Scalable weaving of resilient membranes with on-demand superwettability for high-performance nanoemulsion separations.

This study leverages the ancient craft of weaving to prepare membranes that can effectively treat oil/water mixtures, specifically challenging nanoemulsions. Drawing inspiration from the core-shell architecture of spider silk, we have engineered fibers, the fundamental building blocks for weaving membranes, that feature a mechanically robust core for tight weaving, coupled with a CO2-responsive shell that allows for on-demand wettability adjustments. Tightly weaving these fibers produces membranes with ideal pores, achieving over 99.6% separation efficiency for nanoemulsions with droplets as small as 20 nm. They offer high flux rates, on-demand self-cleaning, and can switch between sieving oil and water nanodroplets through simple CO2/N2 stimulation. Moreover, weaving can produce sufficiently large membranes (4800 cm2) to assemble a module that exhibits long-term stability and performance, surpassing state-of-the-art technologies for nanoemulsion separations, thus making industrial application a practical reality.

RNA epigenetics in pulmonary diseases: Insights into methylation modification of lncRNAs in lung cancer.

Long non-coding RNAs (lncRNAs) are pivotal controllers of gene expression through epigenetic mechanisms, Methylation, a prominent area of study in epigenetics, significantly impacts cellular processes. Various RNA base methylations, including m6A, m5C, m1A, and 2'-O-methylation, profoundly influence lncRNA folding, interactions, and stability, thereby shaping their functionality. LncRNAs and methylation significantly contribute to tumor development, especially in lung cancer. Their roles encompass cell differentiation, proliferation, the generation of cancer stem cells, and modulation of immune responses. Recent studies have suggested that dysregulation of lncRNA methylation can contribute to lung cancer development. Furthermore, methylation modifications of lncRNAs hold potential for clinical application in lung cancer. Dysregulated lncRNA methylation can promote lung cancer progression and may offer insights into potential biomarker or therapeutic target. This review summarizes the current knowledge of lncRNA methylation in lung cancer and its implications for RNA epigenetics and pulmonary diseases.

Intensive Ambulance-Delivered Blood-Pressure Reduction in Hyperacute Stroke.

BACKGROUND: Treatment of acute stroke, before a distinction can be made between ischemic and hemorrhagic types, is challenging. Whether very early blood-pressure control in the ambulance improves outcomes among patients with undifferentiated acute stroke is uncertain. METHODS: We randomly assigned patients with suspected acute stroke that caused a motor deficit and with elevated systolic blood pressure (≥150 mm Hg), who were assessed in the ambulance within 2 hours after the onset of symptoms, to receive immediate treatment to lower the systolic blood pressure (target range, 130 to 140 mm Hg) (intervention group) or usual blood-pressure management (usual-care group). The primary efficacy outcome was functional status as assessed by the score on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days after randomization. The primary safety outcome was any serious adverse event. RESULTS: A total of 2404 patients (mean age, 70 years) in China underwent randomization and provided consent for the trial: 1205 in the intervention group and 1199 in the usual-care group. The median time between symptom onset and randomization was 61 minutes (interquartile range, 41 to 93), and the mean blood pressure at randomization was 178/98 mm Hg. Stroke was subsequently confirmed by imaging in 2240 patients, of whom 1041 (46.5%) had a hemorrhagic stroke. At the time of patients' arrival at the hospital, the mean systolic blood pressure in the intervention group was 159 mm Hg, as compared with 170 mm Hg in the usual-care group. Overall, there was no difference in functional outcome between the two groups (common odds ratio, 1.00; 95% confidence interval [CI], 0.87 to 1.15), and the incidence of serious adverse events was similar in the two groups. Prehospital reduction of blood pressure was associated with a decrease in the odds of a poor functional outcome among patients with hemorrhagic stroke (common odds ratio, 0.75; 95% CI, 0.60 to 0.92) but an increase among patients with cerebral ischemia (common odds ratio, 1.30; 95% CI, 1.06 to 1.60). CONCLUSIONS: In this trial, prehospital blood-pressure reduction did not improve functional outcomes in a cohort of patients with undifferentiated acute stroke, of whom 46.5% subsequently received a diagnosis of hemorrhagic stroke. (Funded by the National Health and Medical Research Council of Australia and others; INTERACT4 ClinicalTrials.gov number, NCT03790800; Chinese Trial Registry number, ChiCTR1900020534.).

A new mode for the diagnosis of angioimmunoblastic T-cell lymphoma.

In order to explore a new mode for the diagnosis of angioimmunoblastic T-cell lymphoma (AITL), 31 cases of AITL and 28 cases of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) were used as the study subjects. Identifying T follicular helper (TFH) cells with CD4, CD10, Bcl-6, and PD-1, identifying proliferative B cells with CD20 and EZH2, identifying proliferative follicular dendritic cells (FDCs) with CD21 and CD23, and analyzing the value of TFH/B/FDC proliferation and immunolocalization in the diagnosis of AITL. (1) Outside the inherent lymphoid follicles, simultaneous proliferation of TFH/B/FDC (a new diagnostic mode) were observed in AITL [83.87%; 26/31], with their immunolocalizations in the same site [83.87%; 26/31], while this phenomenon was not observed in 28 cases of PTCL-NOS (P<0.05). (2) The sensitivity and specificity of using this new mode to diagnose AITL were both high (83.87%, 100%), which was superior to CD2 (100%, 0%), CD3 (100%, 0%), CD4 (100%, 32.14%), CD5 (100%, 25%), CD10 (61.9%, 100%), Bcl-6 (42.86%, 100%), PD-1 (83.87%, 96.43%), and its Youden Index (0.84) was the highest. The areas under the curve (AUC) of CD10, Bcl-6, PD-1, and new mode to diagnosis AITL were 0.81, 0.71, 0.90, and 0.92, respectively, while the new mode had the highest AUC. The simultaneous proliferation of TFH/B/FDC cells outside the inherent lymphoid follicles can be used to assist in the diagnosis of AITL, and the simultaneous spatiotemporal proliferation of TFH/B/FDC cells is a specific immunomorphology of AITL.

Regulatory effect of Yinchenhao decoction on bile acid metabolism to improve the inflammatory microenvironment of hepatocellular carcinoma in mice.

Hepatocellular carcinoma (HCC) is a malignant tumor with extremely high mortality. The tumor microenvironment is the "soil" of its occurrence and development, and the inflammatory microenvironment is an important part of the "soil". Bile acid is closely related to the occurrence of HCC. Bile acid metabolism disorder is not only directly involved in the occurrence and development of HCC but also affects the inflammatory microenvironment of HCC. Yinchenhao decoction, a traditional Chinese medicine formula, can regulate bile acid metabolism and may affect the inflammatory microenvironment of HCC. To determine the effect of Yinchenhao decoction on bile acid metabolism in mice with HCC and to explore the possible mechanism by which Yinchenhao decoction improves the inflammatory microenvironment of HCC by regulating bile acid metabolism, we established mice model of orthotopic transplantation of hepatocellular carcinoma. These mice were treated with three doses of Yinchenhao decoction, then liver samples were collected and tested. Yinchenhao decoction can regulate the disorder of bile acid metabolism in liver cancer mice. Besides, it can improve inflammatory reactions, reduce hepatocyte degeneration and necrosis, and even reduce liver weight and the liver index. Taurochenodeoxycholic acid, hyodeoxycholic acid, and taurohyodeoxycholic acid are important molecules in the regulation of the liver inflammatory microenvironment, laying a foundation for the regulation of the liver tumor inflammatory microenvironment based on bile acids. Yinchenhao decoction may improve the inflammatory microenvironment of mice with HCC by ameliorating hepatic bile acid metabolism.

Postoperative leukocyte counts as a surrogate for surgical stress response in matched robot- and video-assisted thoracoscopic surgery cohorts of patients: A preliminary report.

The objective is to preliminary evaluated postoperative leukocyte counts as a surrogate for the surgical stress response in NSCLC patients who underwent RATS or VATS for further prospective analyses with proper assessment of surgical stress response and tissue trauma. We retrospectively analyzed patients with stageI-IIIA NSCLC who underwent RATS or VATS at a hospital between 8 May 2020 and 31 December 2021. Analysis of leukocytes (including neutrophils and lymphocytes) and albumin on postoperative days (PODs) 1 and 3 in patients with NSCLC treated with RATS or VATS after propensity score matching (PSM). In total, 1824 patients (565 RATS and 1259 VATS) were investigated. The two MIS groups differed significantly with regard to operative time (p < 0.001), chronic lung disease (p < 0.001), the type of pulmonary resection (p < 0.001), the excision site of lobectomy (p = 0.004), and histology of the tumor (p = 0.028). After PSM, leukocyte and neutrophil levels in the RATS group were lower than those in the VATS group on PODs 1 and 3, with those on POD 3 (p < 0.001) being particularly notable. While lymphocyte levels in the RATS group were significantly lower than those in the VATS group only at POD 1 (p = 0.016). There was no difference in albumin levels between the RATS and VATS groups on PODs 1 and 3. The surgical stress response and tissue trauma was less severe in NSCLC patients who underwent RATS than in those who underwent VATS, especially reflected in the neutrophils of leukocytes.

Preoperative exercise training decreases complications of minimally invasive lung cancer surgery: A randomized controlled trial.

OBJECTIVE: Limited evidence exists regarding the efficacy of preoperative exercise in reducing short-term complications after minimally invasive surgery in patients with non-small cell lung cancer. This study aims to investigate the impact of preoperative exercise on short-term complications after minimally invasive lung resection. METHODS: In this prospective, open-label, randomized (1:1) controlled trial at Xiangya Hospital, China (September 2020 to February 2022), patients were randomly assigned to a preoperative exercise group with 16-day alternate supervised exercise or a control group. The primary outcome assessed was short-term postoperative complications, with a follow-up period of 30 days postsurgery. RESULTS: A total of 124 patients were recruited (preoperative exercise group n = 62; control n = 62). Finally, 101 patients (preoperative exercise group; n = 51 and control; n = 50) with a median age of 56 years (interquartile range, 50-62 years) completed the study. Compared with the control group, the preoperative exercise group showed fewer postoperative complications (preoperative exercise 3/51 vs control 10/50; odds ratio, 0.17; 95% CI, 0.04-0.86; P = .03) and shorter hospital stays (mean difference, -2; 95% CI, -3 to -1; P = .01). Preoperative exercise significantly improved depression, stress, functional capacity, and quality of life (all P < .05) before surgery. Furthermore, preoperative exercise demonstrated a significantly lower minimum blood pressure during surgery and lower increases in body temperature on day 2 after surgery, neutrophil-to-lymphocyte ratio, and neutrophil count after surgery (all P < .05). Exploratory research on lung tissue RNA sequencing (5 in each group) showed downregulation of the tumor necrosis factor signaling pathway in the preoperative exercise group compared with the control group. CONCLUSIONS: Preoperative exercise training decreased short-term postoperative complications in patients with non-small cell lung cancer.

Scalable Preparation of Ultraselective and Highly Permeable Fully Aromatic Polyamide Nanofiltration Membranes for Antibiotic Desalination.

Membranes are important in the pharmaceutical industry for the separation of antibiotics and salts. However, its widespread adoption has been hindered by limited control of the membrane microstructure (pore architecture and free-volume elements), separation threshold, scalability, and operational stability. In this study, 4,4',4'',4'''-methanetetrayltetrakis(benzene-1,2-diamine) (MTLB) as prepared as a molecular building block for fabricating thin-film composite membranes (TFCMs) via interfacial polymerization. The relatively large molecular size and rigid molecular structure of MTLB, along with its non-coplanar and distorted conformation, produced thin and defect-free selective layers (~27 nm) with ideal microporosities for antibiotic desalination. These structural advantages yielded an unprecedented high performance with a water permeance of 45.2 L m-2 h-1 bar-1 and efficient antibiotic desalination (NaCl/adriamycin selectivity of 422). We demonstrated the feasibility of the industrial scaling of the membrane into a spiral-wound module (with an effective area of 2.0 m2). This module exhibited long-term stability and performance that surpassed those of state-of-the-art membranes used for antibiotic desalination. This study provides a scientific reference for the development of high-performance TFCMs for water purification and desalination in the pharmaceutical industry.

Spatial distribution characteristics of carbazole and polyhalogenated carbazoles in water column and sediments in the open Western Pacific Ocean.

Polyhalogenated carbazoles (PHCZs), an emerging persistent halogenated organic pollutant, have been detected in the environment. However, our understanding of PHCZs in the ocean remains limited. In this study, 47 seawater samples (covering 50 - 4000 m) and sediment samples (49 surface and 3 cores) were collected to investigate the occurrence and spatial distribution patterns of carbazole and its halogenated derivants (CZDs) in the Western Pacific Ocean. In seawater, the detection frequencies of CZ (97.87%) and 3-CCZ (57.45%) were relatively high. In addition, the average concentration of ΣPHCZs in the upper water (< 150 m, 0.23 ± 0.21 ng/L) was significantly lower than that in the deep ocean (1000 - 4000 m, 0.65 ± 0.56 ng/L, P < 0.05), which may indicate the vertical transport of PHCZs in the marine environment. The concentration of ΣCZDs in surface sediment ranges from 0.46 to 6.48 ng/g (mean 1.54 ng/g), among which CZ and 36-CCZ were the predominant components. Results from sediment cores demonstrate a noteworthy negative correlation between the concentration of CZDs and depth, indicating the ongoing natural degradation process occurring in sediment cores over a long period. This study offers distinctive insights into the occurrence, composition, and vertical features of CZDs in oceanic environments.

Asynchronous application of modified biochar and exogenous fungus Scedosporium sp. ZYY for enhanced degradation of oil-contaminated intertidal mudflat sediment.

Intertidal mudflats are susceptible to oil pollution due to their proximity to discharges from industries, accidental spills from marine shipping activities, oil drilling, pipeline seepages, and river outflows. The experimental study was divided into two periods. In the first period, microcosm trials were carried out to examine the effect of chemically modified biochar on biological hydrocarbon removal from sediments. The modified biochar's surface area increased from 2.544 to 25.378 m2/g, followed by a corresponding increase in the hydrogen-carbon and oxygen-carbon ratio, indicating improved stability and polarity. In the second period, the effect of exogenous fungus - Scedoporium sp. ZYY on the bacterial community structure was examined in relation to total petroleum hydrocarbon (TPH) removal. The maximum TPH removal efficiency of 82.4% was achieved in treatments with the modified biochar, followed by a corresponding increase in Fluorescein diacetate hydrolysis activity. Furthermore, high-throughput 16S RNA gene sequencing employed to identify changes in the bacterial community of the original sediment and treatments before and after fungal inoculation revealed Proteobacteria as the dominant phylum. In addition, it was observed that Scedoporium sp. ZYY promoted the proliferation of specific TPH-degraders, particularly, Hyphomonas adhaerens which accounted for 77% of the total degrading populations in treatments where TPH removal was highest. Findings in this study provide valuable insights into the effect of modified biochar and the fundamental role of exogenous fungus towards the effective degradation of oil-contaminated intertidal mudflat sediments.

Engineering Dual CO2- and Photothermal-Responsive Membranes for Switchable Double Emulsion Separation.

Stimulus-responsive membranes demonstrate promising applications in switchable oil/water emulsion separations. However, they are unsuitable for the treatment of double emulsions like oil-in-water-in-oil (O/W/O) and water-in-oil-in-water (W/O/W) emulsions. For efficient separation of these complicated emulsions, fine control over the wettability, response time, and aperture structure of the membrane is required. Herein, dual-coated fibers consisting of primary photothermal-responsive and secondary CO2-responsive coatings are prepared by two steps. Automated weaving of these fibers produces membranes with photothermal- and CO2-responsive characteristics and narrow pore size distributions. These membranes exhibit fast switching wettability between superhydrophilicity (under CO2 stimulation) and high hydrophobicity (under near-infrared stimulation), achieving on-demand separation of various O/W/O and W/O/W emulsions with separation efficiencies exceeding 99.6%. Two-dimensional low-field nuclear magnetic resonance and correlated spectra technique are used to clarify the underlying mechanism of switchable double emulsion separation. The approach can effectively address the challenges associated with the use of stimulus-responsive membranes for double emulsion separation and facilitate the industrial application of these membranes.

[Clinical Significance of Genetic and Molecular Changes in Primary Myeloid Sarcoma].

OBJECTIVE: To investigate the clinical significance of genetic and molecular changes in primary myeloid sarcoma (MS). METHODS: Fourteen patients with primary MS were selected in Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, The First People's Hospital of Lianyungang from September 2010 to December 2021. AML1-ETO fusion, PML-RARα fusion and CBFß breakage were detected by fluorescence in situ hybridization (FISH), and the mutations of NPM1, CEBPA, FLT3, RUNX1, ASXL1, KIT and TP53 genes were detected by new generation sequencing (NGS). RESULTS: Among 14 patients, the MS occurred in bone, breast, epididymis, lung, chest wall, cervix, small intestine, ovary, lymph nodes and central nervous system. The tumor cells expressed MPO (13 cases), CD34 (7 cases), CD43 (8 cases), CD68 (7 cases), CD99 (8 cases) and CD117 (6 cases). Cytogenetic abnormalities were observed in 4 cases, including 3 cases of AML1-ETO fusion and 1 case of CBFß breakage, while no PML-RARα fusion was detected. There were no significant differences in overall survival (OS) and leukemia-free survival (LFS) between patients with and without AML1-ETO fusion/CBFß breakage (both P >0.05). Among the 14 patients, the number of NPM1, CEBPA, FLT3-ITD, RUNX1, ASXL1, KIT and TP53 gene mutations was 5, 3, 5, 3, 2, 2, 1, respectively, of which 7 cases had at least one mutation in FLT3-ITD, RUNX1, ASXL1 and TP53 gene. The OS and LFS of patients with FLT3-ITD, RUNX1, ASXL1 or TP53 mutation were shorter than those without mutations (both P <0.01). CONCLUSION: The genetic and molecular abnormalities of primary MS can be detected by FISH and NGS techniques. FLT3-ITD, RUNX1, ASXL1 or TP53 mutation indicates a worse prognosis, but further clinical studies are needed to confirm it.

Island-Like Heterogeneous Interface Generating Tandem Toroidal Built-In Electric Field for Efficient Potassium Ions Diffusion.

For large-size potassium accommodation, heterostructure usually suffers severe delamination and exfoliation at the interfaces due to different volume expansion of two-phase during charge/discharge process, resulting in the deconstruction of heterostructures and shortened lifespan of batteries. Here, an innovative strategy is proposed through constructing a microscopic heterostructure system containing copper quantum dots (Cu QDs) highly dispersed in the triphenyl-substituted triazine graphdiyne (TPTG) substrates (TPTG@CuQDs) to solve this problem. The copper quantum dots are uniformly anchored on TPTG substrates, generating a myriad of island-like heterogeneous structures, together with tandem toroidal built-in electric field (BIEF) between every micro heterointerface. The island-like heterostructure endows both benefits of exposed contact interface and robust architecture. Generated tandem toroidal BIEF provides efficient transport pathways with lower energy barriers, reducing the diffusion resistance and facilitating the reaction kinetics of potassium ions. When used as anode, the TPTG@CuQDs exhibit highly reversible capacity and low-capacity degradation (≈0.01% over 5560 cycles at 1 A g-1 ). Moreover, the TPTG@CuQDs-based full cell delivers an outstanding reversible capacity of ≈110 mAh g-1 over 800 cycles at 1 A g-1 . This quantum-scale heterointerface construction strategy offers a new approach toward stable heterostructure design for the application of metal ion batteries.

Alpha-lipoic Acid Prevents Bone Loss in Type 2 Diabetes and Postmenopausal Osteoporosis Coexisting Conditions by Modulating the YAP/Glut4 Pathway.

This study aims to characterize the bone-protecting effects of Alpha-lipoic acid (ALA), a potent antioxidant, against the detrimental effects of the coexistence of type 2 diabetes mellitus (T2DM) and postmenopausal osteoporosis (POP) and identify the possible mechanisms with particular reference to its modulation of YAP/Glut4 pathway. The T2DM and POP coexisting model was induced in mice by high fat diet (HFD) + Streptozocin (STZ) + ovariectomy (OVX). The mice in the treatment groups were given ALA for 10 weeks. In the in vitro study, MC3T3-E1 cells were induced with 500 µM methylglyoxal for 24 h with or without pretreatment with ALA for 24 h. The oxidative and antioxidative biomarkers, bone microarchitecture, histo-morphology, and related protein expression of apoptosis, osteogenic differentiation and the YAP/Glut4 pathway were detected. The results showed ALA could improve glucose tolerance, inhibit oxidative stress and apoptosis and alleviate bone loss. Further study by siRNA technology revealed that the YAP/Glut4 pathway was implicated in the pathogenesis of bone loss due to the coexistence of T2DM and POP. Taken together, the present study has demonstrated for the first time that ALA exerts potent protective effects against bone loss in T2DM and POP coexisting conditions by modulating the YAP/Glut4 pathway.

A comprehensive insight into the abundance and community of anammox bacteria in sediments of Hangzhou Bay, China.

A total of 13 surface sediments were collected from Hangzhou Bay (HZB) for an investigation into the distribution and influencing factors of anammox bacterial community. The anammox bacterial 16S rRNA and hzo genes ranged between 2.34 × 105 to 9.22 × 105 copies/g and 3.68 × 105 to 1.70 × 106 copies/g, respectively. The results of high throughput sequencing (HTS) revealed that the obtained OTUs were affiliated with five known genera, named Ca. Scalindua, Ca. Jettenia, Ca. Brocadia, Ca. Kuenenia and Ca. Anammoxoglobus. RDA analysis indicated that salinity, pH, and water depth influenced the anammox bacterial community. Furthermore, network analysis identified Ca. Scalindua as a key genus. Neutral community model (NCM) and modified stochasticity ratio (MST) indicated that the deterministic process dominated the anammox bacterial community assembly. Overall, this study offers a more comprehensive understanding of the abundance and community of anammox bacteria in the sediments of HZB.

Effects of microplastics on cold seep sediment prokaryotic communities.

Cold seep sediments are an important reservoir of microplastics (MPs) whose impact on the structure and function of prokaryotic community is not well understood. In this study, the impact of 0.2% and 1% (w/w) polyethylene (PE), polystyrene (PS), and polypropylene (PP) MPs on the cold seep sediment prokaryotic community was investigated in a 120-day laboratory incubation experiment. The results revealed that exposure to MPs altered sedimentary chemical properties in a type- and concentration-dependent manner. Furthermore, MPs significantly altered the structure of bacterial community, with some MPs degradation-associated bacterial phyla significantly increasing (p < 0.05). However, in the case of archaea, the changes in the structure of microbial community were less pronounced (p > 0.05). Co-occurrence network analysis revealed that the addition of MPs reduced the network complexity, while PICRUSt2 and FAPROTAX analyses suggested that 0.2% PP and 1% PS MPs had the most significant effects on the nitrogen and carbon cycles (p < 0.05). Overall, this study provides new insights into the effects of MPs on the structure and function of microbial communities in cold seep sediments.

Supramolecular polymers with dual energy storage mechanism for high-performance supercapacitors.

In this paper, we prepared the supramolecular polymers (MWCNT-APP-s) with a dual energy storage mechanism as the electrode materials by the coordination of four transition metal ions with the small molecule chelator (APP) and functionalized carbon nanotubes, respectively. Among four MWCNT-APP-s, MWCNT-APP-Fe has the characteristics of moderate micropore/mesopore, significant hydrophobicity, redox property and functional groups. Interestingly, the redox reaction of Fe3+/Fe2+ and -CN-/-CN- transformation give MWCNT-APP-Fe an energy storage basis of pseudocapacitance, while MWCNTs and the micro/mesopore structure in MWCNT-APP-Fe provide a double-layer energy storage platform. As expected, on base of the dual energy storage mechanism, the symmetric supercapacitor assembled with MWCNT-APP-Fe has a higher specific capacity (Cs, 421 F g-1 at 1 mV s-1) as well as a long-lasting stability of 94.8% capacity retention with 99% Coulombic efficiency after 10,000 cycles at 20 mV s-1. More notably, the relevant aqueous Zn2+ hybrid supercapacitor provides a high capacity (Cm) of 191 mAh g-1 at 0.5 A g-1 and a long duration of over 2000 cycles at 50 A g-1, with a capacity retention of 92.4%. In summary, MWCNT-APP-Fe with a dual energy storage mechanism enables a potential application as an electrode material for high-performance supercapacitor.

Update on the INTEnsive ambulance-delivered blood pressure Reduction in hyper-ACute stroke Trial (INTERACT4): progress and baseline features in 2053 participants.

BACKGROUND AND AIMS: Uncertainty persists over the effects of blood pressure (BP) lowering in acute stroke. The INTEnsive ambulance-delivered blood pressure Reduction in hyper-Acute stroke Trial (INTERACT4) aims to determine efficacy and safety of hyperacute intensive BP lowering in patients with suspected acute stroke. Given concerns over the safety of this treatment in the pre-hospital setting, particularly in relation to patients with intracerebral hemorrhage, we provide an update on progress of the study and profile of participants to date. METHODS: INTERACT4 is an ongoing multicentre, ambulance-delivered, randomized, open-label, blinded endpoint trial of pre-hospital BP lowering in patients with suspected acute stroke and elevated BP in China. Patients are randomized via a mobile phone digital system to intensive (target systolic BP [SBP] <140mmHg within 30 min) or guideline-recommended BP management. Primary outcome is an ordinal analysis of the full range of scores on the modified Rankin scale scores at 90 days. RESULTS: Between March 2020 and April 2023, 2053 patients (mean age 70 years, female 39%) were recruited with a mean BP 178/98 mmHg in whom 45% have a diagnosis of primary intracerebral hemorrhage upon arrival at hospital. At the time of presentation to hospital, the mean SBP was 160 and 170mmHg in the intensive and control groups (Δ10 mmHg), respectively. The independent data and safety monitoring board has not identified any safety concerns and recommended continuation of the trial. The sample size was reduced from 3116 to 2320 after meetings in August 2022 as the stroke mimic rate was persistently lower than initially estimated (6% vs 30%). The study is expected to be completed in late 2023 and the results announced in May 2024. CONCLUSIONS: INTERACT4 is on track to provide reliable evidence of the effectiveness of ambulance-delivered intensive BP lowering in patients with suspected acute stroke. TRIAL REGISTRATION: ClinicalTrials.gov NCT03790800 ; registered on 2 January 2019. Chinese Trial Registry ChCTR1900020534 , registered on 7 January 2019.

LncRNA CALML3-AS1 modulated by m6A modification induces BTNL9 methylation to drive non-small-cell lung cancer progression.

Non-small cell lung cancer (NSCLC) is a common and lethal malignancy. The carcinogenic roles of lncRNA CALML3 antisense RNA 1 (CALML3-AS1) have been documented. However, the function and potential mechanisms of CALML3-AS1 in the progression of NSCLC need to be further explored. The molecule expression was assessed by qRT-PCR and Western blot. The subcellular localization of CALML3-AS1 was observed by fluorescence in situ hybridization (FISH). The malignant behaviors of NSCLC cells were evaluated by CCK-8, colony formation, EdU, wound healing and transwell assays. In vivo xenograft tumor and liver metastatic models were established. The molecular mechanisms were investigated by RIP, RNA pull-down and ChIP assays. The methylation level was detected by MSP. Herein, we found that CALML3-AS1 was upregulated, while butyrophilin-like 9 (BTNL9) was downregulated in NSCLC. Functionally, CALML3-AS1 depletion repressed NSCLC cell malignant phenotypes, in vivo tumor growth, and liver metastasis. Mechanistically, AlkB homolog 5 (ALKBH5) enhanced CALML3-AS1 stability via N6-methyladenosine (m6A) demethylation, whereas m6A reader YTH domain-containing 2 (YTHDC2) destabilized CALML3-AS1. Moreover, CALML3-AS1 inhibited BTNL9 transcription and expression through the recruitment of Zeste homolog 2 (EZH2). Rescue experiments demonstrated that BTNL9 downregulation counteracted sh-CALML3-AS1-mediated antitumor effects on NSCLC. Taken together, CALML3-AS1 modulated by ALKBH5 and YTHDC2 in an m6A modification dependent manner drives NSCLC progression via epigenetically repressing BTNL9.

Alkyne-to-alkene conversion in graphdiyne driving instant reversible deformation of whole carbon film.

The emerging field of soft robotics demands the core actuators and related responsive functional materials with rapid responsiveness and controllable accurate deformation. Here, we developed an alkyne-to-alkene chemical bond conversion way as the driving force to control ultrasensitive and instant reversible deformation of 2D carbon graphdiyne (GDY) film with an asymmetric interface design. The alkyne-to-alkene chemical bond conversion was triggered by acetone through the fast binding and release process. The as-fabricated GDY-based deformation modulator was exhibited to rapidly change shape (within 0.15 seconds) while dipped in an acetone vapor atmosphere and recover to its original form when exposed to air (recovery time < 0.01 seconds), with outstanding properties like large curvature, quick recovery time, excellent stability, and repeatability. It could mimic the movement of mosquito larvae, displaying great promise as micro bionic soft robots. Our results suggest alkyne-to-alkene bond conversion as a unique driving force for developing smart materials for areas like intelligent robotics and bionics.