Efficient Capture and Traceless Release of Functional CD8+ T Cells with a Microfluidic Chip for Enhanced In Vitro and In Vivo CD4-CAR Transduction.

The chimeric antigen receptor (CAR) T cells targeting CD4 expressed cells in acute lymphoblastic leukemia (T-ALL) and acute myeloid leukemia (AML) could reduce the risk of off target effects in normal tissues. However, the efficacy of adoptive cell therapy is predominantly attributed to CD8+ T cells, necessitating their purification before lentivirus transfection to enhance the production of CD4-CAR-T cells. In this study, we developed a microfluidic chip functionalized with an optimized CD8 aptamer, A3t-MU, to facilitate the enrichment and purification of CD8+ T cells. The presented chip showed efficient capture and seamless release of CD8+ T cells from cultured T cells and peripheral blood mononuclear cells (PBMCs). The purity of the released CD8+ T cells reached 98.1%, representing a 13% improvement over the conventional magnetic bead separation method. CD4-CAR was efficiently transduced into the purified CD8+ T cells to construct CAR-T cells. We evaluated the antitumor capability of the CD4-CAR transduced CD8+ T cells (anti-CD4 CD8-CAR T cells) both in vitro and in vivo. The anti-CD4 CD8-CAR T cells exhibited significant cancer-cell-killing capacity across multiple tumor cell lines, including CEM, Jurkat, and MV4-11. Meanwhile, anti-CD4 CD8-CAR T cells significantly inhibited tumor growth in vivo. In conclusion, the presented microfluidic chip offers a cost-effective and high-purity approach for CD8+ T cell separation, enhancing CD4-CAR transduction and achieving efficient antitumor capability both in vitro and in vivo.

Characterization of NiCas12b for In Vivo Genome Editing.

The RNA-guided clustered regularly interspaced short palindromic repeats (CRISPR)/Cas12b system represents the third family of CRISPR-Cas systems that are harnessed for genome editing. However, only a few nucleases have demonstrated activity in human cells, and their in vivo therapeutic potential remains uncertain. In this study, a green fluorescent protein (GFP)-activation assay is conducted to screen a panel of 15 Cas12b orthologs, and four of them exhibited editing activity in mammalian cells. Particularly noteworthy is the NiCas12b derived from Nitrospira sp., which recognizes a "TTN" protospacer adjacent motif (PAM) and facilitates efficient genome editing in various cell lines. Importantly, NiCas12b also exhibits a high degree of specificity, rendering it suitable for therapeutic applications. As proof of concept, the adeno-associated virus (AAV) is employed to introduce NiCas12b to target the cholesterol regulatory gene proprotein convertase subtilisin/ kexin type 9 (Pcsk9) in the mouse liver. After 4 weeks of injections, an impressive is observed over 16.0% insertion/deletion (indel) efficiency, resulting in a significant reduction in serum cholesterol levels. NiCas12b provides a novel option for both basic research and clinical applications.

Spatial distribution, source identification, and potential risks of 14 bisphenol analogues in soil under different land uses in the megacity of Chengdu, China.

This study explored the levels, distribution, potential sources, ecological risks and estrogenic activities of 14 bisphenol analogues (BPs) in soil under eight land-use types in the megacity of Chengdu, China. Eleven BPs were detected in the soil samples and the total concentrations ranged from 32.3 to 570 ng/g d.w. Levels of bisphenol BP (BPBP) in the soil (up to 208 ng/g d.w.) only second to the most dominant compound bisphenol A (BPA) were found. Relatively higher Σ14BP accumulation in the soil was observed in the commercial and residential areas (median: 136 ng/g d.w. and 131 ng/g d.w.) compared with agricultural area (median: 67.5 ng/g d.w.). Source identification indicated the role of atmospheric particulate deposition and consecutive anthropogenic activities in BP emission. The ecotoxicity assessment implied that BPA, bisphenol S (BPS), bisphenol F (BPF) and bisphenol PH (BPPH) might pose low to medium risk to the ecosystem due to their extensive use and biological effects. The calculated 17ß-estradiol equivalents of BPs were in the range of 0.501-7.74 pg E2/g d.w, and the estrogenic activities were inferior to those contributed by natural estrogens in the soil.

Effect of ultrasound-guided transversus abdominis plane block in reducing atelectasis after laparoscopic surgery in children: A randomized clinical trial.

Background: Atelectasis is a commonly observed postoperative complication of general anesthesia in children. Pulmonary protective ventilation strategies have been reported to have a beneficial effect on postoperative atelectasis in children. Therefore, the present study aimed to evaluate the efficacy of the ultrasound-guided transversus abdominis plane (TAP) block technique in preventing the incidence of postoperative atelectasis in children. Materials and methods: This study enrolled 100 consecutive children undergoing elective laparoscopic bilateral hernia repair and randomly divided them into the control and TAP groups. Conventional lung-protective ventilation was initiated in both groups after the induction of general anesthesia. The children in the TAP group received an ultrasound-guided TAP block with 0.3 mL/kg of 0.5% ropivacaine after the induction of anesthesia. Results: Anesthesia-induced atelectasis was observed in 24% and 84% of patients in the TAP (n = 50) and control (n = 50) groups, respectively, before discharge from the post-anesthetic care unit (T3; PACU) (odds ratio [OR], 0.062; 95% confidence interval [CI], 0.019-0.179; P < 0.001). No significant difference was observed between the control and TAP groups in terms of the lung ultrasonography (LUS) scores 5 min after endotracheal intubation (T1). However, the LUS scores were lower in the TAP group than those in the control group at the end of surgery (T2, P < 0.01) and before discharge from the PACU (T3, P < 0.001). Moreover, the ace, legs, activity, cry and consolability (FLACC) pain scores in the TAP group were lower than those in the control group at each postoperative time point. Conclusion: Ultrasound-guided TAP block effectively reduced the incidence of postoperative atelectasis and alleviated pain in children undergoing laparoscopic surgery.

Inhibition of sphingosine kinase 1 attenuates LPS-induced acute lung injury by suppressing endothelial cell pyroptosis.

Acute lung injury (ALI) is a frequent complication of sepsis, with pyroptosis playing a pivotal role. Analysis of Gene Expression Omnibus (GEO) mouse sepsis datasets revealed the upregulation of sphingosine kinase 1 (SphK1) in septic mouse lung tissues, which was validated in lipopolysaccharide (LPS)-treated mice. Therefore, this study aimed to explore the potential role and underlying mechanisms of SphK1, the primary kinase responsible for catalyzing the formation of the bioactive lipid sphingosine-1-phosphat, in sepsis development. Mice received an intraperitoneal injection of SphK1 inhibitor prior to LPS administration. Mouse lung vascular endothelial cells (MLVECs) were exposed to LPS and SphK1 inhibitor. The SphK1 inhibitor mitigated ALI, as evidenced by hematoxylin and eosin (H&E) staining and the wet-to-dry (W/D) weight ratio and reduced Evans blue dye leakage. Furthermore, the SphK1 inhibitor inhibited the activation of the NOD-like receptor protein 3 inflammasome and the subsequent induction of pyroptosis both in vivo and in vitro. Intriguingly, using co-immunoprecipitation (Co-IP) combined with mass spectrometry, our findings revealed that SphK1 associates with pyruvate kinase M2 (PKM2), facilitating PKM2 phosphorylation and its nuclear translocation. TEPP-46, which has the ability to stabilize PKM2 and inhibit the phosphorylation and nuclear translocation of PKM2, markedly reduced the expression of pyroptosis-associated markers and alleviated lung injury. Concludingly, our results suggest that targeting SphK1 is a promising therapeutic strategy for ALI.

Simultaneous desalination and molecular resource recovery from wastewater using an electrical separation system integrated with a supporting liquid membrane.

Separating molecular substances from wastewater has always been a challenge in wastewater treatment. In this study, we propose a new strategy for simultaneous desalination and selective recovery of molecular resources, by introducing a supported liquid membrane (SLM) with molecular selectivity into an asymmetric flow-electrode capacitive deionization. Salts and molecular substances in wastewater are removed after passing through the ion separation chamber and the molecular separation chamber, respectively. Faradaic reactions, i.e., the electrolysis of water with OH-, occurred in the electrochemical cathode electrode provides a sufficient and continuous chemical potential gradient for the cross-SLM transport of phenol (a model molecule substance). By optimizing the formulation of the liquid membrane and the pore size of the support membrane, we obtained the SLM with the best performance for separating phenol. In continuous experiment tests, the electrochemical membrane system showed stable separation performance and long-term stability for simultaneous salts removal and phenol (sodium phenol) recovery from wastewater. Finally, we demonstrate the potential application of this technology for the recovery of different carbon resources. Overall, the electrochemical system based on SLM is suitable for various wastewater treatment needs and provides a new approach for the recovery of molecular resources in wastewater.

Effect of high-frequency oscillation on reduction of atelectasis in perioperative patients: a prospective randomized controlled study.

BACKGROUND: Atelectasis affects approximately 90% of anaesthetized patients, with laparoscopic surgery and pneumoperitoneum reported to exacerbate this condition. High-frequency oscillation therapy applies continuous positive pressure pulses to oscillate the airway, creating a pressure difference in small airways obstructed by secretions. This process helps reduce peak airway pressure, open small airways, and decrease atelectasis incidence, while also facilitating respiratory tract clearance. This study examines the efficacy of high-frequency oscillation on reduction of atelectasis in laparoscopic cholecystectomy (LC) patients under general anaesthesia, evaluated using lung ultrasound. METHODS: Sixty-four patients undergoing laparoscopic cholecystectomy were randomly divided into a control group and a high-frequency oscillation (HFO) group. Both groups underwent total intravenous anaesthesia under invasive arterial monitoring. The HFO group received a 10-minute continuous high-frequency oscillation therapy during surgery, while the control group received no intervention. Lung ultrasound evaluations were performed three times: five minutes post-intubation (T1), at the end of the surgery (T2), and before leaving the Post-Anaesthesia Care Unit (PACU; T3). Blood gas analysis was performed twice: prior to induction with no oxygen supply and before PACU discharge (oxygen supply off). RESULTS: The HFO group displayed a significantly lower incidence of atelectasis at T3 (57.5% vs. 90.3%, OR 6.88, 95%CI (1.74 to 27.24)) compared to the control group. Moreover, the HFO group's PaO2 levels remained consistent with baseline levels before PACU discharge, unlike the control group. Although there was no significant difference in LUS scores between the groups at T1 (8.56 ± 0.15 vs. 8.19 ± 0.18, p = 0.1090), the HFO group had considerably lower scores at T2 (13.41 ± 0.17 vs.7.59 ± 0.17, p < 0.01) and T3 (13.72 ± 0.14 vs.7.25 ± 0.21, p < 0.01). CONCLUSION: Our study indicates that high-frequency oscillation effectively reduces atelectasis in patients undergoing laparoscopic cholecystectomy. Additionally, it can mitigate the decline in oxygen partial pressure associated with atelectasis.

Construction of Indole-Fused Seven- and Eight-Membered Azaheterocycles via a Tandem Pd/NBE-Catalyzed Decarbonylation and Dual C-H Activation Sequence.

Herein, we report the transformation of aromatic acids to indole-fused seven- and eight-membered azaheterocycles. Two C-C bonds are formed via the cleavage of one C-C bond and two C-H bonds. The incorporation of indole moieties into bioactive pharmaceuticals and natural products to construct a medium-sized polyfused heterocycle demonstrates the synthetic utility of the protocol.

Oxidative Three-Component Selenofunctionalization of Alkenes: Convenient Access to Vicinally Functionalized Selenides.

Three-component selenofunctionalization processes of olefins, diselenides and sulfonamides, water, alcohols, or acids utilizing 1-fluoropyridinium triflate (FP-OTf) as a reaction promoter are reported. Under the optimal conditions, a broad range of vicinally functionalized selenide derivatives was accessible with high yields and excellent functional group compatibilities. Mechanistic studies revealed that the FP-OTf played a key role in this selenofunctionalization process.

Preparation and Biomedical Applications of Cucurbit[n]uril-Based Supramolecular Hydrogels.

The cucurbit[n]uril supramolecular hydrogels are driven by weak intermolecular interactions, of which exhibit good stimuli responsiveness and excellent self-healing properties. According to the composition of the gelling factor, supramolecular hydrogels comprise Q[n]-cross-linked small molecules and Q[n]-cross-linked polymers. According to different driving forces, hydrogels are driven by the outer-surface interaction, the host-guest inclusion interaction, and the host-guest exclusion interaction. Host-guest interactions are widely used in the construction of self-healing hydrogels, which can spontaneously recover after being damaged, thereby prolonging their service life. The smart Q[n]s-based supramolecular hydrogel composed is a kind of adjustable and low-toxicity soft material. By designing the structure of the hydrogel or modifying the fluorescent properties, etc., it can be widely used in biomedicine. In this review, we mainly focus on the preparation of Q[n]-based hydrogels and their biomedical applications including cell encapsulation for biocatalysis, biosensors for high sensitivity, 3D printing for potential tissue engineering, drug release for sustained delivery, and interfacial adhesion for self-healing materials. In addition, we also presented the current challenges and prospects in this field.

An integrated approach of high-performance liquid chromatography-mass spectrometry-based chemical profiling, network pharmacology, and molecular docking to reveal the potential mechanisms of Qishen Gubiao granules for treating coronavirus disease 2019.

Qishen Gubiao granules, a traditional Chinese medicine preparation composed of nine herbs, have been widely used to prevent and treat coronavirus disease 2019 with good clinical efficacy. In the present study, an integrated strategy based on chemical profiling followed by network pharmacology and molecular docking was employed, to explore the active components and potential molecular mechanisms of Qishen Gubiao granules in the therapy of coronavirus disease 2019. Using the ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry technique, a total of 186 ingredients corresponding to eight structure types in Qishen Gubiao preparation were identified or structurally annotated with the elucidation of the fragmentation pathways in the typical compounds. The network pharmacology analysis screened 28 key compounds including quercetin, apigenin, scutellarein, luteolin and naringenin acting on 31 key targets, which possibly modulated signal pathways associated with immune and inflammatory responses in the treatment of coronavirus disease 2019. The molecular docking results observed that the top 5 core compounds had a high affinity for angiotensin-converting enzyme 2 and 3-chymotrypsin-like protease. This study proposed a reliable and feasible approach for elucidating the multi-components, multi-targets, and multi-pathways intervention mechanism of Qishen Gubiao granules against coronavirus disease 2019, providing a scientific basis for its further quality evaluation and clinical application.

Photocatalytic Aerobic Cyclization of N-Propargylamides Enabled by Selenium-π-Acid Catalysis.

A dual catalytic approach combining photocatalyst and selenium-π-acid synergy has been used to cyclized of N-propargylamides. This method offers readily access to oxazole aldehydes under chemical oxidant-free conditions with low catalyst loadings, where air acts as a terminal and gratuitous oxidant. The reaction is demonstrated with a range of substrates, including aryl and alkyl propargyl amides, and in the late-stage functionalization of several amide-containing drug molecules. Mechanistic studies suggest that the acridinium catalyst is able to oxidize diselenide and generate singlet oxygen (1 O2 ), which is responsible for this transformation.

Recent Breakthroughs in Supercapacitors Boosted by Macrocycles.

Supercapacitors are essential for electrochemical energy storage because of their high-power density, good cycle stability, fast charging and discharging rates, and low maintenance cost. Macrocycles, including cucurbiturils, calixarene, and cyclodextrins, are cage-like organic compounds (with a nanocavity that contains O and N heteroatoms) with unique potential in supercapacitors. Here, we review the applications of macrocycles in supercapacitor systems, and we illustrate the merits of organic macrocycles in electrodes and electrolytes for improving the electrochemical double-layer capacitors and pseudocapacitance via supramolecular strategies. Then, the observed relationships between electrochemical performance and macrocyclic structures are introduced. This comprehensive review describes recent progress on macrocycle-block supercapacitors for researchers.

Energy transition in Southeast Asian countries: is there a role for governance at country level?

Effective governance is crucial for building environmental policies in order to discourage non-renewable energy use and replace it by renewable resources. Given the significant proportion of fossil fuels in the existing energy mix of ASEAN countries, the transition to renewable energy is critical for emissions to be reduced in this region. As a pioneering one, the present study focuses on the role of governance indicators and economic growth in energy transition in Southeast Asian (ASEAN) countries over the period 2000-2020. For the purpose of empirical investigation, the study applies the recently introduced methods of movement quantile regression (MMQR) with FE-OLS, DOLS, and FMOLS estimation techniques. The findings of indicate that economic growth significantly promotes energy transition in ASEAN countries. Among the governance indicators, political stability, rule of law, and regulatory quality significantly and positively affect energy transition, whereas government effectiveness and control of corruption play negative roles in energy transition. Voice and accountability have no significant effect on energy transition. Political stability and rule of law play significant roles in energy transition at all quantiles, but political stability has a significant effect on energy transition only at higher quantiles (0.60-0.90). Similarly, government effectiveness and control of corruption negatively impact energy transition at medium to higher (0.50-0.90) and at higher quantiles (0.80-0.90), respectively. Policies are recommended on the basis of the findings.

Impact of government governance and environmental taxes on sustainable energy transition in China: fresh evidence using a novel QARDL approach.

Although economies have experienced immense growth in recent times, however, it also comes with environmental and social consequences which question the current practices and threaten the well-being of current as well as the future generation. This realization, thus, pushes institutions to bring change in existing energy-related policies in order to incorporate social and environmental concerns. Clean energy transition, in this regard, is gaining attraction all over the world as it shifts away economies from non-renewable resources. The study, thereby, intends to explore the role of governance and environmental taxes in the energy transition in China economy over the period 1999-2019. The roles of industrialization and economic growth in the transition of energy are taken into consideration. The recently introduced legit quantile autoregressive distributed lag (QARDL) model and Granger causality in quantiles are applied to quarterly data spanning 1999Q1 to 2019Q4 for empirical quantile analysis. Results echoed that governance has a positive impact and environmental resources have a negative impact on energy transition across all quantiles. However, economic growth influences clean energy transition only at extremely higher quantiles (0.60-0.95), and industrialization does not have any effect on energy transition over the entire quantile range. The findings of the Granger causality analysis reveal the presence of a bidirectional causal association between clean energy transition and all the variables. Worthy policies are recommended on the basis of the findings.

Multicolor colorimetric visual detection of Staphylococcus aureus based on Fe3O4-Ag-MnO2 composites nano-oxidative mimetic enzyme.

Novel Fe3O4-Ag-MnO2 composites were successfully synthesized. It was noteworthy that the obtained Fe3O4-Ag-MnO2 composites were found to possess three types of enzyme-mimicking activities, including peroxidase-like, catalase-like and oxidase-like activities. Taking advantage of the oxidase properties of Fe3O4-Ag-MnO2, the direct oxidation of TMB could be catalyzed to generate blue oxidation products without H2O2. The oxidase-like activity of Fe3O4-Ag-MnO2 were carefully studied. Based on the Fe3O4-Ag-MnO2-TMB system, a fast, sensitive and intuitive multicolor colorimetric method for Staphylococcus aureus (S. aureus) detection was established under the optimized conditions. The proposed method allows the detection of S. aureus with a detection limit of 3.7 cfu mL-1 and a linear range of 10-106 cfu mL-1. This new colorimetric method has been successfully proved to be applicable to the detection S. aureus of food samples.