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Abstract The bulk photovoltaic effect (BPVE) in non-centrosymmetric materials has attracted significant attention in recent years due to its potential to surpass the Shockley-Queisser limit. Although these materials are strictly constrained by symmetry, progress has been made in artificially reducing symmetry to stimulate BPVE in wider systems. However, the complexity of these techniques has hindered their practical implementation. In this study, we demonstrate a large intrinsic photocurrent response in centrosymmetric topological insulator Ag2Te, attributed to the surface photogalvanic effect (SPGE), which is induced by symmetry reduction of the surface. Through diverse spatially-resolved measurements on specially designed devices, we directly observe that SPGE in Ag2Te arises from the difference between two opposite photocurrent flows generated from the top and bottom surfaces. Acting as an efficient SPGE material, Ag2Te demonstrates robust performance across a wide spectral range from visible to mid-infrared, making it promising for applications in solar cells and mid-infrared detectors. More importantly, SPGE generated on low-symmetric surfaces can potentially be found in various systems, thereby inspiring a broader range of choices for photovoltaic materials.

BackgroundThyroid hormones significantly influence cardiovascular pathophysiology, yet their prognostic role in acute aortic dissection (AAD) remains inadequately explored. This study assesses the prognostic value of thyroid hormone levels in AAD, focusing on the mediating roles of renal function and coagulation.MethodsWe included 964 AAD patients in this retrospective cohort study. Utilizing logistic regression, restricted cubic splines, and causal mediation analysis, we investigated the association between thyroid hormones and in-hospital mortality and major adverse cardiovascular events (MACEs).ResultsIn AAD patients overall, an increase of one standard deviation in FT4 levels was associated with a 31.9% increased risk of MACEs (OR 1.319; 95% CI 1.098–1.584) and a 36.1% increase in in-hospital mortality (OR 1.361; 95% CI 1.095–1.690). Conversely, a higher FT3/FT4 ratio was correlated with a 20.2% reduction in risk of MACEs (OR 0.798; 95% CI 0.637–0.999). This correlation was statistically significant predominantly in Type A AAD, while it did not hold statistical significance in Type B AAD. Key renal and coagulation biomarkers, including blood urea nitrogen, creatinine, cystatin C, prothrombin time ratio, prothrombin time, and prothrombin time international normalized ratio, were identified as significant mediators in the interplay between thyroid hormones and MACEs. The FT3/FT4 ratio exerted its prognostic influence primarily through the mediation of renal functions and coagulation, while FT4 levels predominantly impacted outcomes via a partial mediation effect on coagulation.ConclusionFT4 levels and the FT3/FT4 ratio are crucial prognostic biomarkers in AAD patients. Renal function and coagulation mediate the association between the thyroid hormones and MACEs.

Background: Aortic dissection (AD) is a lethal aortic disease with limited effective therapeutic strategies. Aging increases the risk of AD, yet the underlying mechanisms remain unclear. This study aims to analyze the association of aging-related genes (Args) and AD using bioinformatic analysis. This helps provide novel insights into AD pathogenesis and contributes to developing novel therapeutic strategies. Methods: mRNA (GSE52093, GSE153434), miRNA (GSE98770) and single-cell RNA-sequencing (scRNA-seq, GSE213740) datasets of AD were downloaded from GEO database. Args were downloaded from Aging Atlas database. Differentially-expressed Args were determined by intersecting Args and differentially-expressed mRNAs of two mRNA datasets. Cytoscape was used to identify hub genes and construct hub gene regulatory networks related to miRNAs. Seurat and clusterProfiler R package were used for investigating expression patterns of hub genes at single-cell level, and functional analysis, respectively. To validate the cellular expression pattern of hub genes, the same analysis was applied to our own scRNA-seq data. Drugs targeting hub Args were determined using the DGIdb database. Results: HGF, CXCL8, SERPINE1, HIF1A, TIMP1, ESR1 and PLAUR were identified as aging-related hub genes in AD. miR-221-3p was predicted to interact with ESR1. A decreased ESR1 expression in smooth muscle cell subpopulation 4 (SMC4) was observed in AD versus normal aortic tissues, which was validated by sequencing 197,605 aortic cells from 13 AD patients. Additionally, upregulated genes of SMC4 in AD tissues were enriched in the “cellular senescence” pathway. These data indicated that decreased ESR1 might promote SMC4 aging during AD formation. Eleven existing drugs targeting hub genes were identified, including ruxolitinib and filgrastim, which are associated with AD. Conclusions: By sequencing transcriptomic data, this study revealed aging-related hub genes and regulatory network involved in AD formation. Additionally, this study proposed a noteworthy hypothesis that downregulated ESR1 may exacerbate AD by promoting SMC aging, which requires further investigation.

Currently, analyzing pharmaceuticals and biomarkers is crucial for ensuring medication safety and protecting life and health, and there is an urgent need to develop new and efficient analytical techniques in view of the limitations of traditional analytical methods. Molecularly imprinted ratiometric fluorescent (MI-RFL) sensors have received increasing attention in the field of analytical detection due to their high selectivity, sensitivity and anti-interference ability, short response time, and visualization. This review summarizes the recent advances of MI-RFL sensors in the field of pharmaceuticals and biomarkers detection. Firstly, the fluorescence sources and working mechanisms of MI-RFL sensors are briefly introduced. On this basis, new techniques and strategies for preparing molecularly imprinted polymers, such as dummy template imprinting, nanoimprinting, multi-template imprinting, and stimulus-responsive imprinting strategies, are presented. Then, dual- and triple-emission types of fluorescent sensors are introduced. Subsequently, specific applications of MI-RFL sensors in pharmaceutical analysis and biomarkers detection are highlighted. In addition, innovative applications of MI-RFL sensors in point-of-care testing are discussed in-depth. Finally, the challenges of MI-RFL sensors for analysis of pharmaceuticals and biomarkers are proposed, and the research outlook and development trends of MI-RFL sensors are prospected.

Defining the copper-based catalysts that are responsible for the catalytic behaviour of oil-paper insulation systems and implementing effective regulation are of great significance. Accelerated ageing experiments were conducted to reveal variations in copper scales and deterioration in insulation properties. As ageing progressed, TEM images demonstrated that copper species were adsorbed and aggregated on the fibre surface in the form of nanoparticles (NPs). The scale of NPs exhibited a continuous increase, from 27.06 nm to 94.19 nm. Cu(I) and Cu(II) species were identified as the active sites for inducing intense free radical reactions, which significantly reduced the activation energy, making the insulating oil more susceptible to oxidation. The role of the antioxidant di-tert-butyl-p-cresol (DBPC) in extending the insulation life was regulated by determining the optimal addition time based on variations in the interfacial tension. After the second addition of DBPC, the ageing rates of the dissipation factor, acidity, micro-water and breakdown voltage in the Cu+DBPC group decreased by 28.8%, 43.2%, 52.9% and 46.7%, respectively, compared to the Cu group. This finding not only demonstrates the crucial role of DBPC in preventing the copper-based catalyst-induced oxidation of insulating oil, but also furnishes a vital foundation for enhancing the long-term stability of transformer insulation systems.

Abstract Background Deregulation of lncRNAs has been observed in human osteosarcoma. This study explored the diagnostic and prognostic significance of EPB41L4A-AS1 and UNC5B-AS1 in osteosarcoma. Methods Relative levels of EPB41L4A-AS1 and UNC5B-AS1 were detected in osteosarcoma tissue samples and cells. The ability to distinguish osteosarcoma from health was assessed by receiver operating characteristic (ROC) curve construction. Kaplan–Meier (K–M) and Cox proportional-hazards analyses were performed for prognosis factors. The bioinformatics approach was used to identify targeting miRNA for EPB41L4A-AS1 and UNC5B-AS1. Kaplan–Meier survival curves and Whitney Mann U tests were conducted for validating the statistical significance. In cell culture experiments, the influence of EPB41L4A-AS1 and UNC5B-AS1 on proliferation, migration, and invasion of the osteosarcoma cell line was examined by CCK-8 and Transwell assays. Results Levels of EPB41L4A-AS1 and UNC5B-AS1 were upregulated in osteosarcoma patients and cells compared with the healthy participants and normal cell lines. EPB41L4A-AS1 and UNC5B-AS1 have a potent ability to distinguish the patients with osteosarcoma from the health. EPB41L4A-AS1 and UNC5B-AS1 levels correlated with SSS stage. Patients with high levels of EPB41L4A-AS1 and UNC5B-AS1 had significantly shorter survival times. EPB41L4A-AS1 and UNC5B-AS1 were independent prognostic indexes for overall survival. miR-1306-5p was a common target for EPB41L4A-AS1 and UNC5B-AS1. A propulsive impact on cell proliferation, migration, and invasion by EPB41L4A-AS1 and UNC5B-AS1 was observed, but can be rescued by miR-1306-5p. Conclusions It was concluded that upregulations of EPB41L4A-AS1 and UNC5B-AS1 expression were diagnostic and prognostic biomarkers for human osteosarcoma. EPB41L4A-AS1 and UNC5B-AS1 contribute to the biological behavior of osteosarcoma via miR-1306-5p.

Abstract New variants in the SARS‐CoV‐2 pandemic are more contagious (Alpha/Delta), evade neutralizing antibodies (Beta), or both (Omicron). This poses a challenge in vaccine development according to WHO. We designed a more universal SARS‐CoV‐2 DNA vaccine containing receptor‐binding domain loops from the huCoV‐19/WH01, the Alpha, and the Beta variants, combined with the membrane and nucleoproteins. The vaccine induced spike antibodies crossreactive between huCoV‐19/WH01, Beta, and Delta spike proteins that neutralized huCoV‐19/WH01, Beta, Delta, and Omicron virus in vitro. The vaccine primed nucleoprotein‐specific T cells, unlike spike‐specific T cells, recognized Bat‐CoV sequences. The vaccine protected mice carrying the human ACE2 receptor against lethal infection with the SARS‐CoV‐2 Beta variant. Interestingly, priming of cross‐reactive nucleoprotein‐specific T cells alone was 60% protective, verifying observations from humans that T cells protect against lethal disease. This SARS‐CoV vaccine induces a uniquely broad and functional immunity that adds to currently used vaccines.

Deficiency in thymidine kinase 2 (TK2) causes mitochondrial DNA depletion. Liver mitochondria are severely affected in Tk2 complete knockout models and have been suggested to play a role in the pathogenesis of the Tk2 knockout phenotype, characterized by loss of hypodermal fat tissue, growth retardation and reduced life span. Here we report a liver specific Tk2 knockout (KO) model to further study mechanisms contributing to the phenotypic changes associated with Tk2 deficiency. Interestingly, the liver specific Tk2 KO mice had a normal life span despite a much lower mtDNA level in liver tissue. Mitochondrial DNA encoded peptide COXI did not differ between the Tk2 KO and control mice. However, the relative liver weight was significantly increased in the male Tk2 KO mouse model. Histology analysis indicated an increased lipid accumulation. We conclude that other enzyme activities can partly compensate Tk2 deficiency to maintain mtDNA at a low but stable level throughout the life span of the liver specific Tk2 KO mice. The lower level of mtDNA was sufficient for survival but led to an abnormal lipid accumulation in liver tissue.

BackgroundRecent studies of fibroblast growth factor 21 (FGF21), first recognized as a regulator of glucose and lipid metabolism, have found that the level of in serum FGF21 is associated with the prognosis of many cardiovascular diseases, but its relationship to acute heart failure (AHF) patients remains unknown. Our study aimed to investigate whether circulating FGF21 could predict the short-term prognosis of AHF patients.MethodsFour hundred and two AHF patients and 19 healthy controls were recruited into the prospective cohort study, and blood samples of participants were collected, in tubes without anticoagulant, within the first 24 h after hospital admission. Serum FGF21 levels were detected by enzyme-linked immunosorbent assay (ELISA). All patients were followed-up at least 6 months after discharge. The primary endpoint was all-cause death, and secondary endpoint was a composite endpoint of death and heart failure readmission. Mortality and composite end point events were analyzed using Kaplan-Meier curves. ROC curves compared the difference between the FGF21 and NT-proBNP in predicting 3- and 6-months mortality. Time-to-event data were evaluated using Kaplan-Meier estimation and Cox proportional hazards models.ResultsIn the present study, the serum FGF21 concentrations were significantly higher in the 402 AHF patients enrolled, compared with the 19 healthy controls (p < 0.001). The average age was 70 (±12) years, and 58% were males. Participants were divided into two groups according to the median FGF21 level (262 pg/ml): a high FGF21 group (n = 201, FGF21 ≥ 262 pg/ml) and low FGF21 group (n = 201, FGF21

Grafting is widely used to increase plant defense responses to various stresses. Grafting-induced cold tolerance is associated with the increase of the antioxidant potential of plants; however, the underlying mechanisms remain unclear. Here, we found that pumpkin rootstocks promote antioxidant enzyme activities and alleviate cold-induced oxidative damage, accompanied by increased abscisic acid (ABA), melatonin, and methyl jasmonate (MeJA) levels in leaves. Increased ABA accumulation in leaves was attributed partly to the increased ABA levels in rootstocks. ABA induced antioxidant enzymes activities and the accumulation of melatonin and MeJA, while inhibition of ABA synthesis blocked the rootstock-induced antioxidant activity and the accumulation of melatonin and MeJA under cold stress. Melatonin and MeJA application also enhanced ABA accumulation in leaves after cold exposure, whereas inhibition of melatonin or MeJA synthesis attenuated the rootstock-induced increase of ABA. Moreover, melatonin and MeJA application alleviated cold-induced oxidative stress, but inhibition of melatonin or MeJA synthesis lowered the rootstock- or ABA-induced antioxidant potential and tolerance to cold. These findings indicate that ABA plays an important role in the grafting-induced cold tolerance by promoting the accumulation of melatonin and MeJA, which in turn, promote ABA accumulation, forming a positive feedback loop.

Background: The existing prediction models lack the generalized applicability for chronic heart failure (CHF) readmission. We aimed to develop and validate a widely applicable nomogram for the prediction of 180-day readmission to the patients.Methods: We prospectively enrolled 2,980 consecutive patients with CHF from two hospitals. A nomogram was created to predict 180-day readmission based on the selected variables. The patients were divided into three datasets for development, internal validation, and external validation (mean age: 74.2 ± 14.1, 73.8 ± 14.2, and 71.0 ± 11.7 years, respectively; sex: 50.2, 48.8, and 55.2% male, respectively). At baseline, 102 variables were submitted to the least absolute shrinkage and selection operator (Lasso) regression algorithm for variable selection. The selected variables were processed by the multivariable Cox proportional hazards regression modeling combined with univariate analysis and stepwise regression. The model was evaluated by the concordance index (C-index) and calibration plot. Finally, the nomogram was provided to visualize the results. The improvement in the regression model was calculated by the net reclassification index (NRI) (with tenfold cross-validation and 200 bootstraps).Results: Among the selected 2,980 patients, 1,696 (56.9%) were readmitted within 180 days, and 1,502 (50.4%) were men. A nomogram was established by the results of Lasso regression, univariate analysis, stepwise regression and multivariate Cox regression, as well as variables with clinical significance. The values of the C-index were 0.75 [95% confidence interval (CI): 0.72–0.79], 0.75 [95% CI: 0.69–0.81], and 0.73 [95% CI: 0.64–0.83] for the development, internal validation, and external validation datasets, respectively. Calibration plots were provided for both the internal and external validation sets. Five variables including history of acute heart failure, emergency department visit, age, blood urea nitrogen level, and beta blocker usage were considered in the final prediction model. When adding variables involving hospital discharge way, alcohol taken and left bundle branch block, the calculated values of NRI demonstrated no significant improvements.Conclusions: A nomogram for the prediction of 180-day readmission of patients with CHF was developed and validated based on five variables. The proposed methodology can improve the accurate prediction of patient readmission and have the wide applications for CHF.

The porous aerostatic bearing is a new supporting structure that is widely used in precision and ultraprecision engineering and the aerospace and other fields. The aerostatic bearing has a good bearing capacity and static stiffness. In this work, the numerical and experimental research on the static characteristics of an aerostatic bearing based on a porous SiC ceramic membrane is presented. The porous ceramic membrane prepared by reactive sintering, with a porosity of 25.8% and a pore size of 20.55 μm, was used as the restrictor to fabricate the aerostatic bearing. It was found that the ceramics have good permeability, and the permeability coefficient reached 2.78 × 10−13 m2 using permeability-test experiments. The effects of the gas-supply pressure and permeability coefficient on the static characteristics of the aerostatic bearing based on porous ceramics were analyzed using Fluent simulation calculation. When the gas-supply pressure was 0.5 MPa and the gas-film thickness was 6 μm, the static stiffness of the aerostatic bearing reached a maximum of 20.9 N/μm, while the bearing capacity was 632.5 N. The numerical results of the static characteristics of the aerostatic bearing are highly consistent with the experimental results, which verifies the accuracy of the Fluent simulation, and provides convenience for studying the static characteristics of aerostatic bearings.

Therapeutic hypothermia is a potent tool in the treatment of neonatal hypoxic-ischemic (HI) injury, yet the underlying mechanisms remain unclear. Here, authors demonstrate how the RNA-binding motif protein RBM3, which is induced by mild cooling while global translation rate is slowed down, contributes substantially to neuroregeneration after adult HI injury, specifically in the subventricular zone and subgranular zone.

This study is aimed at exploring the relationship between serum ferritin and blood lipids and the influence of diabetes and different hs-CRP levels. A total of 8163 subjects were analyzed. Participators were classified according to serum ferritin, diabetes, and two hs-CRP levels. Blood lipids were determined using standardized methods and conditions. Except for HDL-C, there was a significant increase in blood lipids in the progressive ferritin group with normal hs-CRP levels (P0.05). After a sufficient adjustment, there was a positive correlation between serum TG and ferritin and a negative correlation between LDL-C and ferritin. Nonetheless, a negative correlation between LDL-C and ferritin is influenced by diabetes frailly. And, there was no change of relationship between lipids and ferritin in different hs-CRP levels. We found a real relationship between ferritin and lipids after sufficient adjustment for confounders.

To investigate the energy evolution and storage performances of rock under uniaxial cyclic compression, a series of uniaxial cyclic loading and unloading compression tests were conducted on Green sandstone and Yueyang granite. Two methods for calculating the total input energy of the specimen under each cycle were proposed. One is based on the actual stress-strain curve of the specimen (ASC method); the other is based on the stress-strain envelope curve during the loading process (SEC method). The experimental results show that, for those two methods, the total input energy, elastic energy, and dissipated energy of the specimen show a quadratic function increasing trend with the increase of stress levels. Besides, the elastic energy increases linearly with the increase of total input energy for both methods, which confirms that the linear energy storage law is also applicable to rock materials under uniaxial cyclic loading and unloading compression conditions. Moreover, the uniaxial compression energy storage coefficient calculated by the SEC method is highly close to that obtained based on the single cycle loading and unloading test, which indicates that the uniaxial compression energy storage coefficient of rock can also be calculated by multiple cyclic loading and unloading test. In conclusion, the linear energy storage law is a basic physical property of rock materials, and the uniaxial compression energy storage coefficient is a physical index reflecting the energy storage capacity of rock materials.

Neural stem cells (NSCs) reside physiologically in a hypoxic niche to maintain self-renewal and multipotency. Whereas mild hypoxia is known to promote NSC proliferation, severe hypoxia in pathological conditions exerts the reverse effect. The multi-functional RNA-binding protein RBM3 is abundant in NSCs and can be regulated by hypoxic exposure. Although RBM3 has been shown to accelerate cell growth in many cell types, whether and how it affects NSC proliferation in hypoxic environment remains largely unknown. In this study, we tested how RBM3 regulates cell proliferation under hypoxia in C17.2 mouse NSC cell line and in primary mouse NSCs from both the forebrain of postnatal day 0 (P0) mice and the subgranular zone (SGZ) of adult mice. Our results demonstrated that RBM3 expression was highly sensitive to hypoxia, and NSCs were arrested in G0/G1 phase by 5, 2.5, and 1% O2 treatment. When we overexpressed RBM3, hypoxia-induced cell cycle arrest in G0/G1 phase was relieved and more cell transit into S phase was observed. Furthermore, cell viability under hypoxia was also increased by RBM3. In contrast, in RBM3-depleted primary NSCs, less BrdU-incorporated cells were detected, indicating exacerbated cell cycle arrest in G1 to S phase transition. Instead, overexpressed RBM3 significantly increased proliferation ratio in primary NSCs. Our findings indicate RBM3 as a potential target to maintain the proliferation capacity of NSCs under hypoxia, which can be important in NSC-based therapies of acute brain injury and chronic neurodegenerative diseases.

Imatinib is the first line of therapy for patients with metastatic or gastrointestinal stromal tumors (GIST). However, drug resistance limits the long-term effect of imatinib. Long non-coding RNAs (lncRNAs) are emerging as key players in regulating drug resistance in cancer. In this study, we investigated the association between lncRNA CCDC26 and IGF-1R in GIST and their involvement in drug resistance. Considering the key role of lncRNAs in drug resistance in cancer, we hypothesized that IGF-1R is regulated by lncRNAs. The expression of a series of reported drug resistance-related lncRNAs, including CCDC26, ARF, H19, NBR2, NEAT1, and HOTAIR, in GIST cells treated with imatinib H19 was examined at various time-points by qRT-PCR. Based on our results and published literature, CCDC26, a strongly down-regulated lncRNA following imatinib treatment, was chosen as our research target. GIST cells with high expression of CCDC26 were sensitive to imatinib treatment while knockdown of CCDC26 significantly increased the resistance to imatinib. Furthermore, we found that CCDC26 interacted with c-KIT by RNA pull down, and that CCDC26 knockdown up-regulated the expression of IGF-1R. Moreover, IGF-1R inhibition reversed CCDC26 knockdown-mediated imatinib resistance in GIST. These results indicated that treatments targeting CCDC26-IGF-1R axis would be useful in increasing sensitivity to imatinib in GIST.

Abstract The discovery of Lactylation may pave the way for novel approaches to investigating sepsis. This study focused on the prognostic and diagnostic significance of lactylated genes in sepsis. RNA sequencing was performed on blood samples from 20 sepsis patients and 10 healthy individuals at Southwest Medical University in Luzhou, Sichuan, China. Genes associated with sepsis were identified through analysis of RNA sequencing data. Afterward, the genes that were expressed differently were compared with the lactylation genes, resulting in the identification of 55 lactylation genes linked to sepsis. The overlapping genes underwent analysis using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Protein-Protein Network Interactions were used to screen for the core genes. The datasets GSE65682, GSE69528, GSE54514, GSE63042, and GSE95233 were obtained from the GEO database to validate core genes. Survival analysis evaluated the predictive significance of central genes in sepsis, while Receiver Operating Characteristic (ROC) Curve analysis was employed to establish the diagnostic value of genes. Additionally, a meta-analysis was conducted to confirm the precision of RNA-seq data. We obtained five peripheral blood samples, including two from healthy individuals, one from a patient with systemic inflammatory response syndrome (SIRS), and two from patients with sepsis. These samples were used to identify the specific location of core genes using 10×single-cell sequencing. High-throughput sequencing and bioinformatics techniques identified two lactylation-related genes (S100A11 and CCNA2) associated with sepsis. Survival analysis indicated that septic patients with reduced levels of S100A11 had a decreased 28-day survival rate compared to those with elevated levels. Conversely, individuals exhibiting decreased CCNA2 levels demonstrated a greater likelihood of surviving for 28 days than those in the high expression category, indicating a favorable association with survival rates among sepsis patients (P

Abstract Developing broad-spectrum influenza vaccines is crucial for influenza control and potential pandemic preparedness. Here, we reported a novel vaccine design utilizing circular RNA (circRNA) as a delivery platform for multi-subtype neuraminidases (NA) (influenza A N1, N2, and influenza B Victoria lineage NA) immunogens. Individual NA circRNA lipid nanoparticles (LNP) elicited robust NA-specific antibody responses with neuraminidase inhibition activity (NAI), preventing the virus from egressing and infecting neighboring cells. Additionally, the administration of circRNA LNP induced cellular immunity in mice. To achieve a universal influenza vaccine, we combined all three subtypes of NA circRNA-LNPs to generate a trivalent circRNA vaccine. The trivalent vaccine elicited a balanced antibody response against all three NA subtypes and a Th1-biased immune response in mice. Moreover, it protected mice against the lethal challenge of matched and mismatched H1N1, H3N2, and influenza B viruses, encompassing circulating and ancestral influenza virus strains. This study highlights the potential of delivering multiple NA antigens through circRNA-LNPs as a promising strategy for effectively developing a universal influenza vaccine against diverse influenza viruses.

Abstract Quorum sensing (QS) inhibition has emerged as a promising target for directed drug design, providing an appealing strategy for developing antimicrobials, particularly against infections caused by drug‐resistant pathogens. In this study, we designed and synthesized a total of 33 β‐nitrostyrene derivatives using 1‐nitro‐2‐phenylethane (NPe) as the lead compound, to target the facultative anaerobic bacterial pathogen Serratia marcescens. The QS‐inhibitory effects of these compounds were evaluated using S. marcescens NJ01 and the reporter strain Chromobacterium violaceum CV026. Among the 33 new β‐nitrostyrene derivatives, (E)‐1‐methyl‐4‐(2‐nitrovinyl)benzene (m‐NPe, compound 28) was proven to be a potent inhibitor that reduced biofilm formation of S. marcescens NJ01 by 79%. Scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) results revealed that treatment with m‐NPe (50 μg/ml) not only enhanced the susceptibility of the formed biofilms but also disrupted the architecture of biofilms by 84%. m‐NPe (50 μg/ml) decreased virulence factors in S. marcescens NJ01, reducing the activity of protease, prodigiosin, and extracellular polysaccharide (EPS) by 36%, 72%, and 52%, respectively. In S. marcescens 4547, the activities of hemolysin and EPS were reduced by 28% and 40%, respectively, outperforming the positive control, vanillic acid (VAN). The study also found that the expression levels of QS‐ and biofilm‐related genes (flhD, fimA, fimC, sodB, bsmB, pigA, pigC, and shlA) were downregulated by 1.21‐ to 2.32‐fold. Molecular dynamics analysis showed that m‐NPe could bind stably to SmaR, RhlI, RhlR, LasR, and CviR proteins in a 0.1 M sodium chloride solution. Importantly, a microscale thermophoresis (MST) test revealed that SmaR could be a target protein for the screening of a quorum sensing inhibitor (QSI) against S. marcescens. Overall, this study highlights the efficacy of m‐NPe in suppressing the virulence factors of S. marcescens, identifying it as a new potential QSI and antibiofilm agent capable of restoring or improving antimicrobial drug sensitivity.

The aim of this study was to explore the role and mechanism of long non-coding RNA (lncRNA) HIF1A antisense RNA 2 (HIF1A-AS2) in regulating imatinib (IM) resistance in gastrointestinal stromal tumor (GIST) cells under hypoxia. The expression of HIF1A-AS2 was silenced by siRNA in GIST cells. Cytotoxicity, apoptosis, and autophagy were evaluated under normoxic and hypoxic conditions. The expression levels of HIF1A-AS2, HIF1A, apoptosis-associated genes, and autophagy-associated genes were determined by qRT-PCR analysis and western blot. We found that lncRNA HIF1A-AS2 was highly expressed in GIST tissues and cells. Knockdown of HIF1A-AS2 increased the sensitivity of GIST cells to IM and increased apoptosis. Moreover, a hypoxic environment decreased the sensitivity of GIST cells to IM, and the knockdown of HIF1A-AS2 reversed this effect. Mechanistically, the knockdown of HIF1A-AS2 inhibited IM-mediated autophagy. Finally, HIF1A was found to positively regulate HIF1A-AS2 under hypoxic conditions. Collectively, these data demonstrate that hypoxia-induced HIF1A-AS2 promotes IM resistance in GIST cells by regulating autophagy. [ABSTRACT FROM AUTHOR]

Abstract Background Proteinuria is a prevalent symptom of pediatric nephrology, while kidney biopsy remains the gold standard for kidney tissue analysis, and it is currently controversial. We report the rare case that the mutation in the AMN gene was considered to cause chronically isolated proteinuria and also suggest that renal biopsy should be chosen with caution in children with chronic isolated non-nephrotic levels of proteinuria and that genetic testing may be feasible for the early precise diagnosis. Case presentation A 35-month-old boy presented with excessive urine foaming for more than half a month; his proteinuria was considered non-nephrotic range and urine protein electrophoresis was suggestive of mixed proteinuria; other than that, the investigations are non-specific. Given the child’s chronic isolated proteinuria and good renal function, we chose to refine the genetic test rather than a renal biopsy; a compound heterozygous variant was found in the AMN gene of this child which was caused by a point mutation in the father, and a partial chromosomal deletion in the mother. Conclusions Cubilin(encoded by CUBN), amnionless(encoded by AMN), and megalin form a multiligand receptor complex; CUBN or AMN gene variants have been implicated as a hereditary cause of megaloblastic anemia, proteinuria, and neurological impairment. In the past few decades, chronic isolated proteinuria caused by CUBN gene variants is benign, non-progressive, and has normal renal function. However, the child is the first reported case of isolated proteinuria of AMN gene mutation, indicating that the earlier diagnostic genetic sequencing in an otherwise well, not nephrotic proteinuria child may be a convenient, cost-effective, and harmless option, challenging the traditional paradigm.

Sexual selection, one of the central pillars of evolutionary theory, has powerful effects on organismal morphology, behaviour, and population dynamics. However, current knowledge about geographical variation in this evolutionary mechanism and its underlying drivers remains highly incomplete, in part because standardised data on the strength of sexual selection is sparse even for well-studied organisms. Here, we use information on mating systems-including the incidence of polygamy and extra-pair paternity-to estimate the intensity of sexual selection in 10,671 (>99.9%) bird species distributed worldwide. We show that avian sexual selection varies latitudinally, peaking at higher latitudes, although the gradient is reversed in the world's most sexually selected birds-specialist frugivores-which are strongly associated with tropical forests. Phylogenetic models further reveal that the strength of sexual selection is explained by temperature seasonality coupled with a suite of climate-associated factors, including migration, diet, and territoriality. Overall, these analyses suggest that climatic conditions leading to short, intense breeding seasons, or highly abundant and patchy food resources, increase the potential for polygamy in birds, driving latitudinal gradients in sexual selection. Our findings help to resolve longstanding debates about spatial variation in evolutionary mechanisms linked to reproductive biology and also provide a comprehensive species-level data set for further studies of selection and phenotypic evolution in the context of global climatic change.

BackgroundUpadacitinib, a specific JAK1 inhibitor, has minimal effect on other JAK subtypes. It influences the inflammatory process in various ways. Upadacitinib has been approved for conditions such as rheumatoid arthritis, psoriatic arthritis, atopic dermatitis, and ulcerative colitis in various countries. The purpose of this study is to assess the clinical efficacy and safety of upadacitinib in patients with refractory palmoplantar pustulosis who have not responded to conventional treatments (e.g., Acitretin, Tripterygium wilfordii Hook F, cyclosporine, methotrexate).MethodsWe conducted a retrospective collection of clinical data from 28 patients who received upadacitinib treatment at the Department of Dermatology, First Affiliated Hospital of Suzhou University, from July 2022 to December 2023. We evaluated the Palmoplantar Pustulosis Area and Severity Index (PPPASI) scores, Dermatology Life Quality Index (DLQI) scores, and Physician’s Global Assessment (PGA) scores before and after treatment. We also recorded any adverse events during the treatment process.ResultsA total of 28 patients were diagnosed with PPP, including 10 males and 18 females, and 8 patients (3 males and 5 females) were diagnosed with SAPHO syndrome. The mean age was (36.3 ± 10.5) years. After 12 weeks of treatment, PPPASI scores decreased from baseline (13.86 ± 2.76) to (5.56 ± 1.08), with a statistically significant difference (p < 0.05). DLQI scores decreased from (12.55 ± 4.56) to (2.03 ± 1.13), also showing a statistically significant difference (p < 0.05). Additionally, 20 patients achieved a PGA score of 0/1. No severe adverse events were reported during the treatment and follow-up period.ConclusionUpadacitinib could be an additional safe and effective treatment for treating refractory palmoplantar pustulosis with a potential benefit on patients’ quality of life. Further studies are needed to assess its short-and long-term efficacy and safety in larger sample sizes in randomized double-blind controlled trials.

BackgroundWhile bibliometric studies of individual journals have been conducted, to the best of our knowledge, bibliometric mapping has not yet been utilized to analyze the literature published by the Journal of Medical Internet Research (JMIR). ObjectiveIn celebration of the journal’s 25th anniversary, this study aimed to review the entire collection of JMIR publications from 1999 to 2024 and provide a comprehensive overview of the main publication characteristics. MethodsThis study included papers published in JMIR during the 25-year period from 1999 to 2024. The data were analyzed using CiteSpace, VOSviewer, and the “Bibliometrix” package in R. Through descriptive bibliometrics, we examined the dynamics and trend patterns of JMIR literature production and identified the most prolific authors, papers, institutions, and countries. Bibliometric maps were used to visualize the content of published articles and to identify the most prominent research terms and topics, along with their evolution. A bibliometric network map was constructed to determine the hot research topics over the past 25 years. ResultsThis study revealed positive trends in literature production, with both the total number of publications and the average number of citations increasing over the years. And the global COVID-19 pandemic induced an explosive rise in the number of publications in JMIR. The most productive institutions were predominantly from the United States, which ranked highest in successful publications within the journal. The editor-in-chief of JMIR was identified as a pioneer in this field. The thematic analysis indicated that the most prolific topics aligned with the primary aims and scope of the journal. Currently and in the foreseeable future, the main themes of JMIR include “artificial intelligence,” “patient empowerment,” and “victimization.” ConclusionsThis bibliometric study highlighted significant contributions to digital health by identifying key research trends, themes, influential authors, and collaborations. The findings underscore the necessity to enhance publications from developing countries, improve gender diversity among authors, and expand the range of research topics explored in the journal.

In clinical practice, some cases of chronic spontaneous urticaria (CSU) remain difficult to treat, with up to 40% of patients showing no response to even high (4-fold) daily doses of antihistamines. Approximately 30% of CSU patients fail to achieve complete control and relief through treatment with omalizumab and may require alternative therapies. Abrocitinib is a small-molecule oral JAK1 inhibitor that suppresses intracellular signaling of multiple key cytokines involved in inflammation cascades, and has shown beneficial effects in patients with mast cell activation disorders. We conducted a retrospective analysis of the diagnosis and treatment records of adult patients with refractory CSU who were treated with abrocitinib after inadequate response to omalizumab (defined as no response to 300 mg/4 weeks of omalizumab treatment for 6 months, followed by adjustment to 300 mg/2 weeks for a further 3 months without controlling symptoms). We also collected data on relevant treatment modalities, clinical outcomes, and adverse events. Among these patients, various treatment modalities failed to adequately control symptoms, but switching to abrocitinib significantly improved clinical outcomes. Therefore, abrocitinib may represent a new treatment option for patients with refractory CSU.

Mood disorders, including major depressive disorder and bipolar disorder, have a profound impact on more than 300 million people worldwide. It has been demonstrated mood disorders were closely associated with deviations in biogenic amine metabolites, which are involved in numerous critical physiological processes. The peripheral and central alteration of biogenic amine metabolites in patients may be one of the potential pathogeneses of mood disorders. This review provides a concise overview of the latest research on biogenic amine metabolites in mood disorders, such as histamine, kynurenine, and creatine. Further studies need larger sample sizes and multi-center collaboration. Investigating the changes of biogenic amine metabolites in mood disorders can provide biological foundation for diagnosis, offer guidance for more potent treatments, and aid in elucidating the biological mechanisms underlying mood disorders.

Remnant urban forests, or scattered patches of forest within urban areas, serve as crucial biodiversity reservoirs. Investigating how urban environments influence biodiversity within these forests is essential for enhancing conservation strategies. This study examined data from 15 remnant forest patches in Guiyang, China, to assess the impacts of spatiotemporal urban expansion on species richness and functional traits across different life forms and ontogenetic stages in both interior and edge habitats of these patches. Employing generalized linear regression models, we examined variables including the intensity of urban expansion, road density, type of expansion, compound terrain complexity, and the interplay between urbanization levels and the timeframe of urban development. Our results indicated that increased urban expansion intensity positively affected the species richness of shrubs, yet negatively influenced tree richness. Furthermore, high urbanization levels were associated with lower species richness in adult trees and the species in the sapling and shrub layers with high seed mass traits when the duration of urbanization was prolonged. Additionally, we observed that edge-expansion type urban growth notably increased the risk of losing species with resource-conservation traits compared to leapfrog growth patterns. These outcomes highlight the detrimental effects of intensive urban expansion and edge-expansion growth on the conservation of woody plants, especially those characterized by resource conservation traits. They also draw attention to the delayed impacts of urbanization on plant diversity. In response, we advocate for the reduction of urban expansion intensity and control over edge-expansion growth patterns to protect plant diversity in remnant forests. It is also critical to prioritize the conservation of remnant forest patches located in areas that have undergone extensive urbanization for prolonged periods, as these are particularly vulnerable to biodiversity loss.

Objective To identify the effective components and key molecules of Yiqi Huoxu compound(YQHX) in the treatment of pulmonary inflammation and fibrosis in scleroderma, providing basis for the development of drug targets for scleroderma. Methods A mouse model of pulmonary fibrosis was established by a single tracheal perfusion of bleomycin. Twenty-four mice were randomly divided into four groups, i.e. intragastric PBS, bleomycin alone, intragastric Yiqi Huoxue compound, and control. HE staining and Masson staining were used to verify the therapeutic effect of Yiqi Huoxue compound on lung inflammation and fibrosis. The active components and target genes of anti-fiber salvia miltiorrhiza were obtained from TCMSP database. PPI network, GO/KEGG enrichment analysis, molecular docking and other bioinformatics analyses were integrated to identify the main active ingredients and key targets of salvia miltiorrhiza in the treatment of scleroderma, and to analyze the relevant signaling pathways. The expression levels of CD3 antibody, p-PI3K antibody and p-AKT antibody were analyzed by immunohistochemistry to verify the effects of Yiqi Huoxu compound on inflammation and key pathways. Results The results of HE staining and Masson staining showed that the severity of fibrosis and inflammatory infiltration were decreased, suggesting that Yiqi Huoxue compound could significantly improve the pulmonary fibrosis, inflammation and tissue damages. The key component of salvia miltiorrhiza was mainly luteolin. PPI network analysis showed that AKT1, EGFR, ESR1, TNF and IL6 were the core targets of salvia miltiorrhiza in the treatment of scleroderma. KEGG enrichment analysis showed that the genes were mainly enriched in the PI3K-AKT pathway. Molecular docking analysis showed the potential binding sites between luteolin and four key targets. The immunohistochemical results showed that YQHX significantly decreased bleomycin-induced CD3+T cell infiltration, p-PI3K and p-AKT levels in mouse lung tissue. Conclusions YQHX has significant therapeutic effects on lung inflammation and fibrosis. Luteolin may be a key effective molecule in YQHX, and treat scleroderma lung inflammation and fibrosis by targeting the PI3K-AKT pathway.

Abstract Background Hemifacial spasm (HFS) is most effectively treated with microvascular decompression (MVD). However, there are certain challenges in performing MVD for HFS when the vertebral artery (VA) is involved in compressing the facial nerve (VA-involved). This study aimed to introduce a “bridge-layered” decompression technique for treating patients with VA-involved HFS and to evaluate its efficacy and safety to treat patients with HFS. Methods A single-center retrospective analysis was conducted on the clinical data of 62 patients with VA-involved HFS. The tortuous trunk of VA was lifted by a multi-point “bridge” decompression technique to avoid excessive traction of the cerebellum and reduce the risk of damage to the facial-acoustic nerve complex. To fully decompress all the responsible vessels, the branch vessels of VA were then isolated using the “layered” decompression technique. Results Among the 62 patients, 59 patients were cured immediately after the surgery, two patients were delayed cured after two months, and one had occasional facial muscle twitching after the surgery. Patients were followed up for an average of 19.5 months. The long-term follow-up results showed that all patients had no recurrence of HFS during the follow-up period, and no patients developed hearing loss, facial paralysis, or other permanent neurological damage complications. Only two patients developed tinnitus after the surgery. Conclusion The “bridge-layered” decompression technique could effectively treat VA-involved HFS with satisfactory safety and a low risk of hearing loss. The technique could be used as a reference for decompression surgery for VA-involved HFS.

Abstract Developing a mucosal vaccine against SARS-CoV-2 is critical for combatting the epidemic. Here, we investigated long-term immune responses and protection against SARS-CoV-2 for the intranasal vaccination of a triple receptor-binding domain (RBD) scaffold protein (3R-NC) adjuvanted with a flagellin protein (KFD) (3R-NC + KFDi.n). In mice, the vaccination elicited RBD-specific broad-neutralizing antibody responses in both serum and mucosal sites sustained at high level over a year. This long-lasting humoral immunity was correlated with the presence of long-lived RBD-specific IgG- and IgA-producing plasma cells, alongside the Th17 and Tfh17-biased T-cell responses driven by the KFD adjuvant. Based upon these preclinical findings, an open labeled clinical trial was conducted in individuals who had been primed with the inactivated SARS-CoV-2 (IAV) vaccine. With a favorable safety profile, the 3R-NC + KFDi.n boost elicited enduring broad-neutralizing IgG in plasma and IgA in salivary secretions. To meet the challenge of frequently emerged variants, we further designed an updated triple-RBD scaffold protein with mutated RBD combinations, which can induce adaptable antibody responses to neutralize the newly emerging variants, including JN.1. Our findings highlight the potential of the KFD-adjuvanted triple-RBD scaffold protein is a promising prototype for the development of a mucosal vaccine against SARS-CoV-2 infection.

Liver cancer, a common and intractable liver-related disease, is a malignant tumor with a high morbidity, which needs a high treatment cost but still lacks perfect clinical treatment methods. Looking for an effective platform for liver cancer study and drug screening is urgent and important. Traditional analytical methods for liver disease studies mainly rely on the 2D cell culture and animal experiments, which both cannot fully recapitulate physiological and pathological processes of human liver. For example, cell culture can only show basic functions of cells in vitro, while animal models always hold the problem of species divergence. The organoids, a 3D invitro culture system emerged in recent years, is a cell-bound body with different cell types and has partial tissue functions. The organoid technology can reveal the growth state, structure, function and characteristics of the tissue or organ, and plays an important role in reconstructing invitro experimental models that can truly simulate the human liver. In this paper, we will give a brief introduction of liver organoids and review their applications in liver cancer research, especially in liver cancer pathogenesis, drug screening, precision medicine, regenerative medicine, and other fields. We have also discussed advantages and disadvantages of organoids, as well as future directions and perspectives towards liver organoids.

ABSTRACTDental caries is a prevalent oral disease that mainly results from Streptococcus mutans. Susceptibility to S. mutans decreased rapidly after weaning in a well-known rat model. However, owing to the lack of time to establish protective immunity ahead of challenge, the weaning rat model is suboptimal for assessing prophylactic vaccines against S. mutans infection. In this study, we found that, in adult rats, S. mutans cultured under air-restricted conditions showed dramatically increased colonization efficacy and accelerated development of dental caries compared with those cultured under air-unrestricted conditions. We propose that S. mutans cultured under air-restricted conditions can be used to develop an optimal caries model, especially for the evaluation of prophylactic efficacy against S. mutans. Therefore, we used the anti-caries vaccine, KFD2-rPAc, to reevaluate the protection against the challenge of S. mutans. In immunized rats, rPAc-specific protective antibodies were robustly elicited by KFD2-rPAc before the challenge. In addition to inhibiting the initial and long-term colonization of S. mutans in vivo, KFD2-rPAc immunization showed an 83% inhibitory efficacy against the development of caries, similar to that previously evaluated in a weaning rat model. These results demonstrate that culturing under air-restricted conditions can promote S. mutans infection in adult rats, thereby helping establish a rat infection model to evaluate the prophylactic efficacy of vaccines and anti-caries drugs.

Crabapple is a valuable tree species in gardens due to its captivating array of flower and leaf colors, rendering it a favored choice in landscaping. The economic and ornamental values of Malus crabapple are closely associated with the biosynthesis of anthocyanin, a pigment responsible for its vibrant hues. The intricate regulation of anthocyanin biosynthesis involves the concerted activity of various genes. However, the specific mechanism governing this process in crabapple warrants in-depth exploration. In this study, we explored the inhibitory role of MsMYB62-like in anthocyanin biosynthesis. We identified MsDFR and MsANS as two downstream target genes of MsMYB62-like. These genes encode enzymes integral to the anthocyanin biosynthetic pathway. The findings demonstrate that MsMYB62-like directly binds to the promoters of MsDFR and MsANS, resulting in the downregulation of their expression levels. Additionally, our observations indicate that the plant hormone cytokinins exert a suppressive effect on the expression levels of MsMYB62-like, while concurrently upregulating MsDFR and MsANS. This study reveals that the MsMYB62-like-MsDFR/MsANS module plays an important role in governing anthocyanin levels in Malus crabapple. Notably, the regulatory interplay is modulated by the plant hormone cytokinins.

Abstract The conversion of urban montane forest resources into urban parks requires careful assessment to understand its impacts on plant diversity over time. This study aims to enhance urban biodiversity conservation strategies by analyzing how habitat type and park age affect woody plant diversity. We surveyed woody plant species in 60 sample plots across two different habitats (remnant forest vs. artificial green space) within three mountain parks in Guiyang, China, established at different times. The alpha diversity of saplings/seedlings was significantly higher in remnant forests than in artificial green spaces. Artificial green spaces exhibited more homogenous woody plant composition compared with remnant forests. Newer parks showed greater variation in plant composition between the two habitats than older parks. Indicative species in remnant forests were predominantly native, whereas those in artificial green spaces were mainly ornamental species. The transformation of karst mountainous forests into urban parks leads to the homogenization of woody plant composition and impedes the regeneration of saplings/seedlings. Therefore, it is crucial to manage these conversions carefully and strive to preserve as many native species as possible to support urban plant diversity conservation.

Background/objectives Stroke damage to the primary visual cortex induces large, homonymous visual field defects that impair daily living. Here, we asked if vision‐related quality of life (VR‐QoL) is impacted by time since stroke. Subjects/methods We conducted a retrospective meta‐analysis of 95 occipital stroke patients (female/male = 26/69, 27–78 years old, 0.5–373.5 months poststroke) in whom VR‐QoL was estimated using the National Eye Institute Visual Functioning Questionnaire (NEI‐VFQ) and its 10‐item neuro‐ophthalmic supplement (Neuro10). Visual deficit severity was represented by the perimetric mean deviation (PMD) calculated from 24‐2 Humphrey visual fields. Data were compared with published cohorts of visually intact controls. The relationship between VR‐QoL and time poststroke was assessed across participants, adjusting for deficit severity and age with a multiple linear regression analysis. Results Occipital stroke patients had significantly lower NEI‐VFQ and Neuro10 composite scores than controls. All subscale scores describing specific aspects of visual ability and functioning were impaired except for ocular pain and general health, which did not differ significantly from controls. Surprisingly, visual deficit severity was not correlated with either composite score, both of which increased with time poststroke, even when adjusting for PMD and age. Conclusions VR‐QoL appears to improve with time postoccipital stroke, irrespective of visual deficit size or patient age at insult. This may reflect the natural development of compensatory strategies and lifestyle adjustments. Thus, future studies examining the impact of rehabilitation on daily living in this patient population should consider the possibility that their VR‐QoL may change gradually over time, even without therapeutic intervention.

Lichen sclerosus et atrophicus (LSA) is a chronic inflammatory skin lesion with an undefined cause. It is more commonly found in the genital area, particularly in adolescents, premenopausal women and postmenopausal women. LSA is difficult to treat and often recurs. The primary treatment for LSA involves the administration of potent topical corticosteroids. Dupilumab is increasingly being used for the treatment of itching in non-atopic dermatitis patients but there are few reports on its use for the treatment of LSA. Here, we present a case of LSA in a 61-year-old woman with extensive vulvar itching. Over four months of dupilumab therapy, significant therapeutic effects were observed, including vulvar skin thinning and pruritus relief without adverse reactions.

After the resumption of work and production following the COVID-19 pandemic, many cities entered a “transition phase”, characterized by the gradual recovery of emission levels from various sources. Although the overall PM2.5 emission trends have recovered, the specific changes in different sources of PM2.5 remain unclear. Here, we investigated the changes in source contributions and the evolution pattern of pollution episodes (PE) in Wuhan during the “transition period” and compared them with the same period during the COVID-19 lockdown. We found that vehicle emissions, industrial processes, and road dust exhibited significant recoveries during the transition period, increasing by 5.4%, 4.8%, and 3.9%, respectively, during the PE. As primary emissions increased, secondary formation slightly declined, but it still played a predominant role (accounting for 39.1∼ 43.0% of secondary nitrate). The reduction in industrial activities was partially offset by residential burning. The evolution characteristics of PE exhibited significant differences between the two periods, with PM2.5 concentration persisting at a high level during the transition period. The differences in the evolution patterns of the two periods were also reflected in their change rates at each stage, which mostly depend on the pre-PE concentration level. The transition period shows a significantly higher value (8.4 μg m–3 h–1) compared with the lockdown period, almost double the amount. In addition to local emissions, regional transport should be a key consideration in pollution mitigation strategies, especially in areas adjacent to Wuhan. Our study quantifies the variations in sources between the two periods, providing valuable insights for optimizing environmental planning to achieve established goals.

The appearance of recalcitrant organic pollutants such as antibiotics in water bodies has gained a lot of attention owing to their adverse effects on organisms and humans. The current study aims to develop a novel approach to eliminate antibiotic tetracycline (TC) from a synthetic aqueous solution based on the advanced oxidation process triggered by MnSO4-catalyzed NaIO4. A single-factor experiment was performed to observe the impact of pH, NaIO4 concentration, and MnSO4 dosage on TC decomposition, and a three-factor, three-level response surface experiment with TC removal rate as the dependent variable was designed based on the range of factors determined from the single-factor experiment. The single-factor experiment revealed that the ranges of pH, NaIO4 concentration, and MnSO4 dosage need to be further optimized. ANOVA (analysis of variance) results showed that the data from the response surface experiment were consistent with the quadratic model with high R2 (0.9909), and the predicted values were very close to the actual values. After optimization by response surface methodology, the optimal condition obtained was pH = 6.7, [NaIO4] = 0.39 mM, and [MnSO4] = 0.12 mM, corresponding to a TC removal of 96.56%. This optimization condition was fully considered to save the dosage of the high-priced chemical NaIO4. HIGHLIGHTS MnSO4/NaIO4 is a potential advanced oxidative process against antibiotics.; The impact of pH, NaIO4 concentration, and MnSO4 dosage on TC decomposition is investigated.; Box–Behnken model is adopted to determine the scheme of the experiment.; The best experimental condition is optimized using response surface methodology.;

Abstract Over the past few years, dual-targeted chimeric antigen receptor (CAR) T-cell therapy has been employed in the management of hematological malignancies to mitigate treatment failure, particularly in cases of antigen escape. The most widely used approaches include CD19/CD20, CD20/CD22, and BCMA/CD19 CAR T-cells. Alternative immune cells, including natural killer T cells and invariant natural killer T cells, exhibit innate anti-tumor activity and reduced toxicity. This review summarizes several recent clinical trial reports and preclinical studies from the 2023 American Society of Hematology (ASH) annual meeting on dual-targeted CAR T-cell immunotherapy for hematological malignancies.

Fine-grained sediments are Quaternary sediments with grain sizes of not more than 2 mm. They start first when meeting water, their stability is related to the initial water volume triggering debris flow, and thus plays an important role in debris flow hazards early warning. The permeability coefficient is the inter-controlled factor of fine-grained sediment stability. However, there is no hyperspectral model for detecting the fine-grained sediment permeability coefficient in large areas, which seriously affects the progress of debris flow hazards early warning. Therefore, it is of great significance to establish a hyperspectral detection model for the permeability coefficient of fine-grained sediments. Taking Beichuan County, Southwestern China as the case, a permeability coefficient hyperspectral detection model was established. The results show that eight bands are sensitive to the permeability coefficient with a correlation coefficient (R) of 0.6343. T-test on the model shows that P-values for sensitive bands are all less than 0.05, indicating the established model has a good prediction ability with a precision of 85.83%. These sensitive bands also indicate the spectral characteristics of the permeability coefficient. Therefore, it provides a scientific basis for fine-grained sediment stability detection in large areas and lays a theoretical foundation for debris flow hazards’ early warning.

The extraction process of crude polysaccharides from Agrocybe aegerita was optimized, and the antioxidant and anti-aging effects of the crude polysaccharides were evaluated. The optimal extraction parameters for the polysaccharide were identified using the response surface methodology. The DPPH, hydroxy radical, and superoxide anion radical scavenging capacities were evaluated to determine the antioxidant properties of the AAPs. The effects of the AAPs on the lifespan, head-swing frequency, swallowing frequency, body-bending frequency, and stress resistance of Caenorhabditis elegans were determined. The optimal extraction conditions included a solid-to-liquid ratio that resulted in an extraction solution concentration of 0.034 g/mL, an extraction temperature of 92.64 °C, and an extraction time of 2.82 h. Under these conditions, the yield of the AAPs was 11.325% ± 0.996%. The IC50 of the AAPs for superoxide anion radical scavenging was 4.693 mg/mL. The AAPs reached their maximum activity at concentrations of about 2 mg/mL for DPPH and 5 mg/mL for the hydroxyl radical. The AAPs could prolong the lifespan and improve locomotion and the stress resistance of C. elegans. Our findings illustrate the potential of AAPs as an anti-aging and antioxidant agent, highlighting the use of this natural compound in the fields of food and pharmacology.

Due to being lightweight, fine-grained sediments easily flow with water and thus amplify the destructive effect of debris flow hazards. In such hazards, water content and shear strength are key inter-controlled factors relating to the stability of fine-grained sediments and thus control the density, scale, and danger of debris flow hazards. Although the correlation between water content and sediment stability has been studied, there are still some issues to be solved: what is the changing trend of shear strength with increasing water content? What is the water content spatial distribution pattern of fine-grained sediments in debris flow? What is the role/impact of this pattern on debris flow hazards prevention? Therefore, the objective of this research is to show the spatial distribution pattern of water content and establish a correlation between the water content and the shear strength of fine-grained sediments to provide a scientific basis for debris flow hazard prevention. Taking the Beichuan debris flow for our study, with a length of 37.6 km, and a 341 km2 study area, the results show that (1) the average water content shows an increasing trend, from 9.9% in the upstream of the river (SP01–SP05) to 21.7% in the downstream of the river (SP13–SP15). (2) When unsaturated, the correlation between the water content and shear strength is determined by combining the cohesion, normal stress, and internal friction angle; when saturated, the water content is negatively correlated with shear strength. (3) Water content and shear strength are the key inter-controlled factors relating to the stability of fine-grained sediments, and the water content distribution pattern of this research indicates the key locations that require attention: locations with high water content in the downstream river or with high curvature, which is of some significance for debris flow hazard prevention.

Fine-grained sediments in debris flows refer to Quaternary sediments with grain sizes smaller than 2 mm. Their stability is closely related to the initial water threshold that triggers the debris flows and thus controls the density, scale, and damage of the debris flows. Based on this, they play a key “probe” role in early warnings of debris flows. Studies on fine-grained sediment stability are related to the accuracy and efficiency of early warnings of debris flows and thus play an important role in ensuring the safety of people and property. There have been some studies on fine-grained sediment stability in debris flows, but no one has carried out a systematic analysis and summary of this field. Therefore, in response to the urgent need for high-precision early warnings of debris flows, firstly, we review the current research on the aspects of fine-grained sediment stability, initiation, triggering, physical properties, hyperspectral remote sensing, and early warning systems; secondly, we summarize the main problems related to high-precision early warnings of debris flow hazards; and finally, we outline the future directions of research on fine-grained sediment stability in debris flows.

Introduction: Landslides are known to be one of the most frequent types of geological disasters. However, there is not an established method for large-scale, rapid, and high-precision landslide extraction. The quantitative impact of environmental changes on landslide development is also not well understood, which hinders accurate assessments and decision-making in environmental and disaster response. The polar regions, including the Antarctic, the Arctic, and the Tibetan plateau (TP), sensitive to global environmental changes, are significantly affected by global warming. This leads to extensive landslide development, particularly in the southern TP. This research focuses on new landslides in the southern TP, exploring extraction methods and the relationship between landslides and environmental factors.Methods: Utilizing the Google Earth Engine (GEE) and an improved Otsu threshold segmentation algorithm, we processed remote sensing images with 10 m resolution to identify landslide areas. The proposed Normalized Landslide Bare-soil Separation Index (NDLBSI) achieved an 87% pre-extraction accuracy in extracting landslides from Sentinel-2 images from 2019 to 2023. For the pre-extraction results, manual interpretation and correction were carried out, and a model correlating annual landslide changes with environmental factors was established based on least squares multivariate statistical methods.Results: Results show that a significant increase in landslide areas in the southern TP over the past 5 years, correlating with the watershed-wide increase in annual average temperature and vegetation cover, along with a decrease in snow cover area.Discussion: These changes could affect soil and rock moisture, influencing soil stability and landslide occurrence. The study provides valuable insights for large-scale landslide detection and understanding the environmental factors influencing landslides, which is of some significance for landslide hazards early warning.

Background: Trigeminal neuralgia (TN) secondary to a dural arteriovenous fistula (DAVF) is quite rare, and the goal of treatment is to resolve both the fistula and the pain. Case presentation: We herein report a case of TN secondary to a DAVF in a 64-year-old woman with a 1-year history of right-sided TN. Brain magnetic resonance imaging and digital subtraction angiography showed a right tentorial DAVF. Interventional embolization was performed, but the pain was not relieved after the operation. Six months later, we performed microvascular decompression of the trigeminal nerve. During the operation, we electrocoagulated the tortuous and dilated malformed vein, which was compressing the trigeminal nerve, to reduce its diameter and mitigate the compression on the cisternal segment of the trigeminal nerve. That patient's pain was relieved postoperatively. In addition, we reviewed the literature of TN caused by DAVF and found a total of 30 cases, 22 of which were treated by interventional embolization. Of these 22 cases, the interventional embolization healed the fistula with pain relief in 14 cases and healed the fistula without pain relief in 8 cases. We found that the venous drainage methods of the 8 cases were all classified into the posterior mesencephalic group. Conclusions: We believe that this drainage pattern contributes to the more common occurrence of unrelieved pain. For such patients, microvascular decompression can be performed with intraoperative coagulation to narrow the dilated veins until the cisternal segment of the trigeminal nerve is no longer compressed. Satisfactory curative effects can be obtained using this technique.

Background & Aims: Peripartum prophylaxis (PP) with tenofovir disoproxil fumarate (TDF) is the standard of care to prevent mother-to-child transmission of chronic hepatitis B (CHB) infection in mothers who are highly viremic. We investigated the maternal and infant outcomes in a large Chinese cohort of TDF-treated CHB pregnant participants. Methods: In this prospective study, treatment-naive mothers with CHB and highly viremic (HBV DNA ≥200,000 IU/ml) but without cirrhosis were treated with TDF at 24–28 weeks of pregnancy. In accordance with Chinese CHB guidelines, TDF was stopped at delivery or ≥4 weeks postpartum. Serum HBV DNA and alanine aminotransferase were monitored every 6–8 weeks to determine virological relapse (VR). Infants received standard neonatal immunization, and HBV serology was checked at 7–12 months of age. Results: Among 330 participants recruited (median age 30, 82.7% HBeAg+, median HBV DNA 7.82 log IU/ml), TDF was stopped at delivery in 66.4% and at ≥4 weeks in 33.6%. VR was observed in 98.3%, among which 11.6% were retreated with TDF. Timing of TDF cessation did not alter the risk of VR (99.0 vs. 96.9%), clinical relapse (19.5 vs. 14.3%), or retreatment (12.6 vs. 10.1%) (all p > 0.05). A similar proportion of patients developed alanine aminotransferase flare five times (1.1 vs. 2.1%; p = 0.464) and 10 times (0.5 vs. 0%; p = 0.669) above the upper limit of normal (ULN) in the early withdrawal and late withdrawal groups, respectively. No infants developed HBsAg-positivity. Conclusions: PP-TDF and neonatal immunization were highly effective in preventing mother-to-child transmission of HBV in mothers who are highly viremic. Timing of cessation of PP-TDF did not affect the risk of VR or retreatment. Impact and Implications: In pregnant mothers with chronic hepatitis B infection who are started on peripartum tenofovir to prevent mother-to-child-transmission (MTCT), the optimal timing for antiviral withdrawal during the postpartum period remains unknown. This prospective study demonstrates that stopping tenofovir immediately at delivery, compared with longer treatment duration of tenofovir, did not lead to an increased risk of virological relapse, retreatment, or transmission of the virus to the baby. Shortening the duration of peripartum antiviral prophylaxis from 12 weeks to immediately after delivery can be considered. The immediate withdrawal of peripartum tenofovir, combined with standard neonatal immunization schemes, is 100% effective in preventing MTCT among pregnant mothers with CHB who are highly viremic, with a high rate of vaccine response in infants.