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The fungal pathogen Setosphaeria turcica (S. turcica) causes northern corn leaf blight (NCLB), resulting in significant yield and economic losses in maize. To elucidate the metabolic pathways essential for its pathogenicity, we investigated the metabolome of S. turcica during appressorium development, a critical stage for host infection. Our analysis indicated a substantial enrichment of sphingosine and related compounds during this phase. The application of chemical inhibitors to disrupt sphingolipid metabolism confirmed their pivotal role in appressorium formation and pathogenicity. Additionally, silencing of the serine palmitoyl transferase (Spt) core subunit gene StLCB2 led to significant alterations in fungal morphology and growth, accompanied by changes in cell membrane integrity, surface hydrophobicity, melanin, and sphingosine synthesis. These findings underscore the importance of sphingolipids in the pathogenicity of S. turcica and suggest that targeting specific components of the sphingolipid pathway could aid in developing novel fungicides or genetically engineered maize varieties with increased resistance to NCLB., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

The heterotrimeric protein phosphatase 2A (PP2A) complex catalyzes about half of Ser/Thr dephosphorylations in eukaryotic cells. A CAG repeat expansion in the neuron-specific protein PP2A regulatory subunit PPP2R2B gene causes spinocerebellar ataxia type 12 (SCA12). We established five monoallelic missense variants in PPP2R2B (four confirmed as de novo) as a cause of intellectual disability with developmental delay (R149P, T246K, N310K, E37K, I427T). In addition to moderate to severe intellectual disability and developmental delay, affected individuals presented with seizures, microcephaly, aggression, hypotonia, as well as broad-based or stiff gait. We used biochemical and cellular assays, including a novel luciferase complementation assay to interrogate PP2A holoenzyme assembly and activity, as well as deregulated mitochondrial dynamics as possible pathogenic mechanisms. Cell-based assays documented impaired ability of PPP2R2B missense variants to incorporate into the PP2A holoenzyme, localize to mitochondria, induce fission of neuronal mitochondria, and dephosphorylate the mitochondrial fission enzyme dynamin-related protein 1. AlphaMissense-based pathogenicity prediction suggested that an additional seven unreported missense variants may be pathogenic. In conclusion, our studies identify loss-of-function at the PPP2R2B locus as the basis for syndromic intellectual disability with developmental delay. They also extend PPP2R2B-related pathologies from neurodegenerative (SCA12) to neurodevelopmental disorders and suggests that altered mitochondrial dynamics may contribute to mechanisms., (© The Author(s) 2024. Published by Oxford University Press.)

Novel hydroxamic acid and 3,6-amide modified α-mangostin derivatives were synthesized and evaluated their antiproliferative activities against KYSE 30 (esophageal cancer), HCT 116 (colon cancer), and HGC 27 (gastric cancer) cell lines. Most of the new derivatives displayed stronger anti-proliferative activities compared to α-mangostin. Among all the derivatives, compound 4a exhibited the most potent activity, with IC 50 values of 0.57 ± 0.29 μM, 3.27 ± 0.16 μM, and 2.28 ± 1.02 μM against KYSE 30, HCT 116, and HGC 27 cells, respectively. Subsequent mechanism studies revealed that compound 4a inhibited cancer cells proliferation and colonies formation in a concentration-dependent manner. Additionally, compound 4a caused cell cycle arrest in a p53 dependent manner and induced apoptosis in p53 independent way. Meanwhile, 4a suppressed cell cycle related proteins (Cyclin D1 and cyclin B1) expression, increased pro-apoptotic proteins (cleaved PARP, cleaved caspase-7, and cleaved caspase-9) and decreased anti-apoptotic proteins (Bcl-2) expression. Moreover, 4a increased reactive oxygen species (ROS) levels in KYSE 30 cells and upregulated the expression of proteins related to the ROS related MAPK signaling pathway (p-ERK, p-p38, and p-JNK). These findings suggest that compound 4a holds promising potential as an antiproliferative agent by targeting MAPK signaling pathway to inhibit cell cycle progress, induce apoptosis and produce ROS in cancers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The oral safety of Lithocarpus litseifolius (Hance) Chun (sweet tea) that has antihyperglycemic potential has been verified. However, its specific application and action mechanism in the treatment of gestational diabetes mellitus (GDM) are still unclear. Methods: Total water-soluble flavonoids extracted from L. litseifolius (Hance) Chun (sweet tea) were applied to GDM mice. The glucose tolerance, insulin sensitivity, and histopathology of the GDM mice were evaluated through an intraperitoneal glucose tolerance test (IPGTT), an intraperitoneal insulin tolerance test (IPITT), and histochemistry. The possible mechanism was analysed through network pharmacology. Results: Compared with those in GDM model mice (MD group), blood glucose levels indicating both glucose tolerance and insulin sensitivity were improved in GDM mice treated with total water-soluble flavonoids (LLHC group) but were greater than those in normal control mice (NC group). The number of apoptotic liver cells was significantly lower in the LLHC group than in the MD group, but greater than that in the NC group. Multiple targets and signalling pathways that were acted by eight main active ingredients were involved in the process by which total water-soluble flavonoids protect against GDM. The main mechanism involved quercetin (10 targets) and luteolin (8 targets), which acted on the effector target of GAA through six main signalling pathways around the AKT1 core axis. Conclusion: Oral administration of total water-soluble flavonoids can alleviate glucose intolerance and insulin resistance via the inhibition of liver cell apoptosis. The main active ingredients act on GAA through the signalling pathways of the AKT1 core axis., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Junfei Xu et al.)

Ethnopharmacological Relevance: Cornus officinalis is a conventional Chinese medicine for tonifying liver and kidney in ancient China. The active ingredients from Cornus officinalis can delay the progression of cerebral aneurysms, alleviate experimental autoimmune encephalomyelitis, and show a good intervention effect on brain diseases. Loganin, the active ingredient of Cornus officinalis, has a neuroprotective effect on cerebral ischemia-reperfusion injury in mice. It is yet unknown, nevertheless, how Cornus officinalis works to treat ischemic stroke., Aim of the Study: Based on ultra-high performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UHPLC-Q-TOF-MS), network pharmacology and molecular docking, Cornus officinalis's mechanism of intervention in ischemic stroke is explored and verified by experiments., Materials and Methods: To examine the chemical components of Cornus officinalis, UHPLC-Q-TOF-MS was used. The network pharmacology was used to construct the "active ingredient-core target-main pathway" network of Cornus officinalis. Then, the link between the main active components and the key protein targets, as determined by network pharmacology, was verified through the application of molecular docking. The middle cerebral artery occlusion/reperfusion (MCAO/R) rat model used in this study was created using the suture technique. The pharmacological effects of Cornus officinalis were explored by neurological function score, behavior, TTC staining, ultrasound and flow cytometry. Western blot and qPCR were used to confirm the core target., Results: The outcomes of the investigation demonstrated that Cornus officinalis had a potent anti-ischemic stroke effect. UHPLC-Q-TOF-MS method was used to determine 24 chemical constituents in Cornus officinalis, of which 22 components had a close relationship with protein targets relevant to ischemic stroke. The 27 protein targets screened by "active ingredient-core target-main pathway" may be the possible targets of Cornus officinalis in the therapy of ischemic stroke. Most of the 27 protein targets had to do with the inflammatory response, apoptosis and energy metabolism. KEGG enrichment analysis showed that AGE/RAGE ranked high and was closely related to inflammatory response. Molecular docking predicted that the top 10 components in the network diagram had good binding with inflammatory factors IL6, IL-1β and TNF-α protein targets. Western blot research outcomes stated that Cornus officinalis could firmly impede the production of AGE, RAGE, and P-NFκB P65. Cornus officinalis had the potential to prevent ischemic stroke by drastically inhibiting the production of TNF-α, IL-1β, and IL-6, according to the results of qPCR study., Conclusion: This study found that Cornus officinalis can improve the brain injury, motor ability and blood flow velocity of MCAO/R rats and suppress the inflammatory reaction through the AGE/RAGE/NFκB pathway to exert the therapeutic effect on ischemic stroke., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

We analyzed the trends in breast cancer (BC) morbidity, prevalence, and mortality among Chinese residents from 1990 to 2021. We then used joinpoint regression to further assess BC morbidity and mortality. We screened the morbidity, mortality, and prevalence of BC in Chinese residents (1990-2021) from the Global Burden of Disease. We used age-period-cohort (APC) modeling to assess the effects of age, period, and cohort on BC morbidity and mortality separately. We also used the joinpoint model to characterize trends in BC morbidity and mortality in China. From 1990 to 2021, age-standardized rates of morbidity have risen significantly, whereas mortality has declined. We discovered that the risk of morbidity and death rose with age by using the APC model. We also found that mortality and morbidity roughly continued to increase over time, and finally, we found that the later the birth cohort, the lower the mortality and the higher the morbidity. From 1990 to 2021, the burden of BC disease in China will continue to rise, and the situation of BC prevention and control will remain severe. Therefore, regular imaging and palpation examinations should be performed in the regular population over 40 years of age. When treating patients with BC, healthcare workers should develop individualized treatment plans to further reduce mortality., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Nanoplastics (NPs) can adversely affect living organisms. However, the uptake of NPs by plants and the physiological and molecular mechanisms underlying NP-mediated plant growth remain unclear, particularly in the presence of iron minerals and humic acid (HA). In this study, we investigated NP accumulation in rice (Oryza sativa L.) and the physiological effects of exposure to polystyrene NPs (0, 20, and 100 mg L -1 ) in the presence of iron plaque (IP) and HA. NPs were absorbed on the root surface and entered cells, and confocal laser scanning microscopy confirmed NP uptake by the roots. NP treatments decreased root superoxide dismutase (SOD) activity (28.9-44.0%) and protein contents (31.2-38.6%). IP and HA (5 and 20 mg L -1 ) decreased the root protein content (20.44-58.3% and 44.2-45.2%, respectively) and increased the root lignin content (22.3-27.5% and 19.2-29.6%, respectively) under NP stress. IP inhibited the NP-induced decreasing trend of SOD activity (19.2-29.5%), while HA promoted this trend (48.7-50.3%). Transcriptomic and metabolomic analysis (Control, 100NPs, and IP-100NPs-20HA) showed that NPs inhibited arginine biosynthesis, and alanine, aspartate, and glutamate metabolism and activated phenylpropanoid biosynthesis related to lignin. The coexistence of IP and HA had positive effects on the amino acid metabolism and phenylpropanoid biosynthesis induced by NPs. Regulation of genes and metabolites involved in nitrogen metabolism and secondary metabolism significantly altered the levels of protein and lignin in rice roots. These findings provide a scientific basis for understanding the environmental risk of NPs under real environmental conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Pasteurella multocida (P. multocida) can cause infection in various animals, especially livestock and poultry, which can lead to substantial losses to the breeding industry. However, the pathogenesis of avian P. multocida remains largely unknown. In this study, the mechanisms of avian P. multocida pathogenesis were explored. Chicken macrophage HD11 cells were infected with the avian strain PmQ and the bovine strain PmCQ2. PmQ induced higher cytotoxicity and apoptosis and exerted a stronger anti-phagocytotic effect on HD11 cells than PmCQ2. RNA sequencing analysis revealed that focal adhesion (FA)-related genes were significantly downregulated in PmQ-infected HD11 cells compared with that of PmCQ2. Subsequently, phalloidin staining of the F-actin assembly revealed that PmQ more significantly inhibited the formation of FAs in HD11 than PmCQ2. Western blot analysis revealed that the levels of Zyxin and phosphorylated focal adhesion kinase (FAK) were significantly decreased in PmQ-infected cells, confirming that PmQ inhibited FAs. Consequently, PmQ inhibited the FA downstream factor Akt, which decreased NF-κB and FoxO1 phosphorylation, as evidenced by the decreased expression of downstream anti-apoptotic genes (GADD45B, BCL2L1, BCL2A1, and BIRC2) and increased expression of downstream pro-apoptotic genes (BCL6, PKL2, PKL3, and KLF2). Conversely, pharmaceutically inhibiting FA formation using latrunculin A better enhanced PmCQ2-induced than PmQ-induced apoptosis in HD11 cells. Similarly, the knockdown of Zyxin or FoxO1 by siRNA both boosted the PmCQ2-induced apoptosis rates equal to those of PmQ. These results demonstrated that PmQ inhibited Zyxin-dependent FA formation and disrupted the FAK-AKT-FoxO1/NF-κB pathway to induce apoptosis in chicken macrophages. This study thus offers insights into the pathogenesis of avian P. multocida, which could facilitate the development of new strategies against P. multocida infection., Competing Interests: Disclosures The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Scope: Depression as a global neurological disorder, and hippocampal neuronal apoptosis and disorders of the gut microbiota are closely related to it. This study aims to expose the ameliorative effect of enzyme peptides (AP) from brewer's yeast on depressive behavior caused by chronic restraint stress (CRS) in rats., Methods and Results: After 4 weeks of AP intervention, a significant alleviation of depressive behavior in the sucrose preference test (SPT), forced swim test (FST), and light-dark test (LDT) is observed in depressed rats. AP ameliorates neuronal damage with increased the expression of the key CREB/BDNF/TrkB/Akt signaling pathway, which increases the levels of the monoamine neurotransmitters 5-hydroxytryptamine (5-HT) and norepinephrine (NE) in the hippocampus, buffering hyperactivity of the hypothalamo-pituitary-adrenal axis (HPA), and decreasing the serum cortisol (CORT) and adrenocorticotropic hormone (ACTH) levels in rats. In addition, AP modulates the disruption of the rat gut microbiota by chronic restraint stress (CRS), and the changes in the abundance of Lactobacillus animalis and Lactobacillus johnsonii are probably the key for AP performing antidepressant benefits. A strong correlation is found between gut microbiota and biochemical markers of depression., Conclusion: AP, as a natural and safe active substance, has a positive effect in the treatment of depression., (© 2024 Wiley‐VCH GmbH.)

Northern corn leaf blight is a devastating disease caused by Setosphaeria turcica (S. turcica), leading to significant yield losses in maize. S. turcica initiates infection through a specialized structure known as the appressorium, which only forms on conducive substrates. In this study, we introduce a semi‑silicone water polyurethane resin (Si-PUD) that induces only germ tube formation from S. turcica conidia. A mixed coating of Si-PUD and polytetrafluoroethylene successfully triggers appressorium formation. Both coatings maintain optical transparency, chemical resistance, and thermal stability, which facilitate microscopic observations and the development of high-throughput systems. These coatings also demonstrate similar effects on Bipolaris maydis (B. maydis), suggesting their potential universal applicability. Utilizing coating-induced synchronous appressorium formation and proteomic analyses, we identified five genes essential for S. turcica appressorium development. Functional analyses of two zinc binuclear cluster domain-containing transcription factors, StTF1 and StTF2, revealed their critical roles in appressorium development and pathogenicity. This study not only develops a novel method for inducing appressorium formation but also lays the groundwork for rapid screening of environmentally-friendly fungicides that inhibit appressorium development., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Renal fibrosis is a common pathway involved in the progression of various chronic kidney to end-stage diseases, posing a substantial global public health challenge in the search for effective and safe treatments. This study investigated the effects and mechanisms of sacha inchi shell polysaccharide (SISP) on renal fibrosis induced by a high-salt diet (HSD) in mice. By analysing kidney-related protein pathways and the structure of gut microbiota, we found that SISP significantly reduced urinary protein levels induced by a HSD from 41.08 to 22.95 μg/mL and increased urinary creatinine from 787.43 to 1294.50 μmol/L. It reduced renal interstitial collagen fibres by 11.30 %, thereby improving the kidney function. SISP lowered the mRNA expression of TGF-B1, fibronectin, α-SMA, Smad2/3, and TGFBRII, leading to decreased protein levels of TGF-β1, p-Smad2/3, p-TGFβRII, fibronectin, α-SMA, p-Smad2/3/Smad2/3, and p-TGFβRII/TGFβRII. These changes blocked downstream transcription in the TGF-β1/Smad signalling pathway, thereby attenuating renal fibrosis in HSD mice. In addition, SISP altered the intestinal flora imbalance in HSD mice by reducing the relative abundance of the genera, Akkermansia, Faecalibaculum, and unidentified_Ruminococcaceae, and reversing the decline in the levels of the genera, Lactobacillus and Bacteroides. In conclusion, SISP is a promising nutraceutical for renal fibrosis management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Sonopiezocatalytic therapy is an emerging therapeutic strategy that utilizes ultrasound irradiation to activate piezoelectric materials, inducing polarization and energy band bending to facilitate the generation of reactive oxygen species (ROS). However, the efficient generation of ROS is hindered by the long distance of charge migration from the bulk to the material surface. Herein, atomically thin Bi 2 O 2 (OH)(NO 3 ) (AT-BON) nanosheets are rationally engineered through disrupting the weaker hydrogen bonds within the [OH] and [NO 3 ] layer in the bulk material. The ultrathin structure of AT-BON piezocatalytic nanosheets shortens the migration distance of carriers, expands the specific surface area, and accelerates the charge transfer efficiency, showcasing a natural advantage in ROS generation. Importantly, the non-centrosymmetric polar crystal structure grants the nanosheets the ability to separate electron-hole pairs. Under ultrasonic mechanical stress, Bi 2 O 2 (OH)(NO 3 ) nanosheets with the remarkable piezoelectric feature exhibit the desirable in vivo antineoplastic outcomes in both breast cancer model and liver cancer model. Especially, the AT-BON-induced ROS bursts lead to the activation of the Caspase-1-driven pyroptosis pathway. This study highlights the beneficial impact of bulk material thinning on enhancing ROS generation efficiency and anti-cancer effects., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Addressing the inefficiency of current therapeutic approaches for hepatocellular carcinoma is an urgent and pressing challenge. PANoptosis, a form of inflammatory programmed cell death, presents a dependable strategy for combating cancer by engaging multiple cell death pathways (apoptosis, pyroptosis, and necroptosis). In this study, an ultrasmall Bi 2 Sn 2 O 7 nanozyme with ultrasound-magnified multienzyme-mimicking properties is designed and engineered as a PANoptosis inducer through destroying the mitochondrial function of tumor cells and enhancing the intracellular accumulation of toxic reactive oxygen species, finally triggering the activation of PANoptosis process. The role of PANoptosis inducer has been verified by the expression of related proteins, including cleaved Caspase 3, NLRP3, N-GSDMD, cleaved Caspase 1, p-MLKL, and RIPK3. The inclusion of external ultrasonic irradiation significantly augments the enzyodynamic therapeutic efficiency. In vitro and in vivo antineoplastic efficacy, along with inhibition of lung metastasis, validate the benefits of the Bi 2 Sn 2 O 7 -mediated PANoptosis pathway. This study not only elucidates the intricate mechanisms underlying Bi 2 Sn 2 O 7 as a PANoptosis inducer, but also offers a novel perspective for the treatment of hepatocellular carcinoma., (© 2024 Wiley‐VCH GmbH.)

Bone marrow mesenchymal stem cell (BMSC)-derived exosomes possess therapeutic potential against degenerative diseases. This study aimed to investigate the effects of BMSC-derived exosomes on intervertebral disc degeneration (IVDD) and explore the underlying molecular mechanisms. Through transcriptome sequencing and histological analysis, we observed a significant increase in HIF-1α expression in degenerative nucleus pulposus (NP) tissues. The addition of HIF-1α resulted in elevated expression of inflammatory factors IL-1β and IL-6, higher levels of matrix-degrading enzyme MMP13, and lower expression of aggrecan in NP cells. Co-culturing with BMSCs diminished the expression of HIF-1α, MMP13, IL-1β, and IL-6 in degenerative NP cells induced by overload pressure. miRNA chip analysis and PCR validation revealed that miR-145a-5p was the primary miRNA carried by BMSC-derived exosomes. Overexpression of miR-145a-5p was effective in minimizing the expression of HIF-1α, MMP13, IL-1β, and IL-6 in degenerative NP cells. Luciferase reporter assays confirmed USP31 as the target gene of miR-145a-5p, and the regulation of NP cells by BMSC-derived exosomes via miR-145a-5p was dependent on USP31. In conclusion, BMSC-derived exosomes alleviated IVDD through the miR-145a-5p/USP31/HIF-1α signaling pathway, providing valuable insights into the treatment of IVDD., Competing Interests: Declarations Ethical Approval The nucleus pulposus specimens were collected with the approval of the Ethics Committee of the First Affiliated Hospital of the Air Force Medical University of the People’s Liberation Army (Approval number: KY20222063-D-2) and written informed consent was obtained from the specimen donors or their families. All experimental processes were performed with the Guide for the Care and Use of Laboratory Animals (National Institutes of Health, eighth edition, 2011), and approved by the Ethics Committee of the First Affiliated Hospital of the Air Force Medical University of the People’s Liberation Army (Approval number: KY20222063-D-2). Consent for Publication The authors affirm that all participants provided informed consent for publication of the paper. Consent to Participate Informed consent was obtained from all individual participants included in the study. Competing Interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Micro and nanobubbles (MNBs), as an efficient and convenient method, have been widely used in water treatment. Composed of gas and water, MNBs avoid directly introducing potential secondary pollutants. Notably, MNBs exhibit significant advantages through interface reactions in assisting AOPs. They overcome barriers like low mass transfer coefficients and limited reactive sites, and shorten the distance between pollutants and oxidants, achieving higher pollutant removal efficiency. However, there is a lack of systematic summary and in-depth discussion on the fundamental mechanisms of MNBs-assisted AOPs. In this critical review, the characteristics of MNBs related to water treatment are outlined first. Subsequently, the recent applications, performance, and mechanisms of MNBs-assisted AOPs including ozone, plasma, photocatalytic, and Fenton oxidation are overviewed. We conclude that MNBs can improve pollutant removal mainly by enhancing the utilization of reactive oxygen species (ROS) generated by AOPs due to the effective interface reactions. Furthermore, we calculated the electrical energy per order of reaction (EE/O) parameter of different MNBs-assisted AOPs, suggesting that MNBs can reduce the total energy consumption in most of the tested cases. Finally, future research needs/opportunities are proposed. The fundamental insights in this review are anticipated to further facilitate an in-depth understanding of the mechanisms of MNBs-assisted AOPs and supply critical guidance on developing MNBs-based technologies for water treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

CRISPR-Cas tools for mammalian genome editing typically rely on single Cas9 or Cas12a proteins. While type I CRISPR systems in Class I may offer greater specificity and versatility, they are not well-developed for genome editing. Here, we present an alternative type I-C CRISPR system from Desulfovibrio vulgaris (Dvu) for efficient and precise genome editing in mammalian cells and animals. We optimized the Dvu type I-C editing complex to generate precise deletions at multiple loci in various cell lines and pig primary fibroblast cells using a paired PAM-in crRNA strategy. These edited pig cells can serve as donors for generating transgenic cloned piglets. The Dvu type I-C editor also enabled precise large fragment replacements with homology-directed repair. Additionally, we adapted the Dvu-Cascade effector for cytosine and adenine base editing, developing Dvu-CBE and Dvu-ABE systems. These systems efficiently induced C-to-T and A-to-G substitutions in human genes without double-strand breaks. Off-target analysis confirmed the high specificity of the Dvu type I-C editor. Our findings demonstrate the Dvu type I-C editor's potential for diverse mammalian genome editing applications, including deletions, fragment replacement, and base editing, with high efficiency and specificity for biomedicine and agriculture., (© 2024. Science China Press.)

Triple-negative breast cancer (TNBC) remains a significant challenge in terms of treatment, with limited efficacy of chemotherapy due to side effects and acquired drug resistance. In this study, a threose nucleic acid (TNA)-mediated antisense approach is employed to target therapeutic Akt genes for TNBC therapy. Specifically, two new TNA strands (anti-Akt2 and anti-Akt3) are designed and synthesized that specifically target Akt2 and Akt3 mRNAs. These TNAs exhibit exceptional enzymatic resistance, high specificity, enhance binding affinity with their target RNA molecules, and improve cellular uptake efficiency compared to natural nucleic acids. In both 2D and 3D TNBC cell models, the TNAs effectively inhibit the expression of their target mRNA and protein, surpassing the effects of scrambled TNAs. Moreover, when administered to TNBC-bearing animals in combination with lipid nanoparticles, the targeted anti-Akt TNAs lead to reduced tumor sizes and decreased target protein expression compared to control groups. Silencing the corresponding Akt genes also promotes apoptotic responses in TNBC and suppresses tumor cell proliferation in vivo. This study introduces a novel approach to TNBC therapy utilizing TNA polymers as antisense materials. Compared to conventional miRNA- and siRNA-based treatments, the TNA system holds promise as a cost-effective and scalable platform for TNBC treatment, owing to its remarkable enzymatic resistance, inexpensive synthetic reagents, and simple production procedures. It is anticipated that this TNA-based polymeric system, which targets anti-apoptotic proteins involved in breast tumor development and progression, can represent a significant advancement in the clinical development of effective antisense materials for TNBC, a cancer type that lacks effective targeted therapy., (© 2024 The Author(s). Small Methods published by Wiley‐VCH GmbH.)

Objective: This research aimed to improve diagnosis of non-alcoholic fatty liver disease (NAFLD) by deep learning with ultrasound Images and reduce the impact of the professional competence and personal bias of the diagnostician., Method: Three convolutional neural network models were used to classify and identify the ultrasound images to obtain the best network. Then, the features in the ultrasound images were extracted and a new convolutional neural network was created based on the best network. Finally, the accuracy of several networks was compared and the best network was evaluated using AUC., Results: Models of VGG16, ResNet50, and Inception-v3 were individually applied to classify and identify 710 ultrasound images containing NAFLD, demonstrating accuracies of 66.2%, 58.5%, and 59.2%, respectively. To further improve the classification accuracy, two features are presented: the ultrasound echo attenuation coefficient (θ), derived from fitting brightness values within sliding region of interest (ROIs), and the ratio of Doppler effect (ROD), identified through analyzing spots exhibiting the Doppler effect. Then, a multi-input deep learning network framework based on the VGG16 model is established, where the VGG16 model processes ultrasound image, while the fully connected layers handle θ and ROD. Ultimately, these components are combined to jointly generate predictions, demonstrating robust diagnostic capabilities for moderate to severe fatty liver (AUC = 0.95). Moreover, the average accuracy is increased from 64.8% to 77.5%, attributed to the introduction of two advanced features with domain knowledge., Conclusion: This research holds significant potential in aiding doctors for more precise and efficient diagnosis of ultrasound images related to NAFLD., Competing Interests: Conflict of interest The authors declare no competing interests., (Copyright © 2024 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Resistance to osimertinib represents a significant challenge for the successful treatment of non-small cell lung cancer (NSCLC) harboring activating mutations in EGFR. N6-methyladenosine (m6A) on mRNAs is critical for various biological processes, yet whether m6A regulates osimertinib resistance of NSCLC remains unknown. In this study, we demonstrated that developing osimertinib-resistant phenotypes depends on m6A reduction resulting from downexpression of m6A methyltransferase METTL14 in EGFR-mutant NSCLCs. Both in vitro and in vivo assays showed that specific knockdown of METTL14 was sufficient to confer osimertinib resistance and that elevated expression of METTL14 rescued the efficacy of osimertinib in the resistant NSCLC cells. Mechanistically, METTL14 promoted m6A methylation of pro-apoptotic Bim mRNA and increased Bim mRNA stability and expression, resulting in activating the Bim-dependent pro-apoptotic signaling and thereby promoting osimertinib-induced cell apoptosis. Analysis of clinical samples revealed that decreased expression of METTL14 was observed in osimertinib-resistant NSCLC tissues and significantly associated with a poor prognosis. In conclusion, our study reveals a novel regulatory mechanism by which METTL14-mediated m6A methylation of Bim mRNA inhibited osimertinib resistance of NSCLC cells. It offers more evidences for the involvement of m6A modification in regulation of osimertinib resistance and provides potential therapeutic targets for novel approaches to overcome the tolerance of osimertinib and other EGFR tyrosine kinase inhibitors. Implications: This study offers more evidences for the involvement of METTL14-mediated N6-methyladenosine modification in regulation of osimertinib resistance and provides potential therapeutic targets for novel approaches to overcome the tolerance of osimertinib and other EGFR tyrosine kinase inhibitors., (©2024 American Association for Cancer Research.)

Introduction: Sporotrichosis, a prevalent deep fungal infection in clinical settings, currently lacks rapid and accurate diagnostic methodologies. This study explores a novel rapid diagnosis method for sporotrichosis by combining FTA cards and nested PCR with fungal fluorescence staining., Methods: The study involved skin lesion tissues from 26 patients diagnosed with sporotrichosis (Experimental Group). The Positive Control Group consisted of fungal suspensions from clinical strains of Sporothrix, while the Negative Control Group included fungal solutions of other fungi, namely Trichophyton rubrum, Trichophyton mentagrophyte, and Candida albicans. DNA was extracted from the slurry of skin lesions in the Experimental Group and from fungal suspensions in the Control Group using FTA cards, followed by nested PCR amplification. Subsequently, nested PCR amplification was performed. Histopathological examinations, including HE and fluorescence staining, were conducted on paraffin sections prepared from skin lesion tissues in the Experimental Group., Results: Among the 26 clinical skin lesion tissues in the Experimental Group, 8 cases showed a specific positive band upon nested PCR amplification, resulting in a positive rate of 30.8%. In the Control Group, the fungal solution of the clinical strain of Sporothrix showed a specific positive band upon nested PCR amplification, while all other fungi Negative Control Group tested negative. Histopathological examination revealed granulomatous inflammatory changes in most samples after HE staining. Fluorescence staining detected spores in 17 cases, resulting in a detection rate of 65.4% (17/26)., Conclusion: The combination of FTA cards with nested PCR method proved to be simple and rapid but demonstrated a relatively low positive rate. Fungal fluorescence staining significantly improved the sensitivity of detecting sporotrichosis in histopathological examinations, thereby improving the speed and efficiency of diagnosis., (© 2024 S. Karger AG, Basel.)

Metabotropic glutamate receptor 7 (mGluR7) belongs to the family of type III mGluR receptor, playing an important part in the central nervous system (CNS) through response to neurotransmitter regulation, reduction of excitatory toxicity, and early neuronal development. Drugs targeting mGluR7 (mGluR7 agonists, antagonists, and allosteric modulators) may be among the most promising agents for the treatment of CNS disorders, such as psychiatric disorders, neurodegenerative diseases, and neurodevelopmental impairments, though these potential therapies are at early stages and the data are still limited. In this review, we summarized the structure and function of mGluR7 and discussed recent progress on mGluR7 agonists and antagonists. A deeper understanding of mGluR7 will contribute to uncovering the molecular mechanisms of neuroprotection and providing a theoretical basis for the formulation of therapeutic strategies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Lung cancer has emerged as the second most common type of malignant tumor worldwide, and it has the highest mortality rate. The overall 5-year survival rate stands at less than 20%, which is primarily related to the limited therapeutic options and the complexity of the tumor immune microenvironment. In the tumor microenvironment, M1 macrophages are known for their tumor-killing capabilities. Although they are less numerous, they play an important role in tumor immunity. Therefore, increasing M1 macrophages' presence is considered a strategy to enhance targeted phagocytosis and antitumor efficacy in nonsmall cell lung cancer (NSCLC). This study introduces the development of folic acid (FA)-conjugated liposomal nanobubbles for precise delivery of PFH, STAT3 siRNA, and Fe 3 O 4 to the tumor microenvironment. These encapsulated PFH liposomal nanobubbles exhibit significant visualization potential and underwent phase transition when exposed to low-intensity focused ultrasound (LIFU). The release of Fe 3 O 4 activates the IRF5 signaling pathway, converting M2-like macrophages to M1. In addition, STAT3 siRNA effectively interrupts the JAK-STAT3 pathway, inhibiting the polarization of M2-like macrophages in tumor-associated macrophages (TAMs). This dual-action therapy facilitates T-cell activation and proliferation, thereby enhancing the immune response against NSCLC.

Bamboo is an ideal green building material with excellent mechanical properties. Phosphogypsum (PG) is a kind of solid waste residue which is in urgent need of resource utilization and has been used as construction material. In this paper, a kind of round bamboo-fiber reinforced phosphogypsum composite short column was proposed. Axial compression tests of pure bamboo columns, bamboo columns filled with phosphogypsum inside, bamboo columns with phosphogypsum outside and bamboo columns with phosphogypsum inside and outside were carried out to explore the failure mode and mechanical properties of the short columns. The effects of the parameters include bamboo node, hose hoops, size of the bamboo tube and the strength of phosphogypsum on the mechanical properties of the short columns were analyzed, and the theoretical calculation method of the bearing capacity of the short columns was put forward. The results show that the bamboo nodes and hose hoops can improve the bearing capacity, initial stiffness and ductility of the column. The larger the size of the bamboo tube, the better the mechanical properties of the short column. The bearing capacity of round bamboo-phosphogypsum composite short column is higher than that of pure bamboo column. The ductility of bamboo columns with phosphogypsum outside is obviously higher than that of pure bamboo columns. The finite element analysis results are in good agreement with the test results. The theoretical calculation method of the bearing capacity of columns considering the strength reduction coefficient, the bamboo node effect coefficient and the constraint effect in this paper has high accuracy., (© 2024. The Author(s).)

As an AAA + ATPase, thyroid hormone receptor interacting protein 13 (TRIP13) primarily functions in DNA double-strand break repair, chromosome recombination, and cell cycle checkpoint regulation; aberrant expression of TRIP13 can result in chromosomal instability (CIN). According to recent research, TRIP13 is aberrantly expressed in a variety of cancers, and a patient's poor prognosis and tumor stage are strongly correlated with high expression of TRIP13. Tumor cell and subcutaneous xenograft growth can be markedly inhibited by TRIP13 knockdown or TRIP13 inhibitor administration. In the initiation and advancement of human malignancies, TRIP13 seems to function as an oncogene. Based on available data, TRIP13 may function as a biological target and biomarker for cancer. The creation of inhibitors that specifically target TRIP13 may present novel approaches to treating cancer., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Metabolic-associated fatty liver disease (MAFLD), also known as non-alcoholic fatty liver disease (NAFLD), is a worldwide liver disease without definitive or widely used therapeutic drugs in clinical practice. In this study, we confirm that 6-gingerol (6-G), an active ingredient of ginger ( Zingiber officinale Roscoe ) in traditional Chinese medicine (TCM), can alleviate fructose-induced hepatic steatosis. It was found that 6-G significantly decreased hyperlipidemia caused by high-fructose diets (HFD) in rats, and reversed the increase in hepatic de novo lipogenesis (DNL) and triglyceride (TG) levels induced by HFD, both in vivo and in vitro. Mechanistically, chemical proteomics and cellular thermal shift assay (CETSA)-proteomics approaches revealed that stearoyl-CoA desaturase (SCD) is a direct binding target of 6-G, which was confirmed by further CETSA assay and molecular docking. Meanwhile, it was found that 6-G could not alter SCD expression (in either mRNA or protein levels), but inhibited SCD activity (decreasing the desaturation levels of fatty acids) in HFD-fed rats. Furthermore, SCD deficiency mimicked the ability of 6-G to reduce lipid accumulation in HF-induced HepG2 cells, and impaired the improvement in hepatic steatosis brought about by 6-G treatment in HFD supplemented with oleic acid diet-induced SCD1 knockout mice. Taken together, our present study demonstrated that 6-G inhibits DNL by targeting SCD to alleviate fructose diet-induced hepatic steatosis.

This feature article delves into the realm of α-L-threose nucleic acid (TNA), an artificial nucleic acid analog characterized by a backbone comprising an unconventional four-carbon sugar, α-L-threose, with phosphodiester linkages connecting at the 2' and 3' vicinal positions of the sugar ring. Within this article, we encapsulate the potential, progress, current state of the art, and persisting challenges within TNA research. Kicking off with a historical overview of xeno nucleic acids (XNAs), the discussion transitions to the compelling attributes and structure-property relationships of TNAs as advanced tools when contrasted with natural nucleic acids. Noteworthy aspects such as their advantageous spatial arrangements of functional groups around the sugar ring, stable Watson-Crick base pairing, high binding affinity, biostability, biocompatibility, and in vivo bio-safety are highlighted. Moreover, the narrative unfolds the latest advancements in chemical and biological methodologies for TNA synthesis, spanning from monomer and oligomer synthesis to polymerization, alongside cutting-edge developments in enzyme engineering aimed at bolstering large-scale TNA synthesis for in vitro selection initiatives. The article sheds light on the evolution of TNA aptamers over time, expounding on the tools and selection techniques engineered to unearth superior binding aptamers and TNA catalysts. Furthermore, the article accentuates the recent applications of TNAs across diverse domains such as molecular detection, immunotherapy, gene therapy, synthetic biology, and molecular computing. In conclusion, we summarize the key aspects of recent TNA research, address persisting gaps and challenges, and provide crucial insights and future perspectives in the dynamic domain of TNA research.

Tumors have long posed a significant threat to human life and health, and the messenger ribonucleic acid (mRNA) vaccine is seen as an attractive approach for cancer immunotherapy due to its developmental simplicity, rapid manufacture, and increased immune safety and efficiency. In this review, we have summarized details of the developmental history of mRNA vaccines, discussed the basic molecular structure and the effect on the stable and translation level of mRNA, analyzed the underlying immune efficiency and mechanisms on tumors, and assessed the current status of clinical research. We explored the treatment and application prospects of mRNA vaccines, aiming to provide perspectives on the future of mRNA tumor vaccines for ongoing clinical research.

Bluetooth devices have been widely used for pedestrian positioning and navigation in complex indoor scenes. Bluetooth beacons are scattered throughout the entire indoor walkable area containing stairwells, and pedestrian positioning can be obtained by the received Bluetooth packets. However, the positioning performance is sharply deteriorated by the multipath effects originating from indoor clutter and walls. In this work, an ultra-wideband (UWB)-assisted Bluetooth acquisition of signal strength value method is proposed for the construction of a Bluetooth fingerprint library, and a multi-frame fusion particle filtering approach is proposed for indoor pedestrian localization for online matching. First, a polynomial regression model is developed to fit the relationship between signal strength and location. Then, particle filtering is utilized to continuously update the hypothetical location and combine the data from multiple frames before and after to attenuate the interference generated by the multipath. Finally, the position corresponding to the maximum likelihood probability of the multi-frame signal is used to obtain a more accurate position estimation with an average error as low as 70 cm., Competing Interests: The authors declare no conflicts of interest.

Background: Extracellular vesicles (EVs) are cell-secreted membrane vesicles that have become a promising, natural nanoparticle system for delivering either naturally carried or exogenously loaded therapeutic molecules. Among reported cell sources for EV manufacture, human induced pluripotent stem cells (hiPSCs) offer numerous advantages. However, hiPSC-EVs only have a moderate ability for brain delivery. Herein, we sought to develop a stable hiPSC line for producing EVs with substantially enhanced brain targeting by genetic engineering to overexpress rabies viral glycoprotein (RVG) peptide fused to the N terminus of lysosomal associated membrane protein 2B (RVG-Lamp2B) which has been shown capable of boosting the brain delivery of EVs via the nicotinic acetylcholine receptor., Methods: An RVG-Lamp2B-HA expression cassette was knocked into the AAVS1 safe harbor locus of a control hiPSC line using the CRISPR/Cas9-assisted homologous recombination. Western blot was used to detect the expression of RVG-Lamp2B-HA in RVG-edited hiPSCs as well as EVs derived from RVG-edited hiPSCs. Uptake of EVs by SH-SY5Y cells in the presence of various endocytic inhibitors was analyzed using flow cytometry. Biodistribution and brain delivery of intravenously injected control and RVG-modified EVs in wild-type mice were examined using ex vivo fluorescent imaging., Results: Here we report that an RVG-Lamp2B-HA expression cassette was knocked into the AAVS1 safe harbor locus of a control hiPSC line using the CRISPR/Cas9-assisted homologous recombination. The RVG-edited iPSCs have normal karyotype, express pluripotency markers, and have differentiation potential. Expression of RVG-Lamp2B-HA was detected in total cell extracts as well as EVs derived from RVG-edited (vs. control) hiPSCs. The RVG-modified EVs enter neuronal cells via distinct endocytic pathways, compared with control EVs. The biodistribution study confirmed that EVs derived from RVG-edited hiPSCs possess higher brain delivery efficiency., Conclusion: Taken together, we have established stable, genetically engineered hiPSCs for producing EVs with RVG expression, offering the improved ability for brain-targeted drug delivery., (© 2024. The Author(s).)

The immunosuppressive tumor microenvironment (TME) significantly inhibits the effective anti-tumor immune response, greatly affecting the efficacy of immunotherapy. Most tumor-associated macrophages (TAMs) belong to the M2 phenotype, which contributes significantly to the immunosuppressive effects in non-small cell lung cancer (NSCLC) TME. The interaction between signal regulatory protein α (SIRPα) expressed on macrophages and CD47, a transmembrane protein overexpressed on cancer cells, activates the "eat-me-not" signaling pathway, inhibiting phagocytosis. In this study, a folic acid (FA)-modified ultrasound responsive gene/drugs delivery system, named FA@ PFP @ Fe 3 O 4 @LNB-SIRPα siRNA (FA-PFNB-SIRPα siRNA), was developed using 1,2-dioleoacyl-3-trimethylammonium-propane (DOTAP), FA-1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N- [amino (polyethylene glycol)2000] (DSPE-PEG2000-FA), cholesterol, and perfluoropentane (PFP), for the delivery of siRNA encoding SIRPα mRNA and immune adjuvant Fe 3 O 4 nanoparticles. Under ultrasound conditions, the nanobubbles effectively transfected macrophages, inhibiting SIRPα mRNA and protein expression, promoting the phagocytosis of TAMs, and synergistically reversing M2 polarization. This system promotes the infiltration of T cells, enhances the proliferation and activation of cytotoxic T cells, and inhibits the infiltration of immunosuppressive cells in tumor tissues. Administration of FA-PFNB-SIRPα siRNA combined with ultrasound significantly inhibits NSCLC progression. The study highlights the potential of ultrasound nanotechnology-enabled delivery of SIRPα siRNA and Fe 3 O 4 as an effective strategy for macrophage-based immunotherapy to reshape the immunosuppressive TME for cancer therapy., (© 2024. The Author(s).)

Leucine-rich pentatricopeptide repeat-containing protein (LRPPRC), signal transducer and activator of transcription 3 (STAT3), and cyclin-dependent kinase 1 (CDK1) are promising therapeutic targets for cancer treatment. However, there is a lack of effective inhibitors of LRPPRC, STAT3, and CDK1 in clinic. Our previous study has proved that 5,7,4'-Trimethoxyflavone (TMF) is a novel inhibitor of LRPPRC/STAT3/CDK1. However, the extraction rate of TMF from Tangerine Peel is quite low, and the doses of TMF in cells and mice are rather high. Herein, structural modifications of TMF have led to two series of TMF derivatives including sulfonamide substituted at 3'-position (7a-m) and 3',8-position (11a-m). Among all compounds, 7e, 7k, 11e, and 11g exhibited as effective, broad-spectrum, and potent anticancer agents in vitro. Moreover, 7e, 7k, 11e, and 11g showed better antitumor effects than TMF and clinical used chemotherapy drug capecitabine in vivo with no obvious toxicity. Mechanism studies showed that 11g could bind to LRPPRC, STAT3, and CDK1 to disassociate the LRPPRC-JAK2-STAT3 and JAK2-STAT3-CDK1 complexes, resulting in suppression of JAK2/STAT3 signaling pathway. These findings suggest that 11g may serve as a leading compound for cancer therapy as a triple-target (LRPPRC, STAT3, and CDK1) inhibitor., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Patients with Alzheimer's disease (AD) often exhibit characteristic clinical manifestations, particularly neuropsychiatric symptoms. Previous studies have shown that white matter hyperintensity (WMH) is strongly associated with AD progression, as well as neuropsychiatric symptoms. The purpose of this study was to investigate the clinical and neuropsychological characteristics of AD patients with WMH., Methods: This retrospective study involved 104 18-fluorodeoxyglucose-positron emission computed tomography ( 18 FDG-PET-CT)-defined AD patients treated at Tianjin Huanhu Hospital from January 2010 to December 2022. Cranial magnetic resonance imaging (MRI) provided semi-quantitative data on brain structure and WMH. Collect and analyze patient clinical data. Neuropsychological assessments were used to evaluate cognitive function and psychobehavioral traits., Results: Among the 104 patients, 66 were in the WMH group (63.5%) and 38 in the non-white matter hyperintensity (non-WMH) group (36.5%). There were no significant differences in gender, age, age of onset, education, BMI, smoking, drinking, diabetes, coronary heart disease, dementia family history, fasting blood glucose, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) between the two groups. The WMH group showed higher rates of hypertension, homocysteine (Hcy) levels, NPI, and CDR scores as compared to the non-WMH group ( p  < 0.05). MMSE and MoCA scores were significantly lower in the WMH group ( p  < 0.05). In the MMSE subitem analysis, patients in the WMH group showed a decrease in attention, recall, and language scores. In the MOCA subitem analysis, WMH patients had lower scores in executive function, naming, attention, language, abstraction, and orientation ( p  < 0.05). Furthermore, subgroup analysis of NPI showed a higher incidence of delusions, depression, and apathy in the WMH group ( p  < 0.05). According to the hierarchical analysis of mild, moderate and severe dementia groups, the hypertension, leukoencephalopathy, Hcy level, Fazekas total score, PWMH and DWMH scores in the severe dementia group were significantly higher than those in the mild and moderate dementia groups ( p  < 0.05). As the disease progresses, more and more patients show increased white matter hyperintensity., Conclusion: White matter lesions are closely correlated with cognitive decline and psychobehavioral symptoms in AD patients, and may be used as an indicator of disease progression. Priority should be given to early screening and prevention of WMH-related risk factors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Wang, Zhang, Zhou, Zhang, Li and Wu.)

Hydrodynamic cavitation and ozone nanobubble-coupled hydrodynamic cavitation have demonstrated effective algae control in laboratories, but their in-situ potential, especially impact on nutrient salt degradation and microbial communities remain unclear. This study applied two-stage nanobubble technology, combining hydrodynamic cavitation and ozone nanobubbles, in a 3300 m 2 semi-enclosed area of Taihu Lake to address these gaps. Results show that the technology efficiently controls algae, reduces odors, improves anaerobic conditions, and lowers ammonia nitrogen. Over 20 days, chlorophyll-a concentration reduced by 77.46% and cyanobacterial phycocyanin by 89.47%. Additionally, the concentrations of 2-MIB, GSM, and DMTS fell below threshold values. Notably, the relative abundance of Cyanobacteria in sediment dropped from 8.53% in the control area to only 1.59%-3.65% in the experimental area. The technology also achieved a significant reduction in ammonia nitrogen, with removal efficiencies of 78.53% in the water column and 39.17% in sediments, though the removal of total phosphorus was limited. Furthermore, the two-stage nanobubble system enhanced the abundance of nitrogen-cycling microorganisms and genes in the water, while promoting nitrogen- and phosphorus-related microbial communities in sediments and inhibiting the cyanobacteria-associated genus Cyanobium PCC-6307. Thus, Two-stage nanobubble technology can be employed for in-situ algal control in aquatic ecosystems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Acupuncture therapy shows promise in managing aromatase inhibitor-induced arthralgia (AIA) among breast cancer patients. An umbrella review synthesizes findings from systematic reviews and meta-analyses (SRs/MAs) to assess its effectiveness., Summary: This umbrella review aimed to evaluate the effectiveness of acupuncture therapy in treating AIA among breast cancer patients by analyzing existing evidence from SRs/MAs., Key Messages: Six SRs/MAs were analyzed, revealing shortcomings in reporting quality, methodological quality, and evidence quality assessment. Comprehensive searches across eight electronic databases were conducted. PRISMA, AMSTAR 2, and GRADE were utilized to assess reporting, methodological quality, and evidence quality, respectively. Despite methodological shortcomings, a recent meta-subgroup analysis suggests the efficacy of acupuncture therapy for AIA patients, recommending a 10-session treatment course., Conclusion: Acupuncture is identified as a secure and effective remedy for AIA sufferers, yet further high-quality research is needed to strengthen the evidence base and endorse acupuncture as a viable treatment option., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 S. Karger AG, Basel.)

Background: High-intensity focused ultrasound (HIFU) is a promising minimally invasive treatment for liver cancer; however, its efficacy is often limited by the attenuation of ultrasonic energy. This study investigates the effectiveness of B7-H3-targeted microbubbles (T-MBs) in enhancing HIFU ablation of liver cancer and explores their potential for clinical translation., Methods: T-MBs and isotype control microbubbles (I-MBs) were synthesized through the conjugation of biotinylated anti-B7-H3 antibody and isotype control antibody to the microbubble surface, respectively. Contrast-enhanced ultrasound imaging was performed to compare the accumulation of T-MBs and I-MBs in liver cancer at various time points. The efficacy of T-MBs in enhancing HIFU treatment was evaluated by measuring the immediate tumor ablation rate and long-term tumor growth suppression. Additionally, the induced antitumor immune response was assessed through cytokine quantification in serum and tumor tissue, along with immunofluorescence staining conducted on days 1, 3, and 7 post-treatment., Results: T-MBs demonstrated superior liver cancer-specific accumulation, characterized by higher concentrations and prolonged retention compared to I-MBs. The combination of T-MBs with HIFU resulted in significantly enhanced tumor ablation rates and superior tumor growth suppression. Post-treatment analysis revealed a gradual uptick in cytokine levels within the tumor microenvironment, along with progressive infiltration of antitumor immune cells., Conclusion: T-MBs effectively enhance the therapeutic efficacy of HIFU for liver cancer treatment while simultaneously promoting an antitumor immune response. These findings provide a strong experimental foundation for the clinical translation of ultrasound molecular imaging combined with HIFU as a novel approach for tumor therapy., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

High altitude environment is mainly characterized by low oxygen. Due to persistent hypoxia, nonhealing wounds are common in high-altitude areas. Moreover, Basic fibroblast growth factor (bFGF) is a versatile biologically active substance that has crucial impact on wound healing. Given the limited availability of atmospheric oxygen and reduced blood oxygen saturation in high-altitude area, and the challenge that arises from direct oxygen and bFGF delivery to wounds through the traumatized vascular structure, it necessitates an innovative solution for local and permeable delivery of oxygen and bFGF. In this study, we present a strategy that involves revamping traditional gel-based wound dressings through the incorporation of nanoparticles encapsulating oxygen and bFGF, engineered to facilitate the localized delivery of dissolved oxygen and bFGF to wound surfaces. The prospective evaluation of this delivery technique's therapeutic impacts on epithelial, endothelial and fibroblasts cells can be materialized. Further experiment corroborated these effects on a high-altitude wounds' murine model. Given its biocompatibility, efficacy, and utility, we posit that NOB-Gel exhibits remarkable translational potential for managing and hastening the healing process of an array of clinical wounds, more so for wounds inflicted at high altitudes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Masson SAS.)

Background: Spinocerebellar ataxia type 12 (SCA12) is a neurodegenerative disease caused by a CAG/CTG repeat expansion at the PPP2R2B locus., Objective: We investigated how the CAG repeat expansion within the PPP2R2B 7B7D transcript influences the expression of Bβ1 and a potential protein containing a long polyserine tract., Methods: Transcript and protein expression were measured using quantitative PCR (qPCR) and Western blot, respectively, in an SK-N-MC cell model that overexpresses the full-length PPP2R2B 7B7D transcript. The apoptotic effect of a protein containing a long polyserine tract on SK-N-MC cells was evaluated using caspase 3/7 activity., Results: The CAG repeat expansion increases the expression of the PPP2R2B 7B7D transcript, as well as Bβ1 protein, in an SK-N-MC cell model in which the full-length PPP2R2B 7B7D transcript is overexpressed. The CAG repeat expansion within the 7B7D transcript is translated into a long polyserine tract that triggers apoptosis in SK-N-MC cells., Conclusions: The SCA12 mutation leads to overexpression of PPP2R2B Bβ1 and to expression of a protein containing a long polyserine tract; both these effects potentially contribute to SCA12 pathogenesis. © 2024 International Parkinson and Movement Disorder Society., (© 2024 International Parkinson and Movement Disorder Society.)

The small genera Allaeanthus and Malaisia within the Moraceae have important edible, medicinal, and economic value. However, complete plastome blueprints and a well-resolved evolutionary history of these two genera are still lack, thereby limiting their conservation and application. The recent discovery of a new distribution of Allaeanthus kurzii in Hainan, China, marked by the collection of two unique samples, alongside three samples of Malaisia scandens, has opened new avenues for research. This study aimed to compare the Allaeanthus and Malaisia plastomes of Hainan Province samples with those of samples from other regions, focusing on plastome structure, codon usage bias, natural selection, and the evolutionary history of A. kurzii and M. scandens. The results showed that both species had a quadripartite plastome structure, with sizes ranging from 162,134 to 162,170 bp for A. kurzii and 161,235 to 162,134 bp for M. scandens. Both species displayed loss of the infA gene and reduction of the rpl22 gene. Two highly variable regions (petD-trnD-GUC and rpl20-clpP) and three highly variable genes (rpl20, petB, and rpl16) were identified in A. kurzii, while two highly variable regions (ycf2-ndhB and ccsA-ndhE) and three highly variable genes (psbT, rpl36, and ycf2) were found in M. scandens. The protein-coding sequences (CDSs) of the Allaeanthus and Malaisia plastomes exhibited similar patterns of adaptive indices and codon usage frequencies. The genes associated with photosynthesis underwent strong purifying selection. Phylogenetic analysis revealed that Allaeanthus, Broussonetia, and Malaisia constituted a monophyletic group, with Malaisia being more closely related to Broussonetia. Broussonetia diversified approximately 19.78 million years ago, Malaisia approximately 4.74 million years ago, and Allaeanthus approximately 16.18 million years ago. These new plastome-based discoveries will guide conservation planners and medicinal plant breeders and genetic resource development for these species in the region., (© 2024. The Author(s).)

Sturgeons ( Acipenseridae ), ancient fish known for their caviar, produce underutilized by-products like protein-rich cartilage, which is a source of high-quality bioactive peptides. This study investigates immunomodulatory peptides from sturgeon cartilage hydrolysates mechanisms. The study found that sturgeon cartilage hydrolysate F2-7 and its key peptides(DHVPLPLP and HVPLPLP)significantly promoted RAW267.4 cell proliferation, NO release, and phagocytosis ( P  < 0.001).Additionally, western blotting confirmed that F2-7 enhances immune response by increasing the expression of P-IKKα/β, IΚΚ, p65, and P-p65 proteins in the NF-κB signalling pathway ( P  < 0.01). Molecular docking further demonstrated that DHVPLPLP and HVPLPLP bind to NF-κB pathway proteins via hydrogen bonding, with low estimated binding energies (-2.75 and -1.64; -6.04 and -4.75 kcal/mol), thus establishing their role as key immune peptides in F2-7. Therefore, DHVPLPLP and HVPLPLP have the potential to be developed as dietary supplements for immune enhancement. Their ability to enhance immune function provides a theoretical basis for novel immune supplements., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Background: Full-dose BCG bladder perfusion therapy is effective, but there are serious side effects. Whether a low dose of BCG can reduce the side effects of treatment while maintaining its efficacy is still inconclusive., Objective: To compare the efficacy of low-dose and full-dose BCG bladder perfusion therapy and to provide reference for individual treatment of bladder cancer., Methods: All relevant literature published in PubMed, Web of Science, and Embrase databases up to April 2024 was searched. The results and shortcomings of the existing literature are analyzed, the cognitive gaps between different studies are pointed out, and suggestions are made for future research., Results: A total of 32 pieces of literature were included. Twelve studies found that the efficacy of full-dose BCG perfusion was significantly better than that of low-dose BCG perfusion, and 20 studies found no statistical difference between low-dose and full-dose BCG perfusion CONCLUSION: Although there is no significant difference in the efficacy of full-dose and low-dose BCG in bladder perfusion, the trend indicates that the efficacy of full-dose BCG is still the most accurate. In cases where BCG resources are scarce or patients are intolerant, low-dose BCG bladder perfusion therapy may be an alternative to full-dose BCG bladder perfusion therapy. High-quality, large-sample prospective cohort studies (or randomized controlled studies) are still needed in the future., (© 2024. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

The intractability and high mortality rate of castration-resistant prostate cancer (CRPC) remain the most challenging problems in the field of prostate cancer (PCa). Emerging evidence has shown that the dysregulation of Wnt signaling pathways, which are highly conserved cascades that regulate embryonic development and maintain tissue homeostasis, is involved in various stages of PCa occurrence and progression. In this review, we systemically discuss the mechanisms by which the androgen receptor (AR) signaling pathway and Wnt signaling pathways participate in the occurrence of PCa and its progression to CRPC. Specifically, we elaborate on how Wnt signaling pathways induce the malignant transformation of prostate cells, promote the malignant progression of PCa and establish an immunosuppressive prostate tumor microenvironment through interaction with the AR pathway or in an AR-independent manner. We also discuss how Wnt signaling pathways enhances the stemness characteristics of prostate cancer stem cells (PCSCs) to induce the occurrence and metastasis of CPPC. Additionally, we discuss the latest progress in the use of different types of drugs that inhibit the Wnt signaling pathways in the treatment of PCa. We believe that the combination of Wnt signaling-based drugs with endocrine and other therapies is necessary and may enhance the clinical efficacy in the treatment of all types of PCa., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Aims: We aimed to evaluate the risk of cardiovascular disease (CVD) in women with polycystic ovary syndrome (PCOS) and estimate the global incidence of PCOS-associated CVD., Methods and Results: We conducted a meta-analysis across five databases to evaluate the risk of CVD among women with PCOS. The global incidence of PCOS-associated CVD was calculated by a population attributable fraction modelling using the pooled risk ratio (RR), PCOS prevalence, CVD incidence number, and age-standardized rate (ASIR), from the Global Burden of Diseases 2019. An estimated annual percentage change (EAPC) was used to assess the temporal trend of PCOS-associated CVD. The risk of CVD was significantly increased in women with PCOS for an all-age group (pooled RR 1.51, 95% confidence interval 1.36-1.69) and 10- to 54-year-olds (1.37, 1.17-1.59). Globally, from 1990 to 2019, the PCOS-associated CVD cases in women across the all-age group has raised from 102 530 to 235 560. The most affected regions were East Asia and the Pacific (108 430, 66 090-166 150) in 2019. South Asia has the highest increase trend of PCOS-associated CVD ASIRs (EAPC 2.61%, 2.49-2.73). The annual increase in ASIR in PCOS-CVD incidence for the 10-54 age group (EAPC 0.49%, 0.41-0.56) is faster than that of the all-age group (0.34, 0.27-0.42). The middle- or low-middle sociodemographic index countries experienced higher increase trend of CVD due to PCOS in the past 30 years., Conclusion: Women with PCOS have a significantly increased risk of CVD. Efficient measures to enhance its prevention and treatment are important for regions with a high PCOS-associated CVD burden, especially premature CVD in women under 55 years., Competing Interests: Conflict of interest: We declare that all authors have no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Tiarella polyphylla D. Don has been traditionally used to cure asthma and skin eruptions. However, the sequence and the structure of the mitogenome of T. polyphylla remained elusive, limiting the genomic and evolution analysis based on the mitogenome., Results: Using a combination of Illumina and Nanopore sequencing reads, we de novo assembled the complete mitogenome of T. polyphylla. In addition to unveiling the major configuration of the T. polyphylla mitogenome was three circular chromosomes with lengths of 430,435 bp, 126,943 bp, and 55,269 bp, we revealed five (R01-R05) and one (R06) repetitive sequence could mediate the intra- and inter-chromosomal recombination, respectively. Furthermore, we identified 208 short and 25 long tandem segments, seven cp-derived mtDNAs, 106 segments of mtDNAs transferred to the nuclear genome, and 653 predicted RNA editing sites. Based on the sequence of the mitogenomes, we obtained the resolved phylogeny of the seven Saxifragales species., Conclusions: These results presented the mitogenome features and expanded its potential applications in phylogenetics, species identification, and cytoplasmic male sterility (CMS) in the future., (© 2024. The Author(s).)

Aim: To analyze the spectrum of isolated pathogens and antibiotic resistance for ocular infections within 5y at two tertiary hospitals in east China., Methods: Ocular specimen data were collected from January 2019 to October 2023. The pathogen spectrum and positive culture rate for different infection location, such as keratitis, endophthalmitis, and periocular infections, along with antibiotic resistance were analyzed., Results: We included 2727 specimens, including 827 (30.33%) positive cultures. A total of 871 strains were isolated, 530 (60.85%) bacterial and 341 (39.15%) fungal strains were isolated. Gram-positive cocci (GPC) were the most common ocular pathogens. The most common bacterial isolates were Staphylococcus epidermidis (25.03%), Staphylococcus aureus (7.46%), Streptococcus pneumoniae (4.59%), Corynebacterium macginleyi (3.44%), and Pseudomonas aeruginosa (3.33%). The most common fungal genera were Fusarium spp. (12.74%), Aspergillus spp. (6.54%), and Scedosporium spp. (5.74%). Staphylococcus epidermidis strains showed more than 50% resistance to fluoroquinolones. Streptococcus pneumoniae and Corynebacterium macginleyi showed more than 90% resistance to erythromycin. The percentage of bacteria showing multidrug resistance (MDR) significantly decreased ( χ 2 =17.44, P =0.002)., Conclusion: GPC are the most common ocular pathogens. Corynebacterium macginleyi , as the fourth common bacterium, may currently be the local microbiological feature of east China. Fusarium spp. is the most common fungus. More than 50% of the GPC are resistant to fluoroquinolones, penicillins, and macrolides. However, the proportion of MDR strains has been reduced over time., Competing Interests: Conflicts of Interest: Li PP, None; Li L, None; Zhang JF, None; Qin B, None; Kang LH, None; Ji M, None; Guan HJ, None., (International Journal of Ophthalmology Press.)

Ground-level ozone (O 3 ) pollution poses a significant threat to both ecosystem sustainability and human health. The catalytic decomposition of O 3 presents as a promising technology to address the issues of O 3 pollution. This study undertook the synthesis of various functionalized metal-organic framework (MOF) catalysts (i.e., X-MIL-53(Fe) (X = H, NH 2 , NO 3 )) to delve into the influence of ligand functional groups on skeletal structure and catalytic efficacy, particularly focusing on unraveling the mechanism of O 3 catalytic decomposition under humid conditions. NH 2 -MIL-53(Fe) catalyst achieved complete O 3 decomposition under ambient temperature and high humidity conditions (RH=75 %), exhibiting a reaction rates (mol·m -2 ·s -1 ) 129 and 10.5 times greater than that of MIL-53(Fe) and NO 2 -MIL-53(Fe). The NH 2 group promotes electron flow within the backbone towards the hydroxyl group (OH) linked to Fe atom. In humid O 3 , H 2 O molecules augment the interaction between O 3 and NH 2 -MIL-53(Fe), and OH is converted to·O 2 - after deprotonation, promoting O 3 decomposition. Additionally, leveraging three-dimensional (3D) printing technology, a monolithic catalyst for O 3 decomposition was prepared for application. This study not only advances understanding of the mechanisms underlying O 3 decomposition but also offers practical solutions for addressing O 3 pollution at humid conditions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The use of Generally Recognized as Safe (GRAS)-grade microbial cell factories to produce recombinant protein-based nutritional products is a promising trend in developing food and health supplements. In this study, GRAS-grade Kluyveromyces marxianus was employed to express recombinant human heavy-chain ferritin (rhFTH), achieving a yield of 11 g/L in a 5 L fermenter, marking the highest yield reported for ferritin nanoparticle proteins to our knowledge. The rhFTH formed 12 nm spherical nanocages capable of ferroxidase activity, which involves converting Fe 2+ to Fe 3+ for storage. The rhFTH-containing yeast cell lysates promoted cytokine secretion (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and -1β (IL-1β)) and enhanced locomotion, pharyngeal pumping frequency, egg-laying capacity, and lifespan under heat and oxidative stress in the RAW264.7 mouse cell line and the C. elegans model, respectively, whereas yeast cell lysate alone had no such effects. These findings suggest that rhFTH boosts immunity, holding promise for developing ferritin-based food and nutritional products and suggesting its adjuvant potential for clinical applications of ferritin-based nanomedicine. The high-yield production of ferritin nanoparticles in K. marxianus offers a valuable source of ferritin for the development of ferritin-based products.

Disrupted cholesterol homeostasis plays a critical role in the development of multiple diseases, such as cardiovascular disease and cancer. However, the role of cholesterol in inflammatory bowel disease (IBD) remains unclear. In the present study, we investigated whether and how high levels of cholesterol in the diet affect experimental colitis in mice. A normal diet supplemented with 1.25% cholesterol (high cholesterol diet) caused more severe colitis and aggravated the disruption of intestinal tight junction structure, accompanied by higher colonic tissue total cholesterol (TC) levels in a dextran sulfate sodium (DSS)-induced experimental colitis mouse model. Cholesterol aggravated DSS-induced intestinal epithelial barrier impairment and nuclear sterol regulatory element-binding protein 2 (nSREBP2) inhibition both in vivo and in vitro. In addition, nSREBP2 overexpression ameliorated cholesterol-induced intestinal epithelial barrier disruption in Caco2 cells. Interestingly, inhibition of SREBP2 disrupted intestinal epithelial barrier in the absence of cholesterol. Furthermore, SREBP2 regulated the protein expression of tight junction proteins (occludin/Zo-1) via modulating caveolin-1-mediated endocytosis and lysosomal degradation. Analysis of UK Biobank data indicated that, in fully adjusted models, higher serum TC concentrations were an independent protective factor for IBD incidence. The sterol regulatory element-binding factor 2 (SREBF2) gene rs2228313 (G/C) genetic variant was associated with the incidence of IBD and the CC genotype of SREBF2 rs2228313 was associated with higher serum TC levels and decreased the risk of IBD. In summary, a high cholesterol diet aggravates DSS-induced colitis in mice by down-regulating nSREBP2 expression, thereby promoting the endocytic degradation of tight junction proteins. In humans, SREBF2 gene single nucleotide polymorphism rs2228313 and serum TC levels are associated with IBD incidence., (© 2024 Federation of European Biochemical Societies.)

Background: It is well established that smoking is the most significant risk factor for bladder cancer, yet the impact of smoking on the recurrence and progression of non-muscle-invasive bladder cancer (NMIBC) remains a contentious issue., Objective: To review all relevant literature published to date, providing a comprehensive assessment of the effects of smoking on the recurrence and progression of NMIBC, thereby offering a basis for smoking cessation management in NMIBC patients., Methods: A search was conducted for all relevant literature published up to April 2024 in PubMed, Web of Science, and Embase databases. The existing literature results and deficiencies were analyzed, and the gaps in understanding between different studies were highlighted, with recommendations for future research., Results: A total of 24 studies were included in this work. Among them, 14 studies suggested that smoking promotes the recurrence and progression of NMIBC, while another 10 studies concluded that smoking has no effect on the recurrence and progression of NMIBC patients., Conclusions: Our research indicates that smoking increases the risk of recurrence and progression in NMIBC patients, and quitting smoking can improve health-related quality of life. High-quality, large-sample prospective cohort studies (or randomized controlled studies) are still needed in the future., (© 2024. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)