A Superior Bifunctional Electrocatalyst in Which Directional Electron Transfer Occurs Between a Co/Ni Alloy and Fe─N─C Support.

Stable, efficient, and economical bifunctional electrocatalysts for oxygen evolution reaction (OER) and oxygen reduction reaction (ORR) are needed for rechargeable Zn-air batteries. In this study, a directional electron transfer pathway is exploited in a spatial heterojunction of CoyNix@Fe─N─C heterogeneous catalyst for effective bifunctional electrolysis (OER/ORR). Thereinto, the Co/Ni alloy is strongly coupled to the Fe─N─C support through Co/Ni─N bonds. DFT calculations and experimental findings confirm that Co/Ni─N bonds play a bridging role in the directional electron transfer from Co/Ni alloy to the Fe─N─C support, increasing the content of pyridinic nitrogen in the ORR-active support. In addition, the discovered directional electron transfer mechanism enhances both the ORR/OER activity and the durability of the catalyst. The Co0.66Ni0.34@Fe─N─C with the optimal Ni/Co ratio exhibits satisfying bifunctional electrocatalytic performance, requiring an ORR half-wave potential of 0.90 V and an OER overpotential of 317 mV at 10 mA cm-2 in alkaline electrolytes. The assembled rechargeable zinc-air batteries (ZABs) incorporating Co0.66Ni0.34@Fe─N─C cathode exhibits a charge-discharge voltage gap comparable to the Pt/C||IrO2 assembly and high robustness for over 60 h at 20 mA cm-2.

Organic Fluorophores with Large Stokes Shift for the Visualization of Rapid Protein and Nucleic Acid Assays.

Organic small-molecule fluorophores, characterized by flexible chemical structure and adjustable optical performance, have shown tremendous potential in biosensing. However, classical organic fluorophore motifs feature large overlap between excitation and emission spectra, leading to the requirement of advanced optical set up to filter desired signal, which limits their application in scenarios with simple settings. Here, a series of wavelength-tunable small-molecule fluorescent dyes (PTs) bearing simple organic moieties have been developed, which exhibit Stokes shift up to 262 nm, molar extinction coefficients ranged 30,000-100,000 M-1 cm-1, with quantum yields up to 54.8 %. Furthermore, these dyes were formulated into fluorescent nanoparticles (PT-NPs), and applied in lateral flow assay (LFA). Consequently, limit of detection for SARS-CoV-2 nucleocapsid protein reached 20 fM with naked eye, a 100-fold improvement in sensitivity compared to the pM detection level for colloidal gold-based LFA. Besides, combined with loop-mediated isothermal amplification (LAMP), the LFA system achieved the visualization of single copy level nucleic acid detection for monkeypox (Mpox).

A Novel Cell Membrane-Associated RNA Extraction Method and Its Application in the Discovery of Breast Cancer Markers.

Cell membrane-associated RNA (mem-RNA) has been demonstrated to be cell-specific and disease-related and are considered as potential biomarkers for disease diagnostics, drug delivery, and cell screening. However, there is still a lack of methods specifically designed to extract mem-RNA from cells, limiting the discovery and applications of mem-RNA. In this study, we propose the first all-in-one solution for high-purity mem-RNA isolation based on two types of magnetic nanoparticles, named MREMB (Membrane-associated RNA Extraction based on Magnetic Beads), which achieved ten times enrichment of cell membrane components and over 90% recovery rate of RNA extraction. To demonstrate MREMB's potential in clinical research, we extracted and sequenced mem-RNA of typical breast cancer MCF-7, MDA-MB-231, and SKBR-3 cell lines and non-neoplastic breast epithelial cell MCF-10A. Compared to total RNA, sequencing results revealed that membrane/secreted protein-encoding mRNAs and long noncoding RNAs (lncRNAs) were enriched in the mem-RNA, some of which were significantly overexpressed in the three cancer cell lines, including extracellular matrix-related genes COL5A1 and lncRNA TALAM1. The results indicated that MREMB could enrich membrane/secreted protein-coding RNA and amplify the expression differences of related RNAs between cancer and non-neoplastic cells, promising for cancer biomarker discovery.

Photomodulated cryogenic temperature sensing through a photochromic reaction in Na0.5Bi2.5Ta2O9: Er/Yb multicolour upconversion.

Optical temperature sensing of the non-thermally coupled energy levels (N-TCLs) based on fluorescence intensity ratio (FIR) technologies has excellent temperature sensitivity and signal recognition properties. In this study, a novel strategy is established to enhance the low-temperature sensing properties by controlling photochromic reaction process in Na0.5Bi2.5Ta2O9: Er/Yb samples. The maximum relative sensitivity reaches up to 5.99% K-1 at cryogenic temperature of 153 K. After irradiation with commercial laser of 405 nm for 30 s, the relative sensitivity is increased to 6.81% K-1. The improvement is verified to originate from the coupling of optical thermometric and photochromic behaviour at the elevated temperatures. The strategy may open up a new avenue to improve the thermometric sensitivity in photo-stimuli response photochromic materials.

Targeting the RhoA-GEF-H1 pathway of mast cells attenuates experimental airway allergy.

Mast cells are the major effector cells in allergic diseases. RhoA and its downstream pathway is associated with the pathogenesis of airway allergy. The objective of this study is to test a hypothesis that modulating the RhoA-GEF-H1 axis in mast cells can attenuate airway allergy. An airway allergic disorder (AAD) mouse model was employed. Mast cells were isolated from AAD mouse airway tissues to be analyzed by RNA sequencing. We observed that mast cells isolated from the respiratory tract of AAD mice were resistant to apoptosis. Mast cell mediator levels in nasal lavage fluid were correlated with apoptosis resistance in AAD mice. Activation of RhoA in AAD mast cells was related to resistance to apoptosis. Mast cells isolated from the airway tissues in AAD mouse exhibited strong RhoA-GEF-H1 expression. The RhoA-GEF-H1 axis was associated with the lower FasL expression in AAD mast cells. Activation of the RhoA-GEF-H1 axis promoted the production of mediators in mast cells. Inhibition of GEF-H1 facilitated the SIT-induced mast cell apoptosis and enhanced the therapeutic efficacy of AAD. In conclusion, RhoA-GEF-H1 activities are associated with resistance to apoptosis in mast cells isolated from sites of allergic lesions. The state of apoptosis resistance in mast cells is associated with the state of AAD disease. Inhibition of GEF-H1 restores the sensitivity of mast cells to apoptosis inducers, and alleviates experimental AAD in mice.

Intracranial efficacy and safety of furmonertinib 160 mg with or without anti-angiogenic agent in advanced NSCLC patients with BM/LM as salvage therapy.

OBJECTIVES: Central nervous system (CNS) metastases including brain metastases (BM) and leptomeningeal metastases (LM) are frequent in epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC), and are correlated with poor outcomes. In this study, we evaluated the efficacy of single-agent furmonertinib 160 mg or combining with anti-angiogenic agent in NSCLC patients who had developed BM/LM progression from previous tyrosine kinase inhibior (TKI) treatment. METHODS: EGFR-mutated NSCLC patients who developed BM (the BM cohort) or LM progression (the LM cohort) were included, having received furmonertinib 160 mg daily as second-line or later treatment, with or without anti-angiogenic agents. The intracranial efficacy was evaluated by intracranial progression-free survival (iPFS). RESULTS: Totally 12 patients in the BM cohort and 16 patients in the LM cohort were included. Almost one half of patients in the BM cohort and a majority in the LM cohort had a poor physical status, with a Eastern Cooperative Oncology Group performance status (ECOG-PS) ≥2. The administration of single-agent furmonertinib or combination treatment achieved a median iPFS of 3.6 months (95%CI 1.435-5.705) in the BM cohort, and 4.3 months (95%CI 2.094-6.486) in the LM cohort. Subgroup and univariate analysis has shown that a good ECOG-PS correlated with a favorable efficacy of furmonertinib in the BM cohort (median iPFS = 2.1 with ECOG-PS ≥ 2 vs. 14.6 months with ECOG-PS < 2, P < 0.05). Overall, any grade of adverse events (AEs) occured in 46.4% of patients (13/28). Among them, 14.3% of patients (4 of 28) had grade 3 or higher AEs, and were all under control, led to no dose reductions or suspension. CONCLUSION: Single-agent furmonertinib 160 mg or in combination of anti-angiogenic agent is an optional salvage therapy for advanced NSCLC patients who developed BM/LM progression from prior EGFR-TKI treatment, with a promising efficacy and an acceptable safety profile, and is worth of further exploration.

Progress of Hydrophobic Ionogels: A Review.

The emergence of hydrophobic ionogels composed of hydrophobic polymer matrices and hydrophobic ionic liquids has drastically broadened the applications of ionic devices, especially for underwater explorations. Compared with traditional ionogels, hydrophobic ones are capable of achieving long-term stability in ambient and aqueous environments. In this review, the latest research developments of intrinsically hydrophobic ionogels are summarized, with particular emphases placed on the materials, mechanisms and applications. The basic issues about hydrophobic ionogels, including the material systems, dynamic gelation bonds and network structures are elucidated. The up-to-date advent of the ambient/underwater applications of hydrophobic ionogels concerning adhesion, self-healing, and sensing are comprehensively summarized. Special attention is paid to underwater scenarios considering the rapid development of marine explorations and the intrinsic properties of hydrophobic ionogels. Finally, the current challenges and immediate opportunities of this emerging yet fast-developing research field are discussed.

Analysis of organic acid metabolism reveals citric acid and malic acid play major roles in determining acid quality during the development of kiwifruit (Actinidia eriantha).

BACKGROUND: Actinidia eriantha is one of the most important kiwifruit species in Actinidia. The relative high accumulation of organic acids in fruit of A. eriantha is an unfavorable factor for organoleptic quality. To identify key metabolic enzymes and genes involved in organic acids accumulation during fruit development, physiological, biochemical, and molecular experiments were conducted for the dynamic fruit samples of a new kiwifruit cultivar, A. eriantha 'Ganlv 1'. RESULTS: The contents of citric acid and malic acid increased greatly during fruit development, while quinic acid content decreased obviously. Significant positive correlations were observed between fruit titratable acidity and the contents of both citric acid and malic acid, and a significant negative correlation was found between fruit titratable acidity and the quinic acid content. The high accumulation of citric acid was found to be caused by the increased activity of citrate synthase (CS), and the decreased activities of two degradation-related enzymes, mitochondrial aconitase and nicotinamide adenine dinucleotide (NAD)-dependent isocitrate dehydrogenase. In addition, the accumulation of malic acid depended mainly on the increased synthesis catalyzed by NAD-dependent malate dehydrogenase (NAD-MDH) and phosphoenolpyruvate carboxylase. Further analysis suggested that AeCS2 and AeMDH2 played pivotal roles in controlling the activities of CS and NAD-MDH respectively. CONCLUSION: The high accumulation level of citric acid relied on both the strong synthesis ability and the weak degradation ability. The accumulation level of malic acid was mainly affected by the synthesis. The novel information would be helpful for our understanding of the formation of fruit acidity quality. © 2023 Society of Chemical Industry.

A Quantitative Metal-Encoded Conjugate Platform for Targeting Ligand Discovery.

The indiscriminate biodistribution of therapeutics can be a key barrier to their safety and efficacy. Localization of compounds into non-diseased tissues often leads to both toxic and dose-limiting effects. To overcome this barrier, nanomedicine implements targeting agents to localize or selectively uptake drugs at disease sites. However, to date there are only a small number of targeting agents with limited scope for targeting tissues. Small-molecule ligands are particularly attractive as targeting agents due to their relatively low cost, tunability, and ease of conjugation. Currently, there are no systematic approaches to the discovery of new small-molecule targeting ligands. Here, we developed a quantitative metal-encoded conjugate platform to determine the biodistribution of multiple small molecules in vivo. By utilizing lanthanide metal complexes, this platform successfully distinguished known ligands with differential tissue targeting in vivo. This system will facilitate the discovery of small molecules as targeting ligands and can accelerate the identification of novel biological targets for tissue-targeted drug delivery.

Efficacy of first-line treatments in the elderly and non-elderly patients with advanced epidermal growth factor receptor mutated, non-small cell lung cancer: a network meta-analysis.

OBJECTIVE: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are the current standard of care for advanced or metastatic non-small cell lung cancer (NSCLC) patients harboring EGFR activating mutations. However, the optimal strategy for elderly NSCLC patients is still under debate. This study was designed to explore the optimal first-line regimens by comparing diverse strategies for elderly and non-elderly EGFR-mutated NSCLC patients. METHODS: A systematic review was conducted to summarize all available randomized controlled trials (RCTs) from PubMed, EMBASE, Cochrane Central Register of Controlled Trials databases, and international conferences before September 30, 2020. The primary outcome was progression free survival (PFS), and the secondary outcome was overall survival (OS). A network meta-analysis (NMA) was constructed using the Bayesian statistical model to synthesize the survival outcomes of all the treatments. RESULTS: In total, 12 RCTs were deemed eligible for inclusion with 3779 patients who have received 10 diverse treatments including EGFR-TKIs. Results from the Bayesian ranking suggested that osimertinib was most likely to rank the first in overall population and in elderly patients in PFS, with the cumulative probabilities of 42.20% and 31.46%, respectively. In non-elderly group (younger than 65 years old), standard of care (SoC, representing first-generation EGFR-TKIs in this NMA) + chemotherapy ranked the first (31.66%). As for OS, SoC + chemotherapy ranked first in all patients (64.33%), patients younger than 65 years old (61.98%), or older than 65 years old (34.45%). CONCLUSION: The regimen of osimertinib is associated with the most favorable PFS in elderly advanced EGFR-mutated NSCLC patients, while SoC + chemotherapy is the optimal strategy in PFS for non-elderly NSCLC patients harboring EGFR activating mutations, and in OS for both elderly and non-elderly EGFR-mutated advanced NSCLC patients. TRIAL REGISTRATION: INPLASY protocol 2020100061 https://doi.org/10.37766/inplasy2020.20.0061 .

Cerocene and Lanthanocene Chalcogenides: Synthesis, Structure, and Luminescence.

A series of lanthanide chalcogenides {[η5-1,3-(Me3C)2C5H3]2Ln}2(µ-η2:η2-Te2) (Ln = Ce 1, La 2), {[η5-1,3-(Me3C)2C5H3]2Ln(THF)}2(µ-Se) (Ln = Ce 3, La 4), and {[η5-1,3-(Me3C)2C5H3]2Ln(THF)}2(µ-Te) (Ln = Ce 5, La 6) can be readily obtained by the reaction of the alkyl complexes [η5-1,3-(Me3C)2C5H3]2Ln(CH2C6H4-o-NMe2) with elemental selenium or tellurium in the presence of 9-borabicyclo[3.3.1]nonane (9-BBN). The reaction of the alkyl complexes [η5-1,3-(Me3C)2C5H3]2Ln(CH2C6H4-o-NMe2) with 9-BBN in 1:2 molar ratio afforded the lanthanide (cyclooctane-1,5-diyl)dihydroborate complexes [η5-1,3-(Me3C)2C5H3]2Ln[(µ-H)2BC8H14] (Ln = Ce 7, La 8) concomitant with the (Me2N-o-C6H4CH2)BC8H14 release, indicating that [η5-1,3-(Me3C)2C5H3]2LnH may be the reactive species for the synthesis of lanthanide chalcogenides. All the new compounds were characterized by various spectroscopic methods, and their solid-state structures were further confirmed by single-crystal X-ray diffraction analyses. Luminescence spectroscopy was also employed to characterize complexes 1-6. The Ce(III) complexes 3 and 5 display distinct luminescence properties at room temperature, as compared to the corresponding La(III) complexes 4 and 6. The complex {[η5-1,3-(Me3C)2C5H3]2Ce(THF)}2(µ-Te) (5) exhibits unexpectedly red emission in solution which is found to depend strongly on the excitation wavelength.

Fucoxanthin Prevents Long-Term Administration l-DOPA-Induced Neurotoxicity through the ERK/JNK-c-Jun System in 6-OHDA-Lesioned Mice and PC12 Cells.

As the most abundant marine carotenoid extracted from seaweeds, fucoxanthin is considered to have neuroprotective activity via its excellent antioxidant properties. Oxidative stress is regarded as an important starting factor for neuronal cell loss and necrosis, is one of the causes of Parkinson's disease (PD), and is considered to be the cause of adverse reactions caused by the current PD commonly used treatment drug levodopa (l-DA). Supplementation with antioxidants early in PD can effectively prevent neurodegeneration and inhibit apoptosis in dopaminergic neurons. At present, the effect of fucoxanthin in improving the adverse effects triggered by long-term l-DA administration in PD patients is unclear. In the present study, we found that fucoxanthin can reduce cytotoxicity and suppress the high concentration of l-DA (200 µM)-mediated cell apoptosis in the 6-OHDA-induced PC12 cells through improving the reduction in mitochondrial membrane potential, suppressing ROS over-expression, and inhibiting active of ERK/JNK-c-Jun system and expression of caspase-3 protein. These results were demonstrated by PD mice with long-term administration of l-DA showing enhanced motor ability after intervention with fucoxanthin. Our data indicate that fucoxanthin may prove useful in the treatment of PD patients with long-term l-DA administration.

Effects of Sarcoptes scabiei Translationally Controlled Tumor Protein (TCTP) on Histamine Release and Degranulation of KU812 Cells.

Scabies is a common parasitic dermatological infection worldwide that is often neglected. Scabies mites stimulate host inflammatory symptoms via secreted and excreted proteins, which induce basophil and mast cell degranulation and host histamine release. However, the mechanism of degranulation and histamine release is unclear. Moreover, the Sarcoptes scabiei translationally controlled tumor protein (TCTP) is predicted as an excreted protein, which may be involved in host inflammatory response regulation. First, we evaluated S. scabiei TCTP gene (SsTCTP) transcription in larvae, nymphs, and adults by qRT-PCR, and SsTCTP transcription was highest in larvae, followed by nymphs. Second, we found that the S. scabiei TCTP recombinant protein (rSsTCTP) promoted mice histamine release in vivo by Evans blue Miles assay. Therefore, to further explore the possible role of S. scabiei TCTP in host inflammatory response regulation, we established a degranulation model of KU812 cells. The results of the degranulation model suggested that rSsTCTP could induce enhanced degranulation of KU812 cells and increase the secretion of histamine and the expression of IL-4, IL-6, and IL-13 in vitro. In conclusion, we speculate that scabies mites could stimulate host histamine release and Th2 response by excreting S. scabiei TCTP.

Estimating Departure Time Using Thermal Camera and Heat Traces Tracking Technique.

Advancement in science and technology is playing an increasingly important role in solving difficult cases at present. Thermal cameras can help the police crack difficult cases by capturing the heat trace on the ground left by perpetrators, which cannot be spotted by the naked eye. Therefore, the purpose of this study is to establish a thermalfoot model using thermal imaging system to estimate the departure time. To this end, in the current work, we use a thermal camera to acquire the thermal sequence left on the floor, and convert it into the heat signal via image processing algorithm. We establish the model of thermalfoot print as we observe that the residual temperature would exponentially decrease with the departure time according to Newton's Law of Cooling. The correlation coefficients of 107 thermalfoot models derived from the corresponding 107 heat signals are basically above 0.99. In a validation experiment, a residual analysis is conducted and the residuals between estimated departure time points and ground-truth times are almost within a certain range from -150 s to +150 s. The reverse accuracy of the thermalfoot model for estimating departure time at one-third, one-half, two-thirds, three-fourths, four-fifths, and five-sixths capture time points are 71.96%, 50.47%, 42.06%, 31.78%, 21.70%, and 11.21%, respectively. The results of comparison experiments with two subjective evaluation methods (subjective 1: we directly estimate the departure time according to obtained local curves; subjective 2: we utilize auxiliary means such as a ruler to estimate the departure time based on obtained local curves) further demonstrate the effectiveness of thermalfoot model for detecting the departure time inversely. Experimental results also demonstrated that the thermalfoot model has good performance on the departure time reversal within a short time window someone leaves, whereas it is probably only approximately 15% to accurately determine the departure time via thermalfoot model within a long time window someone leaves. The influence of outliers, ROI (Region of Interest) selection, ROI size, different capture time points and environment temperature on the performance of thermalfoot model on departure time reversal can be explored in the future work. Overall, the thermalfoot model can help the police solve crimes to some extent, which in turn brings more guarantees for people's health, social security, and stability.

Total Endovascular Repair With Parallel Stent-Grafts for Postdissection Thoracoabdominal Aneurysm After Prior Proximal Repair.

Purpose: To evaluate the safety and efficacy of total endovascular repair with parallel stent-grafts for postoperative residual dissection thoracoabdominal aortic aneurysm (TAAA). Materials and Methods: A retrospective study was undertaken of 21 patients (mean age 64.0±12.5 years; 17 men) undergoing total endovascular therapy with parallel stent-grafts for postdissection TAAA after prior proximal repair between 2014 and 2016. The preoperative minimum true lumen diameter was 12.3±4.8 mm and the mean extent of dissection was 248.1±48.2 mm. Pre-, intra-, and postoperative medical records were reviewed to assess technical success, spinal cord ischemia, patency of target branch arteries, endoleak, and short-term outcomes of this approach. Results: Technical success was achieved in 17 of 21 patients owing to 4 type I endoleaks at the end of the procedures. A total of 70 branch arteries were revascularized and 14 celiac trunks were covered intentionally without reconstruction. Of 7 intraoperative endoleaks, 2 were managed intraoperatively and 5 (4 type I and 1 type II) disappeared spontaneously within 1 month. No spinal cord or abdominal organ or limb ischemia was observed. Mean follow-up was 16.2±6.1 months. No death or type I or III endoleak occurred during the follow-up; 2 type II endoleaks were observed. Nineteen of the 21 false lumens thrombosed, and the total aortic diameter decreased (57.3±8.4 to 55.3±7.4 mm, p<0.01). Three (4.3%) of 70 target branch arteries occluded during follow-up. The cumulative patency of retrogradely and antegradely revascularized branch arteries was 97.3% vs 100% at 12 months and 91.2% vs 100% at 18 months. Conclusion: Total endovascular therapy with parallel stent-grafts could be an effective alternative in treating postdissection TAAA. Further studies with long-term follow-up and larger sample size are recommended to evaluate the technique.

Association of the Kiwi OmniCup system with maternal and neonatal morbidity: A retrospective cohort study.

OBJECTIVE: To discuss the effect of the Kiwi OmniCup system on reducing adverse maternal and neonatal outcomes and provide a reference for assisted vaginal delivery methods. METHODS: Women who gave birth to singleton term neonates in a cephalic presentation and underwent assisted vaginal delivery from 2017 to 2021 were eligible for inclusion in the study; they were divided into a Kiwi OmniCup system group and a forceps group. Binary logistic regression analysis was used to observe and compare maternal and neonatal outcomes. The primary outcomes were severe maternal and neonatal morbidity. Severe maternal morbidity was defined as the occurrence of at least one of the following outcomes: third- or fourth-degree perineal lacerations, refractory postpartum hemorrhage, thrombotic events, amniotic fluid embolism, admission to the intensive care unit, and maternal death. Severe neonatal morbidity was defined as the occurrence of at least one of the following outcomes: neonatal asphyxia requiring resuscitation or intubation, neonatal head and face injuries, neonatal fracture, and admission to the neonatal intensive care unit for longer than 24 h. RESULTS: The rate of severe neonatal morbidity in the forceps group was significantly higher than that in the Kiwi OmniCup system group, the differences between the two groups were significant (27.2% vs. 42.3%, P < 0.001), and there was no significant difference in the rate of severe maternal morbidity between the two groups (30% vs. 30%, P > 0.05). Binary logistic regression analysis showed that Kiwi OmniCup system-assisted delivery reduced severe neonatal morbidity (adjusted odds ratio 0.49; 95% confidence interval 0.33-0.73) and did not increase severe maternal morbidity compared with forceps-assisted delivery. CONCLUSION: The Kiwi OmniCup system, which can reduce the incidence of severe neonatal morbidity without increasing the incidence of serious adverse maternal outcomes, is worthy of clinical promotion.

Calculation of carbon emissions in wastewater treatment and its neutralization measures: A review.

As the pursuit of "carbon neutrality" gains momentum, the emphasis on low-carbon solutions, emphasizing energy conservation and resource reuse, has introduced fresh challenges to conventional wastewater treatment approaches. Precisely evaluating carbon emissions in urban water supply and drainage systems, wastewater treatment plants, and establishing carbon-neutral operating models has become a pivotal concern in the future of wastewater treatment. Regrettably, limited research has been devoted to carbon accounting and the development of carbon-neutral strategies for wastewater treatment. In this review, to facilitate comprehensive carbon accounting, we initially recognizes direct and indirect carbon emission sources in the wastewater treatment process. We then provide an overview of several major carbon accounting methods and propose a carbon accounting framework. Furthermore, we advocate for a systemic perspective, highlighting that achieving carbon neutrality in wastewater treatment extends beyond the boundaries of wastewater treatment plants. We assess current technical measures both within and outside the plants that contribute to achieving carbon-neutral operations. Encouraging the application of intelligent algorithms for the multifaceted monitoring and control of wastewater treatment processes is paramount. Supporting resource and energy recycling is also essential, as is recognizing the benefits of synergistic wastewater treatment technologies. We advocate a systematic, multi-level planning approach that takes into account a wide range of factors. Our goal is to offer valuable insights and support for the practical implementation of water environment management within the framework of carbon neutrality, and to advance sustainable socio-economic development and contribute to a more environmentally responsible future.

Efficacy of third-generation epidermal growth factor receptor-tyrosine kinase inhibitors in advanced NSCLC with different T790M statuses tested via digital droplet polymerase chain reaction ddPCR and next-generation sequencing.

OBJECTIVES: We hypothesize that digital droplet polymerase chain reaction (ddPCR) would optimize the treatment strategies in epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) relapsed patients. In this study, we compared the efficacy of third-generation TKIs with various T790M statuses via ddPCR and next-generation sequencing (NGS). METHODS: NGS was performed on blood samples of patients progressed from previous EGFR-TKIs for resistance mechanism. T790M-negative patients received further liquid biopsy using ddPCR for T790M detection. RESULTS: A cohort of 40 patients were enrolled, with 30.0% (12/40) T790M-positive via NGS (Group A). In another 28 T790M-negative patients by NGS, 11 (39.3%) were T790M-positive (Group B) and 17 (60.7%) were T790M-negative (Group C) via ddPCR. A relatively longer progression-free survival (PFS) was observed in group A (NR) and group B (10.0 months, 95% CI 7.040-12.889) than in group C (7.0 months, 95% CI 0.000-15.219), with no significant difference across all three groups (p = 0.196), or between group B and C (p = 0.412). EGFR-sensitive mutation correlated with inferior PFS (p = 0.041) and ORR (p = 0.326), and a significantly lower DCR (p = 0.033) in T790M-negative patients via NGS (n = 28). CONCLUSION: This study indicates that ddPCR may contribute as a supplement to NGS in liquid biopsies for T790M detection in EGFR-TKIs relapsed patients and help to optimize the treatment strategies, especially for those without coexistence of EGFR-sensitive mutation. TRIAL REGISTRATION: www.clinicaltrials.gov identifier is NCT05458726.

Unveiling the structural mechanisms of nonpeptide ligand recognition and activation in human chemokine receptor CCR8.

The human CC chemokine receptor 8 (CCR8) is an emerging therapeutic target for cancer immunotherapy and autoimmune diseases. Understanding the molecular recognition of CCR8, particularly with nonpeptide ligands, is valuable for drug development. Here, we report three cryo-electron microscopy structures of human CCR8 complexed with Gi trimers in the ligand-free state or activated by nonpeptide agonists LMD-009 and ZK 756326. A conserved Y1.39Y3.32E7.39 motif in the orthosteric binding pocket is shown to play a crucial role in the chemokine and nonpeptide ligand recognition. Structural and functional analyses indicate that the lack of conservation in Y1143.33 and Y1724.64 among the CC chemokine receptors could potentially contribute to the selectivity of the nonpeptide ligand binding to CCR8. These findings present the characterization of the molecular interaction between a nonpeptide agonist and a chemokine receptor, aiding the development of therapeutics targeting related diseases through a structure-based approach.

A natural IgM hitchhiking strategy for delivery of cancer nanovaccines to splenic marginal zone B cells.

B cell-targeted cancer vaccines are receiving increasing attention in immunotherapy due to the combined antibody-secreting and antigen-presenting functions. In this study, we propose a natural IgM-hitchhiking delivery strategy to co-deliver tumor antigens and adjuvants to splenic marginal zone B (MZB) cells. We constructed nanovaccines (FA-sLip/OVA/MPLA) consisting of classical folic acid (FA)-conjugated liposomes co-loaded with ovalbumin (OVA) and toll-like receptor 4 agonists, MPLA. We found that natural IgM absorption could be manipulated at the bio-nano interface on FA-sLip/OVA/MPLA, enabling targeted delivery to splenic MZB cells. Systemic administration of FA-sLip/OVA/MPLA effectively activated splenic MZB cells via IgM-mediated multiplex pathways, eliciting antigen-specific humoral and cytotoxic T lymphocyte responses, and ultimately retarding E.G7-OVA tumor growth. In addition, combining FA-sLip/OVA/MPLA immunization with anti-PD-1 treatments showed improved antitumor efficiency. Overall, this natural IgM-hitchhiking delivery strategy holds great promise for efficient, splenic MZB cell-targeted delivery of cancer vaccines in future applications.