Transcutaneous auricular vagus nerve stimulation with task-oriented training improves upper extremity function in patients with subacute stroke: a randomized clinical trial.

Background: Transcutaneous auricular vagus nerve stimulation (taVNS) has emerged as a promising brain stimulation modality in poststroke upper extremity rehabilitation. Although several studies have examined the safety and reliability of taVNS, the mechanisms underlying motor recovery in stroke patients remain unclear. Objectives: This study aimed to investigate the effects of taVNS paired with task-oriented training (TOT) on upper extremity function in patients with subacute stroke and explore the potential underlying mechanisms. Methods: In this double-blinded, randomized, controlled pilot trial, 40 patients with subacute stroke were randomly assigned to two groups: the VNS group (VG), receiving taVNS during TOT, and the Sham group (SG), receiving sham taVNS during TOT. The intervention was delivered 5 days per week for 4 weeks. Upper extremity function was measured using the Fugl-Meyer Assessment-Upper Extremity (FMA-UE), the Action Research Arm Test (ARAT). Activities of daily living were measured by the modified Barthel Index (MBI). Motor-evoked potentials (MEPs) were measured to evaluate cortical excitability. Assessments were administered at baseline and post-intervention. Additionally, the immediate effect of taVNS was detected using functional near-infrared spectroscopy (fNIRS) and heart rate variability (HRV) before intervention. Results: The VG showed significant improvements in upper extremity function (FMA-UE, ARAT) and activities of daily living (MBI) compared to the SG at post-intervention. Furthermore, the VG demonstrated a higher rate of elicited ipsilesional MEPs and a shorter latency of MEPs in the contralesional M1. In the VG, improvements in FMA-UE were significantly associated with reduced latency of contralesional MEPs. Additionally, fNIRS revealed increased activation in the contralesional prefrontal cortex and ipsilesional sensorimotor cortex in the VG in contrast to the SG. However, no significant between-group differences were found in HRV. Conclusion: The combination of taVNS with TOT effectively improves upper extremity function in patients with subacute stroke, potentially through modulating the bilateral cortex excitability to facilitate task-specific functional recovery.

Clinical outcomes of hepatic arterial infusion chemotherapy combined with tyrosine kinase inhibitors and anti-PD-1 immunotherapy for unresectable intrahepatic cholangiocarcinoma.

OBJECTIVE: To compare the treatment efficacy and safety of tyrosine kinase inhibitors (TKIs) and anti-programmed cell death 1 (PD-1) immunotherapy combined with transarterial chemoembolization (TACE) or hepatic arterial infusion chemotherapy (HAIC) for patients with unresectable intrahepatic cholangiocarcinoma (ICC). METHODS: Patients with unresectable ICC received TKIs and anti-PD-1 immunotherapy combined with HAIC (HTP group) or TACE (TTP group) were included. The clinicopathological characteristics, treatment efficacy, and adverse events (AEs) were compared between the two groups. The factors associated with response rate to the treatments were evaluated. RESULTS: A total of 58 patients were enrolled, with 39 in the HTP group and 19 in the TTP group. Patients in the HTP group exhibited a better objective response rate (ORR; Response Evaluation Criteria in Solid Tumors [RECIST] 48.7% vs 15.8%, P = 0.02; modified RECIST [mRECIST] 61.5% vs 21.1%, P = 0.004) and disease control rate (DCR; 82.1% vs 36.8%, P = 0.001) compared to the TTP group. The median progression-free survival (PFS) rate was not reached and the 1-year PFS rate was 61.9% in the HTP group, whereas the median PFS was 11.0 months and the 1-year PFS rate was 31.6% in the TTP group. The type of treatment and tumor size were significant factors for the response rate. More patients in the HTP group presented rash, abdominal pain and hand-foot syndrome, but all AEs were relieved after symptomatic treatment, and no treatment-related death occurred. CONCLUSIONS: For unresectable ICC, treatment with a combination of HAIC with TKIs and anti-PD-1 immunotherapy was effective and safe. Tumor size might serve as a significant factor for the response rate following treatment for unresectable ICC.

Silencing miRNA-324-3p protects against cerebral ischemic injury via regulation of the GATA2/A1R axis.

Previous studies have suggested that miR-324-3p is related to the pathophysiology of cerebral ischemia, but the mechanism underlying this relationship is unclear. In this study, we found that miR-324-3p expression was decreased in patients with acute ischemic stroke and in in vitro and in vivo models of ischemic stroke. miR-324-3p agomir potentiated ischemic brain damage in rats subjected to middle cerebral artery occlusion, as indicated by increased infarct volumes and cell apoptosis rates and greater neurological deficits. In a PC12 cell oxygen-glucose deprivation/reoxygenation model, a miR-324-3p mimic decreased cell viability and expression of the anti-apoptotic protein BCL2 and increased expression of the pro-apoptotic protein BAX and rates of cell apoptosis, whereas treatment with a miR-324-3p inhibitor had the opposite effects. Silencing miR-324-3p increased adenosine A1 receptor (A1R) expression through regulation of GATA binding protein 2 (GATA2). These findings suggest that silencing miR-324-3p reduces ischemic brain damage via the GATA2/A1R axis.

Prognostic alternative splicing regulatory network of RBM25 in hepatocellular carcinoma.

RNA-binding motif protein 25 (RBM25) is a poorly characterized RNA-binding protein that is involved in several biological processes and regulates the proliferation and metastasis of tumor cells. The regulatory role of RBM25 in hepatocellular carcinoma (HCC) is unknown. Here, RBM25 expression and outcomes in HCC patients were evaluated using The Cancer Genome Atlas database. RBM25 was overexpressed in HCC patients compared with the healthy group. The high expression of RBM25 in tumor tissues was significantly related to poor overall survival (P<0.001). Overexpression of RBM25 significantly contributed to poorer survival in male patients and N0 stage patients (P<0.001). Spearman analysis and weighted gene co-expression network analysis identified 694 RBM25-related genes. Protein-protein interaction network analysis revealed the Cluster with the highest score, which positively correlated with RBM25. CDCA5 and INCENP were identified as the core functional genes related to RBM25. The overexpression of CDCA5 and INCENP in HCC patients was examined using the Human Protein Atlas database. The findings collectively indicated that RBM25 may interact with CDCA5 and INCENP to regulate HCC. Our detailed characterization of RBM25 protein interactions and related core functional genes provides a basis for further studies aimed at identifying molecular regulatory pathways or splicing events.

Composition- and band-gap-tunable synthesis of wurtzite-derived Cu2ZnSn(S(1-x)Se(x))4 nanocrystals: theoretical and experimental insights.

The wurtzite-derived Cu2ZnSn(S(1-x)Se(x))4 alloys are studied for the first time through combining theoretical calculations and experimental characterizations. Ab initio calculations predict that wurtzite-derived Cu2ZnSnS4 and Cu2ZnSnSe4 are highly miscible, and the band gaps of the mixed-anion alloys can be linearly tuned from 1.0 to 1.5 eV through changing the composition parameter x from 0 to 1. A synthetic procedure for the wurtzite-derived Cu2ZnSn(S(1-x)Se(x))4 alloy nanocrystals with tunable compositions has been developed. A linear tunable band-gap range of 0.5 eV is observed in the synthesized alloy nanocrystals, which shows good agreement with the ab initio calculations.

Linearly arranged polytypic CZTSSe nanocrystals.

Even colloidal polytypic nanostructures show promising future in band-gap tuning and alignment, researches on them have been much less reported than the standard nano-heterostructures because of the difficulties involved in synthesis. Up to now, controlled synthesis of colloidal polytypic nanocrsytals has been only realized in II-VI tetrapod and octopod nanocrystals with branched configurations. Herein, we report a colloidal approach for synthesizing non-branched but linearly arranged polytypic I(2)-II-IV-VI(4) nanocrystals, with a focus on polytypic non-stoichiometric Cu(2)ZnSnS(x)Se(4-x) nanocrystals. Each synthesized polytypic non-stoichiometric Cu(2)ZnSnS(x)Se(4-x) nanocrystal is consisted of two zinc blende-derived ends and one wurtzite-derived center part. The formation mechanism has been studied and the phase composition can be tuned through adjusting the reaction temperature, which brings a new band-gap tuning approach to Cu(2)ZnSnS(x)Se(4-x) nanocrystals.

Large-scale colloidal synthesis of non-stoichiometric Cu(2) ZnSnSe(4) nanocrystals for thermoelectric applications.

Over 10 g of non-stoichiometric Cu(2) ZnSnSe(4) colloidal nanocrystals for thermoelectric applications are prepared after one single reaction. The obtained pellet made from the colloidal nanocrystals shows a peak ZT value of 0.44 at 450 °C, which is similar to those of state-of-the-art Cu(2) ZnSnSe(4) -based bulk materials at the same temperature.

Colloidal synthesis of Cu2CdSnSe4 nanocrystals and hot-pressing to enhance the thermoelectric figure-of-merit.

We report a solution-based synthesis of monodispersed Cu(2)CdSnSe(4) nanocrystals and a study on the thermoelectric properties of these wide-band-gap dense materials compacted from nanocrystals for the first time. With the help of copper dopants and selenium vacancies generated during wet-chemistry synthesis, a large increment in the power factor is observed, and the dimensionless figure-of-merit ZT reaches a peak value of 0.65 at 450 °C.

Landscape genetics: the correlation of spatial and genetic distances of Oncomelania hupensis, the intermediate host snail of Schistosoma japonicum in mainland China.

Two internal transcribed spacer (ITS1 and ITS2) sequences of the non-coding region of the rDNA and a 16S RNA gene fragment of the mtDNA of Oncomelania hupensis, the intermediate host snail of Schistosoma japonicum in mainland China, have been investigated with a view to illustrate the influence of the environment on genetic differentiation. Thirteen populations of O. hupensis snails, representing four types of ecological settings, were collected to compare genetic and spatial distances. The length of the ITS1-5.8S-ITS2 gene sequence showed a range from 752 to 796 bp with a guanine-cytosine (GC) content of 49.1-50.3%, while that of the 16S sequence ranged from 505 to 508 bp with a GC content of 33.5-35.1%. The 5.8S fragment was shown to be highly conserved and it was therefore removed in the subsequent analysis. In contrast, the ITS flanking sequences and the 16S fragment were found useful for further study as their degree of polymorphism amounted to 13.2% and 8.6%, respectively. The genetic relationship was investigated using tools based on maximum parsimony, minimum evolution and neighbour-joining algorithms. Four branches of O. hupensis were found to be clearly represented on the 16S phylogenetic tree, namely (i) the mountainous region population (from Sichuan and Yunnan provinces); (ii) the Karst region population (from Guangxi autonomous region); (iii) the population representing the region of swamps and lakes along the Yangtze River basin which stretches through the Anhui, Hunan, Hubei, Jiangxi, Jiangsu and Zhejiang provinces; and (iv) the littoral, hilly region population (from Fujian province). These four population branches were found to be correlated to environmental features based on the concept of landscape ecology attributing genetic differentiation to differences in ecological features. However, only three main branches could be found on the ITS1-ITS2 phylogenetic tree. The swamps and lakes population (from the Yangtze River basin) and the littoral, hilly population (from Fujian province) were clustered on the third branch in spite of these two populations not being spatially related, i.e. no firm genetic demarcation between their snail populations was found. Thus, it seems that the Fujian population does not constitute a separate branch but belongs to the third branch. This fact, together with the strong genetic evidence that the subspecies O. hupensis guangxiensis represents a discrete branch, support the hypothesis that genetic differentiation of O. hupensis in mainland China is ultimately structured by landscape ecology.

[Complete mitochondrial genome sequence of Oncomelania hupensis (Gastropoda: Rissooidea)].

OBJECTIVE: To sequence and analyze the complete nucleotide sequence of the mitochondrial genome of Oncomelania hupensis. METHODS: Four long fragments were amplified by long PCR using the primers designed based on mtDNA-CO I, Cytb, 16S rRNA and CO III gene sequences, and sequenced by conserved primer-walking. RESULTS: The mitochondrial genome (GenBank accession no. FJ997214) was a circular molecule of 15 182 bp with a total A+T content of 67.32%, and contained 13 protein-coding genes, 2 ribosomal RNA genes, 22 tRNA genes, and an A+T-rich region of 72 bp. All 13 protein-coding genes of the O. hupensis mtDNA used ATG as start codon. Canonical TAA and TAG termination codons were found in 12 protein-coding genes, and the remaining one (ND1) had an incomplete termination codon (T). Two short gene overlaps were found with a length of 4 bp and 7 bp, respectively. The length of 21 total intergenic region of mtDNA was 145bp ranging from 1-30 bp. A total of 22 transferring RNA were found, all of which were typical cloverleaf structure except for two tRNA(Ser), one tRNA(Gln) and one tRNA(Ile). CONCLUSION: The complete sequence of O. hupensis mitochondrial genome has been determined.