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Background: Bronchiectasis has high rates of hemoptysis and recurrent hemoptysis, which is inconsistent among various etiologies. Idiopathic bronchiectasis and post-tuberculous bronchiectasis are two important etiologies in China, but the differences in clinical features and risk factors of recurrent hemoptysis have not been elucidated. Methods: Patients hospitalized for idiopathic bronchiectasis or post-tuberculosis bronchiectasis were included. Patients were followed up for at least 24 months post-BAE. Demographic characteristics and clinical data were collected and analyzed between idiopathic bronchiectasis and post-tuberculosis bronchiectasis. Based on the outcomes of recurrent severe hemoptysis in patients with post-tuberculosis bronchiectasis, Cox regression models were used to identify risk factors for recurrence. Results: Among 417 patients including 352 idiopathic bronchiectasis and 65 post-tuberculous bronchiectasis, 209 (50.1%) were females. Compared with the idiopathic group, the proportion of patients with female (54.5% vs. 26.2%, p

Abstract Background Mammalian enabled (MENA) protein is a member of the enabled/vasodilator stimulated phosphoprotein (Ena/VASP) protein family, which regulates cytoplasmic actin network assembly. It plays a significant role in breast cancer invasion, migration, and resistance against targeted therapy and chemotherapy. However, its role in the efficacy of endocrine therapy for the hormone receptor-positive (HR+) breast cancer patients is not known. This study investigated the role of MENA in the resistance against tamoxifen therapy in patients with HR+ breast cancer and the underlying mechanisms. Methods MENA expression levels in the clinical HR+ breast cancer samples (n = 119) were estimated using immunohistochemistry (IHC) to determine its association with the clinicopathological features, tamoxifen resistance, and survival outcomes. Western blotting (WB) and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) analysis was performed to estimate the MENA protein and mRNA levels in the tamoxifen-sensitive and -resistant HR+ breast cancer cell lines. Furthermore, CCK8, colony formation, and the transwell invasion and migration assays were used to analyze the effects of MENA knockdown on the biological behavior and tamoxifen sensitivity of the HR+ breast cancer cell lines. Xenograft tumor experiments were performed in the nude mice to determine the tumor growth rates and tamoxifen sensitivity of the control and MENA knockdown HR+ breast cancer cells in the presence and absence of tamoxifen treatment. Furthermore, we estimated the growth rates of organoids derived from the HR+ breast cancer patients (n = 10) with high and low MENA expression levels when treated with tamoxifen. Results HR+ breast cancer patients with low MENA expression demonstrated tamoxifen resistance and poorer prognosis compared to those with high MENA expression. Univariate and multivariate Cox regression analysis demonstrated that MENA expression was an independent predictor of tamoxifen resistance in patients with HR+ breast cancer. MENA knockdown HR+ breast cancer cells showed significantly reduced tamoxifen sensitivity in the in vitro experiments and the in vivo xenograft tumor mouse model compared with the corresponding controls. Furthermore, MENA knockdown increased the in vitro invasion and migration of the HR+ breast cancer cells. HR+ breast cancer organoids with low MENA expression demonstrated reduced tamoxifen sensitivity than those with higher MENA expression. Mechanistically, P-AKT levels were significantly upregulated in the MENA-knockdown HR + breast cancer cells treated with or without 4-OHT compared with the corresponding controls. Conclusions This study demonstrated that downregulation of MENA promoted tamoxifen resistance in the HR+ breast cancer tissues and cells by enhancing the AKT signaling pathway. Therefore, MENA is a promising prediction biomarker for determining tamoxifen sensitivity in patients with HR+ breast cancer.

Abstract Tropical cyclones (TCs) cause severe natural hazards and drive intense upper ocean cooling through a series of oceanic and atmospheric physical processes, including vertical mixing and upwelling. Among these processes, TC-induced warming of near-surface waters in the open ocean has rarely been noted. This study provides a detailed analysis of upper ocean responses to 30 TC events observed by two buoys in the western North Pacific between 2016 and 2021. Supplemented with numerical experiments, we suggest that downwelling frequently occurs at the periphery of upwelling regions (around the radius of the 34 knot wind speed) following the passage of a TC. Downwelling is identified via pronounced warm anomalies under a shallow mixed layer depth, and its dynamics are attributed to negative wind stress curl and current-induced convergence. These findings highlight the important role played by TC-induced downwelling and offer insights for reconsidering the influence of TCs on biogeochemical processes.

Eroded soils sustain a substantial part of organic matter in tidal rivers adjacent to estuaries, and photochemical transformations of soils in tidal rivers would influence estuarine elemental cycles. However, complex aquatic environments and diverse soil sources complicate the enrichment of dissolved organic matter (DOM) photoreleased from soils. Here, we conducted a 7-day irradiation experiment for seven kinds of soils from the lower basin of Dagu River (DGR) in the laboratory to study the influence of salinity and soil properties on DOM chemistry by characterizing the content and optical properties of DOM. Results showed that light cultures had higher amount of DOM and humic-like components than dark cultures. Principal component analysis (PCA) and Mantel’s analysis found that salinity and soil properties significantly influence the production of photoreleased DOM, especially humic-like components. Salinity could inhibit the photodissolution of soils, and aged soils with low δ13CSOM released more DOM and humic-like components. Although the DGR is impacted by intruded seawater, high content of photoreleased DOM in seawater cultures still pointed out the important contribution of soil photodissolution to the DOM reservoir of tidal rivers. Considering high proportion of humic-like components in photoreleased DOM, photochemical transformations of soils in tidal rivers would promote the export flux of carbon from estuaries to open seas. This study emphasizes the importance of soil photodissolution of tidal rivers in the carbon transfer from lands to oceans.

BackgroundRapid and accurate diagnosis of the causative agents is essential for clinical management of bloodstream infections (BSIs) that might induce sepsis/septic shock. A considerable number of suspected sepsis patients initially enter the health-care system through an emergency department (ED), hence it is vital to establish an early strategy to recognize sepsis and initiate prompt care in ED. This study aimed to evaluate the diagnostic performance and clinical value of droplet digital PCR (ddPCR) assay in suspected sepsis patients in the ED.MethodsThis was a prospective single-centered observational study including patients admitted to the ED from 25 October 2022 to 3 June 2023 with suspected BSIs screened by Modified Shapiro Score (MSS) score. The comparison between ddPCR and blood culture (BC) was performed to evaluate the diagnostic performance of ddPCR for BSIs. Meanwhile, correlative analysis between ddPCR and the inflammatory and prognostic-related biomarkers were conducted to explore the relevance. Further, the health economic evaluation of the ddPCR was analyzed.Results258 samples from 228 patients, with BC and ddPCR performed simultaneously, were included in this study. We found that ddPCR results were positive in 48.13% (103 of 214) of episodes, with identification of 132 pathogens. In contrast, BC only detected 18 positives, 88.89% of which were identified by ddPCR. When considering culture-proven BSIs, ddPCR shows an overall sensitivity of 88.89% and specificity of 55.61%, the optimal diagnostic power for quantifying BSI through ddPCR is achieved with a copy cutoff of 155.5. We further found that ddPCR exhibited a high accuracy especially in liver abscess patients. Among all the identified virus by ddPCR, EBV has a substantially higher positive rate with a link to immunosuppression. Moreover, the copies of pathogens in ddPCR were positively correlated with various markers of inflammation, coagulation, immunity as well as prognosis. With high sensitivity and specificity, ddPCR facilitates precision antimicrobial stewardship and reduces health care costs.ConclusionsThe multiplexed ddPCR delivers precise and quantitative load data on the causal pathogen, offers the ability to monitor the patient’s condition and may serve as early warning of sepsis in time-urgent clinical situations as ED.ImportanceEarly detection and effective administration of antibiotics are essential to improve clinical outcomes for those with life-threatening infection in the emergency department. ddPCR, an emerging tool for rapid and sensitive pathogen identification used as a precise bedside test, has developed to address the current challenges of BSI diagnosis and precise treatment. It characterizes sensitivity, specificity, reproducibility, and absolute quantifications without a standard curve. ddPCR can detect causative pathogens and related resistance genes in patients with suspected BSIs within a span of three hours. In addition, it can identify polymicrobial BSIs and dynamically monitor changes in pathogenic microorganisms in the blood and can be used to evaluate antibiotic efficacy and survival prognosis. Moreover, the copies of pathogens in ddPCR were positively correlated with various markers of inflammation, coagulation, immunity. With high sensitivity and specificity, ddPCR facilitates precision antimicrobial stewardship and reduces health care costs.

Dysregulation of glycolysis is frequently linked to aggressive tumor activity in colorectal cancer (CRC). Although serine peptidase inhibitor, Kazal type 4 (SPINK4) has been linked to CRC, its exact linkage to glycolytic processes and gene expression remains unclear. Differentially expressed genes (DEGs) were screened from two CRC-related datasets (GSE32323 and GSE141174), followed by expression and prognostic analysis of SPINK4. In vitro techniques such as flow cytometry, western blotting, transwell assay, and quantitative real-time polymerase chain reaction (qRT-PCR) were used to assess SPINK4 expression in CRC cells. Its effects on apoptosis, glycolysis, and the cell cycle were also investigated. Finally, the impact of SPINK4 overexpression on tumor development was assessed using a xenograft model, while histological and immunohistochemical analyses characterized SPINK4 expression patterns in CRC tissues. SPINK4 expression was downregulated in CRC, correlating with poor patient prognosis. In vitro assays confirmed that overexpression of SPINK4 reduced CRC cell proliferation, invasion, and migration, while its knockdown promoted these processes and caused G1 arrest. SPINK4 also regulated apoptosis by altering caspase activation and Bcl-2 expression. Besides, SPINK4 overexpression altered glycolytic activity, reduced 2-Deoxy-D-glucose (2-DG) absorption, and controlled critical glycolytic enzymes, resulting in alterations in metabolic pathways, whereas SPINK4 knockdown reversed this effect. SPINK4 overexpression significantly reduced tumor volume in vivo, indicating its inhibitory role in carcinogenesis. Moreover, high expression of SPINK4, hexokinase 2 (HK2), glucose transporter 1 (GLUT1), lactate dehydrogenase A (LDHA), and pyruvate kinase M2 (PKM2) was observed in CRC tissues. As a key inhibitor of glycolytic metabolism in CRC, SPINK4 promises metabolic intervention in CRC therapy due to its impact on tumor growth and cell proliferation.

Transradial access (TRA) is a safe and comfortable approach and the preferred access for percutaneous coronary intervention. However, TRA is not widely used for peripheral interventions. Currently, there is a lack of data on patient selection, appropriate medical devices, complication prevention, and TRA adoption. Therefore, the Chinese Society of Interventional Oncology of the China Anti-Cancer Association organized nationwide experts to establish a Working Group of China Expert Consensus on TRA in percutaneous peripheral interventions in 2022, and jointly formulated this consensus to better promote the application of TRA in peripheral interventions to guide clinicians on patient selection, technical recommendations, and physician training. This consensus mainly focuses on the current situation, advantages and limitations of TRA in peripheral interventions, anatomical characteristics of the radial artery, patient selection, technical aspects, prevention and management of complications, radiation dose, and learning curve. A consensus was reached through a literature evaluation and by referring to the opinions of the expert group.

Two-dimensional MXenes are generally prepared by the etching of acid solutions. The as-synthesized MXenes are terminated by acid group anions (F–, Cl–, etc.), which affect the electrochemical performance of MXenes. Here, we report a novel method to prepare Mo2C MXene from Mo2Ga2C by the hydrothermal etching of alkali solutions. Highly pure Mo2C MXene was successfully synthesized by the etching of NaOH, while the etchings of LiOH and KOH were failed. The concentration of NaOH, temperature, and time strongly affect the purity of as-prepared MXene. Pure Mo2C MXene could be synthesized by the etching of 20 M NaOH at 180 ℃ for 24 h. After intercalation by hexadecyl trimethyl ammonium bromide at 90 ℃ for 96 h, few-layer Mo2C MXene was obtained. The Mo2C MXene made by NaOH etching after intercalation exhibited excellent performance as anode of lithium-ion battery, compared with general Mo2C MXene made by HF etching and the Mo2C MXene reported in literature. The final discharge specific capacity was 266.73 mAh·g−1 at 0.8 A·g−1, which is 52% higher than that Mo2C made by HF etching (175.77 mAh·g−1). This is because Mo2C MXene made by NaOH etching has lager specific surface area, lower resistance, and pure O/OH termination without acid anion termination. This is the first report to make Mo2C MXene by alkali etching and the samples made by this method exhibited significantly better electrochemical performance than the samples made by general HF etching.

Abstract The presence of defects, such as pores, in materials processed using additive manufacturing represents a challenge during the manufacturing of many engineering components. Recently, ultrasonic vibration-assisted (UV-A) directed energy deposition (DED) has been shown to reduce porosity, promote grain refinement, and enhance mechanical performance in metal components. Whereas it is evident that the formation of such microstructural features is affected by the melt pool behavior, the specific mechanisms by which ultrasonic vibration (UV) influences the melt pool remain elusive. In the present investigation, UV was applied in situ to DED of 316L stainless steel single tracks and bulk parts. For the first time, high-speed video imaging and thermal imaging were implemented in situ to quantitatively correlate the application of UV to melt pool evolution in DED. Extensive imaging data were coupled with in-depth microstructural characterization to develop a statistically robust dataset describing the observed phenomena. Our findings show that UV increases the melt pool peak temperature and dimensions, while improving the wettability of injected particles with the melt pool surface and reducing particle residence time. Near the substrate, we observe that UV results in a 92% decrease in porosity, and a 54% decrease in dendritic arm spacing. The effect of UV on the melt pool is caused by the combined mechanisms of acoustic cavitation, ultrasound absorption, and acoustic streaming. Through in situ imaging we demonstrate quantitatively that these phenomena, acting simultaneously, effectively diminish with increasing build height and size due to acoustic attenuation, consequently decreasing the positive effect of implementing UV-A DED. Thus, this research provides valuable insight into the value of in situ imaging, as well as the effects of UV on DED melt pool dynamics, the stochastic interactions between the melt pool and incoming powder particles, and the limitations of build geometry on the UV-A DED technique.