A nonparametric point-by-point method to measure time-dependent frequency in wavelength modulation spectroscopy.

A nonparametric point-by-point (NPP) method is presented for high-accuracy measurement of the time-dependent frequency (laser frequency) in tunable laser absorption spectroscopy, crucial for ensuring ultimate measurement accuracy. In wavelength modulation spectroscopy in particular, the parametric methods in current use for time-dependent frequency measurement are insufficiently accurate and are difficult to apply to complex modulation scenarios. Based on a multi-scale viewpoint, point-by-point measurement of the frequency is realized by linear superposition of the frequency information mapped from the interferometric signal on a unit scale and on a local scale. Validation experiments indicate that the measurement accuracy of the proposed NPP method is three times that of the existing parametric methods, while effectively immunizing against non-ideal tuning effects. Additionally, the NPP method is suitable for use with arbitrarily complex modulations such as square wave modulation, for which parametric methods are inapplicable.

Efficiency and mechanism of controlling phosphorus release from sediment using a biological aluminum-based P-inactivation agent.

Eutrophication is a significant challenge for surface water, with sediment phosphorus (P) release being a key contributor. Although biological aluminum-based P-inactivation agent (BA-PIA) has shown effectiveness in controlling P release from sediment, the efficiency and mechanism by BA-PIA capping is still not fully understood. This study explored the efficiency and mechanism of using BA-PIA capping controlling P release from sediment. The main mechanisms controlling P release from sediment via BA-PIA capping involved transforming mobile and less stable fractions into stable ones, passivating DGT-labile P and establishing a 13 mm 'P static layer' within the sediment. Additionally, BA-PIA's impact on Fe redox processes significantly influenced P release from the sediment. After BA-PIA capping, notable reductions were observed in total P, soluble reactive P (SRP), and diffusive gradient in thin-films (DGT)-measured labile P (DGT-labile P) concentration in the overlying water, with reduction rates of 95.6%, 92.7%, and 96.5%, respectively. After BA-PIA capping, the diffusion flux of SRP across the sediment-water interface and the apparent P diffusion flux decreased by 91.3% and 97.8%, respectively. Additionally, BA-PIA capping led to reduced concentrations of SRP, DGT-labile P, and DGT-measured labile Fe(II) in the sediment interstitial water. Notably, BA-PIA capping significantly reduced P content and facilitated transformation in the 0∼30 mm sediment layers but not in the 30∼45 mm and 45∼60 mm sediment layers for NaOH-extractable inorganic P and HCl-extracted P. These findings offer a theoretical basis and technical support for the practical application of BA-PIA capping to control P release from sediment.

Genomic characteristics of human respiratory syncytial virus from children in China during 2017-2020.

Acute lower respiratory tract infections (ALRTIs) are a leading cause of mortality in young children worldwide due to human respiratory syncytial virus (RSV). The aim of this study was to monitor genetic variations in RSV and provide genomic data support for RSV prevention and control. A total of 105 complete RSV genome sequences were determined during 2017-2020. Phylogenetic analysis showed that all of the RSVA sequences were of genotype ON1, and all of the RSVB sequences were of genotype BA9. Notably, a phylogenetic tree based on the whole genome had more branches than a tree based on the G gene. In comparison to the RSV prototype sequences, 71.43% (50/70) of the ON1 sequences had five amino acid substitutions (T113I, V131N, N178G, H258Q, and H266L) that occurred simultaneously, and 68.57% (24/35) of the BA9 genotype sequences had 12 amino acid substitutions, four of which (A131T, T137I, T288I, and T310I) occurred simultaneously. In the F gene, there were 19 amino acid substitutions, which were mainly located in the antigenic sites Ø, II, V, and VII. Other amino acid substitutions were found in the NS1, NS2, P, SH, and L proteins. No significant evidence of recombination was found in any of the sequences. These findings provide important data that will be useful for prevention, control, and vaccine development against RSV.

Antibacterial activity and mechanism of Stevia extract against antibiotic-resistant Escherichia coli by interfering with the permeability of the cell wall and the membrane.

Natural plant-derived compounds with broad-spectrum antimicrobial activity have become an effective strategy against multidrug-resistant bacteria. The present study was designed to compare the antibacterial activity of six chlorogenic acid (CA) isomers extracted from stevia and investigated the underlying antibacterial mechanisms involved. The results indicated that isochlorogenic acid C (ICAC) exhibited the strongest antibacterial activity against the tested bacteria, especially E. coli, at a 2 mg/mL minimum inhibitory concentration (MIC) and 8 mg/mL minimum bactericidal concentration (MBC). At the MBC, ICAC inhibited 72.66% of the clinical multidrug-resistant strains. Scanning electron microscopy (SEM) revealed that ICAC induced considerable morphological alterations in E. coli ATCC25922 and C4E2. The significant increase in the activity of extracellular alkaline phosphatase (AKP) indicated that ICAC damages the permeability of the bacterial cell wall. Additionally, the intracellular membrane (IM) permeability and the content of lipopolysaccharide (LPS), a main component of the outer membrane (OM), were determined. The significant decrease in LPS content and increased leakage of intracellular proteins and K+ from E. coli indicated that ICAC could induce the exfoliation of OM and disrupt IM permeability, resulting in the loss of barrier function. The uptake of propidium iodide (PI), a compromised cell membrane nucleic acid stain, and confocal laser scanning microscopy (CLSM) further demonstrated that ICAC disrupted IM integrity. Moreover, the bactericidal effect and damage to bacterial microstructural function occurred in a dose-dependent manner. These data demonstrate that ICAC has excellent antibacterial activity and is a promising approach for overcoming the antibiotic resistance of pathogenic bacteria.

An Injectable Photothermal-Fusing Hydrogel: Achieving Temperature-Controllable Mild Photothermal Therapy to Reverse Chemotherapy-Induced Immune Tolerance.

Mild photothermal therapy (M-PTT) can induce immunogenic cell death (ICD) to reverse the immune tolerance caused by low-dose chemotherapy. However, it still needs convenient strategies to control temperature during M-PTT. In this work, the phase change material lauric acid (LA, melting point 43 °C) was introduced to construct nanoparticles loaded with deferoxamine mesylate (DFO) and cisplatin (CDDP), which were mixed into a supramolecular hydrogel formed by polyvinylpyrrolidone (PVP)/tannic acid (TA)/Fe3+ to obtain FeTP@DLD/DLC. When the temperature reached 43 °C under laser irradiation, DFO was released from melted LA and destroyed the interaction between Fe3+ and TA to cut off the temperature increase, achieving a "photothermal fusing effect". Meanwhile, CDDP was released for low-dose chemotherapy, while the resulting immune tolerance was reversed by M-PTT-induced ICD. Finally, through a single administration, FeTP@DLD/DLC-mediated M-PTT synergized with chemotherapy achieved a potent antitumor effect. This work provided a convenient solution for the revitalization of these traditional antitumor therapies.

Dexmedetomidine attenuates sepsis-associated acute lung injury by regulating macrophage efferocytosis through the ROS/ADAM10/AXL pathway.

BACKGROUND: The lungs are highly susceptible to damage during sepsis, with severe lung injury potentially progressing to acute respiratory distress syndrome and even fatal sepsis. Effective efferocytosis of apoptotic cells is crucial in alleviating inflammation and tissue injury. METHODS: We established a septic lung injury mouse model via intraperitoneal injection of lipopolysaccharide. Lung injury was assessed by histology, immunofluorescence, neutrophil immunohistochemistry staining, and cytokine detection. We extracted alveolar macrophages by bronchoalveolar lavage and primary macrophages from mouse bone marrow to investigate the regulatory effects of Dexmedetomidine (DEX) on efferocytosis. We further validated the molecular mechanisms underlying the regulation of macrophage efferocytosis by DEX through knockdown of AXL expression. Additionally, we examined the efferocytic ability of monocytes isolated from patients. RESULTS: We discovered that DEX treatment effectively alleviated pulmonary injury and inflammation. Lipopolysaccharide reduced macrophage efferocytosis and AXL expression which were reversed by DEX. We also found DEX inhibited the increased activation of A Disintegrin And Metalloproteinase 10 (ADAM10) and the production of soluble AXL. Moreover, our findings demonstrated that DEX decreased the elevated ROS production linked to higher ADAM10 activation. Blocking AXL negated DEX's benefits on efferocytosis and lung protection. Efferocytosis in monocytes from septic lung injury patients was notably lower than in healthy individuals. CONCLUSION: Our findings demonstrated that DEX treatment effectively reduces septic lung injury by promoting macrophage efferocytosis through ROS/ADAM10/AXL signaling pathwway.

Prenatal exposure to per- and polyfluoroalkyl substances, genetic factors, and autistic traits: Evidence from the Shanghai birth cohort.

The epidemiological evidence regarding prenatal PFAS exposure and its interaction with genetic factors on the autistic traits risk is unclear. This study included 1610 mother-child pairs from the Shanghai Birth Cohort (SBC). Ten PFAS were quantified in blood serum collected in the first trimester. Child autistic traits were evaluated at age 4 using a Chinese version of the social responsiveness scale-short form (SRS-SF). We calculated the polygenic risk score (PRS) to evaluate the cumulative genetic effects of autism. Additive interaction models were established to explore whether genetic susceptibility modified the effects of prenatal PFAS exposure. After adjusting for confounders, we found prenatal PFOA exposure was associated with an increased risk of autistic traits in children (OR, 3.05; 95 % CI, 1.14-7.58), and the increased risk associated with PFOA was mitigated among women who reported pre-pregnancy folic acid supplementation. Additionally, an increased risk of autistic traits was observed in children with higher levels of prenatal PFHxS exposure and a high PRS (p for interaction = 0.021). Our findings suggest prenatal PFAS exposure may increase the risk of autistic traits in children, especially in those with a high genetic risk. Further research is warranted to confirm this association and explore the underlying mechanisms.

GeneCompass: deciphering universal gene regulatory mechanisms with a knowledge-informed cross-species foundation model.

Deciphering universal gene regulatory mechanisms in diverse organisms holds great potential for advancing our knowledge of fundamental life processes and facilitating clinical applications. However, the traditional research paradigm primarily focuses on individual model organisms and does not integrate various cell types across species. Recent breakthroughs in single-cell sequencing and deep learning techniques present an unprecedented opportunity to address this challenge. In this study, we built an extensive dataset of over 120 million human and mouse single-cell transcriptomes. After data preprocessing, we obtained 101,768,420 single-cell transcriptomes and developed a knowledge-informed cross-species foundation model, named GeneCompass. During pre-training, GeneCompass effectively integrated four types of prior biological knowledge to enhance our understanding of gene regulatory mechanisms in a self-supervised manner. By fine-tuning for multiple downstream tasks, GeneCompass outperformed state-of-the-art models in diverse applications for a single species and unlocked new realms of cross-species biological investigations. We also employed GeneCompass to search for key factors associated with cell fate transition and showed that the predicted candidate genes could successfully induce the differentiation of human embryonic stem cells into the gonadal fate. Overall, GeneCompass demonstrates the advantages of using artificial intelligence technology to decipher universal gene regulatory mechanisms and shows tremendous potential for accelerating the discovery of critical cell fate regulators and candidate drug targets.

Engineering Macrophage-Derived Exosome to Deliver Pirfenidone: A Novel Approach to Combat Silicotic Pulmonary Fibrosis.

Silicosis is a severe lung disease characterized by diffuse pulmonary fibrosis, for which there is currently no effective treatment. Pirfenidone (PFD) shows great antifibrotic potential but is clinically hindered by low bioavailability and gastrointestinal side effects. To address these limitations, this study develops a PFD delivery system (PFD-Exo) using J774A.1 macrophage-derived exosomes. Firstly, PFD is loaded via sonication, then PFD-Exo is characterized using Raman spectral imaging and UV absorption spectroscopy. Finally, in vitro and in vivo silicosis models are established to evaluate its antifibrotic effects. Results show that PFD-Exo outperforms free PFD in inhibiting TGF-ß1-induced transdifferentiation of primary lung fibroblasts in vitro. In a mouse model of silicosis, PFD-Exo is found to be accumulated in the lungs following intratracheal administration and significantly ameliorates pulmonary inflammation and fibrosis while minimizing gastrointestinal side effects. Mechanistic studies reveal that PFD-Exo modulates the TGF-ß signaling pathway by downregulating SMAD3 and upregulating SMAD7 and NOGGIN. In conclusion, this study provides the first evidence of macrophage-derived exosomes as an effective PFD delivery system for silicosis treatment and offers a promising strategy for other refractory pulmonary diseases.

Fam3a-mediated prohormone convertase switch in α-cells regulates pancreatic GLP-1 production in an Nr4a2-Foxa2-dependent manner.

BACKGROUND: Fam3a has been demonstrated to regulate pancreatic ß-cell function and glucose homeostasis. However, the role and mechanism of Fam3a in regulating α-cell function remain unexplored. METHODS: Glucagon and glucagon-like peptide-1 (GLP-1) levels in pancreas and plasma were measured in global Fam3a knockout (Fam3a-/-) mice. Human islet single-cell RNA sequencing (scRNA-seq) datasets were utilized to analyze gene expression correlations between FAM3A and PCSK1 (encoding PC1/3, which processes proglucagon into GLP-1). Mouse pancreatic α-cell line αTC1.9 cells were transfected with Fam3a siRNA or plasmid for Fam3a knockdown or overexpression to explore the effects of Fam3a on PC1/3 expression and GLP-1 production. The downstream mediator (including Nr4a2) was identified by transcriptomic analysis, and its role was confirmed by Fam3a knockdown or overexpression in αTC1.9 cells. Based on the interacted protein of Nr4a2 and the direct binding to Pcsk1 promoter, the transcription factor Foxa2 was selected for further verification. Nuclear translocation assay and dual-luciferase reporter assay were used to clarify the involvement of Fam3a-Nr4a2-Foxa2 pathway in PC1/3 expression and GLP-1 production. Moreover, α-cell-specific Fam3a knockout (Fam3aα-/-) mice were constructed to evaluate the metabolic variables and hormone levels under normoglycemic, high-fat diet (HFD)-fed and streptozotocin (STZ)-induced diabetic conditions. Exendin 9-39 (Ex9), a GLP-1 receptor antagonist, was used to investigate GLP-1 paracrine effects in Fam3aα-/- mice and in their primary islets. RESULTS: Compared with wild-type mice, pancreatic and plasma active GLP-1 levels were increased in Fam3a-/- mice. Analysis of human islet scRNA-seq datasets showed a significant negative correction between FAM3A and PCSK1 in α-cells. Fam3a knockdown upregulated PC1/3 expression and GLP-1 production in αTC1.9 cells, while Fam3a overexpression displayed inverse effects. Transcriptomic analysis identified Nr4a2 as a key downstream mediator of Fam3a, and Nr4a2 expression in αTC1.9 cells was downregulated and upregulated by Fam3a knockdown and overexpression, respectively. Nr4a2 silencing increased PC1/3 expression, albeit Nr4a2 did not directly bind to Pcsk1 promoter. Instead, Nr4a2 formed a complex with Foxa2 to facilitate Fam3a-mediated Foxa2 nuclear translocation. Foxa2 negatively regulated PC1/3 expression and GLP-1 production. Besides, Foxa2 inhibited the transcriptional activity of Pcsk1 promoter at specific binding sites 10 and 6, and this inhibition was intensified by Nr4a2 in αTC1.9 cells. Compared with Flox/cre littermates, improved glucose tolerance, increased active GLP-1 level in pancreas and plasma, upregulated plasma insulin level in response to glucose, and decreased plasma glucagon level were observed in Fam3aα-/- mice. Primary islets isolated from Fam3aα-/- mice also showed an increase in active GLP-1 and insulin release. In addition, the insulinotropic effect of intra-islet GLP-1 was blocked by Ex9 in Fam3aα-/- mice and in their primary islets. Similarly, HFD-fed Fam3aα-/- mice also exhibited an improved glucose tolerance. Both HFD-fed and STZ-induced diabetic Fam3aα-/- mice showed an increased pancreatic active GLP-1 level, an elevated plasma insulin level and a reduced plasma glucagon level. CONCLUSIONS: Fam3a deficiency in α-cells enhances pancreatic GLP-1 production to improve ß-cell function via paracrine signaling in an Nr4a2-Foxa2-PC1/3-dependent manner. Our study unveils a novel strategy for reprogramming α-cell proglucagon processing output from glucagon to GLP-1 and deepen the understanding of crosstalk between α-cells and ß-cells.

miR-6884-5p inhibits proliferation and epithelial-mesenchymal transition in non-small cell lung cancer cells.

Background: Non-small cell lung cancer (NSCLC) is associated with a high mortality and morbidity rate. MicroRNAs participate in tumorigenesis, progression and metastasis of NSCLC. However, miR-6884-5p has not been previously studied. This study aimed to investigate the role of miR-6884-5p in NSCLC and explore its underlying mechanisms. Methods: We used miR-6884-5p mimics and inhibitors to assess its effects in NSCLC. miR-6884-5p expression levels in NSCLC cell lines were quantified using qRT-PCR. Cell viability was determined using a cell-counting kit 8 assay. Western blot analysis was employed to measure apoptotic proteins. The impact of miR-6884-5p on cell proliferation was assessed via colony formation assay. Furthermore, Transwell assays were utilized to visualize and quantify the effects of miR-6884-5p on NSCLC migration and invasion. Results: miR-6884-5p mimic significantly inhibited NSCLC cell proliferation to 71.21 % and 72.26 % of control at 5 days of culture time in H460 and HC9 cells (both p < 0.01), respectively, while miR-6884-5p inhibitor significantly promoted cell proliferation to 119.66 % and 126.44 % of control at 5 days of culture time in H460 and HC9 cells (both p < 0.05), respectively. In addition, miR-6884-5p promoted apoptosis by reducing the anti-apoptotic protein B-cell lymphoma 2 (BCL2) protein and increasing apoptotic protein BCL2 associated X protein (all p < 0.01 at least). Moreover, miR-6884-5p effectively suppressed transforming growth factor ß1-induced epithelial-mesenchymal transition, as evidenced by the restored expression of E-cadherin (p < 0.01), N-cadherin (p < 0.01) and Vimentin (p < 0.05), leading to the inhibition of migration and invasion in NSCLC cell lines. Conclusions: Our findings demonstrate that miR-6884-5p can inhibit NSCLC cell proliferation, migration, and invasion, suggesting its potential as a therapeutic target for NSCLC treatment.

Single-cell transcriptomic analysis of flowering regulation and vernalization in Chinese cabbage shoot apex.

In Chinese cabbage development the interplay between shoot apex activity and vernalization is pivotal for flowering timing. The intricate relationship between various cell types in the shoot apex meristem and their roles in regulating flowering gene expression in Chinese cabbage is not yet fully understood. A thorough analysis of single-cell types in the Chinese cabbage shoot apex and their influence on flowering genes and vernalization is essential for deeper insight. Our study first established a single-cell transcriptomic atlas of Chinese cabbage after 25 days of non-vernalization. Analyzing 19 602 single cells, we differentiated them into 15 distinct cell clusters using established marker genes. We found that key genes in shoot apex development and flowering were primarily present in shoot meristematic cells (SMCs), companion cells (CCs), and mesophyll cells (MCs). MADS-box protein FLOWERING LOCUS C 2 (BrFLC2), a gene suppressing flowering, was observed in CCs, mirroring patterns found in Arabidopsis. By mapping developmental trajectories of SMCs, CCs, and MCs, we elucidated the evolutionary pathways of crucial genes in shoot apex development and flowering. The creation of a single-cell transcriptional atlas of the Chinese cabbage shoot apex under vernalization revealed distinct alterations in the expression of known flowering genes, such as VERNALIZATION INSENSITIVE 3 (VIN3), VERNALIZATION 1 (VRN1), VERNALIZATION 2 (VRN2), BrFLC, and FLOWERING LOCUS T (FT), which varied by cell type. Our study underscores the transformative impact of single-cell RNA sequencing (scRNA-seq) for unraveling the complex differentiation and vernalization processes in the Chinese cabbage shoot apex. These insights are pivotal for enhancing breeding strategies and cultivation management of this vital vegetable.

A tumor cornification and immune-infiltration-based scheme for anti-PD-1 plus chemotherapy response in advanced squamous cell lung carcinoma.

BACKGROUND: Anti-PD-1 immunotherapy plus chemotherapy (combo) exhibits significantly prolonged survival for squamous cell lung cancer (LUSC). An exploration of predictive biomarkers is still needed. METHODS: High-throughput RNA sequencing (RNA-seq) of 349 LUSC samples from the randomized, multi-center, phase 3 trial ORIENT-12 (ClinicalTrials.gov: NCT03629925) was conducted for biomarker discovery, followed by flow cytometry and multiplex immunohistochemistry (mIHC) in additional clinical cohorts, and in vitro experiments were performed for verification. RESULTS: A high abundance of activated CD8+ T and CD56bright natural killer (NK) cells benefited patients' outcomes (progression-free survival [PFS]; overall survival [OS]) with combo treatment. Tumor cornification level remarkably affected the infiltration of the two crucial immune cells. Thus, a novel scheme of LUSC immune infiltration and cornification characterization-based classification (LICC) was established for combo efficacy prediction. Patients who received combo treatment achieved significant PFS improvements in LICC1 (hazard ratio [HR] = 0.43, 95% confidence interval [CI]: 0.25-0.75, p = 0.0029) and LICC2 (HR = 0.32, 95% CI: 0.17-0.58, p = 0.0002) subtypes but not in the LICC3 subtype (HR = 0.86, 95% CI: 0.60-1.23, p = 0.4053). Via single-cell RNA-seq analysis, the tumor cornification signal was mainly mapped to SPRR3+ tumor cells, whose relationships with activated CD8+ T or CD56bright NK cells were verified using flow cytometry and mIHC. Our data suggest that SPRR3+ tumor cells might evade immune surveillance via the CD24-SIGLEC10 (M2 macrophage) axis to maintain a suppressive tumor microenvironment. CONCLUSIONS: Tumor cornification greatly impacts immune infiltration, and the LICC scheme may guide clinical medication of anti-PD-1+chemo treatment in patients with LUSC. FUNDING: The study was funded by the National Key R&D Program of China, the National Natural Science Foundation of China, Shanghia Multidisplinary Cooperation Building Project for Diagnosis and Treatment of Major Disease, and Innovent Biologics, Inc.

Addition of ruxolitinib and decitabine to modified busulfan/cyclophosphamide conditioning regimen for prophylaxis relapse in high-risk acute myeloid leukemia: the phase 2 prospective study.

The prognosis of patients with high-risk acute myeloid leukemia (AML) is dismal even after allogeneic stem cell transplantation (allo-HSCT), with relapse remaining the leading cause of treatment failure. Here, we investigated whether ruxolitinib and decitabine plus modified busulfan-cyclophosphamide (mBu/Cy) conditioning could reduce relapse in high-risk AML after allo-HSCT. This prospective, single-arm, phase II trial enrolled 37 patients who received allo-HSCT between September 2020 and March 2022 at the First Medical Center of Chinese People's Liberation Army (PLA) General Hospital. Eligible patients (10-62 years) had relapsed/refractory, positive measurable residual disease (MRD) prior to conditioning or adverse genetic abnormalities. Ruxolitinib (35 mg twice daily, days - 15 to - 10) and decitabine (20 mg/m2/day, days - 15 to - 10) were administered followed by mBu/Cy conditioning. All patients achieved engraftment. The cumulative incidences (CIs) of acute graft-versus-host disease (GVHD) grades II-IV and III-IV were 35.0% and 10.5%, respectively. The 1-year cumulative incidence of chronic GVHD was 8.1%. The 1-year CI of relapse was 29.7% among all patients, 0% in patients who achieved the first complete remission (CR1) prior to conditioning, and 0% in those with MRD-negative prior to conditioning. The 1-year non-relapse mortality was 5.4%. The 1-year probabilities of overall survival, disease-free survival, and GVHD-free relapse-free survival were 70.3%, 62.2%, and 54.1%, respectively. In conclusion, the novel conditioning showed primary efficacy in terms of a reduction in relapse in high-risk patients with AML after allo-HSCT, especially in those who achieved CR1 and MRD-negative prior to conditioning. Also, the new conditioning regimen may help reduce the incidence of chronic GVHD. ClinicalTrials.gov identifier: NCT04582604.

Bismuth titanate microplates with tunable oxygen vacancies for piezocatalytic hydrogen peroxide production.

Piezocatalysis offers an encouraging alternative for the sustainable, on-demand, and decentralized production of hydrogen peroxide (H2O2), underscoring the importance of enhancing piezocatalytic efficiency. Enhancing piezocatalysts through defect engineering has shown considerable potential in boosting H2O2 production efficiency. However, the impact of oxygen vacancies on piezocatalytic activity remains unclear. Herein, we used a chemical probe method to quantify negative charges (q-) and superoxide radicals (O2-) to explore the relation between the oxygen vacancy concentration and piezocatalytic performance of bismuth titanate (Bi4Ti3O12) based catalysts. Results indicate that piezocatalytic H2O2 production in pure water demonstrates a volcanic trend with increasing oxygen vacancy concentration. This trend is attributed to the dual role of oxygen vacancies, which reduce the piezoelectric property of the piezocatalyst while simultaneously increasing the concentration of O2-, which is crucial for H2O2 formation through the O2 reduction pathway. This study provides insights into the interplay between oxygen vacancies, piezoelectric properties, and piezocatalytic activity, offering valuable guidance for the design of piezocatalysts for sustainable H2O2 production.

Prognostic efficacy of non-invasive ventilation in patients with overlap syndrome: chronic obstructive pulmonary disease and obstructive sleep apnea.

Background: Limited evidence exists regarding the effects of non-invasive ventilation (NIV) on the prognosis of patients with concomitant chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA), also known as overlap syndrome (OS). This study aimed to assess whether NIV alongside standard care could improve the prognosis of this cohort. Methods: We retrospectively collected data from 229 patients with severe OS treated in Beijing Anzhen Hospital between January 1, 2016 and January 1, 2020, with follow-up until December 1, 2023. All patients were recommended usual care and NIV and were subsequently divided into non-NIV (usual care only) and NIV groups (usual care plus NIV) per their willingness and adherence to NIV. Endpoints included all-cause and acute exacerbation of COPD (AECOPD)-associated death and re-hospitalization. Multivariate analyses were used to determine the relationship of NIV with prognosis. Results: The follow-up lasted for a median of 760 days (interquartile range, 245-1,374 days). Patients in the NIV group showed lower rates of all-cause (37.5% vs. 65.1%, P<0.001) and AECOPD-associated (31.7% vs. 58.7%, P<0.001) death compared with patients in the non-NIV group. Compared with usual care only, NIV treatment was associated with significant reduction in all-cause death [relative risks (RR) =0.459, 95% confidence interval (CI): 0.315-0.668, P<0.001], AECOPD-associated mortality (RR =0.424, 95% CI: 0.283-0.635, P<0.001), and re-hospitalization for all causes (RR =0.455, 95% CI: 0.342-0.605, P<0.001) and for AECOPD (RR =0.421, 95% CI: 0.308-0.575, P<0.001) in Cox hazards models, with significance persisting after multivariable adjustment. Conclusions: NIV may improve outcomes and survival in patients with severe OS of comorbid COPD and OSA. Confirmatory studies are needed to prove benefits.

Study on the removal of Cd from dewatered sludge by combined extraction agents: Peel extract and compound chemical extraction agent.

The recycling of fruit peel resources is a current research hotspot. This study screened and configured a composite extractant consisting of peel and chemical extractant through extraction experiments and explored the heavy metals(HMs) release effect. The results showed that citrus reticulata(CR), citrullus lanatus (CL), 0.16 mol·L-1 nitrilotriacetic acid(NTA) with 0.04 mol·L-1 oxalic acid(NO5), and 0.12 mol·L-1NTA with 0.08 mol·L-1tartaric acid(NT4) had the strongest extraction ability. After the cross-combination was optimized, CR-NO5 (1:50, 6 h, 35 °C) and CL-NT4 (1:50, 36 h, 45 °C) had the highest extraction rates for Cd and Zn, which were 92.6 % and 98.4 %, respectively. The CL series increased the nutrient content of sludge (157.75-177.88 g·kg-1). The four combined extractants increased the proportion of soluble components of HMs in sludge (14-36 %). Therefore, the combined leaching agent will provide a valuable reference for the harmless treatment of HMs in sludge and the resource utilization of peel waste.

Exploring the promise of regulator of G Protein Signaling 20: insights into potential mechanisms and prospects across solid cancers and hematological malignancies.

RGS (Regulator of G protein signaling) proteins have long captured the fascination of researchers due to their intricate involvement across a wide array of signaling pathways within cellular systems. Their diverse and nuanced functions have positioned them as continual subjects of scientific inquiry, especially given the implications of certain family members in various cancer types. Of particular note in this context is RGS20, whose clinical relevance and molecular significance in hepatocellular carcinoma we have recently investigated. These investigations have prompted questions into the prevalence of pathogenic mutations within the RGS20 gene and the intricate network of interacting proteins that could contribute to the complex landscape of cancer biology. In our study, we aim to unravel the mutations within the RGS20 gene and the multifaceted interplay between RGS20 and other proteins within the context of cancer. Expanding on this line of inquiry, our research is dedicated to uncovering the intricate mechanisms of RGS20 in various cancers. In particular, we have redirected our attention to examining the role of RGS20 within hematological malignancies, with a specific focus on multiple myeloma and follicular lymphoma. These hematological cancers hold significant promise for further investigation, as understanding the involvement of RGS20 in their pathogenesis could unveil novel therapeutic strategies and treatment avenues. Furthermore, our exploration has extended to encompass the latest discoveries concerning the potential involvement of RGS20 in diseases affecting the central nervous system, thereby broadening the scope of its implications beyond oncology to encompass neurobiology and related fields.

Anti-PD-1 combined with hypomethylating agent and CAG regimen bridging to allogeneic hematopoietic stem cell transplantation: a novel strategy for relapsed/refractory acute myeloid leukemia.

Introduction: The prognosis of relapsed/refractory acute myeloid leukemia (r/rAML) is dismal, and allogeneic hematopoietic stem cell transplant (allo-HSCT) is a potential cure. Combining anti-PD-1, hypomethylating agent (HMA), and CAG (cytarabine, aclarubicin/idarubicin, granulocyte colony-stimulating factor) regimen has showed primary efficacy in r/rAML. However, pre-transplant exposure to anti-PD-1 may lead to severe graft-versus-host disease (GVHD). This preliminary study aimed to evaluate the safety and efficacy of allo-HSCT in r/rAML patients receiving the anti-PD-1+HMA+CAG regimen. Methods: Fifteen r/rAML patients (12 related haploidentical donors [HIDs], 2 matched siblings, 1 unrelated donor) received this regimen and subsequent peripheral blood HSCT. Results: Four patients with HIDs received a GVHD prophylaxis regimen consisted of Anti-thymocyte globulin and a reduced-dose of post-transplant cyclophosphamide. The median follow-up was 20.9 months (range, 1.2-34.2). The cumulative incidences of acute GVHD grade 2-4 and grade 3-4 were 40% and 13.3%, respectively. The 2-year incidence of moderate-to-severe chronic GVHD, non-relapse mortality, and relapse were 10%, 22.3%, and 22.5%, respectively. The 2-year overall survival and GVHD-free/relapse-free survival rates were 54% and 48.6%, respectively. No death or relapse was observed in the PTCy group. Conclusion: The anti-PD-1+HMA+CAG regimen bridging to allo-HSCT for r/r AML was tolerable with promising efficacy. GVHD prophylaxis with PTCy for HID-HSCT showed preliminary survival advantage.

[Multidimensional biodiversity of subalpine forest communities on the eastern edge of the Qinghai-Tibet Plateau, China]. / é’è—é«˜åŽŸä¸œç¼˜äºšé«˜å±±æ£®æž—ç¾¤è½çš„å¤šç»´åº¦ç”Ÿç‰©å¤šæ ·æ€§.

We analyzed multidimensional biodiversity (including species diversity, functional diversity, and phylogenetic diversity) of needle-broadleaf mixed forests of Abies fargesii var. faxoniana-Betula spp. and needleleaf forests of A. fargesii var. faxoniana in the subalpine regions of eastern edge of Qinghai-Tibet Plateau. We measured leaf functional traits including leaf area, leaf thickness, leaf dry matter content, and specific leaf area. The results showed that leaf thickness (0.28 mm) and leaf dry matter content (319.86 mg·g-1) in the needle-broadleaf mixed forests were significantly lower than in the needleleaf forest (0.39 mm and 371.33 mg·g-1, respectively), while specific leaf area (192.74 cm2·g-1) was significantly higher (100.91 cm2·g-1). Leaf area showed no significant difference between the two forest communities (27.88 and 26.63 cm2, respectively). The phylogenetic signals of all leaf functional traits were significant, except for leaf thickness. The phylogenetic structure of the needle-broadleaf mixed forests and needleleaf forest communities tended toward divergence. Shannon diversity index, Simpson diversity index, species richness, functional richness, functional dispersion, Rao's quadratic entropy, and phylogenetic diversity in the needle-broadleaf mixed forests were all significantly higher than in the needleleaf forest, and these indices were significantly positively correlated. Competitive exclusion played a major role in the assembly of subalpine forest communities, and species diversity, functional diversity, and phylogenetic diversity exhibited synchrony.