Exercise Changes Gut Microbiota: A New Idea to Explain that Exercise Improves Autism.

The effect of exercise interventions on autism spectrum disorder (ASD) has been demonstrated in many studies, and the discovery of a bidirectional relationship between the gut microbiome (GM) and the central nervous system (CNS) has led to the concept of the microbial gut-brain axis (MGBA) and has linked the abnormal GM to a variety of neuropsychiatric disorders, autism being one of them. Research on improving the GM through exercise is also starting to come into focus. However, there are currently few studies on exercise intervention in the GM of autism. The purpose of this review was to find evidence to explore the possible potential effects of exercise to improve the behavior of individuals with autism in the MGBA in this treatment, as well as the potential of GM as an exercise treatment for autism. We will explore (1) changes in GM components of ASD and their relationship to the pathophysiology of ASD; (2) the relationship between exercise and changes in GM components, and (3) the effect of exercise on GM in CNS disorders. Ultimately, we concluded that Streptococcus, Bifidobacterium, Clostridium, Bacteroides, and Blautia may be potential effectors through the MGBA network during exercise to ameliorate ASD targeting microbiotas. They deserve high attention in the follow-up studies.

Palladium-Catalyzed Atroposelective Kinetic C-H Olefination and Allylation for the Synthesis of C-B Axial Chirality.

The direct C-H functionalization of 1,2-benzazaborines, especially asymmetric version, remains a great challenge. Here we report a palladium-catalyzed enantioselective C-H olefination and allylation reactions of 1,2-benzazaborines. This asymmetric approach is a kinetic resolution (KR), providing various C-B axially chiral 2-aryl-1,2-benzazaborines and 3-substituted 2-aryl-1,2-benzazaborines in generally high yields with excellent enantioselectivities (selectivity (S) factor up to 354). The synthetic potential of this reaction is showcased by late-stage modification of complex molecules, scale-up reaction, and applications.

Thyroidectomy for thyroid cancer via transareola single-site endoscopic approach: results of a case-match study with large-scale population.

BACKGROUND: Due to technical challenges, single-site endoscopic thyroidectomy (SSET) is seldom reported and has been attempted in only limited cases. This large-scale study aimed to compare the clinical outcomes of standardized transareola SSET (TASSET) with those of conventional open thyroidectomy (COT) for thyroid cancer. METHODS: The data were prospectively collected, and case-match study was performed at a ratio of 1:1 according to age, sex, body mass index, lesion size, number of lesion foci, lesion side, recurrent laryngeal nerve (RLN) exploration and pathology. Two hundred eligible patients underwent TASSET, and the same number of patients was selected for propensity score matching from 2256 patients who underwent COT. Perioperative data, including surgical profile, oncological and traumatic burdens, and cosmetic satisfaction, were analyzed. RESULTS: No significant differences were observed in blood loss or drainage between TASSET and COT groups. There were no differences in operation time between TASSET and COT (106.39 ± 28.44 vs 102.55 ± 23.10 min, p = 0.154). A total of 3.63 ± 1.82 lymph nodes (LNs) were retrieved from CND with 0.96 ± 1.42 positive in TASSET. In COT, the total and positive LN yields were 3.77 ± 1.91 and 0.99 ± 1.40 (p = 0.445, p = 0.802). Cancer recurrence was not observed in either group. There were no differences in the occurrence of permanent and transient hoarseness or RLN injuries. Postoperative flap seroma or hematoma occurred in 12 TASSET patients and 58 COT patients (p < 0.001). The pain score, CRP level and ESR in TASSET group were lower than those in COT group. TASSET yielded significantly better incision recovery and cosmetic scores than did COT at both the proliferation and stabilization stages. CONCLUSIONS: TASSET is technically feasible and yields enhanced recovery with minimally invasive and cosmetic advantages without compromising the level of safety or cancer eradication.

The role of anlotinib-mediated EGFR blockade in a positive feedback loop of CXCL11-EGF-EGFR signalling in anaplastic thyroid cancer angiogenesis.

BACKGROUND: Hypoxia-induced angiogenesis functions importantly in anaplastic thyroid cancer (ATC) progression. However, the therapeutic potential of broad-spectrum anti-angiogenic agent remains undefined. Anlotinib conventionally targets VEGFR, FGFR and PDGFR. Here, a novel role of anlotinib on ATC angiogenesis was illustrated. METHODS: Molecular expressions were established via tissue microarray. Multiple assays (tubule formation, 3D sprouting and chicken chorioallantoic membrane model) were used for angiogenic evaluation. Panels of molecular screening were achieved by antibody and PCR arrays. The loop binding motif of EGFR for homology modelling was prepared using Maestro. RESULTS: Anlotinib could dose- and time-dependently inhibit cell viability under normoxia and hypoxia and could repress hypoxia-activated angiogenesis more efficiently in vitro and in vivo. CXCL11 and phospho-EGFR were hypoxia-upregulated with a positive correlation. The cancer-endothelium crosstalk could be mediated by the positive CXCL11-EGF-EGFR feedback loop, which could be blocked by anlotinib directly targeting EGFR via a dual mechanism by simultaneous inhibitory effects on cancer and endothelial cells. The AKT-mTOR pathway was involved in this regulatory network. CONCLUSIONS: The newly identified CXCL11-EGF-EGFR signalling provided mechanistic insight into the interaction between cancer and endothelial cells under hypoxia, and EGFR was a novel target. Anlotinib may be the encouraging therapeutic candidate in ATC.

Learning Curve From 450 Cases of Robot-Assisted Pancreaticoduocectomy in a High-Volume Pancreatic Center: Optimization of Operative Procedure and a Retrospective Study.

OBJECTIVE: We aimed to describe our experience and the learning curve of 450 cases of robot-assisted pancreaticoduodenectomy (RPD) and optimize the surgical process so that our findings can be useful for surgeons starting to perform RPD. SUMMARY BACKGROUND DATA: Robotic surgical systems were first introduced 20 years ago. Pancreaticoduodenectomy (PD) is a challenging surgery because of its technical difficulty. RPD may overcome some of these difficulties. METHODS: The medical records of 450 patients who underwent RPD between May 2010 and December 2018 at the Shanghai Ruijin Hospital were retrospectively analyzed. Operative times and estimated blood loss (EBL) were analyzed and the learning curve was determined. A cumulative sum (CUSUM) analysis was used to identify the inflexion points. Other postoperative outcomes, postoperative complications, and long-term follow-up were also analyzed. RESULTS: Operative time improved graduallyovertimefrom405.4 ±â€Š112.9 minutes (case 1-50) to 273.6 ±â€Š70 minutes (case 301-350) (P < 0.001). EBL improved from 410 ±â€Š563.5 mL (case 1-50) to 149.0 ±â€Š103.3 mL (case 351-400) (P< 0.001). According to the CUSUM curve, there were 3 phases in the RPD learning curve. The inflexion points were around cases 100 and 250. The incidence of pancreatic leak in the last 350 cases was significantly lower than that in the first 100 cases (30.0% vs 15.1%, P = 0.003). CONCLUSIONS: RPD is safe and feasible for selected patients. Operative and oncologic outcomes were much improved after experience of 250 cases. Our optimization of the surgical process may have also contributed to this. Future prospective and randomized studies are needed to confirm our results.

Grass carp (Ctenopharyngodon idellus) SHP2 suppresses IFN I expression via decreasing the phosphorylation of GSK3ß in a non-contact manner.

As a tyrosine phosphatase, Src homology 2-containing protein tyrosine phosphatase 2 (SHP2) serves as an inhibitor in PI3K-Akt pathway. In mammals, SHP2 can phosphorylate GSK3ß at Y216 site to control the expression of IFN. So far, the multiple functions of SHP2 have been reported in mammals. However, little is known about fish SHP2. In this study, we cloned and identified a grass carp (Ctenopharyngodon idellus) SHP2 gene (CiSHP2, MT373151). SHP2 is conserved among different vertebrates by amino acid sequences alignment and the phylogenetic tree analysis. CiSHP2 shared the closest homology with Danio rerio SHP2. Simultaneously, SHP2 was also tested in grass carp tissues and CIK (C. idellus kidney) cells. We found that it responded to poly I:C stimulation. CiSHP2 was located in the cytoplasm just as the same as those of mammals. Interestingly, it inhibited the phosphorylation level of GSK3ß in a non-contact manner. Meanwhile CiGSK3ß interacted with and directly phosphorylated CiTBK1. In addition, we found that CiSHP2 also reduced the phosphorylation level of CiTBK1 by CiGSK3ß, and then it depressed the expression of IFN I via GSK3ß-TBK1 axis. These results suggested that CiSHP2 was involved in CiGSK3ß and CiTBK1 activity but not regulated their transcriptional level. At the same time, we also found that CiSHP2 also influenced the activity of CiIRF3. Therefore, fish SHP2 inhibited IFN I expression through blocking GSK3ß-TBK1 signal axis.

Structure and activity of lipid bilayer within a membrane-protein transporter.

Membrane proteins function in native cell membranes, but extraction into isolated particles is needed for many biochemical and structural analyses. Commonly used detergent-extraction methods destroy naturally associated lipid bilayers. Here, we devised a detergent-free method for preparing cell-membrane nanoparticles to study the multidrug exporter AcrB, by cryo-EM at 3.2-Å resolution. We discovered a remarkably well-organized lipid-bilayer structure associated with transmembrane domains of the AcrB trimer. This bilayer patch comprises 24 lipid molecules; inner leaflet chains are packed in a hexagonal array, whereas the outer leaflet has highly irregular but ordered packing. Protein side chains interact with both leaflets and participate in the hexagonal pattern. We suggest that the lipid bilayer supports and harmonizes peristaltic motions through AcrB trimers. In AcrB D407A, a putative proton-relay mutant, lipid bilayer buttresses protein interactions lost in crystal structures after detergent-solubilization. Our detergent-free system preserves lipid-protein interactions for visualization and should be broadly applicable.

Identification and validation of critical alternative splicing events and splicing factors in gastric cancer progression.

Gene expression and alternative splicing (AS) interact in complex ways to regulate biological process which is associated with cancer development. Here, by integrated analysis of gene expression and AS events, we aimed to identify the hub AS events and splicing factors relevant in gastric cancer development (GC). RNA-seq data, clinical data and AS events of 348 GC samples were obtained from the TCGA and TCGASpliceSeq databases. Cox univariable and multivariable analyses, KEGG and GO pathway analyses were performed to identify hub AS events and splicing factor/spliceosome genes, which were further validated in 53 GCs. By bioinformatics methods, we found that gene AS event- and gene expression-mediated GC progression shared the same mechanisms, such as PI3K/AKT pathway, but the involved genes were different. Though expression of 17 hub AS events were confirmed in 53 GC tissues, only 10 AS events in seven genes were identified as critical candidates related to GC progression, notably the AS events (Exon Skip) in CLSTN1 and SEC16A. Expression of these AS events in GC correlated with activation of the PI3K/AKT pathway. Genes with AS events associated with clinical parameters and prognosis were different from the genes whose mRNA levels were related to clinical parameters and prognosis. Besides, we further revealed that QKI and NOVA1 were the crucial splicing factors regulating expression of AS events in GC, but not spliceosome genes. Our integrated analysis revealed hub AS events in GC development, which might be the potential therapeutic targets for GC.

Organ-specific regulation of CHD1 by acute PTEN and p53 loss in mice.

Homozygous deletion of chromodomain helicase DNA binding protein 1 (CHD1) is among the most frequent genetic alterations in prostate cancer. CHD1 is converted from a non-essential to an essential gene for prostate cancer cell survival when phosphatase and tensin homolog (PTEN), another frequently deleted gene in prostate cancer, is disrupted. It remains unknown whether this PTEN-CHD1 genetic and functional relationship also operates in other solid tumors. Here, we address this question by using genetically engineered mouse models. Inducible deletion of Pten and p53 in all somatic cells of adult mice led to widespread PI3K/Akt pathway activation and hyperplastic phenotypes, causing multi-organ failure and lethality. Remarkably, when Chd1 was co-deleted in the Pten/p53 model, the lethality remained unperturbed. At the protein level, Chd1 was stabilized upon Pten deletion in prostate, but not in other organs examined (lung, liver, kidney, colon, mammary). These results shed mechanistic insight on the cancer type-specific copy number alteration pattern of PTEN and CHD1.

ETS variant 5 promotes colorectal cancer angiogenesis by targeting platelet-derived growth factor BB.

ETS transcription factors play important roles in tumor cell invasion, differentiation and angiogenesis. In this study, we initially demonstrated that ETS translocation variant 5 (ETV5) is abnormally upregulated in colorectal cancer (CRC), is positively correlated with CRC tumor size, lymphatic metastasis and tumor node metastasis (TNM) stage and indicates shorter survival and disease-free survival in CRC patients. In vitro and in vivo experiments revealed that the downregulation of ETV5 could significantly suppress CRC cell proliferation. Moreover, overexpression of ETV5 could stimulate CRC angiogenesis in vitro and in vivo, which is consistent with RNA-seq results. Then, we identified platelet-derived growth factor BB (PDGF-BB) as a direct target of ETV5 that plays an important role in ETV5-mediated CRC angiogenesis through an angiogenesis antibody microarray. Additionally, PDGF-BB could activate VEGFA expression via the PDGFR-ß/Src/STAT3 pathway in CRC cells and appeared to be positively correlated with ETV5 in CRC tissues. Finally, we revealed that ETV5 could bind directly to the promoter region of PDGF-BB and regulate its expression through ChIP and luciferase assays. Overall, our study suggested that the transcription factor ETV5 could stimulate CRC malignancy and promote CRC angiogenesis by directly targeting PDGF-BB. These findings suggest that EVT5 may be a potential new diagnostic and prognostic marker in CRC and that targeting ETV5 might be a potential therapeutic option for inhibiting CRC angiogenesis.

Apatinib Inhibits Angiogenesis Via Suppressing Akt/GSK3ß/ANG Signaling Pathway in Anaplastic Thyroid Cancer.

BACKGROUND/AIMS: Anaplastic thyroid carcinoma (ATC) is one of the most lethal human malignancies, and there is no efficient method to slow its process. Apatinib, a novel tyrosine kinase inhibitor (TKI), has been confirmed for its efficacy and safety in the treatment of advanced gastric carcinoma patients. However, the effects of Apatinib in ATC are still unknown. METHODS: In this study, we explored the effects and mechanisms of Apatinib on tumor growth and angiogenesis in vitro and in vitro in ATC cells. Angiogenesis antibodies array was utilized to detect the expression of angiogenesis-related genes after Apatinib treatment in ATC cells. In addition, we used Akt activator, Akt inhibitor and GSK3ß inhibitor to further study the mechanism for how Apatinib suppressed angiogenesis. RESULTS: Apatinib treatment could suppress the growth of ATC cells in a dose- and time-dependent manner via inducing apoptosis and blocking cell cycle progression at G0/G1 phase. Moreover, Apatinib treatment decreased the expression of angiogenin (ANG) and inhibited angiogenesis of ATC cells in vitro and in vitro. We further confirmed that recombinant human ANG (rhANG) significantly abrogated Apatinib-mediated anti-angiogenic ability in ATC cells. Additionally, Apatinib treatment decreased the level of p-Akt and p-GSK3ß. Moreover, the Apatinib-mediated decrease of ANG and anti-angiogenic ability were partly reversed when an Akt activator, SC79, was administered. Furthermore, the anti-angiogenic ability of Apatinib can be enhanced in the presence of Akt inhibitor, and the inhibition of GSK3ß attenuated the anti-angiogenic ability of Apatinib. CONCLUSION: Our results demonstrated that Apatinib treatment inhibited tumor growth, and Apatinib-induced suppression of Akt/GSK3ß/ANG signaling pathway may play an important role in the inhibition of angiogenesis in ATC, supporting a potential therapeutic approach for using Apatinib in the treatment of ATC.

Phos-tag SDS-PAGE resolves agonist- and isoform-specific activation patterns for PKD2 and PKD3 in cardiomyocytes and cardiac fibroblasts.

Protein kinase D (PKD) consists of a family of three structurally related enzymes that are co-expressed in the heart and have important roles in many biological responses. PKD1 is activated by pro-hypertrophic stimuli and has been implicated in adverse cardiac remodeling. Efforts to define the cardiac actions of PKD2 and PKD3 have been less successful at least in part because conventional methods provide a general screen for PKD activation but are poorly suited to resolve activation patterns for PKD2 or PKD3. This study uses Phos-tag SDS-PAGE, a method that exaggerates phosphorylation-dependent mobility shifts, to overcome this technical limitation. Phos-tag SDS-PAGE resolves PKD1 as distinct molecular species (indicative of pools of enzyme with distinct phosphorylation profiles) in unstimulated cardiac fibroblasts and cardiomyocytes; as a result, attempts to track PKD1 mobility shifts that result from agonist activation were only moderately successful. In contrast, PKD2 and PKD3 are recovered from resting cardiac fibroblasts and cardiomyocytes as single molecular species; both enzymes display robust mobility shifts in Phos-tag SDS-PAGE in response to treatment with sphingosine-1-phosphate, thrombin, PDGF, or H2O2. Studies with GF109203X implicate protein kinase C activity in the stimulus-dependent pathways that activate PKD2/PKD3 in both cardiac fibroblasts and cardiomyocytes. Studies with C3 toxin identify a novel role for Rho in the sphingosine-1-phosphate and thrombin receptor-dependent pathways that lead to the phosphorylation of PKD2/3 and the downstream substrate CREB in cardiomyocytes. In conclusion, Phos-tag SDS-PAGE provides a general screen for stimulus-specific changes in PKD2 and PKD3 phosphorylation and exposes a novel role for these enzymes in specific stress-dependent pathways that influence cardiac remodeling.

Confirmation of an anatomic variation of the recurrent laryngeal nerve at site of entry into the larynx in Chinese population.

OBJECTIVE: This study was aimed at analyzing the frequency of the newly reported variation and the frequency of postoperative palsy associated with three different kinds of known variations. METHODS: We conducted a retrospective study on the data of 2068 consecutive Chinese patients who underwent thyroidectomy. The study included 1362 left and 1507 right (2869 in total) RLNs. RESULTS: Among all the RLNs, 548 were found to have variations at the laryngeal entry of the RLN. The most frequent variation was extralaryngeal branching (n=322), followed by the fan-shaped branching (n=201). Our newly identified variation was also noted in 25 of our patients. In these cases, the RLN entered the larynx from sites that were distant from the posterior cricothyroid joint. The distance from the entry of the RLN to the back of cricothyroid joints was over 5mm. Compared to the rates reported from other countries, the rate of the first type of variation is lower, while that of the second type is higher. The frequency of the new variation has not been reported in other populations, but it is consistent with our previous finding. The incidence of postoperative palsy was greater for RLNs with the first and third types of variations than in the normal RLNs. CONCLUSION: We confirmed that the incidence of patients with the new type of variation of the RLN at the entry of the larynx was about 1% in Chinese. Awareness among surgeons regarding this variation is important to avoid postoperative palsy.

The protein kinase D1 COOH terminus: marker or regulator of enzyme activity?

Protein kinase D1 (PKD1) is a Ser/Thr kinase implicated in a wide variety of cellular responses. PKD1 activation is generally attributed to a PKC-dependent pathway that leads to phosphorylation of the activation loop at Ser(744)/Ser(748). This modification increases catalytic activity, including that toward an autophosphorylation site (Ser(916)) in a postsynaptic density-95/disks large/zonula occludens-1 (PDZ)-binding motif at the extreme COOH terminus. However, there is growing evidence that PKD1 activation can also result from a PKC-independent autocatalytic reaction at Ser(744)/Ser(748) and that certain stimuli increase in PKD1 phosphorylation at Ser(744)/S(748) without an increase in autophosphorylation at Ser(916). This study exposes a mechanism that results in a discrepancy between PKD1 COOH-terminal autocatalytic activity and activity toward other substrates. We show that PKD1 constructs harboring COOH-terminal epitope tags display high levels of in vitro activation loop autocatalytic activity and activity toward syntide-2 (a peptide substrate), but no Ser(916) autocatalytic activity. Cell-based studies show that the COOH-terminal tag, adjacent to PKD1's PDZ1-binding motif, does not grossly influence PKD1 partitioning between soluble and particulate fractions in resting cells or PKD1 translocation to the particulate fraction following treatment with PMA. However, a COOH-terminal tag that confers a high level of activation loop autocatalytic activity decreases the PKC requirement for agonist-dependent PKD1 activation in cells. The recognition that COOH-terminal tags alter PKD1's pharmacological profile is important from a technical standpoint. The altered dynamics and activation mechanisms for COOH-terminal-tagged PKD1 enzymes also could model the signaling properties of localized pools of enzyme anchored through the COOH terminus to PDZ domain-containing scaffolding proteins.

Structure of the guanylyltransferase domain of human mRNA capping enzyme.

The enzyme guanylyltransferase (GTase) plays a central role in the three-step catalytic process of adding an (m7)GpppN cap cotranscriptionally to nascent mRNA (pre-mRNAs). The 5'-mRNA capping process is functionally and evolutionarily conserved from unicellular organisms to human. However, the GTases from viruses and yeast have low amino acid sequence identity (∼25%) with GTases from mammals that, in contrast, are highly conserved (∼98%). We have defined by limited proteolysis of human capping enzyme residues 229-567 as comprising the minimum enzymatically active human GTase (hGTase) domain and have determined the structure by X-ray crystallography. Seven related conformational states of hGTase exist in the crystal. The GTP-binding site is evolutionarily and structurally conserved. The positional variations of the oligonucleotide/oligosaccharide binding fold lid domain over the GTP-binding site provide snapshots of the opening and closing of the active site cleft through a swivel motion. The pattern of conserved surface residues in mammals, but not in yeast, supports the finding that the recognition of the capping apparatus by RNA polymerase II and associated transcription factors is highly conserved in mammals, and the mechanism may differ somewhat from that in yeast. The hGTase structure should help in the design of biochemical and molecular biology experiments to explore the proteinprotein and proteinRNA interactions that ensure regulated transcription of genes in humans and other mammals.

Copper-catalysed asymmetric hydroboration of alkenes with 1,2-benzazaborines to access chiral naphthalene isosteres.

Bioisosteric replacement has emerged as a clear strategy for drug-structure optimization. Naphthalene is the core element of many chiral pharmaceuticals and drug candidates. However, as a promising isostere of naphthalene, the chiral version of 1,2-benzazaborine has rarely been explored due to the lack of efficient synthetic methods. Here we describe a copper-catalysed enantioselective hydroboration of alkenes with 1,2-benzazaborines. The method provides a general platform for the atom-economic and efficient construction of diverse chiral 1,2-benzazaborine compounds (more than 60 examples) that bear a 2-carbon-stereogenic centre or allene skeleton in high yields and excellent enantioselectivities. Three 1,2-benzazaborine analogues of bioactive chiral naphthalene-containing molecules have been prepared, and a series of transformations around chiral 1,2-benzazaborines have also been developed. Notably, the hydroboration process of this study reveals that the identity of 1,2-benzazaborine plays an essential role in the rate-determining step and catalyst resting state.

Parathyroidectomy for solitary parathyroid adenoma via trans-areola single site endoscopic approach: Results of a case-match study.

BACKGROUND: This study aimed to establish the standardized procedure of trans-areola single site endoscopic parathyroidectomy (TASSEP), and to compare the performance of TASSEP with that of conventional open parathyroidectomy (COP). METHODS: This study enrolled 40 patients with primary hyperparathyroidism (PHPT) who underwent TASSEP, and included 40 of 176 PHPT patients who underwent COP based on propensity score matching. The retrospective analysis was conducted based on prospectively collected data. Perioperative outcomes, including surgical profile, surgical burden and cosmetic results and follow-up were reported. The learning curve was described using a cumulative sum (CUSUM) analysis. RESULTS: 40 TASSEPs were completed successfully without conversions or severe complications. There was no statistically significant difference in operation time between TASSEP and COP groups (80.83 ± 11.95 vs. 76.95 ± 7.30 min, p = 0.084). Experience of 17 cases was necessitated to reach the learning curve of TASSEP. Postoperative pain score and traumatic index (C-reactive protein and erythrocyte sedimentation rate) in TASSEP were apparently lower than those in COP group (p < 0.05). During the proliferation and stabilization phases, TASSEP was associated with significantly better incision recovery and cosmetic scores. Postoperative serum calcium and PTH levels throughout the follow-up period indicated satisfactory surgical qualities in both groups. CONCLUSION: Based on precise preoperative localization and intraoperative planning facilitated by three-dimensional (3D) virtual modeling, TASSEP can be feasibly performed on selected patients with satisfactory success rates and low complication rates, providing preferable cosmetic results and alleviating the surgical burden to a certain extent.

Characterization of Ca2+-ATPase, LMCA1, with native cell membrane nanoparticles system.

Ca2+-ATPases are membrane pumps that transport calcium ions across the cell membrane and are dependent on ATP. The mechanism of Listeria monocytogenes Ca2+-ATPase (LMCA1) in its native environment remains incompletely understood. LMCA1 has been investigated biochemically and biophysically with detergents in the past. This study characterizes LMCA1 using the detergent-free Native Cell Membrane Nanoparticles (NCMNP) system. As demonstrated by ATPase activity assays, the NCMNP7-25 polymer is compatible with a broad pH range and Ca2+ ions. This result suggests that NCMNP7-25 may have a wider array of applications in membrane protein research.

The proposed modification of TNM staging and therapeutic strategy for skip metastasis in papillary thyroid carcinoma: A multicenter retrospective cohort study.

BACKGROUND: Skip metastasis is a special type of lateral lymph node metastasis, which is not classified definitely by the eighth edition of the AJCC TNM staging system. The aim of the research was to study the prognosis of skip metastasis in PTC patients, and carry out a more appropriate N staging for skip metastasis. METHODS: Study subjects were 3167 patients with papillary thyroid carcinoma (PTC), who underwent thyroidectomy at three clinical centers from 2016 to 2019. We identified two well-balanced cohorts matched on the basis of propensity score. RESULTS: During a median follow-up of 42 months, recurrence occurred in 68 (4.3%) patients with lymph node metastasis. 34 cases recurred in 1120 patients with central lymph node metastasis (N1a), and 34 recurred in 461 patients with lateral lymph node metastasis (N1b), among which 73 patients were diagnosis with skip metastasis. The RFS of N1a was significantly lower than that of N1b (p < 0.001). After propensity-score matching, recurrence rate was significantly lower in the skip metastasis group than in the LLNM group (p = 0.039), whereas the rate was similar in the skip metastasis groups and the CLNM group (p = 0.29). CONCLUSIONS: In conclusion, our study indicated that, among patients with LLNM, those with positive skip metastasis showed significantly lower recurrence, exhibiting a similar rucurrence tendency as patients with CLNM. Thus, skip metastasis could be categorized into N1a stage rather than N1b stage based on the AJCC TNM staging system. The downstaging of skip metastasis may reveal more conservative treatment strategy.

Outcomes of Surgical Treatment for Graves' Disease: A Single-Center Experience of 216 Cases.

BACKGROUND: The role of surgery in the treatment of Graves' disease (GD) needs to be revisited. The aims of the present retrospective study were to evaluate the outcomes of the current surgical strategy as a definitive treatment of GD at our center and to explore the clinical association between GD and thyroid cancer. METHODS: A patient cohort of 216 cases from 2013 to 2020 was involved in this retrospective study. The data of the clinical characteristics and follow-up results were collected and analyzed. RESULTS: There were 182 female and 34 male patients. The mean age was 43.9 ± 15.0 years old. The mean duration of GD reached 72.2 ± 92.7 months. Of the 216 cases, 211 had been treated with antithyroid drugs (ATDs) and hyperthyroidism had been completely controlled in 198 cases. A total (75%) or near-total (23.6%) thyroidectomy was performed. Intraoperative neural monitoring (IONM) was applied to 37 patients. The failure of ATD therapy (52.3%) was the most common surgical indication, followed by suspicion of a malignant nodule (45.8%). A total of 24 (11.1%) patients had hoarseness after the operation and 15 (6.9%) patients had transient vocal cord paralysis; 3 (1.4%) had this problem permanently. No bilateral RLN paralysis occurred. A total of 45 patients had hypoparathyroidism and 42 of them recovered within 6 months. Sex showed a correlation with hypoparathyroidism through a univariate analysis. A total of 2 (0.9%) patients underwent a reoperation because of hematomas. A total of 104 (48.1%) cases were diagnosed as thyroid cancer. In most cases (72.1%), the malignant nodules were microcarcinomas. A total of 38 patients had a central compartment node metastasis. A lateral lymph node metastasis occurred in 10 patients. Thyroid carcinomas were incidentally discovered in the specimens of 7 cases. The patients with concomitant thyroid cancer had a significant difference in body mass index, duration of GD, gland size, thyrotropin receptor antibodies and nodule(s) detected. CONCLUSION: Surgical treatments for GD were effective, with a relatively low incidence of complications at this high-volume center. Concomitant thyroid cancer is one of the most important surgical indications for GD patients. Careful ultrasonic screening is necessary to exclude the presence of malignancies and to determine the therapeutic plan.