. AVA and AVB are neither functionally equivalent nor strictly reciprocally inhibitory. AVA, but not AVB, maintains a depolarized membrane potential. While AVA phasically inhibits the forward promoting interneuron AVB at a fast timescale, it maintains a tonic, extrasynaptic excitation on AVB over the longer timescale. We propose that AVA, with tonic and phasic activity of opposite polarities on different timescales, acts as a master neuron to break the symmetry between the underlying forward and backward motor circuits. This master neuron model offers a parsimonious solution for sustained locomotion consisted of mutually exclusive motor states.

A Rare Case of Benign Recurrent Intrahepatic Cholestasis Initially Diagnosed in Middle-age.

Background: Repeated episodes of jaundice and pruritus are common in a group of autosomal recessive liver diseases known as benign recurrent intrahepatic cholestasis. Benign recurrent intrahepatic cholestasis (BRIC) is divided into two types, type 1 and type 2, and is caused by mutations in the ATP8B1 and ABCB11 genes. Here, we report a rare case of BRIC type 2 mutation. Case presentation: A 45-year-old Chinese man had three frequent episodes of jaundice marked by extensive excoriation and severe pruritis, although he had no prior history of jaundice. Laboratory investigations showed no evidence of liver damage caused by viral, autoimmune, or acquired metabolic etiologies. The CT scan revealed an enlarged gallbladder with numerous punctate high-density shadows, while no wall thickening was observed. Endoscopic ultrasonography showed no evidence of dilation of the intrahepatic and extrahepatic bile duct, as well as the absence of gallstone. Diagnostic evaluation: Immunohistochemical examinations of liver biopsy samples showed cytokeratin-7 positive hepatocytes, suggesting chronic intrahepatic cholestasis. The reticulin fiberstaining demonstrated that the portions of the hepatic plate in the center of the lobule were asymmetrically organized,and somewhat enlarged, with collapsed areas indicating intralobular inflammation. Moreover, there were areas of collapse that indicated the presence of intralobular inflammation. Whole exome sequencing revealed mutations in the ABCB11 gene; c.3084A>G, p.A1028A homozygous mutation (chr2-169789016), and c.2594C>T, p.A865V heterozygous mutation (chr2-169801131). Based on these findings, the final diagnosis of the patient was metabolism-related jaundice. Treatment: Apart from receiving tapering dosage of prednisone to lower bilirubin levels, the patient received no extra care. Conclusion: The comprehensive diagnosis of a middle-aged male patient with BRIC-2, which involved extensive radiological, hematological, and genetic investigations, informed a tailored tapering prednisone regimen, highlighting the importance of personalized medicine in managing atypical presentations of this rare cholestatic disorder.

The epithelial Na+ channel UNC-8 promotes an endocytic mechanism that recycles presynaptic components to new boutons in remodeling neurons.

Circuit refinement involves the formation of new presynaptic boutons as others are dismantled. Nascent presynaptic sites can incorporate material from recently eliminated synapses, but the recycling mechanisms remain elusive. In early-stage C. elegans larvae, the presynaptic boutons of GABAergic DD neurons are removed and new outputs established at alternative sites. Here, we show that developmentally regulated expression of the epithelial Na+ channel (ENaC) UNC-8 in remodeling DD neurons promotes a Ca2+ and actin-dependent mechanism, involving activity-dependent bulk endocytosis (ADBE), that recycles presynaptic material for reassembly at nascent DD synapses. ADBE normally functions in highly active neurons to accelerate local recycling of synaptic vesicles. In contrast, we find that an ADBE-like mechanism results in the distal recycling of synaptic material from old to new synapses. Thus, our findings suggest that a native mechanism (ADBE) can be repurposed to dismantle presynaptic terminals for reassembly at new, distant locations.

UBR-1 ubiquitin ligase regulates the balance between GABAergic and glutamatergic signaling.

Excitation/inhibition (E/I) balance is carefully maintained by the nervous system. The neurotransmitter GABA has been reported to be co-released with its sole precursor, the neurotransmitter glutamate. The genetic and circuitry mechanisms to establish the balance between GABAergic and glutamatergic signaling have not been fully elucidated. Caenorhabditis elegans DVB is an excitatory GABAergic motoneuron that drives the expulsion step in the defecation motor program. We show here that in addition to UNC-47, the vesicular GABA transporter, DVB also expresses EAT-4, a vesicular glutamate transporter. UBR-1, a conserved ubiquitin ligase, regulates DVB activity by suppressing a bidirectional inhibitory glutamate signaling. Loss of UBR-1 impairs DVB Ca2+ activity and expulsion frequency. These impairments are fully compensated by the knockdown of EAT-4 in DVB. Further, glutamate-gated chloride channels GLC-3 and GLC-2/4 receive DVB's glutamate signals to inhibit DVB and enteric muscle activity, respectively. These results implicate an intrinsic cellular mechanism that promotes the inherent asymmetric neural activity. We propose that elevated glutamate in ubr-1 mutants, being the cause of the E/I shift, potentially contributes to Johanson Blizzard syndrome.

mEMbrain: an interactive deep learning MATLAB tool for connectomic segmentation on commodity desktops.

Connectomics is fundamental in propelling our understanding of the nervous system's organization, unearthing cells and wiring diagrams reconstructed from volume electron microscopy (EM) datasets. Such reconstructions, on the one hand, have benefited from ever more precise automatic segmentation methods, which leverage sophisticated deep learning architectures and advanced machine learning algorithms. On the other hand, the field of neuroscience at large, and of image processing in particular, has manifested a need for user-friendly and open source tools which enable the community to carry out advanced analyses. In line with this second vein, here we propose mEMbrain, an interactive MATLAB-based software which wraps algorithms and functions that enable labeling and segmentation of electron microscopy datasets in a user-friendly user interface compatible with Linux and Windows. Through its integration as an API to the volume annotation and segmentation tool VAST, mEMbrain encompasses functions for ground truth generation, image preprocessing, training of deep neural networks, and on-the-fly predictions for proofreading and evaluation. The final goals of our tool are to expedite manual labeling efforts and to harness MATLAB users with an array of semi-automatic approaches for instance segmentation. We tested our tool on a variety of datasets that span different species at various scales, regions of the nervous system and developmental stages. To further expedite research in connectomics, we provide an EM resource of ground truth annotation from four different animals and five datasets, amounting to around 180 h of expert annotations, yielding more than 1.2 GB of annotated EM images. In addition, we provide a set of four pre-trained networks for said datasets. All tools are available from https://lichtman.rc.fas.harvard.edu/mEMbrain/. With our software, our hope is to provide a solution for lab-based neural reconstructions which does not require coding by the user, thus paving the way to affordable connectomics.

Nanoscale implant anchorage aided by cement line deposition into titanium dioxide nanotubes.

The success of titanium dental implants relies on osseointegration, the load-bearing connection between bone tissue and the device that, in contact osteogenesis, comprises the deposition of bony cement line matrix onto the implant surface. Titanium dioxide nanotubes (NTs) are considered a promising surface for improved osseointegration, yet the mechanisms of cement line integration with such features remains elusive. Herein, we illustrate cement line deposition into NTs on the surface of titanium implants with two underlaying microstructures: a machined surface or a blasted/acid etched surface placed in the tibiae of Wistar rats. After retrieval, scanning electron microscopy of tissue reflected from the implant surface indicated minimal incursion of the cement line matrix into the NTs. To investigate this further, focused ion beam was utilized to prepare cross-sectional samples that could be characterized using scanning transmission electron microscopy. The cement line matrix covered NTs regardless of underlying microstructure, which was further confirmed by elemental analysis. In some instances, cement line infiltration into the NTs was noted, which reveals a mechanism of nanoscale anchorage. This study is the first to demonstrate cement line deposition into titanium NTs, suggesting nano-anchorage as a mechanism for the success of the NT modified surfaces in vivo.

mEMbrain: an interactive deep learning MATLAB tool for connectomic segmentation on commodity desktops.

Connectomics is fundamental in propelling our understanding of the nervous system’s organization, unearthing cells and wiring diagrams reconstructed from volume electron microscopy (EM) datasets. Such reconstructions, on the one hand, have benefited from ever more precise automatic segmentation methods, which leverage sophisticated deep learning architectures and advanced machine learning algorithms. On the other hand, the field of neuroscience at large, and of image processing in particular, has manifested a need for user-friendly and open source tools which enable the community to carry out advanced analyses. In line with this second vein, here we propose mEMbrain, an interactive MATLAB-based software which wraps algorithms and functions that enable labeling and segmentation of electron microscopy datasets in a user-friendly user interface compatible with Linux and Windows. Through its integration as an API to the volume annotation and segmentation tool VAST, mEMbrain encompasses functions for ground truth generation, image preprocessing, training of deep neural networks, and on-the-fly predictions for proofreading and evaluation. The final goals of our tool are to expedite manual labeling efforts and to harness MATLAB users with an array of semi-automatic approaches for instance segmentation. We tested our tool on a variety of datasets that span different species at various scales, regions of the nervous system and developmental stages. To further expedite research in connectomics, we provide an EM resource of ground truth annotation from 4 different animals and 5 datasets, amounting to around 180 hours of expert annotations, yielding more than 1.2 GB of annotated EM images. In addition, we provide a set of 4 pre-trained networks for said datasets. All tools are available from https://lichtman.rc.fas.harvard.edu/mEMbrain/ . With our software, our hope is to provide a solution for lab-based neural reconstructions which does not require coding by the user, thus paving the way to affordable connectomics.

[Establishment and Analysis of Risk Prediction Model for Metabolic Dysfunction-Associated Fatty Liver Disease in Physical Examination Population].

Objective: To analyze the risk factors of metabolic dysfunction-associated fatty liver disease (MAFLD) in the physical examination population, to establish a risk prediction model for the occurrence of MAFLD, and to provide management strategies for the prevention and occurrence of the disease. Methods: A total of 14664 people who underwent physical examination at the Physical Examination Center, West China Hospital, Sichuan University between January 2018 and December 2021 were selected as research subjects. The subjects were divided into a MAFLD group ( n=4013) and a non-MAFLD group ( n=10651) according to whether they had MAFLD. The differences in biochemical indices, for example, glycolipid metabolism levels, were compared and logistic regression was conducted to analyze the risk factors for MAFLD, thereby establishing a nomogram prediction model. The prediction effect of the model was validated and evaluated with the consistency index (C-index) and the calibration curve. Results: Among the 14664 subjects who underwent physical examination, 4013 were MAFLD patients, presenting an overall prevalence of 27.37%, with significantly higher prevalence in men than that in women (38.99% vs. 10.06%, P<0.001). Compared with those of the non-MAFLD group, the levels of glucose (GLU), total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyl transpeptidase (GGT) and uric acid (UA) were increased ( P<0.05), while the high density lipoprotein cholesterol (HDL-C) level was decreased ( P<0.05) in the MAFLD group. The results of logistic regression analysis showed that male sex, age, body mass index, GLU, TG and hypertension were all independent risk factors of MAFLD, while HDL-C was a protective factor of MAFLD. The risk factors were used to establish a nomogram risk prediction model and the C-index and calibration curve showed that the nomogram model produced good predictive performance. The receiver operating characteristic (ROC) curve showed that the nomogram model had good predictive value for the risk of MAFLD. Conclusion: We found a relatively high prevalence of MAFLD in the physical examination population, and the nomogram model established with routine physical examination screening can provide indications for the clinical screening and analysis of high-risk patients, which has an early warning effect on the high-risk population.

Functional imaging and quantification of multineuronal olfactory responses in C. elegans.

Many animals perceive odorant molecules by collecting information from ensembles of olfactory neurons, where each neuron uses receptors that are tuned to recognize certain odorant molecules with different binding affinity. Olfactory systems are able, in principle, to detect and discriminate diverse odorants using combinatorial coding strategies. We have combined microfluidics and multineuronal imaging to study the ensemble-level olfactory representations at the sensory periphery of the nematode Caenorhabditis elegans. The collective activity of C. elegans chemosensory neurons reveals high-dimensional representations of olfactory information across a broad space of odorant molecules. We reveal diverse tuning properties and dose-response curves across chemosensory neurons and across odorants. We describe the unique contribution of each sensory neuron to an ensemble-level code for volatile odorants. We show that a natural stimuli, a set of nematode pheromones, are also encoded by the sensory ensemble. The integrated activity of the C. elegans chemosensory neurons contains sufficient information to robustly encode the intensity and identity of diverse chemical stimuli.

Localization and density of tertiary lymphoid structures associate with molecular subtype and clinical outcome in colorectal cancer liver metastases.

BACKGROUND: Tertiary lymphoid structures (TLSs) have been proposed to assess the prognosis of patients with cancer. Here, we investigated the prognostic value and relevant mechanisms of TLSs in colorectal cancer liver metastases (CRCLM). METHODS: 603 patients with CRCLM treated by surgical resection from three cancer centers were included. The TLSs were categorized according to their anatomic subregions and quantified, and a TLS scoring system was established for intratumor region (T score) and peritumor region (P score). Differences in relapse-free survival (RFS) and overall survival (OS) between groups were determined. Multiplex immunohistochemical staining (mIHC) was used to determine the cellular composition of TLSs in 40 CRCLM patients. RESULTS: T score positively correlated with superior prognosis, while P score negatively associated with poor survival (all p<0.05). Meanwhile, T score was positively associated with specific mutation subtype of KRAS. Furthermore, TLSs enrichment gene expression was significantly associated with survival and transcriptomic subtypes of CRCLM. Subsequently, mIHC showed that the densities of Treg cells, M2 macrophages and Tfh cells were significantly higher in intratumor TLSs than in peritumor TLSs (p=0.029, p=0.047 and p=0.041, respectively), and the frequencies of Treg cells and M2 macrophages were positively correlated with P score, while the frequencies of Tfh cells were positively associated with T scores in intratumor TLSs (all p<0.05). Next, based on the distribution and abundance of TLSs, an Immune Score combining T score and P score was established which categorized CRCLM patients into four immune classes with different prognosis (all p<0.05). Among them, patients with higher immune class have more favorable prognoses. The C-index of Immune Class for RFS and OS was higher than Clinical Risk Score statistically. These results were also confirmed by the other two validation cohorts. CONCLUSIONS: The distribution and abundance of TLSs is significantly associated with RFS and OS of CRCLM patients, and a novel immune class was proposed for predicting the prognosis of CRCLM patients.

The prognostic significance of clinicopathological characteristics in early-onset versus late-onset colorectal cancer liver metastases.

PURPOSE: This study aimed to explore the prognostic significance of clinicopathological characteristics in early-onset versus late-onset colorectal liver metastases (CRLM). METHODS: The data of CRLM patients who underwent hepatectomy from September 2010 to September 2020 were retrospectively analyzed. According to the age of primary cancer diagnosis, patients were divided into early-onset CRLM (EOCRLM) and late-onset CRLM (LOCRLM) groups. Clinicopathological parameters were compared between the two groups. Cox regression model and Kaplan-Meier method were used to analyze the effect of clinicopathological parameters on overall survival (OS) and recurrence-free survival (RFS). RESULTS: In total, 431 CRLM patients were identified, 130 with EOCRLM and 301 with LOCRLM. Compared with LOCRLM patients, EOCRLM patients had lower American Society of Anesthesia (ASA) grade and longer operation time (204 vs. 179 min). More aggressive features were presented in EOCRLM patients including synchronous liver metastases (76.9% vs. 61.1%) and bilobar involvement (43.8% vs. 33.2%). No significant difference in OS or RFS was found between the two groups. Multivariate analysis of EOCRLM group showed that preoperative CA19-9 level and RAS/BRAF status were predictive of OS, while bilobar involvement and preoperative CEA level were associated with RFS. In LOCRLM group, the number of CRLM, preoperative CA19-9 level, and BRAF status were associated with OS, while the number of CRLM was associated with RFS. CONCLUSIONS: The preoperative CA19-9 level, RAS/BRAF status, bilobar involvement, and preoperative CEA level were predictive of EOCRLM patient prognosis, while the number of CRLM, preoperative CA19-9 level, and BRAF status were predictive of LOCRLM patient prognosis.

High-valent Cu(III)-CF3 compound-mediated esterification reaction.

Cu(III)-CF3 compounds are reported herein as novel coupling reagents to mediate ester synthesis from carboxyl acids and alcohols/phenols. Carboxylic acids are transformed to trifluoromethyl ester and acyl fluoride activated species that interact with each other. The broad substrate scope and late-stage application of this method are demonstrated. This study opens up new opportunities to develop interesting reactions using Cu(III)-CF3 compounds without transferring a CF3 group to the products.

N-end Rule-Mediated Proteasomal Degradation of ATGL Promotes Lipid Storage.

Cellular lipid storage is regulated by the balance of lipogenesis and lipolysis. The rate-limiting triglyceride hydrolase ATGL (desnutrin/PNPLA2) is critical for lipolysis. The control of ATGL transcription, localization, and activation has been intensively studied, while regulation of the protein stability of ATGL is much less explored. In this study, we showed that the protein stability of ATGL is regulated by the N-end rule in cultured cells and in mice. The N-end rule E3 ligases UBR1 and UBR2 reduce the level of ATGL and affect lipid storage. The N-end rule-resistant ATGL(F2A) mutant, in which the N-terminal phenylalanine (F) of ATGL is substituted by alanine (A), has increased protein stability and enhanced lipolysis activity. ATGLF2A/F2A knock-in mice are protected against high-fat diet (HFD)-induced obesity, hepatic steatosis, and insulin resistance. Hepatic knockdown of Ubr1 attenuates HFD-induced hepatic steatosis by enhancing the ATGL level. Finally, the protein levels of UBR1 and ATGL are negatively correlated in the adipose tissue of obese mice. Our study reveals N-end rule-mediated proteasomal regulation of ATGL, a finding that may potentially be beneficial for treatment of obesity.

Post-embryonic remodeling of the C. elegans motor circuit.

During development, animals can maintain behavioral output even as underlying circuitry structurally remodels. After hatching, C. elegans undergoes substantial motor neuron expansion and synapse rewiring while the animal continuously moves with an undulatory pattern. To understand how the circuit transitions from its juvenile to mature configuration without interrupting functional output, we reconstructed the C. elegans motor circuit by electron microscopy across larval development. We observed the following: First, embryonic motor neurons transiently interact with the developing post-embryonic motor neurons prior to remodeling of their juvenile wiring. Second, post-embryonic neurons initiate synapse development with their future partners as their neurites navigate through the juvenile nerve cords. Third, embryonic and post-embryonic neurons sequentially build structural machinery needed for the adult circuit before the embryonic neurons relinquish their roles to post-embryonic neurons. Fourth, this transition is repeated region by region along the body in an anterior-to-posterior sequence, following the birth order of neurons. Through this orchestrated and programmed rewiring, the motor circuit gradually transforms from asymmetric to symmetric wiring. These maturation strategies support the continuous maintenance of motor patterns as the juvenile circuit develops into the adult configuration.

Extrasynaptic signaling enables an asymmetric juvenile motor circuit to produce symmetric undulation.

In many animals, there is a direct correspondence between the motor patterns that drive locomotion and the motor neuron innervation. For example, the adult C. elegans moves with symmetric and alternating dorsal-ventral bending waves arising from symmetric motor neuron input onto the dorsal and ventral muscles. In contrast to the adult, the C. elegans motor circuit at the juvenile larval stage has asymmetric wiring between motor neurons and muscles but still generates adult-like bending waves with dorsal-ventral symmetry. We show that in the juvenile circuit, wiring between excitatory and inhibitory motor neurons coordinates the contraction of dorsal muscles with relaxation of ventral muscles, producing dorsal bends. However, ventral bending is not driven by analogous wiring. Instead, ventral muscles are excited uniformly by premotor interneurons through extrasynaptic signaling. Ventral bends occur in anti-phasic entrainment to activity of the same motor neurons that drive dorsal bends. During maturation, the juvenile motor circuit is replaced by two motor subcircuits that separately drive dorsal and ventral bending. Modeling reveals that the juvenile's immature motor circuit is an adequate solution to generate adult-like dorsal-ventral bending before the animal matures. Developmental rewiring between functionally degenerate circuit solutions, which both generate symmetric bending patterns, minimizes behavioral disruption across maturation.

Unilateral adrenal tuberculosis whose computed tomography imaging characteristics mimic a malignant tumor: A case report.

BACKGROUND: Adrenal tuberculosis usually presents with bilateral involvement. It has special characteristics in computed tomography (CT) images, such as small size, low attenuation in the center, and peripheral rim enhancement, which differ from those of primary tumors. CASE SUMMARY: A 42-year-old female presented to the hospital with low back pain. She had been diagnosed with hypertension as well as pulmonary and cerebral tuberculosis but denied having any fever, fatigue, anorexia, night sweats, cough, or weight loss. Abdominal CT revealed an irregular 6.0 cm × 4.5 cm mass with uneven density in the right adrenal gland, while the left adrenal gland was normal. No abnormalities were observed in plasma total cortisol (8 am), adrenocorticotropic hormone, aldosterone/renin ratio, blood catecholamines, or urine catecholamines. A fine-needle aspiration biopsy of the right adrenal gland provided evidence of tuberculosis. After three years of anti-tuberculosis treatments, the large mass in the right adrenal gland was reduced to a slight enlargement. CONCLUSION: This is a case of unilateral adrenal tuberculosis with CT imaging characteristics mimicking those of a malignant tumor. Extended anti-tuberculosis therapy is recommended in such cases.

[Jiao's scalp acupuncture combined with virtual reality rehabilitation training for motor dysfunction in patients with Parkinson's disease: a randomized controlled trial].

OBJECTIVE: To compare the clinical efficacy between Jiao's scalp acupuncture combined with virtual reality (VR) rehabilitation training and VR rehabilitation training alone for motor dysfunction in patients with Parkinson's disease (PD). METHODS: A total of 52 patients with PD were randomly divided into an observation group and a control group, 26 cases in each group. The patients in both groups were treated with routine basic treatment, and the patients in the control group were treated with VR rehabilitation training. The patients in the observation group were treated with Jiao's scalp acupuncture on the basis of the control group. The scalp points included the movement area, balance area and dance tremor control area. Both groups were treated once a day, 5 times a week for a total of 8 weeks. Before treatment and 4 and 8 weeks into treatment, the gait parameters (step distance, step width, step speed and step frequency), timed "up and go" test (TUGT) time and unified Parkinson's disease rating scale part Ⅲ (UPDRS-Ⅲ) score were compared between the two groups, and the clinical efficacy was evaluated. RESULTS: Four weeks into treatment, except for the step width in the control group, the gait parameters of the two groups were improved, the TUGT time was shortened, and the UPDRS-Ⅲ scores were reduced (P<0.01, P<0.05); the step distance in the observation group was better than that in the control group, and the UPDRS-Ⅲ score in the observation group was lower than that in the control group (P<0.05). Eight weeks into treatment, the gait parameters of the two groups were improved, the TUGT time was shortened, and the UPDRS-Ⅲ scores were reduced (P<0.01); the step distance and step speed in the observation group were better than those in the control group, the TUGT time in the observation group was shorter than that in the control group, and the UPDRS-Ⅲ score in the observation group was lower than that in the control group (P<0.05, P<0.01). The total effective rate was 92.3% (24/26) in the observation group, which was higher than 69.2% (18/26) in the control group (P<0.05). CONCLUSION: Jiao's scalp acupuncture combined with VR rehabilitation training could improve the gait parameters, walking ability and motor function in patients with PD. The clinical effect is better than VR rehabilitation training alone.

Signal requirement for cortical potential of transplantable human neuroepithelial stem cells.

The cerebral cortex develops from dorsal forebrain neuroepithelial progenitor cells. Following the initial expansion of the progenitor cell pool, these cells generate neurons of all the cortical layers and then astrocytes and oligodendrocytes. Yet, the regulatory pathways that control the expansion and maintenance of the progenitor cell pool are currently unknown. Here we define six basic pathway components that regulate proliferation of cortically specified human neuroepithelial stem cells (cNESCs) in vitro without the loss of cerebral cortex developmental potential. We show that activation of FGF and inhibition of BMP and ACTIVIN A signalling are required for long-term cNESC proliferation. We also demonstrate that cNESCs preserve dorsal telencephalon-specific potential when GSK3, AKT and nuclear CATENIN-ß1 activity are low. Remarkably, regulation of these six pathway components supports the clonal expansion of cNESCs. Moreover, cNESCs differentiate into lower- and upper-layer cortical neurons in vitro and in vivo. The identification of mechanisms that drive the neuroepithelial stem cell self-renewal and differentiation and preserve this potential in vitro is key to developing regenerative and cell-based therapeutic approaches to treat neurological conditions.

Escape steering by cholecystokinin peptidergic signaling.

Escape is an evolutionarily conserved and essential avoidance response. Considered to be innate, most studies on escape responses focused on hard-wired circuits. We report here that a neuropeptide NLP-18 and its cholecystokinin receptor CKR-1 enable the escape circuit to execute a full omega (Ω) turn. We demonstrate in vivo NLP-18 is mainly secreted by the gustatory sensory neuron (ASI) to activate CKR-1 in the head motor neuron (SMD) and the turn-initiating interneuron (AIB). Removal of NLP-18 or CKR-1 or specific knockdown of CKR-1 in SMD or AIB neurons leads to shallower turns, hence less robust escape steering. Consistently, elevation of head motor neuron (SMD)'s Ca2+ transients during escape steering is attenuated upon the removal of NLP-18 or CKR-1. In vitro, synthetic NLP-18 directly evokes CKR-1-dependent currents in oocytes and CKR-1-dependent Ca2+ transients in SMD. Thus, cholecystokinin peptidergic signaling modulates an escape circuit to generate robust escape steering.