EGCG-vanadium nanomedicine with neutral pH Fenton reaction activity inhibits heat shock proteins for enhanced photothermal/chemodynamic therapy.

A burgeoning interest has recently focused on the development of nanomedicine to integrate noninvasive photothermal therapy (PTT) and chemodynamic therapy (CDT) for synergistic tumor treatments, owing to PTT's amplification effect on CDT. However, challenges emerge as hyperthermia often induces an unwarranted overexpression of cytoprotective heat shock proteins (HSPs), thereby curtailing PTT efficacy. Additionally, the nearly neutral tumor intracellular pH (pHi ≈ 7.2) that handicaps the Fenton reaction poses a leading limitation to CDT. Addressing these hurdles, we introduce EVP, a nanomedicine developed through the straightforward assembly of epigallocatechin gallate (EGCG), vanadium sulfate (VOSO4), and Pluronic F-127 (PF127). EVP comprehensively downregulates overexpressed HSPs (HSP 60, 70, 90) through the collaborative action of EGCG and vanadyl (VO2+). Moreover, the tumor intracellular pH-processed Fenton-like reaction by VO2+ ensures highly efficient hydroxyl radicals (OH) production in cytosols, overcoming the stringent acidity requirement for CDT. Additionally, the hyperthermia induced by PTT augments OH production, further enhancing CDT efficacy. In vitro and in vivo experiments validate EVP's excellent biocompatibility and potent tumor inhibition, highlighting its substantial potential in tumor therapy.

Exonuclease editor promotes precision of gene editing in mammalian cells.

BACKGROUND: Many efforts have been made to improve the precision of Cas9-mediated gene editing through increasing knock-in efficiency and decreasing byproducts, which proved to be challenging. RESULTS: Here, we have developed a human exonuclease 1-based genome-editing tool, referred to as exonuclease editor. When compared to Cas9, the exonuclease editor gave rise to increased HDR efficiency, reduced NHEJ repair frequency, and significantly elevated HDR/indel ratio. Robust gene editing precision of exonuclease editor was even superior to the fusion of Cas9 with E1B or DN1S, two previously reported precision-enhancing domains. Notably, exonuclease editor inhibited NHEJ at double strand breaks locally rather than globally, reducing indel frequency without compromising genome integrity. The replacement of Cas9 with single-strand DNA break-creating Cas9 nickase further increased the HDR/indel ratio by 453-fold than the original Cas9. In addition, exonuclease editor resulted in high microhomology-mediated end joining efficiency, allowing accurate and flexible deletion of targeted sequences with extended lengths with the aid of paired sgRNAs. Exonuclease editor was further used for correction of DMD patient-derived induced pluripotent stem cells, where 30.0% of colonies were repaired by HDR versus 11.1% in the control. CONCLUSIONS: Therefore, the exonuclease editor system provides a versatile and safe genome editing tool with high precision and holds promise for therapeutic gene correction.

Screening Methods for Cervical Cancer.

Cervical cancer seriously affects the health of women worldwide. Persistent infection of high-risk HPV (Human Papilloma Virus) can lead to cervical cancer. There is a great need for timely and efficient screening methods for cervical cancer. The current screening methods for cervical cancer are mainly based on cervical cytology and HPV testing. Cervical  cytology is made of Pap smear and liquid-based cytology, while HPV testing is based on immunological and nucleic acid level detection methods.  This review introduces cervical cancer screening methods based on cytology and human papillomavirus testing in detail. The advantages and limitations of the screening methods are also summarized and compared.

Surgical outcomes of robotic thyroidectomy for thyroid tumors over 4 cm via the bilateral axillo-breast approach.

The study investigated the feasibility of robotic bilateral axillo-breast approach (BABA) thyroidectomy for patients with thyroid tumors larger than 4 cm. BABA thyroidectomy has previously shown safety and effectiveness for thyroid surgeries but lacked extensive data on its application to larger tumors. Between October 2008 and August 2022, there were 74 patients underwent robotic BABA thyroidectomy due to thyroid nodules exceeding 4 cm in size. The mean patient age was 40.3 years. Fine needle aspiration results classified the tumors as benign (50.0%), atypia of undetermined significance (27.0%), follicular neoplasm (16.2%), suspicious for malignancy/malignancy (5.4%), or lymphoma (1.4%). The average tumor size was 4.9 cm, with the majority (85.1%) undergoing thyroid lobectomy, and the rest (14.9%) receiving total thyroidectomy. The mean total operation time was 178.4 min for lobectomy and 207.3 min for total thyroidectomy. Transient vocal cord palsy (VCP) was found in 3 patients (4.1%), and there was no permanent VCP. Among patients who underwent total thyroidectomy, transient hypoparathyroidism was observed in three (27.2%), and permanent hypoparathyroidism was observed in one (9.1%). There were no cases of open conversion, tumor spillage, bleeding, flap injury, or tumor recurrence. In conclusion, robotic BABA thyroidectomy may be a safe treatment option for large-sized thyroid tumors that carries no significant increase in complication rates.

Intervention of hypertension by acupuncture-related therapies: A network meta-analysis.

BACKGROUND: The prevalence of essential hypertension contributed significantly to morbidity and mortality rates. Acupuncture-related therapies were commonly employed in hypertension treatment. Nevertheless, a lack of conclusive evidence left uncertainties regarding the optimal strategies for managing hypertensive populations. OBJECTIVES: Conduct a comprehensive systematic review to evaluate the existing clinical evidence about the effectiveness of acupuncture and moxibustion-related therapies in managing hypertension, by employing network meta-analysis techniques. METHODS: A comprehensive electronic search was conducted across n of databases. This search covered studies available up to October 2022. Randomized controlled trials assessing acupuncture and moxibustion-related therapies in managing hypertension based on traditional Chinese medicine were screened. Primary outcome measures included the antihypertensive effectiveness rate, variations in blood pressure and the incorporation of Traditional Chinese Medicine (TCM) syndrome manifestations. The review follows the guidelines outlined in the PRISMA statement. RESULTS: We identified a total of 24 trials with 1867 patients, which evaluated the efficacy of various acupuncture-related therapies for hypertension management. Network meta-analysis showed that moxibustion and auricular point sticking combined with medication therapy had the best effect in terms of antihypertensive effective rate (medication + moxibustion + auricular pressure vs. medication = 1.29 [1.09, 1.54]; sucra = 85.9, p < .05) and hypertension symptom improvement (medication + moxibustion + auricular pressure vs. medication = -1.55 [-2.98, -0.13]; sucra = 96.1, p < .05). Acupuncture combined with moxibustion combined with medication therapy had the best effect in reducing systolic pressure (medication + moxibustion + acupuncture vs. medication = -8.50 [-10.19, -6.80]; sucra = 100, p < .05) and diastolic blood pressure (medication + moxibustion + acupuncture versus medication = -4.72 [-6.71, -2.72]; sucra = 99.71, p < 0.05). CONCLUSIONS: Network meta-analysis suggested that the combined use of moxibustion and auricular point application in conjunction with drug therapy showed the highest likelihood of being the most effective treatment in terms of antihypertensive efficiency rates and improvement in hypertension symptoms. Furthermore, the combination of acupuncture and moxibustion alongside drug treatment emerged as the most promising approach for reducing systolic blood pressure and diastolic blood pressure. Limited by the methodological quality and quantity of the included studies, the results need to be interpreted with caution. It is necessary to conduct more high-quality randomized controlled trials of acupuncture-related therapies for the adjuvant treatment of hypertension in the future. IMPLICATIONS FOR PRACTICE: Clinicians can use acupuncture-related therapies to inform their treatment decisions and potentially incorporate acupuncture-related therapies into their hypertension management protocols.

A hydrogel-functionalized silver nanocluster for bacterial-infected wound healing.

The ever-growing challenges of traditional antibiotic therapy and chronic wound healing have created a hot topic for the development and application of new antimicrobial agents. Silver nanoclusters (Ag NCs) with ultrasmall sizes (<2 nm) and antibacterial effects are promising candidates for next-generation antibiotics, particularly against multi-drug resistant strains. However, the biosafety in the clinical application of Ag NCs remains suboptimal despite some existing studies of Ag NCs for biomedical applications. Considering this, an ultrasmall Ag NC with excellent water solubility was synthesized by a two-phase ligand-exchange method, which exhibits broad-spectrum antibacterial performance. The minimum inhibitory concentrations of Ag NCs against MRSA, S. aureus, P. aeruginosa and E. coli were evaluated as 50, 80, 5 and 5 µg mL-1, respectively. Furthermore, a carbomer hydrogel was prepared to be incorporated into the Ag NCs for achieving excellent biocompatibility and biosafety. In vitro experiments demonstrate that the Ag NC-gel exhibits good antibacterial properties with lower cytotoxicity. Finally, in vivo experiments suggest that this ultrasmall Ag NC functionalized with the hydrogel can serve as an effective and safe antimicrobial agent to aid in wound healing.

Determination of twelve neonicotinoid pesticides in chili using an improved QuEChERS method with UPLC-Q-TOF/MS.

In this study, a QuEChERS method based on citrate was developed and utilized for the analysis of twelve neonicotinoid pesticides in fresh red chilies, fresh green chilies, and dried chilies, coupled with ultra-high performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-Q-TOF/MS). In the sample preparation, acetonitrile containing 1% formic acid was used as the extraction solvent. Anhydrous sodium sulfate replaced the traditional anhydrous magnesium sulfate for water removal, effectively eliminating the issues of salt caking. Graphitized carbon black, octadecyl silica, and primary secondary amine were used as cleaning agents. The method showed good sensitivity, with the limits of quantification below 0.03 mg/kg for fresh chilies and below 0.15 mg/kg for dried chilies. Values of matrix effects ranged from -19.5% to 8.4%, and the recovery was 86.9% - 105.2%. The analytical method provided an effective tool for the high throughput detection of neonicotinoid pesticide residues in multiple chili matrices.

Heteropolyacid promoted lignin-MOF derived spherical catalyst for catalytic hydrogen transfer of 5-hydroxymethylfurfural.

Catalytic conversion of biomass-derived value-added chemicals was of great significance for the utilization of renewable biomass resources to instead of fossil chemicals. Biomass-derived lignin was regarded as an important support and 5-hydroxymethylfurfural (HMF) was a vital platform chemical derived from cellulose. Herein, a series of lignin-MOF hybrid catalysts were prepared and modified with different heteropolyacids (HPAs), which were then successfully introduced into the selective conversion of HMF to 5-hydroxymethylfurfuryl alcohol (MFA). The effect of different HPA, calcination temperature, etc. were all studied, and all catalysts were well characterized. It was confirmed that silicotungstic acid modified catalyst (Ni3Co-MOF-LS@HSiW) exhibited the best catalytic performance, while the highest conversion of HMF was up to 100%, with the best MFA yield of 86.5%. The finding in this study could provide novel insights for the utilization of lignin and preparation of value-added biomass-derived chemicals.

Revisiting the pathophysiology of intracranial hemorrhage in fetuses with Chiari II malformation - novel imaging biomarkers of disease severity?

BACKGROUND AND PURPOSE: Intracranial hemorrhage (ICH) has emerged as a notable concern in Chiari II malformation (CM II), yet its origins and clinical implications remain elusive. This study aims to validate the in-utero prevalence of ICH in CM II and investigate contributing factors, and visualize the findings in a network format. MATERIALS AND METHODS: A single-center retrospective review of fetal MRI scans obtained in fetuses with CM II presenting (January 2007 to December 2022) was performed for ICH utilizing EPI-T2* blood-sensitive sequence. Fetuses with aqueduct stenosis (AS) were included as a control group. The incidence of ICH and corresponding gestational ages were compared between CM II and AS cases, and morphometric measurements (inner/outer CSF spaces, posterior fossa, venous structure) were compared among the four 1:1 age-matched groups: CM II+ICH, CM II-ICH, AS+ICH, and AS-ICH. Additionally, a co-occurrence network was constructed to visualize associations between phenotypic features in ICH cases. RESULTS: A total of 101 fetuses with CM II and 90 controls with AS at a median gestational age of 24.4 weeks and 22.8 weeks (P=.138) were included. Prevalence of ICH in fetuses with CM II was higher compared to the AS cases (28.7% vs 18.9%, P=.023), accompanied by congested veins (deep vein congestion mainly in young fetuses, and cortical veins may also be affected in older fetuses). ICH was notably correlated with specific anatomical features, essentially characterized by reduced outer cerebrospinal fluid spaces and clivus-supraocciput angle. The co-occurrence network analysis reveals complex connections including bony defects, small posterior fossa dimensions, vermis ectopia, reduced CSF spaces as well as venous congestion and venous sinus stenosis as pivotal components within the network. CONCLUSIONS: The high prevalence of ICH - detected by fetal MRI -among fetuses with CM emphasizes the pathophysiological importance of venous congestion, ICH, and vasogenic edema. As indicators of disease severity, these features may serve as helpful additional imaging biomarkers for the identification of potential candidates for fetal surgery.ABBREVIATIONS: CM II＝Chiari type II malformation; AS＝aqueduct stenosis; ICH ＝Intracranial hemorrhage.

Machine learning and deep learning to identifying subarachnoid haemorrhage macrophage-associated biomarkers by bulk and single-cell sequencing.

We investigated subarachnoid haemorrhage (SAH) macrophage subpopulations and identified relevant key genes for improving diagnostic and therapeutic strategies. SAH rat models were established, and brain tissue samples underwent single-cell transcriptome sequencing and bulk RNA-seq. Using single-cell data, distinct macrophage subpopulations, including a unique SAH subset, were identified. The hdWGCNA method revealed 160 key macrophage-related genes. Univariate analysis and lasso regression selected 10 genes for constructing a diagnostic model. Machine learning algorithms facilitated model development. Cellular infiltration was assessed using the MCPcounter algorithm, and a heatmap integrated cell abundance and gene expression. A 3 × 3 convolutional neural network created an additional diagnostic model, while molecular docking identified potential drugs. The diagnostic model based on the 10 selected genes achieved excellent performance, with an AUC of 1 in both training and validation datasets. The heatmap, combining cell abundance and gene expression, provided insights into SAH cellular composition. The convolutional neural network model exhibited a sensitivity and specificity of 1 in both datasets. Additionally, CD14, GPNMB, SPP1 and PRDX5 were specifically expressed in SAH-associated macrophages, highlighting its potential as a therapeutic target. Network pharmacology analysis identified some targeting drugs for SAH treatment. Our study characterised SAH macrophage subpopulations and identified key associated genes. We developed a robust diagnostic model and recognised CD14, GPNMB, SPP1 and PRDX5 as potential therapeutic targets. Further experiments and clinical investigations are needed to validate these findings and explore the clinical implications of targets in SAH treatment.

Nature Products Chlorophyll Derivatives for NIR-II Fluorescence Bioimaging and Plant-imaging.

The second near-infrared window (NIR-II, 1000 - 1700 nm) fluorescence imaging has attracted significant attention in research fields because of its unique advantages compared with conventional optical windows (400 - 900 nm). A variety of NIR-II fluorophores have been actively studied because they serve as a key component of fluorescence imaging. Among them, organic small molecule NIR-II fluorophores display outstanding imaging performance and many advantages, but types of small molecule NIR-II fluorophores with high biocompatibility are still quite limited. Novel molecular scaffolds based NIR-II dyes are highly desired. Herein, we hypothesized that chlorophyll is a new promising molecular platform for discovery NIR-II fluorophores. Thus, seven derivatives of derivatives were selected to characterize their optical properties. Interestingly, six chlorophyll derivatives displayed NIR-II fluorescence imaging capability. This characteristic allowed the successful NIR-II imaging of green leaves of various plants. Furthermore, most of these fluorophores showed capacity to monitor viscosity change because of their sensitive for viscosity. For demonstration of its biomedical applications, these probes were successfully used for NIR-II fluorescence-guided surgical resection of lymph nodes. In summary, chlorophylls are novel valuable tool molecules for NIR-II fluorescence imaging and have potential to expand their applications in biomedical field and plant science.

Assessment of the 2023 ACR/EULAR antiphospholipid syndrome classification criteria in a Chinese cohort: Impact on clinical practice.

OBJECTIVES: To evaluate the effectiveness of the 2023 ACR/EULAR criteria for antiphospholipid syndrome (APS) in a Chinese cohort, and compare them with the Sapporo and revised Sapporo criteria. METHODS: A cohort comprising 436 patients diagnosed with APS and 514 control subjects was enrolled, including 83 with seronegative APS and 86 classified as antiphospholipid antibody (aPL) carriers. We assessed IgG and IgM anticardiolipin antibodies (aCL) and anti-ß2-glycoprotein I (aß2GPI) antibodies using ELISA, along with a systematic collection of lupus anticoagulant data. Subsequently, we compared the sensitivity and specificity across the three classification criteria. RESULTS: The 2023 ACR/EULAR criteria exhibited improved specificity at 98 %, surpassing the revised Sapporo (90 %) and original Sapporo (91 %) criteria. However, this came with decreased sensitivity at 82 %, in contrast to higher sensitivities in the revised Sapporo (98 %) and Sapporo (91 %) criteria. Examining individual components sheds light on the scoring system's rationale within the new criteria. The inclusion of microvascular thrombosis, cardiac valve disease, and thrombocytopenia improved the identification of nine patients previously classified as "probable APS". Insufficient scoring in 78 previously diagnosed APS individuals was linked to traditional risk factor evaluations for thrombotic events, the emphasis on determining whether obstetric events are linked to severe preeclampsia (PEC) or placental insufficiency (PI), and the lower scores assigned to IgM aCL and/or aß2GPI antibody. Seronegative APS remained a challenge, as non-criteria aPL and other methods were not included. CONCLUSIONS: The new criteria presented notable advancements in specificity. This study provides detailed insights into the strengths and possible challenges of the 2023 ACR/EULAR criteria, enhancing our understanding of their impact on clinical practice.

Decreasing mitochondrial fission ameliorates HIF-1α-dependent pathological retinal angiogenesis.

Angiogenesis plays a critical role in many pathological processes, including irreversible blindness in eye diseases such as retinopathy of prematurity. Endothelial mitochondria are dynamic organelles that undergo constant fusion and fission and are critical signalling hubs that modulate angiogenesis by coordinating reactive oxygen species (ROS) production and calcium signalling and metabolism. In this study, we investigated the role of mitochondrial dynamics in pathological retinal angiogenesis. We showed that treatment with vascular endothelial growth factor (VEGF; 20 ng/ml) induced mitochondrial fission in HUVECs by promoting the phosphorylation of dynamin-related protein 1 (DRP1). DRP1 knockdown or pretreatment with the DRP1 inhibitor Mdivi-1 (5 µM) blocked VEGF-induced cell migration, proliferation, and tube formation in HUVECs. We demonstrated that VEGF treatment increased mitochondrial ROS production in HUVECs, which was necessary for HIF-1α-dependent glycolysis, as well as proliferation, migration, and tube formation, and the inhibition of mitochondrial fission prevented VEGF-induced mitochondrial ROS production. In an oxygen-induced retinopathy (OIR) mouse model, we found that active DRP1 was highly expressed in endothelial cells in neovascular tufts. The administration of Mdivi-1 (10 mg·kg-1·d-1, i.p.) for three days from postnatal day (P) 13 until P15 significantly alleviated pathological angiogenesis in the retina. Our results suggest that targeting mitochondrial fission may be a therapeutic strategy for proliferative retinopathies and other diseases that are dependent on pathological angiogenesis.

Synthetic Cells from Droplet-Based Microfluidics for Biosensing and Biomedical Applications.

Synthetic cells function as biological mimics of natural cells by mimicking salient features of cells such as metabolism, response to stimuli, gene expression, direct metabolism, and high stability. Droplet-based microfluidic technology presents the opportunity for encapsulating biological functional components in uni-lamellar liposome or polymer droplets. Verified by its success in the fabrication of synthetic cells, microfluidic technology is widely replacing conventional labor-intensive, expensive, and sophisticated techniques justified by its ability to miniaturize and perform batch production operations. In this review, an overview of recent research on the preparation of synthetic cells through droplet-based microfluidics is provided. Different synthetic cells including lipid vesicles (liposome), polymer vesicles (polymersome), coacervate microdroplets, and colloidosomes, are systematically discussed. Efforts are then made to discuss the design of a variety of microfluidic chips for synthetic cell preparation since the combination of microfluidics with bottom-up synthetic biology allows for reproductive and tunable construction of batches of synthetic cell models from simple structures to higher hierarchical structures. The recent advances aimed at exploiting them in biosensors and other biomedical applications are then discussed. Finally, some perspectives on the challenges and future developments of synthetic cell research with microfluidics for biomimetic science and biomedical applications are provided.

M2 Tumor-Associated Macrophages-Derived Exosomal MALAT1 Promotes Glycolysis and Gastric Cancer Progression.

M2-polarized tumor-associated macrophages (M2 TAMs) promote cancer progression. Exosomes mediate cellular communication in the tumor microenvironment (TME). However, the roles of exosomes from M2 TAMs in gastric cancer progression are unclear. Herein, it is reported that M2 TAMs-derived exosomes induced aerobic glycolysis in gastric cancer cells and enhanced their proliferation, metastasis, and chemoresistance in a glycolysis-dependent manner. It is identified that MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) is enriched in M2 TAM exosomes and confirmed that MALAT1 transfer from M2 TAMs to gastric cancer cells via exosomes mediates this effect. Mechanistically, MALAT1 interacted with the δ-catenin protein and suppressed its ubiquitination and degradation by ß-TRCP. In addition, MALAT1 upregulated HIF-1α expression by acting as a sponge for miR-217-5p. The activation of ß-catenin and HIF-1α signaling pathways by M2 TAM exosomes collectively led to enhanced aerobic glycolysis in gastric cancer cells. Finally, a dual-targeted inhibition of MALAT1 in both gastric cancer cells and macrophages by exosome-mediated delivery of siRNA remarkably suppressed gastric cancer growth and improved chemosensitivity in mouse tumor models. Taken together, these results suggest that M2 TAMs-derived exosomes promote gastric cancer progression via MALAT1-mediated regulation of glycolysis. The findings offer a potential target for gastric cancer therapy.

Recent progress in radioactive seed implantation brachytherapy of non-small cell lung cancer: a narrative review.

Background and Objective: Brachytherapy, a new form of radiation therapy, has been used to treat lung cancer and consists of two main forms of treatment: endobronchial brachytherapy and radioactive seed implantation brachytherapy (RSI-BT), the latter of which is used to treat non-small cell lung cancer (NSCLC). The use of RSI-BT in the treatment of NSCLC at our centre has yielded some positive results. Methods: To more fully consider the context of this application, we conducted a search of PubMed from 2018 to March 5, 2023. The search included a combination of the MeSH terms: "brachytherapy" and "lung neoplasm". Key Content and Findings: The majority of NSCLC patients who received RSI-BT achieved positive benefits. Most patients had a progression-free survival (PFS) of between 12 and 18 months. Additionally, radioactive particle stent implantation as a specific RSI-BT has shown therapeutic potential in the treatment of malignant airway obstruction. With the application of new technologies, RSI-BT will become more precise, efficient and inexpensive. Conclusions: This review demonstrates that RSI-BT can be therapeutic in the treatment of both early and advanced NSCLC with manageable complications. There have also been reports on the combination of RSI-BT with other therapies, but more research is needed on the combination of RSI-BT with them.

Hyposalinity stress reduces mussel byssus secretion but does not cause detachment.

Environmental stressors such as salinity fluctuations can significantly impact the ecological dynamics of mussel beds. The present study evaluated the influence of hyposalinity stress on the detachment and survival of attached mussels by simulating a mussel farming model in a laboratory setting. Byssus production and mechanical properties of thread in response to varying salinity levels were assessed, and histological sections of the mussel foot were analyzed to identify the changes in the byssus secretory gland area. The results showed that hyposalinity stress (20 and 15 psu) led to a significant decrease in mussel byssus secretion, delayed initiation of new byssus production, and reduced plaque adhesion strength and breaking force of byssal threads compared to the control (30 psu) (p < 0.05). The complete suppression of byssal thread secretion in mussels under salinity conditions of 10 and 5 psu, leading to lethality, indicates the presence of a blockade in byssus secretion when mussels are subjected to significant physiological stressors. Histological analysis further demonstrated a decrease in the percentage of foot secretory gland areas in mussels exposed to low salinities. However, contrary to expectations, the study found that mussels did not exhibit marked detachment from ropes in response to the reduced salinity levels during one week of exposure. Hyposalinity stress exposure reduced the byssal secretion capacity and the mechanical properties of threads, which could be a cause for the detachment of suspension-cultured mussels. These results highlight the vulnerability of mussels to hyposalinity stress, which significantly affects their byssus mechanical performance.

Radial endobronchial ultrasound - guided bronchoscopy for the diagnosis of peripheral pulmonary lesions: A systematic review and meta-analysis of prospective trials.

Background: The diagnostic yield of radial endobronchial ultrasound (r-EBUS) for the diagnosis of peripheral pulmonary lesions (PPLs) varies between studies and is affected by multiple factors. We aimed to evaluate the efficacy and safety of r-EBUS, and to explore the factors influencing the diagnostic yield of r-EBUS in patients with PPLs. Methods: The PubMed, Web of Science, and EMBASE databases were searched to identify relevant studies that used r-EBUS for diagnosing PPLs from the date of inception to Dec 2022. Meta-analysis was conducted using Review Manager 5.4 and Stata 15.1. Results: An analysis of 46 studies with a total of 7252 PPLs was performed. The pooled diagnostic yield of r-EBUS was 73.4 % (95 % CI: 69.9%-76.7 %), with significant heterogeneity detected among studies (I2 = 90 %, P < 0.001). Further analysis demonstrated PPLs located in the middle or lower lobe, >2 cm in size, malignant in type, solid in appearance on computerized tomography (CT), present in bronchus sign, the within probe location, and the addition of rapid on-site evaluation (ROSE) were associated with increased diagnostic yield, whereas use of a guide sheath (GS), bronchoscopy type, and a multimodality approach failed to influence the outcome. The pooled incidence rates of overall complications, pneumothorax and moderate and severe bleeding were 3.1 % (95 % CI: 2.1%-4.3 %), 0.4 % (95 % CI: 0.1%-0.7 %) and 1.1 % (95 % CI: 0.5%-2.0 %), respectively. Conclusions: r-EBUS has an appreciable diagnostic yield and an excellent safety manifestation when used to deal with PPLs.

Redox Relay-Induced C-S Radical Cross-Coupling Strategy: Application in Nontraditional Site-Selective Thiocyanation of Quinoxalinones.

Oxidative cross-coupling is a powerful strategy to form C-heteroatom bonds. However, oxidative cross-coupling for constructing C-S bond is still a challenge due to sulfur overoxidation and poisoning transition-metal catalysts. Now, electrochemical redox relay using sulfur radicals formed in situ from inorganic sulfur source offers a solution to this problem. Herein, electrochemical redox relay-induced C-S radical cross-coupling of quinoxalinones and ammonium thiocyanate with bromine anion as mediator is presented. The electrochemical redox relay comprised initially the formation of sulfur radical via indirect electrochemical oxidation, simultaneous electrochemical reduction of the imine bond, electro-oxidation-triggered radical coupling involving dearomatization-rearomatization, and the reformation of the imine bond through anodic oxidation. Applying this strategy, various quinoxalinones bearing multifarious electron-deficient/-rich substituents at different positions were well compatible with moderate to excellent yields and good steric hindrance compatibility under constant current conditions in an undivided cell without transition-metal catalysts and additional redox reagents. Synthetic applications of this methodology were demonstrated through gram-scale preparation and follow-up transformation. Notably, such a unique strategy may offer new opportunities for the development of new quinoxalinone-core leads.