Two C-terminal isoforms of Aplysia tachykinin-related peptide receptors exhibit phosphorylation-dependent and phosphorylation-independent desensitization mechanisms.

Diversity, a hallmark of G protein-coupled receptor (GPCR) signaling, partly stems from alternative splicing of a single gene generating more than one isoform for a receptor. Additionally, receptor responses to ligands can be attenuated by desensitization upon prolonged or repeated ligand exposure. Both phenomena have been demonstrated and exemplified by the deuterostome tachykinin signaling system, although the role of phosphorylation in desensitization remains a subject of debate. Here, we describe the signaling system for tachykinin-related peptides (TKRPs) in a protostome, mollusk Aplysia. We cloned the Aplysia TKRP precursor, which encodes three TKRPs (apTKRP-1, apTKRP-2a, and apTKRP-2b) containing the FXGXR-amide motif. In situ hybridization and immunohistochemistry showed predominant expression of TKRP mRNA and peptide in the cerebral ganglia. TKRPs and their posttranslational modifications were observed in extracts of central nervous system ganglia using mass spectrometry. We identified two Aplysia TKRP receptors (apTKRPRs), named apTKRPR-A and apTKRPR-B. These receptors are two isoforms generated through alternative splicing of the same gene and differ only in their intracellular C termini. Structure-activity relationship analysis of apTKRP-2b revealed that both C-terminal amidation and conserved residues of the ligand are critical for receptor activation. C-terminal truncates and mutants of apTKRPRs suggested that there is a C-terminal phosphorylation-independent desensitization for both receptors. Moreover, apTKRPR-B also exhibits phosphorylation-dependent desensitization through the phosphorylation of C-terminal Ser/Thr residues. This comprehensive characterization of the Aplysia TKRP signaling system underscores the evolutionary conservation of the TKRP and TK signaling systems, while highlighting the intricacies of receptor regulation through alternative splicing and differential desensitization mechanisms.

Analytical Model of Optical-Field-Driven Subcycle Electron Tunneling Pulses from Two-Dimensional Materials.

We develop analytical models of optical-field-driven electron tunneling from the edge and surface of free-standing two-dimensional (2D) materials. We discover a universal scaling between the tunneling current density (J) and the electric field near the barrier (F): In(J/|F|ß) ∝ 1/|F| with ß values of 3/2 and 1 for edge emission and vertical surface emission, respectively. At ultrahigh values of F, the current density exhibits an unexpected high-field saturation effect due to the reduced dimensionality of the 2D material, which is absent in the traditional bulk material. Our calculation reveals the dc bias as an efficient method for modulating the optical-field tunneling subcycle emission characteristics. Importantly, our model is in excellent agreement with a recent experiment on graphene. Our results offer a useful framework for understanding optical-field tunneling emission from 2D materials, which are helpful for the development of optoelectronics and emerging petahertz vacuum nanoelectronics.

Unlocking a Fast Track for Magnesium Migration in Cu1.8S1-xSex via Anion-Tuning Chemistry.

Rechargeable magnesium batteries (rMBs) are promising candidates for next-generation batteries in which sulfides are widely used as cathode materials. The slow kinetics, low redox reversibility, and poor magnesium storage stability induced by the large Coulombic resistance and ionic polarization of Mg2+ ions have obstructed the development of high-performance rMBs. Herein, a Cu1.8S1-xSex cathode material with a two-dimensional sheet structure has been prepared by an anion-tuning strategy, achieving improved magnesium storage capacity and cycling stability. Element-specific synchrotron radiation analysis is evidence that selenium incorporation has indeed changed the chemical state of Cu species. Density functional theory calculations combined with kinetics analysis reveal that the anionic substitution endows the Cu1.8S1-xSex electrode with favorable charge-transfer kinetics and low ion diffusion barrier. The principal magnesium storage mechanisms and structural evolution process have been revealed in details based on a series of ex situ investigations. Our findings provide an effective heteroatom-tuning tactic of optimizing electrode structure toward advanced energy storage devices.

Construction of V2O5@MXene Cathodes toward a High Specific Capacity Aqueous Aluminum-Ion Battery.

Aqueous aluminum-ion batteries (AAIBs) are considered a strong candidate for the new generation of energy storage devices. The lack of suitable cathode materials has been a bottleneck factor hindering the future development of AAIBs. In this work, we design and construct a highly effective cathode with dual morphologies. Two-dimensional (2D) layered MXene materials possessed good conductivity and hydrophilicity, which are used as the substrates to deposit rod-shaped vanadium oxides (V2O5) to form a three-dimensional (3D) cathode. The cathode design provides a strong boost for the rapid electrochemical activities of rod-shaped V2O5 by embedding/extracting both protons (H+) and aluminum-ion (Al3+). As a result, the V2O5@MXene cathode based AAIB delivers an ultrahigh initial specific capacity of 626 mAh/g at 0.1 A/g with a stable cycle performance up to 100 cycles. This work is a breakthrough for the development of cathode materials for AAIBs.

Olink Profiling of Aqueous Humor Identifies Novel Biomarkers for Wet Age-Related Macular Degeneration.

Metabolic dysfunction is recognized as a contributing factor in the pathogenesis of wet age-related macular degeneration (wAMD). However, the specific metabolism-related proteins implicated in wAMD remain elusive. In this study, we assessed the expression profiles of 92 metabolism-related proteins in aqueous humor (AH) samples obtained from 44 wAMD patients and 44 cataract control patients. Our findings revealed significant alterations in the expression of 60 metabolism-related proteins between the two groups. Notably, ANGPTL7 and METRNL displayed promising diagnostic potential for wAMD, as evidenced by area under the curve values of 0.88 and 0.85, respectively. Subsequent validation studies confirmed the upregulation of ANGPTL7 and METRNL in the AH of wAMD patients and in choroidal neovascularization (CNV) models. Functional assays revealed that increased ANGPTL7 and METRNL played a pro-angiogenic role in endothelial biology by promoting endothelial cell proliferation, migration, tube formation, and spouting in vitro. Moreover, in vivo studies revealed the pro-angiogenic effects of ANGPTL7 and METRNL in CNV formation. In conclusion, our findings highlight the association between elevated ANGPTL7 and METRNL levels and wAMD, suggesting their potential as novel predictive and diagnostic biomarkers for this condition. These results underscore the significance of ANGPTL7 and METRNL in the context of wAMD pathogenesis and offer new avenues for future research and therapeutic interventions.

Amentoflavone reverses epithelial-mesenchymal transition in hepatocellular carcinoma cells by targeting p53 signalling pathway axis.

Epithelial-mesenchymal transition (EMT) and its reversal process are important potential mechanisms in the development of HCC. Selaginella doederleinii Hieron is widely used in Traditional Chinese Medicine for the treatment of various tumours and Amentoflavone is its main active ingredient. This study investigates the mechanism of action of Amentoflavone on EMT in hepatocellular carcinoma from the perspective of bioinformatics and network pharmacology. Bioinformatics was used to screen Amentoflavone-regulated EMT genes that are closely related to the prognosis of HCC, and a molecular prediction model was established to assess the prognosis of HCC. The network pharmacology was used to predict the pathway axis regulated by Amentoflavone. Molecular docking of Amentoflavone with corresponding targets was performed. Detection and evaluation of the effects of Amentoflavone on cell proliferation, migration, invasion and apoptosis by CCK-8 kit, wound healing assay, Transwell assay and annexin V-FITC/propidium iodide staining. Eventually three core genes were screened, inculding NR1I2, CDK1 and CHEK1. A total of 590 GO enrichment entries were obtained, and five enrichment results were obtained by KEGG pathway analysis. Genes were mainly enriched in the p53 signalling pathway. The outcomes derived from both the wound healing assay and Transwell assay demonstrated significant inhibition of migration and invasion in HCC cells upon exposure to different concentrations of Amentoflavone. The results of Annexin V-FITC/PI staining assay showed that different concentrations of Amentoflavone induces apoptosis in HCC cells. This study revealed that the mechanism of Amentoflavone reverses EMT in hepatocellular carcinoma, possibly by inhibiting the expression of core genes and blocking the p53 signalling pathway axis to inhibit the migration and invasion of HCC cells.

The novel TERF2::PDGFRB fusion gene enhances tumorigenesis via PDGFRB/STAT5 signalling pathways and sensitivity to TKI in ph-like ALL.

Patients with Philadelphia chromosome-like acute lymphoblastic leukaemia (Ph-like ALL) often face a grim prognosis, with PDGFRB gene fusions being commonly detected in this subgroup. Our study has unveiled a newfound fusion gene, TERF2::PDGFRB, and we have found that patients carrying this fusion gene exhibit sensitivity to dasatinib. Ba/F3 cells harbouring the TERF2::PDGFRB fusion display IL-3-independent cell proliferation through activation of the p-PDGFRB and p-STAT5 signalling pathways. These cells exhibit reduced apoptosis and demonstrate sensitivity to imatinib in vitro. When transfused into mice, Ba/F3 cells with the TERF2::PDGFRB fusion gene induce tumorigenesis and a shortened lifespan in cell-derived graft models, but this outcome can be improved with imatinib treatment. In summary, we have identified the novel TERF2::PDGFRB fusion gene, which exhibits oncogenic potential both in vitro and in vivo, making it a potential therapeutic target for tyrosine kinase inhibitors (TKIs).

SIRT2 regulates high mobility group protein B1 nucleoplasmic shuttle and degradation via deacetylation in microglia.

High mobility group protein B1 (HMGB1) acts as a pathogenic inflammatory response to mediate ranges of conditions such as epilepsy, septic shock, ischemia, traumatic brain injury, Parkinson's disease, Alzheimer's disease and mass spectrometry. HMGB1 promotes inflammation during sterile and infectious damage and plays a crucial role in disease development. Mobilization from the nucleus to the cytoplasm is the first important step in the release of HMGB1 from activated immune cells. Here, we demonstrated that Sirtuin 2 (SIRT2) physically interacts with and deacetylates HMGB1 at 43 lysine residue at nuclear localization signal locations, strengthening its interaction with HMGB1 and causing HMGB1 to be localized in the cytoplasm. These discoveries are the first to shed light on the SIRT2 nucleoplasmic shuttle, which influences HMGB1 and its degradation, hence revealing novel therapeutic targets and avenues for neuroinflammation treatment.

Adverse Skeletal Muscle Adaptations in Individuals Born Preterm-A Comprehensive Review.

Infants born preterm face an increased risk of deleterious effects on lung and brain health that can significantly alter long-term function and quality of life and even lead to death. Moreover, preterm birth is also associated with a heightened risk of diabetes and obesity later in life, leading to an increased risk of all-cause mortality in young adults born prematurely. While these preterm-birth-related conditions have been well characterized, less is known about the long-term effects of preterm birth on skeletal muscle health and, specifically, an individual's skeletal muscle hypertrophic potential later in life. In this review, we discuss how a confluence of potentially interrelated and self-perpetuating elements associated with preterm birth might converge on anabolic and catabolic pathways to ultimately blunt skeletal muscle hypertrophy, identifying critical areas for future research.

Associations of serum uric acid variability with neuroimaging metrics and cognitive decline: a population-based cohort study.

BACKGROUND: The relationship between variation in serum uric acid (SUA) levels and brain health is largely unknown. This study aimed to examine the associations of long-term variability in SUA levels with neuroimaging metrics and cognitive function. METHODS: This study recruited 1111 participants aged 25-83 years from a multicenter, community-based cohort study. The SUA concentrations were measured every two years from 2006 to 2018. We measured the intraindividual SUA variability, including the direction and magnitude of change by calculating the slope value. The associations of SUA variability with neuroimaging markers (brain macrostructural volume, microstructural integrity, white matter hyperintensity, and the presence of cerebral small vessel disease) and cognitive function were examined using generalized linear models. Mediation analyses were performed to assess whether neuroimaging markers mediate the relationship between SUA variation and cognitive function. RESULTS: Compared with the stable group, subjects with increased or decreased SUA levels were all featured by smaller brain white matter volume (beta = - 0.25, 95% confidence interval [CI] - 0.39 to - 0.11 and beta = - 0.15, 95% CI - 0.29 to - 0.02). Participants with progressively increased SUA exhibited widespread disrupted microstructural integrity, featured by lower global fractional anisotropy (beta = - 0.24, 95% CI - 0.38 to - 0.10), higher mean diffusivity (beta = 0.16, 95% CI 0.04 to 0.28) and radial diffusivity (beta = 0.19, 95% CI 0.06 to 0.31). Elevated SUA was also associated with cognitive decline (beta = - 0.18, 95% CI - 0.32 to - 0.04). White matter atrophy and impaired brain microstructural integrity mediated the impact of SUA increase on cognitive decline. CONCLUSIONS: It is the magnitude of SUA variation rather than the direction that plays a critical negative role in brain health, especially for participants with hyperuricemia. Smaller brain white matter volume and impaired microstructural integrity mediate the relationship between increased SUA level and cognitive function decline. Long-term stability of SUA level is recommended for maintaining brain health and preventing cognitive decline.

α-MnO2 Cathode with Oxygen Vacancies Accelerated Affinity Electrolyte for Dual-Ion Co-Encapsulated Aqueous Aluminum Ion Batteries.

Aluminum batteries (ABs) are identified as one of the most promising candidates for the next generation of large-scale energy storage elements because of their efficient three-electron reaction. Compared to ionic electrolytes, aqueous aluminum-ion batteries (AAIBs) are considered safer, less costly, and more environmentally friendly. However, considerable cycling performance is a key issue limiting the development of AAIBs. Stable, efficient, and electrolyte-friendly cathodes are most desirable for AAIBs. Herein, a rod-shaped defect-rich α-MnO2 is designed as a cathode, which is capable to deliver high performance with stable cycling for 180 cycles at 500 mA g-1 and maintains a discharge specific capacity of ≈100 mAh g-1. In addition, the infiltrability simulation is effectively utilized to corroborate the rapid electrochemical reaction brought about by the defective mechanism. With the formation of oxygen vacancies, the dual embedding of protons and metal ions is activated. This work provides a brand-new design for the development and characterization of cathodes for AAIBs.

Heterostructures Assembled from Bi2O2CO3 and MXene for Boosted Potassium-Ion Storage by Arousing the Built-in Electric Field.

Bismuth-based materials have been recognized as the appealing anodes for potassium-ion batteries (PIBs) due to their high theoretical capacity. However, the kinetics sluggishness and capacity decline induced by the structure distortion predominately retard their further development. Here, a heterostructure of polyaniline intercalated Bi2O2CO3/MXene (BOC-PA/MXene) hybrids is reported via simple self-assembly strategy. The ingenious design of heterointerface-rich architecture motivates significantly the interior self-built-in electric field (IEF) and high-density electron flow, thus accelerating the charge transfer and boosting ion diffusion. As a result, the hybrids realize a high reversible specific capacity, satisfying rate capability as well as long-term cycling stability. The in/ex situ characterizations further elucidate the stepwise intercalation-conversion-alloying reaction mechanism of BOC-PA/MXene. More encouragingly, the full cell investigation further highlights its competitive merits for practical application in further PIBs. The present work not only opens the way to the design of other electrodes with an appropriate working mechanism but also offers inspiration for built-in electric-field engineering toward high-performance energy storage devices.

Rational Construction of 3D Self-Supported MOF-Derived Cobalt Phosphide-Based Hollow Nanowall Arrays for Efficient Overall Water Splitting At large Current Density.

Developing efficient nonprecious bifunctional electrocatalysts for hydrogen and oxygen evolution reactions (HER and OER) in the same electrolyte with a low overpotential and large current density presents an appealing yet challenging goal for large-scale water electrolysis. Herein, a unique 3D self-branched hierarchical nanostructure composed of ultra-small cobalt phosphide (CoP) nanoparticles embedded into N, P-codoped carbon nanotubes knitted hollow nanowall arrays (CoPʘNPCNTs HNWAs) on carbon textiles (CTs) through a carbonization-phosphatization process is presented. Benefiting from the uniform protrusion distributions of CoP nanoparticles, the optimum CoPʘNPCNTs HNWAs composites with high abundant porosity exhibit superior electrocatalytic activity and excellent stability for OER in alkaline conditions, as well as for HER in both acidic and alkaline electrolytes, even under large current densities. Furthermore, the assembled CoPʘNPCNTs/CTs||CoPʘNPCNTs/CTs electrolyzer demonstrates exceptional performance, requiring an ultralow cell voltage of 1.50 V to deliver the current density of 10 mA cm-2 for overall water splitting (OWS) with favorable stability, even achieving a large current density of 200 mA cm-2 at a low cell voltage of 1.78 V. Density functional theory (DFT) calculation further reveals that all the C atoms between N and P atoms in CoPʘNPCNTs/CTs act as the most efficient active sites, significantly enhancing the electrocatalytic properties. This strategy, utilizing 2D MOF arrays as a structural and compositional material to create multifunctional composites/hybrids, opens new avenues for the exploration of highly efficient and robust non-noble-metal catalysts for energy-conversion reactions.

Robust and Corrosion-Resistant Overall Water Splitting Electrode Enabled by Additive Manufacturing.

Electrolysis of water has emerged as a prominent area of research in recent years. As a promising catalyst support, copper foam is widely investigated for electrolytic water, yet the insufficient mechanical strength and corrosion resistance render it less suitable for harsh working conditions. To exploit high-performance catalyst supports, various metal supports are comprehensively evaluated, and Ti6Al4V (Ti64) support exhibited outstanding compression and corrosion resistance. With this in mind, a 3D porous Ti64 catalyst support is fabricated using the selective laser sintering (SLM) 3D printing technology, and a conductive layer of nickel (Ni) is coated to increase the electrical conductivity and facilitate the deposition of catalysts. Subsequently, Co0.8Ni0.2(CO3)0.5(OH)·0.11H2O (CoNiCH) nanoneedles are deposited. The resulting porous Ti64/Ni/CoNiCH electrode displayed an impressive performance in the oxygen evolution reaction (OER) and reached 30 mA cm-2 at an overpotential of only 200 mV. Remarkably, even after being compressed at 15.04 MPa, no obvious structural deformation is observed, and the attenuation of its catalytic efficiency is negligible. Based on the computational analysis, the CoNiCH catalyst demonstrated superior catalytic activity at the Ni site in comparison to the Co site. Furthermore, the electrode reached 30 mA cm-2 at 1.75 V in full water splitting conditions and showed no significant performance degradation even after 60 h of continuous operation. This study presents an innovative approach to robust and corrosion-resistant catalyst design.

Dual anti-angiogenic and anti-inflammatory action of tRNA-Cys-5-0007 in ocular vascular disease.

BACKGROUND: Intravitreal injections of angiogenesis inhibitors have proved efficacious in the majority of patients with ocular angiogenesis. However, one-fourth of all treated patients fail to derive benefits from intravitreal injections. tRNA-derived small RNA (tsRNA) emerges as a crucial class of non-coding RNA molecules, orchestrating key roles in the progression of human diseases by modulating multiple targets. Through our prior sequencing analyses and bioinformatics predictions, tRNA-Cys-5-0007 has shown as a potential regulator of ocular angiogenesis. This study endeavors to elucidate the precise role of tRNA-Cys-5-0007 in the context of ocular angiogenesis. METHODS: Quantitative reverse transcription PCR (qRT-PCR) assays were employed to detect tRNA-Cys-5-0007expression. EdU assays, sprouting assays, transwell assays, and Matrigel assays were conducted to elucidate the involvement of tRNA-Cys-5-0007 in endothelial angiogenic effects. STZ-induced diabetic model, OIR model, and laser-induced CNV model were utilized to replicate the pivotal features of ocular vascular diseases and evaluate the influence of tRNA-Cys-5-0007 on ocular angiogenesis and inflammatory responses. Bioinformatics analysis, luciferase activity assays, RNA pull-down assays, and in vitro studies were employed to elucidate the anti-angiogenic mechanism of tRNA-Cys-5-0007. Exosomal formulation was employed to enhance the synergistic anti-angiogenic and anti-inflammatory efficacy of tRNA-Cys-5-0007. RESULTS: tRNA-Cys-5-0007 expression was down-regulated under angiogenic conditions. Conversely, tRNA-Cys-5-0007 overexpression exhibited anti-angiogenic effects in retinal endothelial cells, as evidenced by reduced proliferation, sprouting, migration, and tube formation abilities. In diabetic, laser-induced CNV, and OIR models, tRNA-Cys-5-0007 overexpression led to decreased ocular vessel leakage, inhibited angiogenesis, and reduced ocular inflammation. Mechanistically, these effects were attributed to the targeting of vascular endothelial growth factor A (VEGFA) and TGF-ß1 by tRNA-Cys-5-0007. The utilization of an exosomal formulation further potentiated the synergistic anti-angiogenic and anti-inflammatory efficacy of tRNA-Cys-5-0007. CONCLUSIONS: Concurrent targeting of tRNA-Cys-5-0007 for anti-angiogenic and anti-inflammatory therapy holds promise for enhancing the effectiveness of current anti-angiogenic therapy.

The P2 protein of wheat yellow mosaic virus acts as a viral suppressor of RNA silencing in Nicotiana benthamiana to facilitate virus infection.

Wheat yellow mosaic virus (WYMV) causes severe viral wheat disease in Asia. The WYMV P1 protein encoded by RNA2 has viral suppressor of RNA silencing (VSR) activity to facilitate virus infection, however, VSR activity has not been identified for P2 protein encoded by RNA2. In this study, P2 protein exhibited strong VSR activity in Nicotiana benthamiana at the four-leaf stage, and point mutants P70A and G230A lost VSR activity. Protein P2 interacted with calmodulin (CaM) protein, a gene-silencing associated protein, while point mutants P70A and G230A did not interact with it. Competitive bimolecular fluorescence complementation and competitive co-immunoprecipitation experiments showed that P2 interfered with the interaction between CaM and calmodulin-binding transcription activator 3 (CAMTA3), but the point mutants P70A and G230A could not. Mechanical inoculation of wheat with in vitro transcripts of WYMV infectious cDNA clone further confirmed that VSR-deficient mutants P70A and G230A decreased WYMV infection in wheat plants compared with the wild type. In addition, RNA silencing, temperature, ubiquitination and autophagy had significant effects on accumulation of P2 protein in N. benthamiana leaves. In conclusion, WYMV P2 plays a VSR role in N. benthamiana and promotes virus infection by interfering with calmodulin-related antiviral RNAi defense.

Genetic and clinical characteristics of acute B-cell lymphoblastic leukemia with MEF2D fusions and report of two novel MEF2D rearrangements.

The MEF2D rearrangement is a recurrent chromosomal abnormality detected in approximately 2.4-5.3% of patients with acute B-cell lymphoblastic leukemia (B-ALL). Currently, MEF2D-rearranged B-ALL is not classified as an independent subtype in the WHO classification. Consequently, the clinical significance of MEF2D rearrangement in B-ALL remains largely unexplored. In this study, we retrospectively screened 260 B-ALL patients with RNA sequencing data collected between November 2018 and December 2022. Among these, 10 patients were identified with MEF2D rearrangements (4 with MEF2D::HNRNPUL1, 3 with MEF2D::BCL9, 1 with MEF2D::ARID1B, 1 with MEF2D::DAZAP1 and 1 with MEF2D::HNRNPM). Notably, HNRNPM and ARID1B are reported as MEF2D fusion partners for the first time. The patient with the MEF2D::HNRNPM fusion was resistant to chemotherapy and chimeric antigen receptor T-cell therapy and relapsed early after allogenic stem cell transplantation. The patient with MEF2D::ARID1B experienced early extramedullary relapse after diagnosis. All 10 patients achieved complete remission after induction chemotherapy. However, 9/10 (90%) of whom experienced relapse. Three of the 9 patients relapsed with aberrant expression of myeloid antigens. The median overall survival of these patients was only 11 months. This small cohort showed a high incidence of early relapse and short survival in patients with MEF2D rearrangements.

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.

Outcomes of Breast-Conserving Therapy in Patients With Inflammatory Breast Cancer: A Meta-Analysis.

INTRODUCTION: Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer. Currently, patients who respond to neoadjuvant chemotherapy (NAC) are treated with mastectomy and axillary lymph node dissection. This study aimed to synthesize real-world data to evaluate the feasibility of breast-conserving therapy (BCT), sentinel lymph node (SLN), and sentinel lymph node biopsy (SLNB) for patients with IBC who respond to NAC. METHODS: PubMed, Embase, and Cochrane Library databases were searched for relevant articles. Clinical studies that compared mastectomy with BCT for IBC treatment were reviewed. The primary outcomes were local recurrence rate and 5-y survival rate in patients with IBC who responded to NAC. Furthermore, the SLN detection rate and false-negative rate (FNR) for SLNB were also evaluated. RESULTS: In the final analysis, 17 studies were included. The pooled estimates of the local recurrence rate for mastectomy and no surgical intervention were 18.6% and 15.9%, respectively (P = 0.956). Five-y survival was similar for mastectomy, partial mastectomy, and no surgical intervention (45.8%, 57.1%, and 39.4%, respectively). The pooled estimates of the SLN detection rate and FNR for SLNB were 81.9% and 21.8%, respectively. CONCLUSIONS: Among patients with IBC who respond to NAC, the local recurrence and 5-y survival rates in those undergoing BCT are noninferior to the rates in those undergoing mastectomy; therefore, BCT could be a feasible option for surgical management. However, a poor SLN detection rate and a high FNR were found in patients undergoing SLNB. Further large-scale clinical studies are required to confirm our findings.

Copper-Catalyzed Multicomponent Coupling Reaction of Primary Aromatic Amines, Rongalite, and Alkynes: Access to N-Aryl Propargylamines.

In this work, a practical copper-catalyzed multicomponent coupling reaction of primary aromatic amines, rongalite, and alkynes for the direct synthesis of N-aryl propargylamines has been developed. This method could overcome the substrate limitation in A3 coupling reactions of primary aromatic amines, formaldehyde, and alkynes. Mechanistic studies revealed that rongalite acts as not only the active C1 unit but also the accelerator to activate the in situ-generated N-arylmethanimines for the coupling reaction with alkynes. This coupling reaction is highly efficient and features a broad substrate scope, as well as utility with scale-up synthesis and converting the corresponding product N-aryl propargylamines into useful heterocyclic skeletons.