Generation of transgenic fish cell line with α-lactalbumin nanocarriers co-delivering Tol2 transposase mRNA and plasmids.

Fish cells, such as grass carp (Ctenopharyngodon idella) kidney (CIK) cells, are harder to transfect than mammalian cells. There is a need for an efficient gene delivery system for fish cells. Here, we used CIK cell line as a model to develop a strategy to enhance RNA and plasmid DNA transfection efficiency using a nanocarrier generated from α-lactalbumin (α-NC). α-NC absorbed nucleic acid cargo efficiently and exhibited low cytotoxicity. Plasmid transfection was more efficient with α-NC than with liposomal transfection reagents. We used α-NC to co-transfect Tol2 transposase mRNA and a plasmid containing Cas9 and GFP, generating a stable transgenic CIK cell line. Genome and RNA sequencing revealed that the Cas9 and GFP fragments were successfully inserted into the genome of CIK cells and efficiently transcribed. In this study, we established an efficient transfection system for fish cells using α-NC, simplifying the process of generating stable transgenic fish cell lines.

Efficient CdIn2S4/MgIn2S4 heterojunction for ultrasensitive detection of lung cancer marker neuron-specific enolase.

In this work, a photoelectrochemical (PEC) immunosensor was constructed for the ultrasensitive detection of lung cancer marker neuron-specific enolase (NSE) based on a microflower-like heterojunction of cadmium indium sulfide and magnesium indium sulfide (CdIn2S4/MgIn2S4, CMIS) as photoactive material. Specifically, the well-matched energy level structure and narrow energy level gradients between CdIn2S4 and MgIn2S4 could accelerate the separation of electron-hole (e--h+) pairs in the CMIS heterojunction to enhance the photocurrent of CMIS, which was increased 5.5 and 80 times compared with that of single CdIn2S4 and MgIn2S4, respectively. Meanwhile, using CMIS as photoactive material, increasing the biocompatibility by dropping Pt NPs on the surface of CMIS to immobilize the antibody through Pt-N bond. Fe3O4-Ab2, acting as the quencher, competitively consumes electron donors and absorbs light, leading to photocurrent quenching. With the increasing of quencher, the photocurrent decreased. Hence, the developed "signal-off" PEC immunosensor realized the trace detection of NSE within the range from 1.0 fg/mL to 10 ng/mL with a low detection limit of 0.34 fg/mL. This strategy provided a new perspective for establishing ternary metal sulfide heterojunction to construct PEC immunosensor for sensitive detection of disease biomarkers.

The impact of emotion regulation strategies on disordered eating behavior in children and adolescents with type 1 diabetes: a cross-sectional study.

Objective: Difficulties in emotion regulation (DERs) can contribute to disordered eating behavior in children and adolescents with type 1 diabetes (T1D), although it is unknown how DERs may affect eating behavior in these children and adolescents. This study examined the relationship between disordered eating behaviors and emotion regulation in children and adolescents with T1D. Methods: For this cross-sectional study, 128 patients (aged 8-16 years) were recruited to complete the Diabetes Eating Problem Survey-Revised (DEPS-R) and Difficulties in Emotion Regulation Scale (DERs). Results: The mean age of the 128 patients (99 females) who completed the DEPS-R was 11.63 ± 2.27 years. The participants' mean DEPS-R score was 17.78 ± 8.56 points. Of the total sample, 61 participants' scores surpassed the established threshold, resulting in a DEPS-R positivity rate of 47.66%. The participants' mean total DERS score was 72.3 ± 21.15 points, and it was found that children and adolescents with T1D who had a positive DEPS-R screening result had significant differences in emotional regulation and that eating behavior disorders were positively correlated with emotional regulation and all dimensions scores. Conclusions: The prevalence of disordered eating behavior is high among children and adolescents with T1D. DERs are related to disordered eating behavior in children and adolescents with T1D. The novel finding that DERs may be a predictor of eating problems lends preliminary support for the inclusion of DERs in future risk models and as a potential target for intervention.

Variation in plant functional traits explains the substitution distribution and allocation strategy of Stipa species across natural grasslands of Ningxia, Northern China.

Functional traits reflect plants' adaptability to their environment, and environmental gradients influence their distribution. But few studies have investigated the link between these traits and species substitution patterns or the relevant ecological factors. We measured the aboveground (leaf) and belowground (root) functional traits of Stipa species in 17 plots across natural grasslands in Ningxia in Northern China. Redundancy analysis was used to explore the relationships between Stipa's functional traits and its species substitution distribution. Then, on the species substitution gradient, principal component analysis (PCA) was used to verify and quantify the leaf economic spectrum (LES), root economic spectrum (RES), and whole-plant economic spectrum (WPES), with the relation between these spectra investigated by fitting standardized major axis regressions. The effects of aboveground, belowground, and whole-plant ecological factors were quantified and ranked by variance decomposition and hierarchical partitioning. Our results showed that functional traits drive the substitution distribution of Stipa species, in being variously coupled with its desert, typical, and meadow steppe habitat types. The leaf, root, and whole-plant economic spectra of Stipa species in desert steppe exhibit a "quick investment-acquisition" strategy. In typical steppe, the leaf and whole-plant economic spectra of Stipa species correspond to a "fast investment-acquisition" strategy, whereas the root economic spectrum adopts a "slow investment-acquisition" strategy. On meadow steppe, the leaf, root, and whole-plant economic spectra of Stipa species similarly adopt a "slow investment-acquisition" strategy. Finally, when considering the environmental factors involved, we find that the substitution distribution of Stipa spp. is chiefly a response to shifting soil patterns, these mainly driven by soil total nitrogen and nitrogen/phosphorus ratio. Collectively, these findings provide an important reference for the ecological restoration and reconstruction of grassland ecosystems, to better understand the relationship between plant functional traits and ecological niche attributes, and thus guide the reasonable restoration of grassland vegetation.

RBP4 promotes denervation-induced muscle atrophy through STRA6-dependent pathway.

BACKGROUNDS: Fat infiltration of skeletal muscle has been recognized as a common feature of many degenerative muscle disorders. Retinol binding protein 4 (RBP4) is an adipokine that has been demonstrated to be correlated with the presence and severity of sarcopenia in the elderly. However, the exact role and the underlying mechanism of RBP4 in muscle atrophy remains unclear. METHODS: Denervation-induced muscle atrophy model was constructed in wild-type and RBP4 knockout mice. To modify the expression of RBP4, mice were received intramuscular injection of retinol-free RBP4 (apo-RBP4), retinol-bound RBP4 (holo-RBP4) or oral gavage of RBP4 inhibitor A1120. Holo-RBP4-stimulated C2C12 myotubes were treated with siRNAs or specific inhibitors targeting signalling receptor and transporter of retinol 6 (STRA6)/Janus kinase 2 (JAK2)/Signal transducer and activator of transcription 3 (STAT3) pathway. Fat accumulation, myofibre cross-sectional area, myotube diameter and the expression of muscle atrophy markers and myogenesis markers were analysed. RESULTS: The expression levels of RBP4 in skeletal muscles were significantly up-regulated more than 2-fold from 7 days and sustained for 28 days after denervation. Immunofluorescence analysis indicated that increased RBP4 was localized in the infiltrated fatty region in denervated skeletal muscles. Knockout of RBP4 alleviated denervation-induced fatty infiltration and muscle atrophy together with decreased expression of atrophy marker Atrogin-1 and MuRF1 as well as increased expression of myogenesis regulators MyoD and MyoG. By contrast, injection of retinol-bound holo-RBP4 aggregated denervation-induced ectopic fat accumulation and muscle atrophy. Consistently, holo-RBP4 stimulation also had a dose-dependent effect on the reduction of C2C12 myotube diameter and myofibre cross-sectional area, as well as on the increase of Atrogin-1and MuRF1 expression and decrease of MyoD and MyoG expression. Mechanistically, holo-RBP4 treatment increased the expression of its membrane receptor STRA6 (>3-fold) and promoted the phosphorylation of downstream JAK2 and STAT3. Inhibition of STRA6/JAK2/STAT3 pathway either by specific siRNAs or inhibitors could decrease the expression of Atrogin-1 and MuRF1 (>50%) and decrease the expression of MyoD and MyoG (>3-fold) in holo-RBP4-treated C2C12 myotube. RBP4 specific pharmacological antagonist A1120 significantly inhibited the activation of STRA6/JAK2/STAT3 pathway, ameliorated ectopic fat infiltration and protected against denervation-induced muscle atrophy (30% increased myofibre cross-sectional area) in mice. CONCLUSIONS: In conclusion, our data reveal that RBP4 promotes fat infiltration and muscle atrophy through a STRA6-dependent and JAK2/STAT3 pathway-mediated mechanism in denervated skeletal muscle. Our results suggest that lowering RBP4 levels might serve as a promising therapeutic approach for prevention and treatment of muscle atrophy.

Orthogonal magnetic orbitals in high spin Cu-VO units: structure, magnetism and EPR study of anisotropic heterometallic complexes.

Molecular-based magnetic materials are expected to serve as building blocks for quantum bits. To realize high-dimensional Hilbert space and addressability, we constructed anisotropic multi-level systems based on CuII and VIV with orthogonal magnetic orbitals. The crystal structures and intramolecular magnetic couplings of four CuIIVOII complexes [{CuVO(appen)2}2], [{CuVO(fhma)2EDA}2], [{CuVO(hfca)2EDA}2] and [CuVO(hfca)2DPEDA]n are characterized. Due to the orthogonal magnetic orbitals of CuII and VIV, the Cu-V pairs in the four complexes have strong ferromagnetic couplings, and the coupling strength is linearly related to the dihedral angle between the two equatorial planes of the two coordination polyhedra. Because of the triplet ground state, the system can be described by an effective Hamiltonian model consisting of two S = 1 spins coupled together. The anisotropy parameters of [{CuVO(hfca)2EDA}2] and [CuVO(hfca)2DPEDA]n were obtained by the simulation of X-band continuous wave electron paramagnetic resonance (cw-EPR) spectra, confirming that both complexes have zero-field splitting addressable on the relative energy scale. The results indicate that constructing multi-centre complexes based on orthogonal magnetic orbitals is a promising strategy for designing multidimensional quantum bits.

[Research progress in targeting DNA G-quadruplexes using natural products].

DNA G-quadruplex(G4) is a guanine-rich single-stranded DNA sequence that spontaneously folds into a spherical four-stranded DNA secondary structure in oncogene promoter sequences and telomeres. G4s are highly associated with the occurrence and development of cancer and have emerged as promising anticancer targets. Natural products have long been important sources of anticancer drug development. In recent years, significant progress has been made in the discovery of natural drugs targeting DNA G4s, with many DNA G4s have been confirmed as promising targets of natural products, including MYC-G4, KRAS-G4, PDGFR-ß-G4, BCL-2-G4, VEGF-G4, and telomeric G4. This review summarizes the research progress in discovering natural small molecules that target DNA G4s and their binding mechanisms. It also discusses the opportunities of and challenges in developing drugs targeting DNA G4s. This review will serve as a valuable reference for the research on natural products, particularly in the development of novel antitumor medications.

Impaired embryo development potential associated with thyroid autoimmunity in euthyroid infertile women with diminished ovarian reserve.

Purpose: The aim of this study was to evaluate the associations of thyroid autoimmunity (TAI) with the number of oocytes retrieved (NOR), fertilization rate (FR), and embryo quality (EQ) in euthyroid women with infertility and diminished ovarian reserve (DOR). Methods: This retrospective cohort study involved 1,172 euthyroid women aged 20-40 years with infertility and DOR who underwent an oocyte retrieval cycle. TAI was diagnosed in the presence of serum thyroperoxidase antibody (TPOAb) concentrations higher than 34 IU/ml and/or serum thyroglobulin antibody (TgAb) concentrations exceeding 115.0 IU/ml. Among these women, 147 patients with TAI were classified as the TAI-positive group, while 1,025 patients without TAI were classified as the TAI-negative group. Using generalized linear models (GLMs) adjusted for confounding factors, we evaluated the associations of TAI and the serum TPOAb and TgAb concentrations and NOR, FR, and EQ in this study's subjects. The TPOAb and TGAb values were subjected to log10 transformation to reduce skewness. Logistic regression models were used to estimate the effects of TPOAb and TgAb concentrations on the probabilities of achieving a high NOR (≥7) and high FR (>60%). Results: For the whole study population, women with TAI had a significantly lower NOR and poorer EQ than women without TAI (P < 0.001 for both). Interestingly, in the TSH ≤2.5 subgroup, the TAI-positive group also had a significantly lower NOR and poorer EQ than the TAI-negative group (P < 0.001 for both). Furthermore, negative associations were observed between log10(TPOAb) concentrations and NOR and the number of high-quality embryos and available embryos (P < 0.05 for all). The log10(TgAb) concentrations were inversely associated with NOR and the number of high-quality embryos (P < 0.05 for all). In the regression analysis, the log10(TPOAb) concentrations had lower probabilities of achieving a high NOR [adjusted odds ratio (aOR): 0.56; 95% confidence interval (95% CI) 0.37, 0.85; P = 0.007]. Conclusions: TAI and higher TPOAb and TgAb concentrations were shown to be associated with reductions in the NOR and EQ in the study population. Our findings provide further evidence to support systematic screening and treatment for TAI in euthyroid women with infertility and DOR.

The Inflammatory Response and Long-Term Outcomes Between Open and Laparoscopic Pancreatoduodenectomy:A Propensity-Matched Single-Institution Study.

Background: In recent years, although laparoscopic pancreatoduodenectomy (LPD) has experienced rapid development both domestically and internationally, however, there are still varying opinions toward LPD. Methods: From January 2020 to July 2022, the data were collected. We compared the inflammatory response at various postoperative time points and evaluated long-term outcomes between the two groups. Results: In the early stage, the LPD group exhibited lower values of white blood cells, C-reactive protein, neutrophils, and platelets after surgery compared with open pancreatoduodenectomy (OPD) (P all<0.05). However, no statistically significant differences were observed in terms of procalcitonin, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio. Before propensity score matching, no statistical significance was observed between two groups, whether in terms of disease-free survival (DFS) (P = .406) or overall survival (OS) (P = .851). However, to further control for confounding factors, propensity score matching was used. The analysis revealed that DFS still showed no significant difference (P = .928), but, in the term of OS, a statistical significance was observed between the two groups. Conclusion: LPD demonstrates a comparable long-term outcomes to OPD and even slightly superior OS. Moreover, the LPD group exhibits a lower inflammatory response during early postoperative period.

A novel strategy for improving bowel preparation based on social software-enhanced education: A prospective, multicenter, randomized controlled study.

BACKGROUND AND AIM: The compliance and timeliness of oral laxatives have always been the key factors restricting bowel preparation (BP). We have constructed a novel enhanced-educational content and process based on social software (SS) for BP to optimize these issues. METHODS: A multicenter, prospective, randomized controlled study was conducted at 13 hospitals in China from December 2019 to December 2020. A total of 1774 enrollees received standard instructions for BP and were randomly assigned (1:1) to the SS group (SSG) that received a smartphone-based enhanced-education strategy starting 4 h before colonoscopy or the control group (CG). RESULTS: A total of 3034 consecutive outpatient colonoscopy patients were assessed for eligibility, and 1774 were enrolled and randomly assigned. Ultimately, data from 1747 (SSG vs CG: 875 vs 872) enrollees were collected. The BP adequacy rate was 92.22% (95% CI: 90.46-93.98) in the SSG vs 88.05% (95% CI: 85.91-90.18) in the CG (P = 0.005), and the total Boston Bowel Preparation Scale scores (6.89 ± 1.15 vs 6.67 ± 1.15, P < 0.001) of those in the SSG were significantly higher than those in the CG. The average number of polyps detected in the SSG was considerably higher than that in the CG (0.84 ± 2.00 vs 0.53 ± 1.19, P = 0.037), and the average diameter of the polyps was significantly lower than that of the control group (4.0 ± 2.5 vs 4.9 ± 3.7, P < 0.001). CONCLUSIONS: This SS-enhanced education strategy can improve the BP adequacy rate and increase the average number of polyps detected, especially those of small diameter.

Clinical Features and Analysis in Pituitary Stalk Interruption Syndrome.

Objective: Pituitary stalk interruption syndrome (PSIS) is characterized by the absence of pituitary stalk, pituitary hypoplasia, and ectopic posterior pituitary. Because the etiology and clinical cognition of PSIS remain elusive, we analyzed the clinical features of PSIS in Chinese patients. Methods: A retrospective analysis was conducted on the clinical presentation, laboratory data, imaging examination, and management of 24 PSIS inpatients from our center over 10 years. Results: Among the 24 PSIS patients, there were 22 males (91.7%) and 2 females (8.3%). Growth hormone deficiency was present in all 24 cases (100%), hypogonadism in 24 cases (100%), secondary adrenal insufficiency in 22 cases (91.2%), and hypothyroidism in 21 cases (87.5%). 20 cases (83.3%) of PSIS patients exhibited deficiencies in four anterior pituitary hormones, 3 cases (12.5%) exhibited deficiencies in three anterior pituitary hormones, and 1 case (4.2%) exhibited deficiencies in two anterior pituitary hormones, with none exhibiting deficiencies in posterior pituitary hormones. Among the 24 PSIS patients, 12 had a history of growth hormone therapy before admission, and 12 had no such history. Additionally, 19 cases (79.2%) with PSIS were complicated by dyslipidemia, 15 cases (62.5%) were complicated by nonalcoholic fatty liver disease, and 9 cases (37.5%) were complicated by hyperuricemia. Conclusions: PSIS often presents with growth retardation and hypogonadotropic hypogonadism, but in some cases, short stature is not exhibited. PSIS is prone to complications such as dyslipidemia, nonalcoholic fatty liver disease, and hyperuricemia, increasing the risk of cardiovascular and cerebrovascular diseases. In clinical practice, the diagnostic ability of PSIS should be improved, and pituitary function and complications should be evaluated in a timely manner to avoid delayed treatment.

Genome-wide association study and candidate gene identification for agronomic traits in 182 upward-growing fruits of C. frutescens and C. annuum.

Pepper agronomic traits serve as pivotal indicators for characterizing germplasm attributes and correlations. It is important to study differential genotypic variation through phenotypic differences of target traits. Whole genome resequencing was used to sequence the whole genome among different individuals of species with known reference genomes and annotations, and based on this, differential analyses of individuals or populations were carried out to identify SNPs for agronomic traits related to pepper. This study conducted a genome-wide association study encompassing 26 key agronomic traits in 182 upward-growing fruits of C. frutescens and C. annuum. The population structure (phylogenetics, population structure, population principal component analysis, genetic relationship) and linkage disequilibrium analysis were realized to ensure the accuracy and reliability of GWAS results, and the optimal statistical model was determined. A total of 929 SNPs significantly associated with 26 agronomic traits, were identified, alongside the detection of 519 candidate genes within 100 kb region adjacent to these SNPs. Additionally, through gene annotation and expression pattern scrutiny, genes such as GAUT1, COP10, and DDB1 correlated with fruit traits in Capsicum frutescens and Capsicum annuum were validated via qRT-PCR. In the CH20 (Capsicum annuum) and YB-4 (Capsicum frutescens) cultivars, GAUT1 and COP10 were cloned with cDNA lengths of 1065 bp and 561 bp, respectively, exhibiting only a small number of single nucleotide variations and nucleotide deletions. This validation provides a robust reference for molecular marker-assisted breeding of pepper agronomic traits, offering both genetic resources and theoretical foundations for future endeavors in molecular marker-assisted breeding for pepper.

Excited-State Dynamics of a CRABPII-Based Microbial Rhodopsin Mimic.

Microbial rhodopsin, a pivotal photoreceptor protein, has garnered widespread application in diverse fields such as optogenetics, biotechnology, biodevices, etc. However, current microbial rhodopsins are all transmembrane proteins, which both complicates the investigation on the photoreaction mechanism and limits their further applications. Therefore, a specific mimic for microbial rhodopsin can not only provide a better model for understanding the mechanism but also can extend the applications. The human protein CRABPII turns out to be a good template for design mimics on rhodopsin due to the convenience in synthesis and the stability after mutations. Recently, Geiger et al. designed a new CRABPII-based mimic M1-L121E on microbial rhodopsin with the 13-cis, syn (13C) isomerization after irradiation. However, it still remains a question as to how similar it is compared with the natural microbial rhodopsin, in particular, in the aspect of the photoreaction dynamics. In this article, we investigate the excited-state dynamics of this mimic by measuring its transient absorption spectra. Our results reveal that there are two components in the solution of mimic M1-L121E at pH 8, known as protonated Schiff base (PSB) and unprotonated Schiff base (USB) states. In both states, the photoreaction process from 13-cis, syn(13C) to all-trans,anti (AT) is faster than that from the inverse direction. In addition, the photoreaction process in the PSB state is faster than that in the USB state. We compared the isomerization time of the PSB state to that of microbial rhodopsin. Our findings indicate that M1-L121E exhibits behaviors similar to those of microbial rhodopsins in the general pattern of PSB isomerization, where the isomerization from 13C to AT is much faster than its inverse direction. However, our results also reveal significant differences in the excited-state dynamics of the mimic relative to the native microbial rhodopsin, including the slower PSB isomerization rates as well as the unusual USB photoreaction dynamics at pH = 8. By elucidating the distinctive characteristics of mimics M1-L121E, this study enhances our understanding of microbial rhodopsin mimics and their potential applications.

Novel strategy of S. mutans gcrR gene over-expression plus antibacterial dimethylaminohexadecyl methacrylate suppresses biofilm acids and reduces dental caries in rats.

OBJECTIVE: Streptococcus mutans (S. mutans) is a major contributor to dental caries, with its ability to synthesize extracellular polysaccharides (EPS) and biofilms. The gcrR gene is a regulator of EPS synthesis and biofilm formation. The objectives of this study were to investigate a novel strategy of combining gcrR gene over-expression with dimethylaminohexadecyl methacrylate (DMAHDM), and to determine their in vivo efficacy in reducing caries in rats for the first time. METHODS: Two types of S. mutans were tested: Parent S. mutans; and gcrR gene over-expressed S. mutans (gcrR OE S. mutans). Bacterial minimum inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) were measured with DMAHDM and chlorhexidine (CHX). Biofilm biomass, polysaccharide, lactic acid production, live/dead staining, colony-forming units (CFUs), and metabolic activity (MTT) were evaluated. A Sprague-Dawley rat model was used with parent S. mutans and gcrR OE S. mutans colonization to determine caries-inhibition in vivo. RESULTS: Drug-susceptibility of gcrR OE S. mutans to DMAHDM or CHX was 2-fold higher than that of parent S. mutans. DMAHDM reduced biofilm CFU by 3-4 logs. Importantly, the combined gcrR OE S. mutans+ DMAHDM dual strategy reduced biofilm CFU by 5 logs. In the rat model, the parent S. mutans group had a higher cariogenicity in dentinal (Dm) and extensive dentinal (Dx) regions. The DMAHDM + gcrR OE group reduced the Dm and Dx caries to only 20 % and 0 %, those of parent S. mutans + PBS control group (p < 0.05). The total caries severity of gcrR OE + DMAHDM group was decreased to 51 % that of parent S. mutans control (p < 0.05). SIGNIFICANCE: The strategy of combining S. mutans gcrR over-expression with antibacterial monomer reducing biofilm acids by 97 %, and reduced in vivo total caries in rats by 48 %. The gcrR over-expression + DMAHDM strategy is promising for a wide range of dental applications to inhibit caries and protect tooth structures.

Neural Progenitor Cell-Mediated Magnetic Nanoparticles for Magnetic Resonance Imaging and Photothermal Therapy of Glioma.

Glioma is the most common primary malignant tumor in the brain. The diagnostic accuracy and treatment efficiency of glioma are facing great challenges due to the presence of the blood-brain barrier (BBB) and the high infiltration of glioma. There is an urgent need to explore the combination of diagnostic and therapeutic approaches to achieve a more accurate diagnosis, as well as guidance before and after surgery. In this work, we induced human induction of pluripotent stem cell into neural progenitor cells (NPCs) and synthesized nanoprobes labeled with enhanced green fluorescent protein (EGFP, abbreviated as MFe3O4-labeled EGFP-NPCs) for photothermal therapy. Nanoprobes carried by NPCs can effectively penetrate the BBB and target glioma for the purpose of magnetic resonance imaging and guiding surgery. More importantly, MFe3O4-labeled EGFP-NPCs can effectively induce local photothermal therapy, conduct preoperative tumor therapy, and inhibit the recurrence of postoperative glioma. This work shows that MFe3O4-labeled EGFP-NPCs is a promising nanoplatform for glioma diagnosis, accurate imaging-guided surgery, and effective photothermal therapy.

Safety and effectiveness of tunneled peripherally inserted central catheters versus conventional PICC in adult cancer patients.

OBJECTIVES: This study aimed to compare the safety and effectiveness of tunneled peripherally inserted central catheters (T-PICC) vs. conventional PICCs (C-PICC) in adult cancer patients. METHODS: A multicentre randomized controlled trial was conducted between April 2021 and January 2022 in seven hospitals in China. 564 participants were randomly assigned to T-PICC or C-PICC. These data were collected and compared: the baseline characteristics and catheterization-related characteristics, periprocedural complications, and long-term complications. RESULTS: Five-hundred fifty-three participants (aged, 52.6 ± 12.3 years; female, 39.1%) were ultimately analyzed. No significant differences in periprocedural complications were found between the T-PICC and C-PICC groups (all p > 0.05). Compared with C-PICC, T-PICC significantly reduced the incidence of long-term complications (26.4% vs. 39.9%, p < 0.001). Specifically, reduced complications were found in central line-associated bloodstream infection (1.8% vs. 5.1%, p = 0.04), thrombosis (1.1% vs. 4.0%, p = 0.03), catheter dislodgement (4.7% vs. 10.1%, p = 0.01), non-infectious oozing (17.3% vs. 28.6%, p = 0.002), local infection (3.6% vs. 7.6%, p = 0.04), skin irritation (6.1% vs. 10.9%, p = 0.046), and reduced unplanned catheter removal (2.2% vs. 7.2%, p = 0.005). No significant differences were found between T-PICC and C-PICC regarding catheter occlusion (6.5% vs. 5.8%, p = 0.73) or skin damage (2.2% vs. 2.9%, p = 0.58). CONCLUSION: T-PICC is safe and effectively reduces long-term complications. CLINICAL RELEVANCE STATEMENT: The tunneled technique is effective in reducing PICC-related long-term complications. Thus, it is recommended for cancer patients at high risk of PICC-related complications. TRIAL REGISTRATION: The registration number on https://www.chictr.org.cn/ is ChiCTR2100044632. The name of the trial registry is "A multicenter randomized controlled study of clinical use of tunneled vs. non-tunneled PICC". KEY POINTS: Cather-related complications are associated with the technique of catheterization. Compared with conventional PICC, tunneled PICC reduced catheter-related long-term complications. Tunneled PICC placement provides an alternative catheterization method for cancer patients.

Target engagement and immunogenicity of an active immunotherapeutic targeting pathological α-synuclein: a phase 1 placebo-controlled trial.

Investigational therapeutics that target toxic species of α-synuclein (αSyn) aim to slow down or halt disease progression in patients with Parkinson's disease (PD). Here this 44-week, randomized, placebo-controlled, double-blind, single-center phase 1 study investigated safety, tolerability and immunogenicity of UB-312, an active immunotherapeutic targeting pathological αSyn, in patients with PD. The primary outcome measures were adverse event frequency and change in anti-αSyn antibody titers in blood and cerebrospinal fluid (CSF). Exploratory outcomes were changes in clinical scales and biomarker-based target engagement as measured by seed amplification assays. Twenty patients were randomized 7:3 (UB-312:placebo) into 300/100/100 µg or 300/300/300 µg (weeks 1, 5 and 13) intramuscular prime-boost dose groups. Safety was similar across groups; adverse events were mostly mild and transient. Two patients experienced three serious adverse events in total, one possibly treatment related; all resolved without sequalae. Anti-αSyn antibodies in serum from 12/13 and CSF from 5/13 patients who received three UB-312 doses confirmed immunogenicity. Mean serum titers (in log-dilution factor) increased from baseline by 1.398 and 1.354, and peaked at week 29 at 2.520 and 2.133, for 300/100/100 µg and 300/300/300 µg, respectively. CSF titers were 0 at baseline and were 0.182 and 0.032 at week 21, respectively. Exploratory analyses showed no statistical differences in clinical scales but a significant reduction of αSyn seeds in CSF of a subset of UB-312-treated patients. These data support further UB-312 development. ClinicalTrials.gov: NCT04075318 .

MorphBungee: A 65-nm 7.2-mm2 27-µJ/image Digital Edge Neuromorphic Chip with On-Chip 802-frame/s Multi-Layer Spiking Neural Network Learning.

This paper presents a digital edge neuromorphic spiking neural network (SNN) processor chip for a variety of edge intelligent cognitive applications. This processor allows high-speed, high-accuracy and fully on-chip spike-timing-based multi-layer SNN learning. It is characteristic of hierarchical multi-core architecture, event-driven processing paradigm, meta-crossbar for efficient spike communication, and hybrid and reconfigurable parallelism. A prototype chip occupying an active silicon area of 7.2 mm2 was fabricated using a 65-nm 1P9M CMOS process. when running a 256-256-256-256-200 4-layer fully-connected SNN on downscaled 16 × 16 MNIST images. it typically achieved a high-speed throughput of 802 and 2270 frames/s for on-chip learning and inference, respectively, with a relatively low power dissipation of around 61 mW at a 100 MHz clock rate under a 1.0V core power supply, Our on-chip learning results in comparably high visual recognition accuracies of 96.06%, 83.38%, 84.53%, 99.22% and 100% on the MNIST, Fashion-MNIST, ETH-80, Yale-10 and ORL-10 datasets, respectively. In addition, we have successfully applied our neuromorphic chip to demonstrate high-resolution satellite cloud image segmentation and non-visual tasks including olfactory classification and textural news categorization. These results indicate that our neuromorphic chip is suitable for various intelligent edge systems under restricted cost, energy and latency budgets while requiring in-situ self-adaptative learning capability.

Dose-response study of propofol combined with two different doses of esketamine for laryngeal mask airway insertion in women undergoing hysteroscopy.

Objective: To prospectively determine the median effective dose (ED50) of propofol for inhibiting a response to laryngeal mask airway (LMA) insertion when combined with different doses of esketamine in female patients. Methods: A total of 58 female patients (aged 20-60 years, ASAⅠ-Ⅱ) scheduled for elective hysteroscopy were enrolled and randomly divided into 2 groups, one of which was administered 0.2 mg/kg of esketamine (K1 group, n = 28) and the other 0.3 mg/kg of esketamine (K2 group, n = 30). The 2 groups received the corresponding doses of esketamine intravenously, followed by an intravenous injection of propofol (injection time was 30 s). The initial dose of propofol was 2 mg/kg, and the dose ratio of propofol in the adjacent patients was 0.9. If a positive reaction occurred due to LMA insertion, the dose ratio in the next patient was increased by 1 gradient; if not, the dose ratio was decreased by 1 gradient. The ED50, 95 % effective dose (ED95) and 95 % confidence interval (CI) of propofol for inhibiting a response to LMA insertion in the 2 esketamine groups were calculated using probit analysis. Results: The ED50 of propofol for inhibiting a response to LMA insertion in female patients was 1.95 mg/kg (95 % CI, 1.82-2.08 mg/kg) in the K1 group and 1.60 mg/kg (95 % CI, 1.18-1.83 mg/kg) in the K2 group. The ED95 of propofol for inhibiting a response to LMA insertion in female patients was 2.22 mg/kg (95 % CI, 2.09-2.86 mg/kg) in the K1 group and 2.15 mg/kg (95 % CI, 1.88-3.09 mg/kg) in the K2 group. Conclusion: Propofol combined with 0.3 mg/kg of esketamine has low ED50 and ED95 effective doses for inhibiting an LMA insertion response in female patients undergoing hysteroscopy and surgery. There were no significant adverse effects, but the additional dose of propofol and airway pressure were significantly higher than those in the group administered 0.2 mg/kg of esketamine. Based on the results, we recommend the combination of propofol with 0.2 mg/kg esketamine for optimal conditions during LMA insertion in women undergoing hysteroscopy.

The influence of electrode types to the visually induced gamma oscillations in mouse primary visual cortex.

The local field potential (LFP) is an extracellular electrical signal associated with neural ensemble input and dendritic signaling. Previous studies have linked gamma band oscillations of the LFP in cortical circuits to sensory stimuli encoding, attention, memory, and perception. Inconsistent results regarding gamma tuning for visual features were reported, but it remains unclear whether these discrepancies are due to variations in electrode properties. Specifically, the surface area and impedance of the electrode are important characteristics in LFP recording. To comprehensively address these issues, we conducted an electrophysiological study in the V1 region of lightly anesthetized mice using two types of electrodes: one with higher impedance (1 MΩ) and a sharp tip (10 µm), while the other had lower impedance (100 KΩ) but a thicker tip (200 µm). Our findings demonstrate that gamma oscillations acquired by sharp-tip electrodes were significantly stronger than those obtained from thick-tip electrodes. Regarding size tuning, most gamma power exhibited surround suppression at larger gratings when recorded from sharp-tip electrodes. However, the majority showed enhanced gamma power at larger gratings when recorded from thick-tip electrodes. Therefore, our study suggests that microelectrode parameters play a significant role in accurately recording gamma oscillations and responsive tuning to sensory stimuli.