Identification of Sodium- and Chloride-Sensitive Sites in the Slack Channel.

The Slack channel (KCNT1, Slo2.2) is a sodium-activated and chloride-activated potassium channel that regulates heart rate and maintains the normal excitability of the nervous system. Despite intense interest in the sodium gating mechanism, a comprehensive investigation to identify the sodium-sensitive and chloride-sensitive sites has been missing. In the present study, we identified two potential sodium-binding sites in the C-terminal domain of the rat Slack channel by conducting electrophysical recordings and systematic mutagenesis of cytosolic acidic residues in the rat Slack channel C terminus. In particular, by taking advantage of the M335A mutant, which results in the opening of the Slack channel in the absence of cytosolic sodium, we found that among the 92 screened negatively charged amino acids, E373 mutants could completely remove sodium sensitivity of the Slack channel. In contrast, several other mutants showed dramatic decreases in sodium sensitivity but did not abolish it altogether. Furthermore, molecular dynamics (MD) simulations performed at the hundreds of nanoseconds timescale revealed one or two sodium ions at the E373 position or an acidic pocket composed of several negatively charged residues. Moreover, the MD simulations predicted possible chloride interaction sites. By screening predicted positively charged residues, we identified R379 as a chloride interaction site. Thus, we conclude that the E373 site and the D863/E865 pocket are two potential sodium-sensitive sites, while R379 is a chloride interaction site in the Slack channel.SIGNIFICANCE STATEMENT The research presented here identified two distinct sodium and one chloride interaction sites located in the intracellular C-terminal domain of the Slack (Slo2.2, KCNT1) channel. Identification of the sites responsible for the sodium and chloride activation of the Slack channel sets its gating property apart from other potassium channels in the BK channel family. This finding sets the stage for future functional and pharmacological studies of this channel.

Knowledge of Alzheimer's disease and associated factors among adults in Zhuhai, China: a cross-sectional analysis.

BACKGROUND: This study aimed to assess the public knowledge regarding Alzheimer's Disease (AD) in Zhuhai, China, focusing on identifying knowledge gaps and the influence of demographic and health factors. METHODS: A cross-sectional study was conducted in Zhuhai, China, from October to November 2022. A total of 1986 residents from 18 communities were selected employing stratified multi-stage equi-proportional sampling. Questionnaires covering general information and the Alzheimer's Disease Knowledge Scale (ADKS) were investigated face-to-face. Ordinal multiclass logistic regression was applied to assess the relationship between AD awareness and demographic and health characteristics. RESULTS: The average ADKS score was 18.5 (SD = 3.36) in Zhuhai. The lowest awareness rates were observed in the "Symptoms" and "Caregiving" subdomains of ADKS, with rates of 51.01% and 43.78%, respectively. The correct rates for the 30 ADKS questions ranged from 16.62 to 92.6%, showing a bimodal pattern with clusters around 80% and 20%. Women (OR = 1.203, 95% CI: 1.009-1.435), individuals aged 60 years or older (OR = 2.073, 95% CI: 1.467-2.932), those living in urban areas (OR = 1.361, 95% CI: 1.117-1.662), higher average monthly household income per capita (OR = 1.641, 95% CI: 1.297-2.082), and without any neurological or mental disorders (OR = 1.810, 95% CI: 1.323-2.478) were more likely to have higher levels of awareness about Alzheimer's disease. CONCLUSIONS: Adults in Zhuhai show a limited knowledge of AD, particularly in the 'Symptoms' and 'Caregiving' subdomains. Upcoming health campaigns must focus on bridging the knowledge gaps in different subdomains of AD, especially among subgroups with lower awareness, as identified in our study.

Ccp1-Ndc80 switch at the N terminus of CENP-T regulates kinetochore assembly.

Kinetochores, a protein complex assembled on centromeres, mediate chromosome segregation. In most eukaryotes, centromeres are epigenetically specified by the histone H3 variant CENP-A. CENP-T, an inner kinetochore protein, serves as a platform for the assembly of the outer kinetochore Ndc80 complex during mitosis. How CENP-T is regulated through the cell cycle remains unclear. Ccp1 (counteracter of CENP-A loading protein 1) associates with centromeres during interphase but delocalizes from centromeres during mitosis. Here, we demonstrated that Ccp1 directly interacts with CENP-T. CENP-T is important for the association of Ccp1 with centromeres, whereas CENP-T centromeric localization depends on Mis16, a homolog of human RbAp48/46. We identified a Ccp1-interaction motif (CIM) at the N terminus of CENP-T, which is adjacent to the Ndc80 receptor motif. The CIM domain is required for Ccp1 centromeric localization, and the CIM domain-deleted mutant phenocopies ccp1Δ. The CIM domain can be phosphorylated by CDK1 (cyclin-dependent kinase 1). Phosphorylation of CIM weakens its interaction with Ccp1. Consistent with this, Ccp1 dissociates from centromeres through all stages of the cell cycle in the phosphomimetic mutant of the CIM domain, whereas in the phospho-null mutant of the domain, Ccp1 associates with centromeres during mitosis. We further show that the phospho-null mutant disrupts the positioning of the Ndc80 complex during mitosis, resulting in chromosome missegregation. This work suggests that competitive exclusion between Ccp1 and Ndc80 at the N terminus of CENP-T via phosphorylation ensures precise kinetochore assembly during mitosis and uncovers a previously unrecognized mechanism underlying kinetochore assembly through the cell cycle.

[DNA barcode screening, identification of germplasm resources, and analysis of genetic diversity of Anemarrhena asphodeloides].

Anemarrhena asphodeloides is a common medicinal material used in clinical prescriptions and Chinese patent medicine. In this study, the Illumina platform was used to obtain the chloroplast genome sequences of seven kinds of A. asphodeloides from different areas. The specific DNA barcodes were screened by comparative genomics analysis, and the DNA barcodes were used to identify the germplasm resources and analyze the genetic diversity of A. asphodeloides samples from different areas in China. All the seven chloroplast genomes had a ring structure. The total length was 156 801-156 930 bp, and 113 genes were annotated, including 79 protein-coding genes, 30 tRNA genes, and four rRNA genes. The comparative genomics analysis showed that rps16, trnG-GCC, atpF, rpoB, ycf3, rpl16, ndhF, trnS-GCU＿trnG-GCC, petN-psbM, and ndhF-rpl32 were potential candidates for specific DNA barcodes of A. asphodeloides. In this study, the second intron of ycf3 and atpF intron sequences with a sequence length of 700-800 bp and easy amplification were selected for polymerase chain reaction(PCR) amplification and sequencing of 594 samples from 26 areas. The sequence analysis showed that six and eight haplotypes of ycf3 and atpF sequences could be identified, respectively, and 17 haplotypes could be identified by combined analysis of the two sequences, which were named Hap1-Hap17. The haplotype diversity(H_d), nucleotide diversity(P_i), and genetic distance of A. asphodeloides in 26 populations were 0.68, 0.93×10~(-3), and 0-0.003 1, respectively, indicating that the genetic diversity within the species of A. asphodeloides is rich. The intermediary adjacent network analysis showed that Hap5 was the oldest haplotype, which was mainly distributed in Yixian county of Baoding, Hebei province, Hequ county of Xinzhou, Shanxi province, and Xiangfen county of Linfen, Shanxi province. This study has important guiding significance for the identification of A. asphodeloides species, the protection and development of germplasm resources, and the identification of production areas, and it provides a research basis for further revealing the genetic evolution law of A. asphodeloides.

Two types of peptides derived from the neurotoxin GsMTx4 inhibit a mechanosensitive potassium channel by modifying the mechanogate.

Atrial fibrillation is the most common sustained cardiac arrhythmia in humans. Current atrial fibrillation antiarrhythmic drugs have limited efficacy and carry the risk of ventricular proarrhythmia. GsMTx4, a mechanosensitive channel-selective inhibitor, has been shown to suppress arrhythmias through the inhibition of stretch-activated channels (SACs) in the heart. The cost of synthesizing this peptide is a major obstacle to clinical use. Here, we studied two types of short peptides derived from GsMTx4 for their effects on a stretch-activated big potassium channel (SAKcaC) from the heart. Type I, a 17-residue peptide (referred to as Pept 01), showed comparable efficacy, whereas type II (i.e., Pept 02), a 10-residue peptide, exerted even more potent inhibitory efficacy on SAKcaC compared with GsMTx4. We identified through mutagenesis important sequences required for peptide functions. In addition, molecular dynamics simulations revealed common structural features with a hydrophobic head followed by a positively charged protrusion that may be involved in peptide channel-lipid interactions. Furthermore, we suggest that these short peptides may inhibit SAKcaC through a specific modification to the mechanogate, as the inhibitory effects for both types of peptides were mostly abolished when tested with a mechano-insensitive channel variant (STREX-del) and a nonmechanosensitive big potassium (mouse Slo1) channel. These findings may offer an opportunity for the development of a new class of drugs in the treatment of cardiac arrhythmia generated by excitatory SACs in the heart.

Au Nanowires Decorated Ultrathin Co3 O4 Nanosheets toward Light-Enhanced Nitrate Electroreduction.

Nitrate is a reasonable alternative instead of nitrogen for ammonia production due to the low bond energy, large water-solubility, and high chemical polarity for good absorption. Nitrate electroreduction reaction (NO3 RR) is an effective and green strategy for both nitrate treatment and ammonia production. As an electrochemical reaction, the NO3 RR requires an efficient electrocatalyst for achieving high activity and selectivity. Inspired by the enhancement effect of heterostructure on electrocatalysis, Au nanowires decorated ultrathin Co3 O4 nanosheets (Co3 O4 -NS/Au-NWs) nanohybrids are proposed for improving the efficiency of nitrate-to-ammonia electroreduction. Theoretical calculation reveals that Au heteroatoms can effectively adjust the electron structure of Co active centers and reduce the energy barrier of the determining step (*NO → *NOH) during NO3 RR. As the result, the Co3 O4 -NS/Au-NWs nanohybrids achieve an outstanding catalytic performance with high yield rate (2.661 mg h-1 mgcat -1 ) toward nitrate-to-ammonia. Importantly, the Co3 O4 -NS/Au-NWs nanohybrids show an obviously plasmon-promoted activity for NO3 RR due to the localized surface plasmon resonance (LSPR) property of Au-NWs, which can achieve an enhanced NH3 yield rate of 4.045 mg h-1 mgcat -1 . This study reveals the structure-activity relationship of heterostructure and LSPR-promotion effect toward NO3 RR, which provide an efficient nitrate-to-ammonia reduction with high efficiency.

TcpC inhibits toll-like receptor signaling pathway by serving as an E3 ubiquitin ligase that promotes degradation of myeloid differentiation factor 88.

TcpC is a virulence factor of uropathogenic E. coli (UPEC). It was found that TIR domain of TcpC impedes TLR signaling by direct association with MyD88. It has been a long-standing question whether bacterial pathogens have evolved a mechanism to manipulate MyD88 degradation by ubiquitin-proteasome pathway. Here, we show that TcpC is a MyD88-targeted E3 ubiquitin ligase. Kidney macrophages from mice with pyelonephritis induced by TcpC-secreting UPEC showed significantly decreased MyD88 protein levels. Recombinant TcpC (rTcpC) dose-dependently inhibited protein but not mRNA levels of MyD88 in macrophages. Moreover, rTcpC significantly promoted MyD88 ubiquitination and accumulation in proteasomes in macrophages. Cys12 and Trp106 in TcpC are crucial amino acids in maintaining its E3 activity. Therefore, TcpC blocks TLR signaling pathway by degradation of MyD88 through ubiquitin-proteasome system. Our findings provide not only a novel biochemical mechanism underlying TcpC-medicated immune evasion, but also the first example that bacterial pathogens inhibit MyD88-mediated signaling pathway by virulence factors that function as E3 ubiquitin ligase.

Cucurbit[7]uril-Mediated Supramolecular Bactericidal Nanoparticles: Their Assembly Process, Controlled Release, and Safe Treatment of Intractable Plant Bacterial Diseases.

A safe, biocompatible, and stimuli-responsive cucurbit[7]uril-mediated supramolecular bactericidal nanoparticle was fabricated by encapsulating a highly bioactive carbazole-decorated imidazolium salt (A1, EC50 = 0.647 µg/mL against phytopathogen Xanthomonas oryzae pv oryzae) into the host cucurbit[7]uril (CB[7]), thereby leading to self-assembled topographies from microsheets (A1) to nanospheroidal architectures (A1@CB[7]). The assembly behaviors were elucidated by acquired single-crystal structures, 1H NMR, ITC, and X-ray powder diffraction experiments. Complex A1@CB[7] displayed lower phytotoxicity and could efficiently switch on its potent antibacterial ability via introducing a simple competitor 1-adamantanamine hydrochloride (AD). In vivo antibacterial trials against rice bacterial blight revealed that A1@CB[7] could relieve the disease symptoms after being triggered by AD and provide a workable control efficiency of 42.6% at 100 µg/mL, which was superior to bismerthiazol (33.4%). These materials can provide a viable platform for fabricating diverse stimuli-responsive supramolecular bactericides for managing bacterial infections with improved safety.

[Research progress on application of multi-enzyme-catalyzed cascade reactions in enzymatic synthesis of natural products].

As a biocatalyst, enzyme has the advantages of high catalytic efficiency, strong reaction selectivity, specific target products, mild reaction conditions, and environmental friendliness, and serves as an important tool for the synthesis of complex organic molecules. With the continuous development of gene sequencing technology, molecular biology, genetic manipulation, and other technologies, the diversity of enzymes increases steadily and the reactions that can be catalyzed are also gradually diversified. In the process of enzyme-catalyzed synthesis, the majority of common enzymatic reactions can be achieved by single enzyme catalysis, while many complex reactions often require the participation of two or more enzymes. Therefore, the combination of multiple enzymes together to construct the multi-enzyme cascade reactions has become a research hotspot in the field of biochemistry. Nowadays, the biosynthetic pathways of more natural products with complex structures have been clarified, and secondary metabolic enzymes with novel catalytic activities have been identified, discovered, and combined in enzymatic synthesis of natural/unnatural molecules with diverse structures. This study summarized a series of examples of multi-enzyme-catalyzed cascades and highlighted the application of cascade catalysis methods in the synthesis of carbohydrates, nucleosides, flavonoids, terpenes, alkaloids, and chiral molecules. Furthermore, the existing problems and solutions of multi-enzyme-catalyzed cascade method were discussed, and the future development direction was prospected.

[Current research status and application prospect of numerical simulation in traditional Chinese medicine drying].

With the rapid development of computer technology, numerical simulation has gradually become an important method to study drying process and improve drying equipment. Using computer to simulate the drying process of traditional Chinese medicine(TCM) is characterized by intuitiveness, scientificity, and low cost, which serves as an auxiliary means for technical innovation in TCM drying. This paper summarizes the theories of different drying methods and the research status of numerical simulation in drying, introduces the modeling methods and software of numerical simulation, and expounds the significance of numerical simulation modeling in shortening the research and development cycle, improving drying equipment, and optimizing drying parameters. However, the current numerical simulation method for drying process has problems, such as low accuracy, lack of quantitative indicators for the control of simulation results on the process, and insufficient in-depth research on the mechanism of drug quality changes. Furthermore, this paper put forward the application prospect of numerical simulation in TCM drying, providing reference for the further study of numerical simulation in this field.

[Application prospect of reaction engineering approach in studying drying behavior of single droplet during spray drying of traditional Chinese medicine].

Spray drying technology is one of the most commonly used unit operations in the production of traditional Chinese medicine(TCM) preparations, offering advantages such as short drying time and uniform product quality. However, due to the properties of TCM extracts, such as high viscosity, strong hygroscopicity, and poor flowability, there is limited scope to solve the problems of wall adhesion and clumping in spray drying from the macroscopic perspective of pharmaceutical production. Therefore, it has become a trend to study and optimize the spray drying process from the microscopic point of view by investigating single droplet evaporation behavior. Based on the reaction engineering approach(REA), the single droplet drying system, as a novel method for studying droplets, collects parameter data on individual TCM droplets during the drying process and uses the REA to process the data and establish predictive models. This approach is crucial for understanding the mechanism of TCM spray drying. This paper summarized and analyzed the cha-racteristics of various single droplet systems, the application of REA in single droplet drying systems, and its significance in optimizing the process, predicting drying states, and shortening the development cycle in the field of TCM spray drying, and looked ahead to the prospects of this method, including the introduction of new parameters and imaging techniques, aiming to provide a reference for further research in the field of TCM spray drying.

[Specific DNA barcodes, germplasm resources, and genetic diversity of Eleutherococcus senticosus].

Eleutherococcus senticosus is one of the Dao-di herbs in northeast China. In this study, the chloroplast genomes of three E. senticosus samples from different genuine producing areas were sequenced and then used for the screening of specific DNA barcodes. The germplasm resources and genetic diversity of E. senticosus were analyzed basing on the specific DNA barcodes. The chloroplast genomes of E. senticosus from different genuine producing areas showed the total length of 156 779-156 781 bp and a typical tetrad structure. Each of the chloroplast genomes carried 132 genes, including 87 protein-coding genes, 37 tRNAs, and 8 rRNAs. The chloroplast genomes were relatively conserved. Sequence analysis of the three chloroplast genomes indicated that atpI, ndhA, ycf1, atpB-rbcL, ndhF-rpl32, petA-psbJ, psbM-psbD, and rps16-psbK can be used as specific DNA barcodes of E. senticosus. In this study, we selected atpI and atpB-rbcL which were 700-800 bp and easy to be amplified for the identification of 184 E. senticosus samples from 13 genuine producing areas. The results demonstrated that 9 and 10 genotypes were identified based on atpI and atpB-rbcL sequences, respectively. Furthermore, the two barcodes identified 23 genotypes which were named H1-H23. The haplotype with the highest proportion and widest distribution was H10, followed by H2. The haplotype diversity and nucleotide diversity were 0.94 and 1.82×10~(-3), respectively, suggesting the high genetic diversity of E. senticosus. The results of the median-joining network analysis showed that the 23 genotypes could be classified into 4 categories. H2 was the oldest haplotype, and it served as the center of the network characterized by starlike radiation, which suggested that population expansion of E. senticosus occurred in the genuine producing areas. This study lays a foundation for the research on the genetic quality and chloroplast genetic engineering of E. senticosus and further research on the genetic mechanism of its population, providing new ideas for studying the genetic evolution of E. senticosus.

[Electroencephalogram characteristics of 26 children with febrile infection-related epilepsy syndrome]. / 26ä¾‹å„¿ç«¥å‘çƒ­æ„ŸæŸ“ç›¸å ³æ€§ç™«ç—«ç»¼åˆå¾çš„è„‘ç”µå›¾åˆ†æž.

OBJECTIVES: To investigate the electroencephalogram (EEG) characteristics and progression of febrile infection-related epilepsy syndrome (FIRES) in children, aiming to enhance diagnosis and treatment approaches. METHODS: A retrospective analysis was conducted on 26 children with FIRES between May 2017 and December 2021. RESULTS: All 26 children (100%) presented with fever at the onset, followed by frequent convulsions that rapidly progressed into convulsive status. Ventilator support was required for 22 cases (85%). During the acute phase, EEG features demonstrated the disappearance of background activity and physiological sleep cycles in all children. Diffuse slow waves and multifocal slow spike slow waves were observed as abnormal waves during the interictal period. A characteristic pattern of focal low amplitude fast wave initiation was detected in all children during seizure episodes. In the chronic phase, the background EEG activity gradually recovered, and the presence of abnormal waves was relatively limited. The characteristic pattern of focal slow wave rhythm initiation was evident during seizure episodes. Additionally, extreme δ brushes were observed in four cases (15%). CONCLUSIONS: These findings suggest that EEG manifestations in children with FIRES exhibit distinctive patterns during the acute and chronic stages, providing significant value for early diagnosis and clinical staging. Extreme δ brushes may be one of the distinctive markers of children with FIRES.

Entanglement, Coherence, and Extractable Work in Quantum Batteries.

We investigate the connection between quantum resources and extractable work in quantum batteries. We demonstrate that quantum coherence in the battery or the battery-charger entanglement is a necessary resource for generating nonzero extractable work during the charging process. At the end of the charging process, we also establish a tight link of coherence and entanglement with the final extractable work: coherence naturally promotes the coherent work while coherence and entanglement inhibit the incoherent work. We also show that obtaining maximally coherent work is faster than obtaining maximally incoherent work. Examples ranging from the central-spin battery and the Tavis-Cummings battery to the spin-chain battery are given to illustrate these results.

Iron-Doped Cobalt Phosphide Nanohoops for Electroreduction of Nitrate to Ammonia.

Heteroatom doping can effectively tune the electronic structure of an electrocatalyst to accelerate the adsorption/desorption of reaction intermediates, which sharply increases their intrinsic electroactivity. Herein, we successfully prepare iron (Fe)-doped cobalt phosphide (CoP) nanohoops (Fe/CoP NHs) with different Fe/Co atomic ratios as highly active electrocatalysts for the nitrate electrocatalytic reduction reaction (NIT-ERR). Electrochemical measurements reveal that appropriate Fe doping can improve the electroactivity of cobalt phosphide nanohoops for the NIT-ERR. In a 1 M KOH electrolyte, the Fe/CoP NHs with the optimized chemical composition can achieve an efficient ammonia (NH3) generation rate of 27.6 mg h-1 mgcat-1 for the conversion of NO3- into NH3 and a Faradaic efficiency of 93.3% at a -0.25 V potential, which exceed the values of various previously reported nanomaterials in an alkaline electrolyte.

Oxygen-Vacancy-Rich Cu2O Hollow Nanocubes for Nitrate Electroreduction Reaction to Ammonia in a Neutral Electrolyte.

The electrocatalytic nitrate reduction reaction (NO3--ERR) to ammonia (NH3) is a promising strategy for NH3 production. Cu-based nanomaterials have been regarded as a kind of effective NO3--ERR catalysts. In this work, high-quality hollow Cu2O nanocubes (Cu2O h-NCs) are facilely synthesized by a simple one-step reduction method. The as-prepared Cu2O h-NCs reveal high selectivity and activity for NO3--ERR, which is ascribed to abundant oxygen vacancies, high surface area, hollow architecture, low mass transfer resistance, and strong adsorbing ability toward NO3-. In fact, Cu2O h-NCs can achieve a Faradic efficiency of 92.9% and an NH3 yield of 56.2 mg h-1 mgcat-1 for NH3 production at -0.85 V (vs RHE) potential, which exceeds those of other transition-metal-based NO3--ERR electrocatalysts.

Risk factors for the mortality of hemodialysis patients with COVID-19: A multicenter study from the overall hemodialysis population in Wuhan.

INTRODUCTION: Maintenance hemodialysis (MHD) patients are highly threatened in the novel coronavirus disease 2019 (COVID-19) pandemic, but evidence of risk factors for mortality in this population is still lacking. METHODS: We followed outcomes of the overall MHD population of Wuhan, including 7154 MHD patients from 65 hemodialysis centers, from January 1 to May 4, 2020. Among them, 130 were diagnosed with COVID-19. The demographic and clinical data of them were collected and compared between survivors and nonsurvivors. RESULTS: Compared to the corresponding period of last year, the all-cause mortality rate of the Wuhan MHD population significantly rose in February, and dropped down in March 2020. Of the 130 COVID-19 cases, 51 (39.2%) were deceased. Advanced age, decreased oxygen saturation, low diastolic blood pressure (DBP) on admission, and complications including acute cardiac injury (HR 5.03 [95% CI 2.21-11.14], p < 0.001), cerebrovascular event (HR 2.80 [95% CI 1.14-6.86], p = 0.025) and acute respiratory distress syndrome (HR 3.50 [95% CI 1.63-7.51], p = 0.001) were identified as independent risk factors for the death of COVID-19. The median virus shedding period of survivors was 25 days, longer than the general population. CONCLUSIONS: Maintenance hemodialysis patients are a highly vulnerable population at increased risk of mortality and prolonged virus shedding period in the ongoing COVID-19 pandemic. Advanced age, decreased oxygen saturation, low DBP on admission, and complications like acute cardiac injury are parameters independently associated with poor prognosis.

Analysis and comparison of a spinal cord injury model with a single-axle-lever clip or a parallel-moving clip compression in rats.

STUDY DESIGN: Experimental animal study. OBJECTIVES: To assess the feasibility of a custom-designed parallel-moving (PM) clip, compared with a single-axle-lever (SAL) clip, for the development of a compressional spinal cord injury (SCI) model in rats. SETTING: Hospital laboratory in China. METHODS: We used a PM clip and a SAL clip with same compression rate, to develop a SCI model in rats, and set a sham group as a blank control. Within 3 weeks, each group of rats was evaluated for behavioral (Basso-Beattie-Bresnahan locomotor rating score, BBB), and electrophysiological changes (somatosensory evoked potential), and historical staining to observe the differences between the three groups. In particular, the mechanical results of the PM group were calculated. RESULTS: The BBB scores for the SAL and PM groups were significantly lower than those for the sham group (P < 0.05), no significant difference between the two methods (P > 0.05), but the values corresponding to the PM group had smaller standard deviations. The interpeak-latency (IPL) was significantly prolonged (P < 0.0001) and the peak-peak amplitude (PPA) was significantly reduced (P < 0.01) in SAL and PM groups than those in the sham group, but there was no statistical difference in both IPL and PPA between the two SCI groups (P > 0.05). Histological staining showed obvious pathological changes in two SCI groups, and the shape of the lesion zone in the PM group was more symmetrical than that in the SAL groups. CONCLUSIONS: The use of a compressional SCI model in rats with the PM clip we designed is an appropriate method to quantify the injury. The degree of the injury caused by this clip is more stable and uniform than those with classical methods.

Structural basis for activity of TRIC counter-ion channels in calcium release.

Trimeric intracellular cation (TRIC) channels are thought to provide counter-ion currents that facilitate the active release of Ca2+ from intracellular stores. TRIC activity is controlled by voltage and Ca2+ modulation, but underlying mechanisms have remained unknown. Here we describe high-resolution crystal structures of vertebrate TRIC-A and TRIC-B channels, both in Ca2+-bound and Ca2+-free states, and we analyze conductance properties in structure-inspired mutagenesis experiments. The TRIC channels are symmetric trimers, wherein we find a pore in each protomer that is gated by a highly conserved lysine residue. In the resting state, Ca2+ binding at the luminal surface of TRIC-A, on its threefold axis, stabilizes lysine blockage of the pores. During active Ca2+ release, luminal Ca2+ depletion removes inhibition to permit the lysine-bearing and voltage-sensing helix to move in response to consequent membrane hyperpolarization. Diacylglycerol is found at interprotomer interfaces, suggesting a role in metabolic control.

Analysis of factors influencing cervical lymph node metastasis of papillary thyroid carcinoma at each lateral level.

OBJECTIVE: To analyze the clinicopathological characteristics of patients with papillary thyroid carcinoma (PTC) and its influence on the distribution of lymph node metastasis at each lateral level of the neck to guide precise treatment of the lateral area. METHODS: The clinicopathological data of patients with PTC initially diagnosed and treated at our hospital from February 2014 to September 2021 were collected; the metastatic status of each lateral level was recorded, and correlations were analyzed. RESULTS: A total of 203 patients were enrolled in this study. There were 67 males and 136 females, with an average age of 41.1 years. In the lateral cervical area, lymph node metastasis was found at level IIa in 81 patients (39.9%); level III, 171 patients (84.2%); level IV, 122 patients (60%); and level Vb, 18 patients (8.9%). Correlation analysis showed that age (r = 0.198, P < 0.01) and sex (r = 0.196, P < 0.01) were weakly correlated with the number of positive lymph nodes in the central region. The tumor size (r = 0.164, P < 0.05) was weakly correlated with lymph node metastasis at level IV. The presence of multiple tumor foci was weakly correlated with lymph node metastasis at level IIa (r = 0.163, P < 0.05) and Vb (r = 0.143, P < 0.05). The tumor location (r = - 0.168, P < 0.05) was weakly correlated with lymph node metastasis at level III. The number of positive lymph nodes in the central region (r = 0.189, P < 0.01) was weakly correlated with lymph node metastasis at level IV. Binary logistic regression analysis showed that the risk of metastasis of multifocal tumors was higher than that of unifocal tumors by 1.958 times at level IIa (P = 0.021, OR = 1.958) and 2.929 times at level Vb (P = 0.049, OR = 2.929). The higher the tumor was located, the higher the risk of metastasis at level III (P = 0.014, OR = 0.563). Every additional positive lymph node in the central region increased the risk of metastasis at level IV by 1.126 times (P = 0.009, OR = 1.126). CONCLUSIONS: For patients with pathological evidence of lateral metastasis, standard dissection of level IIa through Vb is recommended; selective dissection requires careful consideration. Patients with multifocal tumors have a high risk of metastasis at levels IIa and Vb, which requires special attention during the operation.