Reach-to-grasp movements require integrating information on both object location and grip type, but how these elements are planned and to what extent they interact remains unclear. We designed a new experimental paradigm in which monkeys sequentially received reach and grasp cues with delays, requiring them to retain and integrate both cues to grasp the goal object with appropriate hand gestures. Neural activity in the dorsal premotor cortex (PMd) revealed that reach and grasp were similarly represented yet not independent. Upon receiving the second cue, the PMd continued encoding the first, but over half of the neurons displayed incongruent modulations: enhanced, attenuated, or even reversed. Population-level analysis showed significant changes in encoding structure, forming distinct neural patterns. Leveraging canonical correlation analysis, we identified a shared subspace preserving the initial cue's encoding, contributed by both congruent and incongruent neurons. Together, these findings reveal a novel perspective on the interactive planning of reach and grasp within the PMd, providing insights into potential applications for brain-machine interfaces.
Animals ; Motor Cortex/physiology* ; Hand Strength/physiology* ; Macaca mulatta ; Psychomotor Performance/physiology* ; Neurons/physiology* ; Male ; Cues ; Movement/physiology* ; Gestures

Intestinal flora imbalance is closely related to the pathogenesis of rheumatoid arthritis (RA). The existing studies have explored the monomer components such as tripterygium glycosides, total glycosides of Chaenomeles speciosa, and triterpenoid saponins of Clematis, Chinese materia medica such as Tripterygium wilfordii, Caulis Sinomenii, Radix Paeoniae Alba, Fructus Gardeniae, Fructus Chebulae, Radix Ginseng, Radix et Rhizoma Rhei, Rhizoma Atractylodis Macrocephalae, Pterostilbene, and Ginger, as well as the mechanisms of Danggui Sini Decoction, Danggui Niantong Decoction, Duhuo Jisheng Decoction, Yunpi Jiedu Tongluo Qushi Decoction, Qingre Huoxue Decoction, Compound Fengshining, Qingre Yangyin Chushi Decoction, Aconitum Decoction, Zhijing Powder, Jinwu Jiangu Capsule, and Fermented Chinese Medicine Qushi Chubi Decoction in intervening RA by regulating intestinal flora, suggesting that Chinese materia medica can restore intestinal homeostasis, reduce joint inflammation and play a role in the prevention and treatment of RA by regulating immune response, improving intestinal mucosal barrier and regulating intestinal metabolites.

Objective To conduct a unique and pioneering molecular epidemiological investigation of a case of Eurasian avian-like H1N1 swine influenza identified in Yunnan Province in 2022(the fourth such case in the province)and to understand its genetic characteristics so as to reveal its potential impact on human health.Methods Real-time fluorescent quantitative PCR detection technology was used for the nucleic acid testing of the case's pharyngeal swab samples,close contacts,and environmental samples from the living area.Positive samples were subjected to virus isolation using MDCK cells.Cell cultures were authenticated using erythrocyte agglutination assay with guinea pig blood and real-time fluorescence quantitative RT-PCR.Whole genome sequencing was performed using the Illumina MiseqNext-generation sequencing platform,and a phylogenetic tree was constructed using MEGA 7.0 software to analyze the genetic molecular characteristics.Results The first G5 genotype Eurasian avian-like H1N1 swine influenza virus in Yunnan Province was successfully isolated,and the whole genome sequence of the virus was obtained.This virus possessed the molecular characteristics associated with increased adaptability,virulence,or transmissibility in mammals and had a nucleotide consistency of 99.2％～99.7％with a porcine strain isolated in Jiangsu province.These findings underscored the potential threat this virus poses to human health.Conclusion The study underscores the importance of further monitoring swine influenza in preventing new influenza virus subtypes that can infect humans.

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

Objective:To analyze the clinical features and immunotherapy responsiveness of patients with myelin oligodendrocyte glycoprotein immunoglobulin G-antibody associated disease (MOGAD) with epilepsy, and display the risk factors of epilepsy in MOGAD.Methods:Eighty-nine patients with MOGAD diagnosed at the First Affiliated Hospital of Zhengzhou University between October 2019 and May 2023 were enrolled and classified into 2 groups upon MOGAD with ( n=29) or without epilepsy ( n=60). The Expanded Disability Status Scale (EDSS) and Clinical Assessment Scale for Autoimmune Encephalitis (CASE) were used for evaluation of severity, and EDSS or CASE scores on the 30th day after first-line immunotherapy initiation lower than that on admission were defined as well treatment responsiveness. The differences of general data, clinical manifestations, cerebrospinal fluid (CSF) and peripheral blood biochemical examination results, and immunotherapy reactivity between the 2 groups were thoroughly explicated. In addition, the risk factors of epilepsy in MOGAD were analyzed by univariate and multivariate Logistic regression analysis. Results:Compared with patients with MOGAD without epilepsy, patients with MOGAD with epilepsy were characterized by lower age of onset [24.5(10.3, 34.0) years vs 11.0(6.5, 20.0) years, Z=-2.348, P=0.019], higher percentage of male patients [43.3%(26/60) vs 75.9%(22/29), χ 2=8.326, P=0.004], higher virus infection rate [28.3%(17/60) vs 51.7%(15/29), χ 2=4.645, P=0.031], higher incidence of prodromal symptoms [11.7%(7/60) vs 34.5%(10/29), χ 2=6.586, P=0.010], higher blood-brain barrier breakdown rate [35.0%(21/60) vs 58.6%(17/29), χ 2=4.458, P=0.035], higher percentage of CSF albumin level>450 mg/L [48.3%(29/60) vs 75.9%(22/29), χ 2=6.056, P=0.014] and higher creatine kinase level [45.50(28.50, 69.75) U/L vs 57.50(41.75, 97.25) U/L, Z=-2.349, P=0.019]; more epilepsy [0(0) vs 29/29 (100.0%), χ 2=89.000, P<0.001] and disturbance of consciousness [0(0) vs 6/29(20.7%), χ 2=10.224, P=0.001] as clinical manifestations, and more cerebral cortex lesions [30/60(50.0%) vs 25/29(86.2%), χ 2=10.856, P=0.001] on magnetic resonance imaging. Nevertheless, the patients with MOGAD without epilepsy were featured with more visual impairment [23/60(38.3%) vs 3/29(10.3%), χ 2=7.406, P=0.007], limb weakness [18/60(30.0%) vs 1/29(3.4%), χ 2=8.209, P=0.004], sensory disturbance [15/60(25.0%) vs 0(0), Fisher exact probability test, P=0.002] and more cervical cord lesions [22/60(36.7%) vs 4/29(13.8%), χ 2=4.946, P=0.026] on magnetic resonance imaging. Immunotherapy responsiveness was relatively poor in the MOGAD with epilepsy group [EDSS score lower than that on admission: 15/29(51.7%) vs 46/60(76.7%), χ 2=5.641, P=0.018; CASE score lower than that on admission: 16/29(55.2%) vs 47/60(78.3%), χ 2=5.072, P=0.024] compared with the MOGAD without epilepsy group. Male was the independent risk factor of epilepsy in MOGAD ( OR=7.078, 95% CI 1.709-29.326, P=0.007). Conclusions:Compared with patients with MOGAD without epilepsy, patients with MOGAD with epilepsy reported more male patients, lower age of onset and higher incidence of prodromal symptoms, blood-brain barrier dysfunction rate, virus infection rate, CSF albumin level and creatine kinase level; clinical phenotypes were mainly meningoencephalitis and more cerebral cortex lesions were shown on magnetic resonance imaging. MOGAD with epilepsy was closely related to poor immunotherapy responsiveness, and gender was found to be the independent risk factor for epilepsy in MOGAD.

Objective:To establish a polymerase chain reaction(PCR)method to accurately discriminate the crude materials and aqueous extract of Zaocys dhumnades,Elaphe carinata,Elaphe meollendorff and Ptyas korros.Methods:Specific primers were designed using mitochondrial Cytb gene(CO1)as a target gene,and annealing temperature,number of cycles and the type of DNA polymerases were optimized.The mixed samples were detected by this method.Results:By this multiplex allele-specific PCR identification method,135,182,246 and 197 bp of specific fragments were amplified from DNA templates of Zaocys dhumnades,Elaphe carinata,Elaphe meollendorffi and Ptyas korros,respectively,following the conditions:cycle number of 35,annealing temperature of 62 ℃.The adulterants and the blank control showed no bands.The method could simultaneously and accurately identify the snake-derived components in the mixed samples.Conclusion:The method can be used to identify the samples of Zaocys dhumnades,Elaphe carinata,Elaphe meollendorffi and Ptyas korros simultaneously,accurately and rapidly,and is suitable for the identification of standard decoctiond and formula granules samples.

Objective:To investigate the effect of low density lipoprotein cholesterol (LDL-C) on the progression of retinal arteriosclerosis by using a deep learning model.Methods:A cohort study was performed.Data of 1 928 individuals who underwent the medical examination at Beijing Yijiandian Clinic between January 2016 and August 2023 were reviewed, including baseline demographics, physical examination, serological test and fundus photography.Retinal arteriosclerosis was identified using a deep learning model.Five groups were divided according to LDL-C levels, including 389 subjects in group 1 (0.64-1.90 mmol/L), 387 subjects in group 2 (1.91-2.26 mmol/L), 384 subjects in group 3 (2.27-2.57 mmol/L), 385 subjects in group 4 (2.58-2.95 mmol/L), and 383 subjects in group 5 (2.96-6.06 mmol/L).The association between LDL-C levels and progression of retinal arteriosclerosis and the dose-response relationship were analyzed by logistic regression analysis and restricted cubic spline (RCS) regression model.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Peking University People's Hospital (No.2021PHB058-001).Written informed consent was obtained from each subject.Results:The incidence of retinal arteriosclerosis progression was 22.10% (426/1 928) during the mean follow-up (66.84±6.58) months.The proportions of fundus progression in groups 1, 2, 3, 4, and 5 were 15.68%(61/389), 21.71%(84/387), 21.35%(82/384), 25.71%(99/385), and 26.11%(100/383), respectively, with statistical significant differences among them ( χ2=15.97, P=0.003).Using group 1 as a reference, LDL-C 2.58-2.95 mmol/L was an independent risk factor for progression of retinal arteriosclerosis ( OR=1.52, 95% CI: 1.04-2.22), and RCS analysis showed an " L" shaped association.The effect of LDL-C on retinal arteriosclerosis showed a threshold effect, with the risk of retinal arteriosclerosis progression increasing with increasing LDL-C when LDL-C was <2.34 mmol/L ( OR=1.97, 95% CI: 1.10-3.62), and stabilizing when LDL-C was ≥2.34 mmol/L. Conclusions:LDL-C has a threshold effect on the impact of retinal arteriosclerosis progression, and the threshold is 2.34 mmol/L.

Objective:To analyze the relations of blood-brain barrier (BBB) integrity with clinical features and their response to immunotherapy in patients with autoimmune encephalitis (AE).Methods:One hundred and forty-seven AE patients confirmed in Department of Neurology, First Affiliated Hospital of Zhengzhou University from August 2015 to December 2021 were chosen; their clinical and laboratory data were collected retrospectively. In accordance with cerebrospinal fluid (CSF) albumin/serum albumin (QAlb) value of 7, patients were classified into normal BBB group ( n=101, QAlb value ≤7.00) and damaged BBB group ( n=46, QAlb value >7.00). Modified Rankin Scale (mRS) and Clinical Assessment Scale for Autoimmune Encephalitis (CASE) were used to evaluate the severity on admission and 30 d after first-line immunotherapy; and good immunotherapy responsiveness was defined as CASE or mRS scores 30 d after first-line immunotherapy lower than those at admission. Differences of general data, clinical manifestations, CSF and peripheral blood biochemical results, and response to immunotherapy between the two groups were compared and analyzed. Results:The damaged BBB group had significantly higher proportions of patients with decreased consciousness level (58.7% vs. 37.6%), increased CSF protein, increased immunoglobulin G (IgG) and increased 24 h intramural IgG synthesis rate, and significantly higher fibrinogen in peripheral blood than normal BBB group ( P<0.05). On 30 th d of treatment, mRS scores of patients in damaged BBB group were significantly higher than those of patients in normal BBB group ( P<0.05), and the differences of CASE scores and mRS scores before and after treatment in damaged BBB group were significantly lower than those in normal BBB group (0.50±0.46 vs. 3.24±2.93, 0.70±0.62 vs. 1.15±1.04, P<0.05). In damaged BBB group, good immunotherapy response rate in patients receiving single immunotherapy was significantly lower than that in patients receiving two or three combinations of first-line immunotherapy ( P<0.05). Conclusion:BBB integrity is closely related to clinical characteristics and response to immunotherapy of AE; combined first-line immunotherapy is recommended for AE patients with BBB injury.

Aortic dissection, especially Stanford type A aortic dissection, is an acutely progressive and highly fatal cardiovascular disease.Early prevention and timely treatment can greatly reduce mortality and reduce the burden on families and society.However, due to the etiological mechanism is still unclear, the clinical treatment is still mainly surgery, and the early prevention and drug application are very limited.And some recent studies have found that ferroptosis may play an important role in the occurrence and development of aortic dissection, revealing the relationship between them may provide ideas for the prevention, treatment and scientific research of the disease.

Abstract: Objective To investigate the molecular characteristics of the H9N2 avian influenza virus (AIV) causing human infection in Yunnan Province in 2019, and to provide the scientific basis for the prevention and control of avian influenza in Yunnan Province. Methods Influenza virus typing was performed by real-time RT-PCR in two influenza-like illness samples, and the Illumina Miseq high-throughput sequencer was used to determine the viral genome sequence. HA and NA gene sequence alignment and phylogenetic tree construction were performed using Mega7.0 software. Results Real-time RT-PCR results showed that two influenza-like illness samples were positive for H9N2 subtype. The full length of HA and NA were obtained by genomic sequencing. Sequence system evolution analysis showed that the HA and NA of the two AIVs in Yunnan Province were in the same evolutionary clade as A/Chicken/Zhejiang/HJ/2007 and belonged to the G57 type. The HA nucleotide and amino acid homology of the two AIVs were 93.92% and 95.00%, respectively, and the NA nucleotide and amino acid homology was 93.31% and 82.03%, respectively. The nucleotide (amino acid) homology of HA was 92.29%-96.94% (93.77%-98.43%) and 92.84%-94.92% (94.18%-96.23%), respectively, and NA nucleotide homology (amino acid) were 91.81%-97.60% (77.82%-94.83%), 94.38%-97.22% (85.47%-94.55%), respectively, compared with that of human infected H9N2 epidemic strains obtained in China from 2015 to 2020. Both AIVs HA protein cleavage site sequences were PSRSSR↓GLF, which was in line with the characteristics of low pathogenic influenza. The analysis of HA protein receptor binding site showed that amino acids at positions 109, 161, 163, 191, 202, 203 and 234 were consistent with the reference strains, while amino acids at position 198 were mutated to T. N166D and 168N mutations were also found in HA protein, and both AIVs had 7 potential glycosylation sites. Analysis of the erythrocyte binding site of NA gene found that there were amino acid mutations at positions 369, 402, 403, and 432, and amino acid deletion at positions 63-65 was found in the NA genes. There were 4 and 5 potential glycosylation sites in the two AIVs, respectively, and no drug resistance site mutations were found. Conclusions　The receptor binding sites, erythrocyte binding sites and glycosylation sites of HA and NA genes of H9N2 AIV in Yunnan Province have different degrees of variation, and monitoring and prevention and control should be strengthened.