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Defective glucose-stimulated insulin secretion (GSIS) and β-cell senescence are hallmarks in diabetes. The mitochondrial enzyme pyruvate carboxylase (PC) has been shown to promote GSIS and β-cell proliferation in the clonal β-cell lines, yet its physiological relevance remains unknown. Here, we provide animal and human data showing a role of PC in protecting β-cells against senescence and maintaining GSIS under different physiological and pathological conditions. β-cell-specific deletion of PC impaired GSIS and induced β-cell senescence in the mouse models under either a standard chow diet or prolonged high-fat diet feeding. Transcriptomic analysis indicated that p53-related senescence and cell cycle arrest are activated in PC-deficient islets. Overexpression of PC inhibited hyperglycemia- and aging-induced p53-related senescence in human and mouse islets as well as INS-1E β-cells, whereas knockdown of PC provoked senescence. Mechanistically, PC interacted with MDM2 to prevent its degradation via the MDM2 binding motif, which in turn restricts the p53-dependent senescent program in β-cells. On the contrary, the regulatory effects of PC on GSIS and the tricarboxylic acid (TCA) anaplerotic flux are p53-independent. We illuminate a function of PC in controlling β-cell senescence through the MDM2-p53 axis., Competing Interests: Competing interests statement:The authors declare no competing interest.

Ethnopharmacological Relevance: Hyperlipidemia as a major health issue has attracted much public attention. As a geographical indication product of China, Liupao tea (LPT) is a typical representative of traditional Chinese dark tea that has shown good potential in regulating glucose and lipid metabolism. LPT has important medicinal value in hyperlipidemia prevention. However, the active ingredients and metabolic mechanisms by which LPT alleviates hyperlipidemia remain unclear., Aim of the Study: This study aimed to systematically investigate the metabolic mechanisms and active ingredients of LPT extract in alleviating hyperlipidemia., Materials and Methods: Firstly, we developed a mouse model of hyperlipidemia to study the pharmacodynamics of LPT. Subsequently, network pharmacology and molecular docking were performed to predict the potential key active ingredients and core targets of LPT against hyperlipidemia. LC-MS/MS was used to validate the identity of key active ingredients in LPT with chemical standards. Finally, the effect and metabolic mechanisms of LPT extract in alleviating hyperlipidemia were investigated by integrating metabolomic, lipidomic, and gut microbiome analyses., Results: Results showed that LPT extract effectively improved hyperlipidemia by suppressing weight gain, remedying dysregulation of glucose and lipid metabolism, and reducing hepatic damage. Network pharmacology analysis and molecular docking suggested that four potential active ingredients and seven potential core targets were closely associated with roles for hyperlipidemia treatment. Ellagic acid, catechin, and naringenin were considered to be the key active ingredients of LPT alleviating hyperlipidemia. Additionally, LPT extract modulated the mRNA expression levels of Fxr, Cyp7a1, Cyp8b1, and Cyp27a1 associated with bile acid (BA) metabolism, mitigated the disturbances of BA and glycerophospholipid (GP) metabolism in hyperlipidemia mice. Combining fecal microbiota transplantation and correlation analysis, LPT extract effectively improved species diversity and abundance of gut microbiota, particularly the BA and GP metabolism-related gut microbiota, in the hyperlipidemia mice., Conclusions: LPT extract ameliorated hyperlipidemia by modulating GP and BA metabolism by regulating Lactobacillus and Dubosiella, thereby alleviating hyperlipidemia. Three active ingredients of LPT served as the key factors in exerting an improvement on hyperlipidemia. These findings provide new insights into the active ingredients and metabolic mechanisms of LPT in improving hyperlipidemia, suggesting that LPT can be used to prevent and therapeutic hyperlipidemia., 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.)

Ethnopharmacological Relevance: Pueraria lobata is essential medicinal and edible homologous plants widely cultivated in Asian countries. Therefore, P. lobata is widely used in the food, health products and pharmaceutical industries and have significant domestic and international market potential and research value. P. lobata has remarkable biological activities in protecting liver, relieving alcoholism, antioxidation, anti-tumor and anti-inflammation in clinic. However, the potential mechanism of ethyl acetate extract of Pueraria lobata after 70% alcohol extraction (APL) ameliorating nonalcoholic fatty liver disease (NAFLD) has not been clarified., Aim of the Study: This study aimed to investigate the ameliorative effect of P. lobata extract on human hepatoma cells and injury in rats, and to evaluate its therapeutic potential for ameliorating NAFLD., Methods: Firstly, the effective part of P. lobata extract was determined as APL by measuring its total substances and antioxidant activity. And then the in vitro and in vivo models of NAFLD were adopted., HepG2 cells were incubated with palmitic acid (PA) and hydrogen peroxide (H 2 O 2 ). In order to evaluate the effect of APL, Simvastatin and Vitamin C (VC) were used as positive control. Various parameters related to lipogenesis and fatty acid β-oxidation were studied, such as intracellular lipid accumulation, reactive oxygen species (ROS), Western Blot, mitochondrial membrane potential, apoptosis, and the mechanism of APL improving NAFLD. The chemical components of APL were further determined by HPLC and UPLC-MS, and molecular docking was carried out with Keap1/Nrf2/HO-1 pathway related proteins., Results: APL significantly reduced lipid accumulation and levels of oxidative stress-related factors in vitro and in vivo. Immunohistochemical、Western Blot and PCR analysis showed that the expressions of Nrf2 and HO-1 were up-regulated in APL treatment. The Nrf2 inhibitor ML385 can block the rescue by APL of cellular oxidative stress and lipid accumulation induced by H 2 O 2 and PA, demonstrating its dependence on Nrf2. UPLC/MS analysis showed that there were 3'-hydroxyl puerarin, puerarin, 3'-methoxy puerarin, daidzein, genistin, ononin, daidzin and genistein., Conclusion: This study further clarified the mechanism of P. lobata extract in improving NAFLD, which provided a scientific basis for developing new drugs to protect liver injury and laid a solid foundation for developing P. lobata Chinese herbal medicine resources., 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.)

Intercalation engineering is a promising strategy to promote zinc-ion storage of layered cathodes; however, is impeded by the complex fabrication routes and inert electrochemical behaviors of intercalators. Herein, an organic imidazole intercalation strategy is proposed, where V 2 O 5 and NH 4 V 3 O 8 (NVO) model materials are adopted to verify the feasibility of the imidazole intercalator in improving the zinc storage capabilities of vanadium-based cathodes. The intercalated imidazole molecules could not only expand interlayer spacing and strengthen structural stability by serving as extra "pillars" but also provide extra coordination sites for zinc storage via the coordination reaction between Zn 2+ and the C═N group. This gives rise to a dual-mode ion storage mechanism and favorable electrochemical performances. As a result, imidazole-intercalated V 2 O 5 delivers a capacity of 179.9 mAh g -1 after 5000 cycles at 20 A g -1 , while the imidazole-intercalated NVO harvests a high capacity output of 170.2 mAh g -1 after 700 cycles at 2 A g -1 . This work is anticipated to boost the application potentials of vanadium-based cathodes in aqueous zinc-ion batteries.

The conventional behavior recognition strategy for wearable sensors used in high-temperature environments typically requires an external power supply, and the manufacturing process is cumbersome. Herein, we present a rational design strategy based on fully flexible printable materials and a customized device-manufacturing process for skin-conformable triboelectric nanogenerator sensors. In detail, using high temperature-resistant ink and 3D printing technology to manufacture a coaxial triboelectric nanogenerator (C-TENG) sensor, the C-TENG exhibits high stretchability (>400%), a wide working range (>250 °C), and high output voltage (>100 V). The C-TENG can be worn on various parts of the human body, providing a robust skin-device interface that recognizes diverse human behaviors. Using machine learning algorithms, behaviors such as walking, running, sitting, squatting, climbing stairs, and falling can be identified, achieving 100% behavior recognition accuracy through the selective input and optimization of an appropriate dataset. This paper provides a research perspective for the customization, extension, and rapid fabrication of heat-resistant, fully flexible TENGs.

Introduction: Carbamazepine (CBZ) is a commonly used antiseizures medications (ASM), but its adverse drug reactions (ADRs) can impact the successful management of epilepsy. There are currently limited systematic studies on ADRs related to CBZ, necessitating further investigation., Areas Covered: Using the FDA Adverse Event Reporting System (FAERS) database , we extracted reports where CBZ was the primary suspect, conducting subgroup analyses stratified by sex and age. Four risk signal detection methods ROR, PRR, BCPNN, and EGBM were employed to systematically analyze the ADRs associated with CBZ., Expert Opinion: In the epilepsy population, ADRs related to CBZ often involve examinations, hereditary disorders, and infections. Subgroup analysis showed differences in ADR signals among male, female, elderly, and young patients. Human Herpesvirus 6 Infection and Dermatitis Exfoliative were consistent CBZ-induced ADRs, unaffected by age or sex. The study also identified previously overlooked ADRs such as bone metabolism abnormalities, ocular toxicity, and ototoxicity. Many ADRs linked to CBZ remain underreported. It is crucial to enhance monitoring and information dissemination about CBZ use in epileptic patients. Adjusting medication regimens for high-risk individuals, potentially incorporating acupuncture, traditional Chinese medicine, or alternative anti-seizure medications, should be considered when necessary.

G protein subunit Gamma 5 (GNG5) has been found to be involved in regulating glioma progression. However, its function and mechanism in glioblastoma (GBM) progression need to be further elucidated. GBM cell proliferation, apoptosis, invasion and stemness were assessed by cell counting kit 8 assay, EdU assay, flow cytometry, transwell assay and sphere formation assay. The mRNA and protein levels of GNG5 and Yin Yang 1 (YY1) were determined by quantitative real-time PCR and western blot (WB). Detection of the glucose consumption, lactate production and ATP/ADP ratios were used to assess cell glycolysis. Besides, Wnt/β-catenin pathway-related protein levels were examined by WB. Mice xenograft model was also constructed to explore GNG5 roles in vivo. GNG5 was highly expressed in GBM, and its silencing inhibited GBM cell proliferation, invasion, stemness and glycolysis, while promoted apoptosis. Transcription factor YY1 could bind to the GNG5 promoter region and induce its expression. GNG5 overexpression reversed the inhibitory effects of YY1 silencing on GBM cell growth, invasion, stemness and glycolysis. YY1/GNG5 axis could activate the Wnt/β-catenin pathway, and Wnt/β-catenin pathway agonists SKL2001 could revert the effects of GNG5 silencing on GBM cell progression. Furthermore, GNG5 facilitated GBM tumor growth by mediating the Wnt/β-catenin pathway. YY1-mediated GNG5 promoted GBM progression through the Wnt/β-catenin pathway., (© 2024. The Author(s).)

The purpose of this study was to explore the mechanism of action of Piceatannol (PIC) in attenuating oxidative damage to sperm during cryopreservation. Semen samples were collected and homogenized into six equal parts for freeze-thawing experiments. Four different concentrations of PIC were utilized as cryoprotectants during the freeze-thawing process, maintaing a semen to PIC ratio of 1:1, while sperm motility after freezing and thawing was analyzed using computer-assisted sperm analysis (CASA). Sperm plasma membrane integrity was assessed via the hypo-osmotic swelling (HOS) test. The levels of reactive oxygen species (ROS), superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) activities, long with the ability to scavenge sperm malondialdehyde (MDA), were examined in sperm following the addition of PIC. Quantitative real-time PCR (qRT-PCR) was performed to detect the expression levels of Keap1, Nrf2, GCLC, GCLM, and HMOX1 in sperm. The mechanism by which PIC protects sperm during cryopreservation from oxidative stress damage was further verified. Treatment with PIC at a dose of 5.0 μmol/L significantly improved both sperm motility and viability while effectively reducing ROS levels in frozen sperm. Additionally, the integrity of the sperm plasma membrane was significantly enhanced. Furthermore, the expression level of Keap1 was significantly reduced, whereas the expression levels of GCLC, GCLM, HMOX1, and Nrf2 were significantly increased (p < 0.05) after the addition of PIC. Notably, a significant attenuation of sperm motility and viability was observed in this treatment group when PIC treatment was accompanied by the addition of an Nrf2 inhibitor, resulting in a significant elevation of ROS levels. The finding that PIC modulates ROS in frozen sperm via the Keap1-Nrf2/ARE pathway thereby enhancing sperm viability levels after freezing and thawing provides a novel approach to optimize semen cryopreservation., (© 2024. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

The ferroelectric-type characteristics in metal-insulator-metal (MIM) structures with amorphous dielectrics are observed, which may open a new window for a class of new ferroelectric devices. However, the working principles of these ferroelectric devices are not well explained. It has been proposed that oxygen ion (O 2- ) and charged vacancy (V o 2+ ) migrations are associated with this ferroelectric-like behavior. In this work, a systematic experimental design is carried out to investigate the origin of O 2- and V o 2+ (from the interface or bulk oxide?), the transport species (O 2- , V o 2+ , or both of these two species?), and the ion transport mode (long-range transport or local movement?). The experimental results answered all these questions. In addition, the role of the thickness of the dielectrics is also studied. This work sets the fundamentals of these amorphous oxide-based devices, guiding future explorations to engineer them.

Most of the traditional fluorescent molecules have the advantages of high fluorescence quantum yield, good stability, and excellent structural adjustability, but they exhibit the characteristics of fluorescence quenching caused by aggregation, which restricts their application in aqueous solutions or solids. The excellent luminescence properties and photosensitive potential of aggregation-induced emission (AIE) materials in a condensed state have made them widely concerned in the scientific research field, so it is very challenging to regulate the transformation of traditional aggregation-caused quenching (ACQ) fluorophores into AIE fluorophores. In this study, the traditional coumarin fluorophore was used as a matrix. After conjugating the triphenylamine AIE group, the triphenylphosphine cation was linked through the alkyl chain to obtain a molecular probe NCTPP with excellent AIE characteristic, water solubility, mitochondrial green light imaging, chemotherapy and photodynamic therapy capabilities. As far as we know, it was the first time that the photosensitivity of coumarin fluorescent molecules was imparted by the ACQ-AIE conversion method.

An in vivo mouse model of Clonorchis sinensis (C. sinensis) infection with or without the administration of autophagy inhibitor chloroquine (CQ) stimulation was established to assess the possible involvement of autophagic response during C. sinensis infection. Abnormal liver function was observed at 4, 6, and 8 weeks post-infection, as indicated by elevated levels of ALT/GPT, AST/GOT, TBIL, and α-SMA in the infected groups. These findings indicated that C. sinensis infection activated autophagy, as shown by a decreased LC3II/I ratio and accumulated P62 expression in infected mice. Interestingly, CQ administration exhibited dual and opposing effects during the infection. In the early stage of infection, the engagement of CQ appeared to mitigate symptoms by reducing inflammation and fibrotic responses. However, in the later stage of infection, CQ might contribute to parasite survival by evading autophagic targeting, thereby exacerbating hepatic impairment and worsening liver fibrosis. Autophagy in liver was suppressed throughout the infection. These observations attested that C. sinensis infection triggered autophagy, and highlighted a complex role for CQ, with both protective and detrimental effects, in the in vivo process of C. sinensis infection., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Cytochrome P450 monooxygenases are associated with the detoxification of xenobiotics, and overexpression of P450 genes has been proven to be associated with insecticide resistance in insect species. Our previous study has revealed that multiple CYP6AE genes were significantly overexpressed in a resistant strain of Spodoptera exigua , and among these genes, CYP6AE70 was particularly highly expressed. However, the functional roles of the CYP6AE genes in insecticide resistance remain unknown in this pest. Here, we investigate the relationship between the CYP6AE genes and insecticide resistance by focusing on CYP6AE70 . The expression of CYP6AE70 was increased after exposure to chlorpyrifos, cypermethrin, and deltamethrin. Ectopic overexpression of P450 in transgenic flies by the GAL4/UAS system dramatically enhanced the tolerance to these three insecticides. Furthermore, the recombinant CYP6AE70 was functionally expressed in Sf9 cells, and metabolic assays revealed that the recombinant P450 protein could efficiently metabolize chlorpyrifos, cypermethrin, and deltamethrin. Finally, molecular modeling and docking also showed that this P450 protein were tightly bound to the three insecticides. These results determine that the upregulation of CYP6AE genes results in resistance to multiple insecticides in S. exigua . This study improves our understanding of P450-mediated insecticide resistance and will help us to design more effective resistance management for pest control.

Biodegradable versatile inorganic nanomaterials are highly desirable in the field of nanomedicine. Here, for the first time, we report a kind of novel two-dimensional biodegradable l-cysteine-iodine (l-Cys-I) nanosheet with high computed tomography (CT) imaging ability and sonosensitization efficacy. Such l-Cys-I nanosheets consist of iodine molecules and l-Cys, where the iodine molecules are coordinated and stabilized by l-Cys and cross-linked to form nanosheets through disulfide bonds. The large and convenient functional surface is further modified with targeting moieties DSPE-PEG-RGD and cancer drug doxorubicin (DOX) to construct a nanotheranostic nanoplatform (CIRD). Under ultrasound irradiation, the CIRD nanosheets assist in tremendous reactive oxygen species generation and controllable DOX release, leading to remarkable anticancer performance both in vitro and in vivo due to the synergistic sonodynamic therapy (SDT) and chemotherapy. Our results validate that the CIRD nanosheets enable effective body excretion and negligible systemic toxicity owing to the biodegradation properties. The CIRD nanosheets, with biodegradability, biocompatibility, and versatility, hold great promise in nanotheranostics.

Wearable sensors enable the noninvasive continuous analysis of biofluid, which is of great importance for healthcare monitoring. In this work, a wearable sensor was seamlessly integrated with a microfluidic chip which was prepared by a three-dimensional printing technology for noninvasive and multiplexed analysis of metabolite and electrolytes in human sweat. The microfluidic chip could enable rapid sampling of sweat, which avoids the sweat evaporation and contamination. Using a Zn metal-organic framework as a sacrificial template, the hexagonal rod-shaped porous carbon nanorod (PCN) with high porosity, a large specific surface area, and excellent conductivity was synthesized and exhibited the robust electrocatalytic ability of uric acid (UA) oxidation. Therefore, the PCN-based sensor showed high sensitivity and good selectivity of UA with a wide linear range of 10-200 μM and a low detection limit of 4.13 μM. Meanwhile, the potentiometry-based ion-selective electrode was constructed for detection of pH and K + , respectively, with good sensitivity, selectivity, reproducibility, and stability. In addition, the testing under different bending states demonstrated that mechanical deformation had little effect on the electrochemical performance of the wearable sensors. Furthermore, we evaluated the utility of the wearable sensor for multiplexed real-time analysis of UA, pH, and K + in sweat during aerobic exercise, and the effect of the amount of consumed purine-rich foods on uric acid metabolite levels in sweat and urine was further investigated. The relationship between urine UA and sweat UA was obtained. Overall, this wearable sensor enables multiple electrolyte and metabolite analysis in different noninvasive biofluids, suggesting its potential application in personalized disease prevention.

Nanolabels can enhance the detection performance of electrochemical biosensing methods, yet their practical application is hindered by complex preparation, batch-to-batch variability, and poor long-term storage stability. Herein, we present a novel electrochemical method for miRNA detection based on the just-in-time generation of zeolitic imidazolate framework-8 (ZIF-8) nanolabels initiated by nucleic acids. In this design, the target miRNA-21 is captured with magnetic beads and polyadenylated by Escherichia coli Poly(A) polymerase ( E PP), producing miRNA-21 molecules with poly(A) tails (miR-21-poly(A)). These molecules are then adsorbed onto a bare gold electrode (AuE) surface via adenine-gold affinity interactions, serving as nucleation sites for the rapid in situ formation of ZIF-8 nanoparticles. The ZIF-8 nanoparticles function as signal labels, impeding electron transfer at the electrode interfaces and thereby generating a notable electrochemical signal. The developed method demonstrated exceptional sensitivity, with a detection limit (LOD) as low as 2.3 aM and a linear detection range from 10 aM to 1000 fM. The practical application of the developed method was validated by using it to evaluate miRNA-21 expression levels in various biological samples, including cell lines, tumor tissues, and clinical blood samples from non-small cell lung cancer (NSCLC) patients. This approach simplifies the detection process by eliminating the need for presynthesized nanomaterials and premodified electrodes. Its simplicity and high sensitivity make this method a promising tool for point-of-care testing and a wide range of biomedical research applications.

Enhanced weathering of (ultra)mafic rocks has been proposed as a promising approach to sequester atmospheric CO 2 and mitigate climate change. However, these silicate rocks contain varying amounts of trace metals, which are essential cofactors of metallaenzymes in methanogens. We found that weathering of crushed peridotite and basalt significantly promoted the growth and methanogenesis of a model methanogen─ Methanosarcina acetivorans C2A under the condition of excess substrate. The released trace metals from peridotite and basalt, especially Fe, Ni, and Co, accounted for the promotion effect. Observation at different spatial scales showed a close association between the rocks and cells. Proteomic analysis revealed that rock amendment significantly enhanced the expression of core metalloenzymes in the methylotrophic methanogenesis pathway. Our study uncovers a previously unrecognized but important negative effect of enhanced rock weathering on methane production, which may counteract the carbon sequestration effort.

Antibacterial therapy targeting the regulation of macrophage polarization may be a useful approach for normalizing the immune environment and accelerating wound healing. Inspired by black phosphorus-based nanoplatforms, more stable yet less-explored violet phosphorus nanosheets (VPNSs) are expected to provide a superior solution for effectively combating bacterial infections. In this study, an average thickness of 5-7 nm VPNSs are fabricated through the liquid-phase exfoliation method to serve as an immunoregulatory dressing for the treatment of infected wounds. VPNSs attenuated excessive reactive oxygen species (ROS) and reduced the accumulation of proinflammatory M1 macrophages, showing notable antioxidant and anti-inflammatory properties. Comprehensive RNA sequencing further elucidated the potential immunoregulatory mechanisms of VPNSs, including modulation of the inflammatory response and enzyme regulator activity. Additionally, the inherent photothermal properties of the VPNSs contributed significantly to their antibacterial efficacy. When combined with near-infrared laser irradiation, VPNSs showed remarkable effectiveness in reducing infection-related complications and expediting wound healing in infected skin wound models. The rapid promotion of wound healing through ROS clearance, the regulation of macrophage polarization, and hyperthermia generation underscores the potential of the violet-phosphorus-based nanoplatforms as clinically viable agents for treating infected wounds. This study suggests that VPNSs are promising candidates for clinical anti-infective and anti-inflammatory applications., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Vitreoretinal diseases pose significant threats to vision, often requiring vitrectomy and substitution of vitreous humor to restore ocular structure and visual function. However, existing substitutes have limitations that compromise patient outcomes. Supramolecular hydrogels, particularly peptide-based formulations, have emerged as promising alternatives due to their superior optical clarity, biocompatibility, and viscoelasticity. In this study, we designed and evaluated two peptide hydrogels, 3K-OX and 3E-OX, bearing positive and negative charges, respectively, as potential vitreous substitutes. Our in vitro findings revealed that the physicochemical properties of the negatively charged peptide hydrogel, 3E-OX, closely resembled those of the native vitreous body, exhibiting optimal light transmittance, refractive index, molecular permeability, and biocompatibility. Animal studies further confirmed the safety and biocompatibility of 3E-OX as a promising vitreous substitute. Notably, we introduced optical coherence tomography for retinal microvascular detection in non-pigmented rabbits, presenting a novel approach to evaluate the performance of intraocular tamponade materials. This work not only expands the utility of peptide hydrogels but also provides valuable insights into the design of vitreous substitutes., Competing Interests: Declaration of competing interest All the authors have no conflicts to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

As a class of predominantly used cathode interlayers (CILs) in organic solar cells (OSCs), perylene-diimide (PDI)-based polymers exhibit intriguing characteristics of excellent charge transporting capacity and suitable energy levels. Despite that, PDI-based CILs with satisfied film-forming ability and adequate solvent resistance are rather rare, which not only limits the further advance of OSC performances but also hinders the practical use of PDI CILs. Herein, we designed and synthesized two non-conjugated PDI polymers for achieving high power conversion efficiency (PCE) in diverse types of OSCs. The utilization of oligo (ethylene glycol) (OEG) linkage enhanced the n-doping effect of PDI polymers, leading to an improved ability of the CIL to reduce work function and improve electron transporting capability. Moreover, the introduction of the non-ionic OEG chain effectively improve the wetting property and solvent resistance of PDI polymers, so the PPDINN CIL can withstand diverse processing conditions in fabricating different OSCs, including conventional, inverted and blade-coated devices. The binary OSC with conventional structure using PPDINN CIL showed a PCE of 18.6 %, along with an improved device stability. Besides, PPDINN is compatible with the large-area blade-coating technique, and a PCE of 16.6 % was achieved in the 1-cm 2 OSC where a blade-coated PPDINN was used., (© 2024 Wiley-VCH GmbH.)

The filamentous temperature-sensitive (Fts) protein FtsEX plays a pivotal role in Escherichia coli ( E. coli ) cell division by facilitating the activation of peptidoglycan hydrolysis through the adaptor EnvC. FtsEX belongs to the type VII ATP-binding cassette (ABC) transporter superfamily, which harnesses ATP energy to induce mechanical force, triggering a cascade of conformational changes that activate the pathway. However, the precise mechanism by which FtsEX initiates mechanotransmission remains elusive. Due to the inherent instability of this type of ABC transporter protein in vitro, the conformation of FtsEX has solely been determined in the stabilized ATP-bound state. To elucidate the dynamics of FtsEX, we characterized FtsEX and EnvC of various functional structures through cryo-electron microscopy (cryo-EM) and homology modeling. We validated the structures by molecular dynamics simulations. By site-directed mutagenesis and phenotype screening, we also identified the functional residues involved in allosteric communication between FtsE and FtsX as well as FtsX and EnvC. Additionally, we discovered a potential role of phospholipids in stabilizing the complex conformation during mechanotransmission. This comprehensive exploration significantly enhances our understanding of the intricate mechanisms governing bacterial cell division and unveils potential molecular targets for developing innovative antimicrobial drugs to combat antibiotic resistance., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.)

The abnormal mechanical behaviour of a lumbar intervertebral disc (IVD) is commonly recognized as a direct indicator of intervertebral disc degeneration (IDD). However, current methods cannot evaluate the patient-specific mechanical performance of an IVD in vivo during movement. This study establishes a patient-specific (PS) model that combines the kinematics parameters of the lumbar spine obtained with a dual fluoroscopic imaging system (DFIS) and a finite-element (FE) method for the first time to reveal the mechanical behaviours of IVDs in vivo under seven motions. Three healthy participants were recruited for this study. CT images were obtained to create finite-element models of L3-L5 spine segments. Meanwhile, participants were required to take specific positions including upright standing, flexion, extension, left and right lateral bending, as well as left and right axial torsion in the DFIS. The in vivo kinematic parameters, calculated by registering the CT images with images obtained with DFIS, were considered as loading conditions in FE simulations. Significant differences of von Mises stresses and principal strains were found between PS model and GN model which employing a generalized moment as loading conditions, former resulting in up to 76.74 % lower strain than the GN model. Also, considerable differences were observed for five anatomical regions of the IVD (L3-L5). Under all motions, the stress in the centre region (nucleus pulposus) was the lowest, while the stress in the posterior region was the highest in extension motion. Therefore, activities such as stretching with an extension, should be avoided by patients with a herniated disc, in which the posterior region was the herniation site. The PS model combining in vivo kinematics and FE simulations shows the potential in the design and assessment of patient-specific implants., 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.)

T-2 toxin is a major cause of Kashin-Beck disease (KBD), which is characterised by cartilage damage. N6-adenosine-methyltransferase-like 3 (METTL3) regulates cartilage injury; however, its role in T-2 toxin-induced cartilage injury remains elusive. Herein, we investigated the involvement of METTL3-mediated m6A modification in T-2 toxin-induced cartilage damage. METTL3-mediated m6A methylation levels were correlated with cartilage extracellular matrix (ECM) degradation, which was exacerbated following METTL3 silencing. Cathepsin K (Ctsk) was identified as a downstream target of METTL3 using m6A-methylated RNA immunoprecipitation（MeRIP）sequencing and RNA sequencing. Silencing Ctsk aggravated HT-2 toxin-induced ECM degradation. Increasing the m6A methylation levels in vivo via dietary methionine supplementation mitigated cartilage damage. In summary, HT-2 toxin induced cartilage ECM degradation by regulating the METTL3-mediated m6A modification of Ctsk. These findings highlight the METTL3/m6A/Ctsk axis as a potential therapeutic target for the treatment of KBD and other cartilage-associated diseases., (Copyright © 2024. Published by Elsevier B.V.)

Here, we report that four functional fragments of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) spike protein including receptor binding motif (RBM), fusion peptide (FP), heptad repeat 1 (HR1) and heptad repeat 2 (HR2) were chosen to develop a recombinant S subunit protein vaccine. This recombinant protein consisting of S230 amino acids (aa) (S230) bound specifically to the antibody from COVID-19-patients serum, which showed very strong antigenicity. The S230 was then engineered to present on the surface of Hepatitis B core (HBc) virus-like particles (VLPs) to develop HBc-S230 chimeric VLPs vaccine. Both vaccines induced strong humoral and cellular immune responses in mice, however, HBc-S230 chimeric VLPs elicited significantly higher immunogenicity than the S230. HBc-S230 chimeric VLPs promoted to generate not only dramatically higher levels of S230-specific serum antibodies, but also marked higher CD4+/CD8 + T cells ratio and substantially higher yields of IFN-γ and IL-6. Furthermore, HBc-S230 chimeric VLPs induced serum antibodies that could effectively neutralize the infection with three SARS-CoV-2 pseudoviruses (Wild type, Delta and Omicron). Our results demonstrated that HBc-S230 chimeric VLPs immunization conveyed the humoral immunity, which lasted longer than six months. Clearly, HBc-S230 chimeric VLPs enhanced immunogenicity of the S230, which could provide potent and durable protection against SARS-CoV-2 infection, indicating that HBc-S230 chimeric VLPs possessed great potential for developing highly immunogenic vaccines against SARS-CoV-2., 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 B.V. All rights reserved.)

The selective photoreduction of nitrate to nontoxic nitrogen gas has emerged as an energy-efficient and environmentally friendly route for nitrate removal. However, the coexisting high-concentration chloride ions in wastewater can exert a significant influence on nitrate reduction due to the competitive adsorption and corrosion of Cl - on photocatalysts. Herein, we prepared ethylene glycol-Cu/TiO 2- x (EG-Cu/TiO 2- x ) through a solvothermal reaction of Cu-doped TiO 2 in an EG solution. The photodegradation of nitrate using EG-Cu/TiO 2- x without adding sacrificial agents can efficiently occur in near-neutral pH solutions containing 50 mM Cl - with 95.26% of NO 3 - removal and 76.52% of N 2 selectivity. Moreover, the photocatalyst performance remained at a high level after 8 cycles. In this work, NO 3 - was first converted to NH 4 + by Cu 0 and Ti 3+ , followed by the NH 4 + -to-N 2 conversion by photogenerated chlorine free radicals. Compared to HO • , Cl • , and Cl 2 •- , ClO • is proved to play the predominant role in transforming NH 4 + to N 2 . The EG radicals produced by UV light impede Cl - adsorption on Cu, protecting Cu 0 from being corroded. What's more, photoelectrons can reduce Ti 4+ to Ti 3+ and protect Cu 0 from being oxidized, enabling the stability of reactive sites. This work provides novel insights and understanding on designing photocatalysts for NO 3 - removal in solutions containing chloride ions, highlighting the significance of eliminating Cl - by EG radicals and adjusting the conversion process of NO 3 - for the efficient removal of NO 3 - .

Purpose: To investigate the clinical outcomes following arthroscopic chondral nail fixation for acetabular cartilage delamination (ACD) in patients with femoroacetabular impingement syndrome (FAIS), and the presentation of ACD on MRI at follow-up., Methods: A retrospective review was performed between March 2021 and March 2022 at our institute. Patients undergoing primary hip arthroscopy for FAIS and diagnosed with ACD intraoperatively were included. Exclusion criteria were incomplete data or loss of minimum 2-year follow-up, and concomitant hip conditions including hip osteoarthritis with a Tönnis grade > 1, avascular necrosis, Legg-Calvé-Perthes disease, osteoid osteoma, synovial chondromatosis, pigmented villonodular synovitis, and developmental dysplasia of the hip (DDH). Patients who underwent chondral nail fixation were matched 1:1 with a control cohort of patients who only underwent simple debridement. Preoperative and minimum 2-year postoperative patient-reported outcome (PRO) scores including Visual Analog pain Scale (VAS), modified Harris Hip Score (mHHS), and percentage of achieving minimal clinically important difference (MCID) and patient acceptable symptom state (PASS) were collected and compared. MRI was performed preoperatively and at final follow-up to assess ACD., Results: Fifty-eight patients were included in the study (29 patients in each group). Both groups demonstrated improved VAS and mHHS following surgery (all with P < .05). The chondral nail group demonstrated better postoperative VAS (P = .022) compared to the control group, while the postoperative mHHS was comparable between the two groups (P = .852). No significant difference was found in the achievement of MCID between the two groups (all with P > .05). More patients in the chondral nail group achieved PASS of VAS compared to the control group (75.9% vs 48.3%, P = .030). No patient underwent revision surgery or conversion to total hip arthroplasty (THA). The chondral nail group demonstrated significantly higher rate of ACD healing on MRI compared to the control group (P < .001)., Conclusion: Patients undergoing arthroscopic chondral nail fixation for treating ACD demonstrated significant pain relief, more achievement of PASS of VAS, and higher rate of ACD healing on MRI compared to those undergoing simple debridement., Level of Evidence: Level III; retrospective cohort study., (Copyright © 2024. Published by Elsevier Inc.)

Urbanization and industrialization have driven rapid socio-economic development, leading to a significant population shift from rural areas to cities. This demographic transition has resulted in substantial changes in rural settlements, presenting considerable challenges for rural revitalization. Given the spatial differentiation, it is crucial to analyze the spatiotemporal evolution patterns and driving mechanisms of rural settlements under various development scenarios and at multiple scales within a county. Such analysis is essential for rational planning and sustainable development. This study analyzes the spatial and temporal evolution patterns and driving mechanisms of rural settlements in Xunwu County, Jiangxi Province, China, using land use dynamics, hot and cold spot analysis, and center of gravity migration models. The Multiscale Geographically Weighted Regression Model (MGWR) is employed to explore their transformation driving mechanisms. The results show that during 2010-2020 in the study area, the total change rate of rural settlements was 39.82%, with a dynamic degree of 2.87%. The average centroid of the settlements is located in Wenfeng Township, gradually migrating southeastward by 3.7 km. Cold spots are shrinking northward, while hotspots are gathering in Chengjiang Town. Socio-economic conditions dominate the evolution of rural clusters in this region, showing obvious spatial heterogeneity. This is followed by locational conditions that are weakening in influence, while the impact of natural geographical conditions exists in the northeast region. The research findings offer a scientifically rigorous and well-founded analysis of the evolution and driving mechanisms of rural settlements. This analysis provides a solid theoretical basis for policy planning in urban-rural integrated development and supports the sustainable growth of rural communities., (© 2024. The Author(s).)

Topologically ordered phases of matter elude Landau's symmetry-breaking theory, featuring a variety of intriguing properties such as long-range entanglement and intrinsic robustness against local perturbations. Their extension to periodically driven systems gives rise to exotic new phenomena that are forbidden in thermal equilibrium. Here, we report the observation of signatures of such a phenomenon-a prethermal topologically ordered time crystal-with programmable superconducting qubits arranged on a square lattice. By periodically driving the superconducting qubits with a surface code Hamiltonian, we observe discrete time-translation symmetry breaking dynamics that is only manifested in the subharmonic temporal response of nonlocal logical operators. We further connect the observed dynamics to the underlying topological order by measuring a nonzero topological entanglement entropy and studying its subsequent dynamics. Our results demonstrate the potential to explore exotic topologically ordered nonequilibrium phases of matter with noisy intermediate-scale quantum processors., (© 2024. The Author(s).)

Contrast-induced acute kidney injury (CIAKI) is a common complication with limited treatments. Intermedin (IMD), a peptide belonging to the calcitonin gene-related peptide family, promotes vasodilation and endothelial stability, but its role in mitigating CIAKI remains unexplored. This study investigates the protective effects of IMD in CIAKI, focusing on its mechanisms, particularly the cAMP/Rac1 signaling pathway. Human umbilical vein endothelial cells (HUVECs) were treated with iohexol to simulate kidney injury in vitro. The protective effects of IMD were assessed using CCK8 assay, flow cytometry, ELISA, and Western blotting. A CIAKI rat model was utilized to evaluate renal peritubular capillary endothelial cell injury and renal function through histopathology, immunohistochemistry, immunofluorescence, Western blotting, and transmission electron microscopy. In vitro, IMD significantly enhanced HUVEC viability and mitigated iohexol-induced toxicity by preserving intercellular adhesion junctions and activating the cAMP/Rac1 pathway, with Rac1 inhibition attenuating these protective effects. In vivo, CIAKI caused severe damage to peritubular capillary endothelial cell junctions, impairing renal function. IMD treatment markedly improved renal function, an effect negated by Rac1 inhibition. IMD protects against renal injury in CIAKI by activating the cAMP/Rac1 pathway, preserving peritubular capillary endothelial integrity and alleviating acute renal injury from contrast media. These findings suggest that IMD has therapeutic potential in CIAKI and highlight the cAMP/Rac1 pathway as a promising target for preventing contrast-induced acute kidney injury in at-risk patients, ultimately improving clinical outcomes.

Pyroptosis is a critical pathological mechanism implicated in myocardial damage following myocardial infarction (MI), and the crosstalk between macrophages and pyroptotic cardiomyocytes presents a formidable challenge for anti-pyroptosis therapies of MI. However, as single-target pyroptosis inhibitors frequently fail to address this crosstalk, the efficacy of anti-pyroptosis treatment post-MI remains inadequate. Therefore, the exploration of more potent anti-pyroptosis approaches is imperative for improving outcomes in MI treatment, particularly in addressing the crosstalk between macrophages and pyroptotic cardiomyocytes. Here, in response to this crosstalk, we engineered an anti-pyroptosis biomimetic nanoplatform (NM@PDA@PU), employing polydopamine (PDA) nanoparticles enveloped with neutrophil membrane (NM) for targeted delivery of puerarin (PU). Notably, network pharmacology is deployed to discern the most efficacious anti-pyroptosis drug (puerarin) among the 7 primary active monomers of TCM formulations widely applied in clinical practice and reveal the effect of puerarin on the crosstalk. Additionally, targeted delivery of puerarin could disrupt the malignant crosstalk between macrophages and pyroptotic cardiomyocytes, and enhance the effect of anti-pyroptosis by not only directly inhibiting cardiomyocytes pyroptosis through NLRP3-CASP1-IL-1β/IL-18 signal pathway, but reshaping the inflammatory microenvironment by reprogramming macrophages to anti-inflammatory M2 subtype. Overall, NM@PDA@PU could enhance anti-pyroptosis effect by disrupting the crosstalk between M1 macrophages and pyroptotic cardiomyocytes to protect cardiomyocytes, ameliorate cardiac function and improve ventricular remodeling, which providing new insights for the efficient treatment of MI., 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.)

Graphitic carbon nitride (g-C 3 N 4 ) is a fascinating material with potential applications in photocatalysis due to its good chemical stability, high thermal stability, and relative ease of synthesis. In this work, ultrathin g-C 3 N 4 is constructed using a hybridized method, which combines the advantages of thermal and liquid-phase stripping methods. This sample can improve performance in degrading organic pollutants several times, and the highest enhancement efficiency occurs in an alkaline environment. In addition, photocatalytic production of hydrogen peroxide can be increased to 2.6 times that of the bulk sample. These improved properties are due to the increase in specific surface area, the generation of free radicals, and adsorption capacity. This work presents a one-step exfoliation method for bulk g-C 3 N 4 for more surface-active sites and strong redox capacity.

Colonizing in the gastrointestinal tract, Escherichia coli confronts diverse acidic challenges and evolves intricate acid resistance strategies for its survival. The lysine-mediated decarboxylation (Cad) system, featuring lysine decarboxylase CadA, lysine/cadaverine antiporter CadB, and transcriptional activator CadC, plays a crucial role in E. coli's adaptation to moderate acidic stress. While the activation of the one-component system CadC and subsequent upregulation of cadBA operon in response to acid and lysine presence have been proposed, the molecular mechanisms governing the transition of CadC from an inactive to an active state remain elusive. Under neutral conditions, CadC is inhibited by forming a complex with lysine-specific permease LysP, stabilized in this inactive state by a disulfide bond. Our study unveils that, in an acidic environment, the disulfide bond in CadC is reduced by the disulfide bond isomerase DsbC, exposing R184 to periplasmic proteases, namely DegQ and DegP. Cleavage at R184 by DegQ and DegP generates an active N-terminal DNA-binding domain of CadC, which binds to the cadBA promoter, resulting in the upregulated transcription of the cadA and cadB genes. Upon activation, CadA decarboxylates lysine, producing cadaverine, subsequently transported extracellularly by CadB. We propose that accumulating cadaverine gradually binds to the CadC pH-sensing domain, preventing cleavage and activation of CadC as a feedback mechanism. The identification of DegP, DegQ, and DsbC completes a comprehensive roadmap for the activation and regulation of the Cad system in response to moderate acidic stress in E. coli., (© 2024. The Author(s).)

It remains a challenging issue to achieve durably stable photocatalytic CO 2 reduction over heterojunctions owing to their inherent structural assembly features. Herein, a unique partial encapsulation architecture is fabricated on the 3D/2D CoWO 4 /C 3 N 5 heterojunction by embedding CoWO 4 microspheres on C 3 N 5 nanosheets, which achieves efficient, durable, stable, and selective photocatalytic CO 2 reduction. For the optimal 5%-CoWO 4 /C 3 N 5 heterojunction, the yield of selective CO 2 reduction to CO is 7.70 and 3.82 times higher than those of CoWO 4 and C 3 N 5 in 4 h, respectively, and it maintains a stable CO generation rate within 20 cycles over 80 h. A series of characterization experiments and density functional theory calculations reveal that the structural stability is reinforced significantly via strong interfacial interaction owing to the unique partial encapsulation architecture fabricated on the 3D/2D CoWO 4 /C 3 N 5 heterojunction, the separation efficiency of photogenerated carriers is improved by inducing a built-in electric field and triggering the S-scheme charge-transport path, and the high CO product selectivity is attributed to the much lower free energy required for the generation path of CO compared to that for CH 4 .

Introduction: Atorvastatin, one of the most widely used drugs, has attracted controversy regarding its potential adverse reactions to acute kidney injury(AKI). This study aims to provide evidence in support of the safe use of atorvastatin., Areas Covered: Using the FDA Adverse Event Reporting System (FAERS) database (Q1 2004 to Q1 2024), we extracted reports where atorvastatin was the primary suspect and categorized them into five populations: the general population, acute myocardial infarction (AMI), ischemic stroke (IS), type 2 diabetes mellitus (T2DM), and hyperlipidemia (HLD). We performed subgroup analyses by gender and age strata within these populations, assessing positive signals through disproportionality analysis using four criteria: Ratio of Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayes Geometric Mean (EGBM). The statistical analysis evaluated differences between adverse drug reaction (ADR) occurrence and nonoccurrence, as well as between high and low induction time groups., Expert Opinion: In the general population, evidence for a positive signal of AKI was insufficient. However, the sub-group analysis revealed a risk in males, with older individuals more often affected in both AMI and IS populations. In T2DM, positive signals were evident in younger age groups. For the HLD population, evidence of a positive AKI signal was insufficient across gender and age strata. Overall, atorvastatin is generally safe, but clinical vigilance for AKI is warranted in T2DM, AMI, and IS populations, particularly in older adults (65+ years).

Objective: The study aims to evaluate the efficacy of neuromodulatory strategies for people who have drug-resistant epilepsy (DRE)., Methods: We searched electronic repositories, including PubMed, Web of Science, Embase, and the Cochrane Library, for randomized controlled trials, their ensuing open-label extension studies, and prospective studies focusing on surgical or neuromodulation interventions for people with DRE. We used seizure frequency reduction as the primary outcome. A single-arm meta-analysis synthesized data across all studies to assess treatment effectiveness at multiple time points. A network meta-analysis evaluated the efficacy of diverse therapies in randomized controlled trials. Grading of Recommendations, Assessment, Development, and Evaluations was applied to evaluate the overall quality of the evidence., Results: Twenty-eight studies representing 2936 individuals underwent 10 treatments were included. Based on the cumulative ranking in the network meta-analysis, the top 3 neuromodulatory options were deep brain stimulation (DBS) with 27% probability, responsive neurostimulation (RNS) with 22.91%, and transcranial direct current stimulation with 24.31%. In the single-arm meta-analysis, in the short-to-medium term, seizure control is more effective with RNS than with invasive vagus nerve stimulation (inVNS), which in turn is slightly more effective than DBS, though the differences are minimal. However, in the long term, inVNS appears to be less effective than both DBS and RNS. Trigeminal nerve stimulation, transcranial magnetic stimulation, and transcranial alternating current stimulation did not demonstrate significant seizure frequency reduction., Conclusions: Regarding long-term efficacy, RNS and DBS outperformed inVNS. While transcranial direct current stimulation and transcutaneous auricular VNS showed promise for treating DRE, further studies are needed to confirm their long-term efficacy., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: The prevalence of chronic conditions is increasing. Given that the majority of chronic patients are managed by primary healthcare providers, there is a need to integrate primary care with public health to address the prevailing situation and enhance patient outcomes. The purpose of this study is to establish, implement and evaluate an integrated primary care and public health model in China for patients with chronic conditions., Methods: This prospective, multicentre and observational study will be conducted at 12 township hospitals on patients (n=7200) diagnosed with chronic conditions (hypertensive, diabetic or stroke). Participants were divided into two groups: pilot areas and mainstream areas follow-up groups. The primary outcome will be the difference in the proportion of controlled chronic conditions among the two groups. Secondary outcomes will be the differences in mean change in diastolic and systolic blood pressures, fasting glucose, total cholesterol and triglyceride, death from any cause and participant-reported physical and psychological health status., Ethics and Dissemination: Ethics approval was obtained from the Ethics Committee of Tongji Medical College, Huazhong University of Science and Technology. We plan to publish the results of this study in a peer-reviewed journal article., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The Pseudomonas putida F1 genome and those of many other pseudomonads contain two tandem genes encoding acyl-CoA ligases Pput&#95;1340 ( fadD1 ) and Pput&#95;1339 ( fadD2 ) with Pput&#95;1339 ( fadD2 ) being the upstream gene. The fadD designation was assigned when both genes were found to complement the growth of an Escherichia coli acyl-CoA synthetase fadD deletion strain with oleic acid as sole carbon source. Site-directed mutagenesis showed that residues of the ATP/AMP domain required for function of E. coli FadD were also essential for full function of FadD1 and FadD2. Growth of the constructed ∆ fadD1 , ∆ fadD2, and ∆ fadD1 ∆ fadD2 strains was tested in minimal medium with different chain length fatty acids as sole carbon sources. Lack of FadD1 significantly retarded growth with different chain length fatty acids and lack of both FadD1 and FadD2 further retarded growth. Derivatives of the ∆ fabA ∆ desA unsaturated fatty acid auxotrophic strain carrying a deletion of either ∆ fadD1 or ∆ fadD2 were constructed. Growth of the ∆ fabA ∆ desA ∆ fadD1 strain was very weak, whereas the ∆ fabA ∆ desA ∆ fadD2 strain grew as well as the ∆ fabA ∆ desA parent strain. Overexpression of either fadD1 or fadD2 restored growth of the ∆ fabA ∆ desA ∆ fadD1 strain with fadD2 overexpression having a greater effect than fadD1 overexpression. The ∆ fadD1 or ∆ fadD2 genes are cotranscribed although the expression level of fadD1 is much higher than that of fadD2 . This is attributed to a fadD1 promoter located within the upstream FadD2 coding sequence., Importance: Pseudomonas bacteria demonstrate a great deal of metabolic diversity and consequently colonize a wide range of ecological niches. A characteristic of these bacteria is a pair of genes in tandem annotated as acyl-CoA ligases involved in fatty acid degradation. The Pseudomonas putida F1 genome is annotated as having at least nine genes encoding acyl-CoA ligases which are scattered around the chromosome excepting the tandem pair. Since similar tandem pairs are found in other pseudomonads, we have constructed and characterized deletion mutants of the tandem ligases. We report that the encoded proteins are authentic acyl-CoA ligases involved in fatty acid degradation.

Dissolved organic matter (DOM) occurs ubiquitously in various water matrices and affects the chemical speciation and toxicity of emerging contaminants, such as cyclophosphamide (CP). However, the effects of CP in aquatic organisms with the presence of DOM have been relatively less addressed. In this study, zebrafish eggs < 4 h post fertilization (hpf) were exposed to CP (0 and 50 μg/L) and humic acid (HA, a main component of DOM, 0, 3, 10, and 30 mg-C/L) until 7 days post fertilization, and its toxicity was evaluated by behavioral approaches and transcription of nervous-related genes. An increase in swimming velocity and anxiety was noticed in zebrafish larvae exposed to CP. The related genes of neurotransmitter (drd1, mao, thp1b, and gad2), neurodevelopment (gli2b, nrd, and gfap), and neuroinflammation (thfα, casp3, and il-6) were upregulated by CP. In the presence of HA (3 mg-C/L), the behaviors and gene transcripts of zebrafish larvae were enhanced, while at 10 mg-C/L, they were mitigated. This study has demonstrated that DOM at low concentration increases the toxicity of CP and at high concentration alleviates its toxicity. This study highlights the importance of emerging contaminant exposure with the presence of DOM on their toxicities in aquatic organisms., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Methylmercury (MeHg) is a bioaccumulating neurotoxin mainly produced by anaerobic microorganisms, with methanogen being one of the important methylators. A critical aspect for understanding the mechanism for microbial mercury (Hg) methylation is the origin of the methyl group. However, the origin of methyl group in methanogen-mediated Hg methylation remains unclear. This study aims to identify the source of methyl group for MeHg synthesis in methanogens. Our study revealed that Hg methylation in Methanospirillum hungatei JF-1 is closely related to methanogenesis process, according to the results of proteomic study and substrate limitation study. Next, we proved that nearly all methyl group in MeHg derives from the Wolfe cycle in this species, rather than the previously demonstrated acetyl-coenzyme A pathway, based on the results of 13 C labeling study. We then proposed the Wolfe cycle-dependent Hg methylation mechanism in this species. Further genome analyses and 13 C labeling experiments indicated that the involvement of the Wolfe cycle in Hg methylation is probably a universal feature among Hg-methylating methanogens. These findings reveal a unique Hg methylation mechanism in methanogens. Our study broadens the carbon substrates and controlling factors for MeHg synthesis in the environment, which can inform the prediction of MeHg production potential and remediation strategies for MeHg contamination., Competing Interests: Competing interests statement:The authors declare no competing interest.

Objective: This study aims to evaluate the predictive performance and methodological quality of post-stroke readmission prediction models, identify key predictors associated with readmission, and provide guidance for selecting appropriate risk assessment tools., Methods: A comprehensive literature search was conducted from inception to February 1, 2024. Two independent researchers screened the literature and extracted relevant data using the CHARMS checklist., Results: Eleven studies and 16 prediction models were included, with sample sizes ranging from 108 to 803,124 cases and outcome event incidences between 5.2% and 50.0%. The four most frequently included predictors in the models were length of stay, hypertension, age, and functional disability. Twelve models reported an area under the curve (AUC) ranging from 0.520 to 0.940, and five models provided calibration metrics. Only one model included both internal and external validation, while six models had internal validation. Eleven studies were found to have a high risk of bias (ROB), predominantly in the area of data analysis., Conclusion: This systematic review included 16 readmission prediction models for stroke, which generally exhibited good predictive performance and can effectively identify high-risk patients likely to be readmitted. However, the generalizability of these models remains uncertain due to methodological limitations. Rather than developing new readmission prediction models for stroke, the focus should shift toward external validation and the iterative adaptation of existing models. These models should be tailored to local settings, extended with new predictors if necessary, and presented in an interactive graphical user interface., (© 2024 The Author(s). Public Health Nursing published by Wiley Periodicals LLC.)

Greenberger-Horne-Zeilinger (GHZ) states, also known as two-component Schrödinger cats, play vital roles in the foundation of quantum physics and the potential quantum applications. Enlargement in size and coherent control of GHZ states are both crucial for harnessing entanglement in advanced computational tasks with practical advantages, which unfortunately pose tremendous challenges as GHZ states are vulnerable to noise. Here we propose a general strategy for creating, preserving, and manipulating large-scale GHZ entanglement, and demonstrate a series of experiments underlined by high-fidelity digital quantum circuits. For initialization, we employ a scalable protocol to create genuinely entangled GHZ states with up to 60 qubits, almost doubling the previous size record. For protection, we take a different perspective on discrete time crystals (DTCs), originally for exploring exotic nonequilibrium quantum matters, and embed a GHZ state into the eigenstates of a tailor-made cat scar DTC to extend its lifetime. For manipulation, we switch the DTC eigenstates with in-situ quantum gates to modify the effectiveness of the GHZ protection. Our findings establish a viable path towards coherent operations on large-scale entanglement, and further highlight superconducting processors as a promising platform to explore nonequilibrium quantum matters and emerging applications., (© 2024. The Author(s).)

Background: Elevated polycyclic aromatic hydrocarbon (PAH) levels are associated with exacerbation of asthma. Chrysene is one of the most prevalent unsubstituted PAHs in the environment. Transient receptor potential ankyrin 1 (TRPA1) can be used as a chemoreceptor to detect inhaled stimuli and plays an important role in the occurrence and deterioration of asthma. Whether exposure to a high concentration of chrysene in the environment can activate TRPA1 and contribute to the development of asthma, potentially through the dysfunction of the bronchial epithelial barrier, remains unclear., Methods: A cell-based assay was performed to verify the downregulation of the expression of E-cadherin and tight junction (TJ) proteins by chrysene in bronchial epithelial cells to explore the role of chrysene-mediated TRPA1 activation in the regulation of TJ protein expression through the extracellular signal-regulated protein kinase (ERK) pathway. Animal tests were conducted to determine whether chrysene could enhance airway hyperresponsiveness (AHR) induced by house dust mites (HDMs) and disrupt barrier function, thereby contributing to asthma., Results: The cell-based assay revealed that chrysene could disrupt the function of the bronchial epithelial barrier and decrease the expression levels of E-cadherin, zonula occludens-1 (ZO-1), occludin, and claudin-5 through the ERK pathway. Chrysene induced airway epithelial barrier dysfunction primarily through TRPA1 instead of transient receptor potential vanilloid 1. TRPA1 knockdown was able to attenuate chrysene-induced downregulation of TJ protein expression and downregulate ERK activation (p-ERK). Compared with exposure to HDM alone, coexposure to chrysene and HDM resulted in an increased incidence of AHR, disruption of barrier function, and eosinophilic inflammatory responses in a mouse model of asthma. Coexposure to chrysene and HDM increased TRPA1 expression. The animal test verified that the TRPA1 inhibitor HC030031 could suppress chrysene and HDM-induced asthma in mice., Conclusions: Our findings showed that chrysene contributed to the breakdown of the function of the bronchial epithelial barrier through the TRPA1-ERK axis and therefore acted as an adjuvant to contribute to asthma., 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: Bone mass at different life stages is instrumental for developing effective, long-term osteoporosis prevention strategies. We aimed to investigate the developmental patterns of bone mass across the entire lifespan among the Chinese population and to compare these patterns with those of different racial groups, including Whites, Blacks, and Mexicans in the US population., Methods: Our study analyzed data from the China Body Composition Life-course (BCL, 2013-2023) Study and the US National Health and Nutrition Examination Survey (NHANES, 2005-2018). We measured bone mineral content (BMC) and density (BMD) using dual-energy x-ray absorptiometry (DXA) at various anatomical sites, including the whole-body, lumbar spine, total hip, and femoral neck., Results: In the Chinese population, whole-body BMC and BMD increased rapidly during childhood and adolescence, with males and females achieving approximately 90.6% and 95.7% of their respective peak bone mass. Peak bone mass for whole-body, total hip, and femoral neck BMC/BMD occurred generally between the ages of 21 and 30, whereas the lumbar spine BMD peak did approximately a decade later. After reaching the peak, a gradual bone loss was observed from ages 30 to 40, with an acceleration post age 40, especially in females. Comparative analyses indicated that Chinese individuals exhibited the lowest bone mass levels and accrual rates over their lifespan, followed successively by Whites, Mexicans, and Blacks., Conclusion: By exploring bone mass changes and racial disparities among the Chinese and US populations, this study emphasizes the need for establishing sex- and ethnic- specific public health strategies to prioritize bone health throughout the entire life course., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Cascade conversion of chitin into soluble and functional chitooligosaccharides has gained great attention. However, the biotransformation route is still limited to the low catalytic performances of chitin deacetylases (CDAs) and complicated procedures. In this study, a CDA from Arthrobacter sp. Jub115 (ArCDA) was identified and characterized, which showed a higher catalytic stability than the reported CDAs, with residual activity of 80.49%, 71.12%, and 56.09% after incubation at 30, 35, and 40 °C for 24 h, respectively. Additionally, ArCDA was identified to have a broad substrate spectrum toward β-chitin and N -acetyl chitooligosaccharides. Moreover, an engineered chitin-degrading bacteria (CDB) with cell-surface-displayed deacetylase ArCDA and chitinase SaChiB was constructed to simplify catalysis procedures, facilitating the chitobiose production of 294.30 ± 16.43 mg/L in 10 h. This study not only identified a CDA with the desirable catalytic performance but also provided a strategy for constructing CDB, facilitating the high-value utilization of chitin.

Stimuli-responsive peptides, particularly pH-responsive variants, hold significant promise in biomedical and technological applications by leveraging the broad pH spectrum inherent to biological environments. However, the limited number of natural pH-responsive amino acids within biologically relevant pH ranges presents challenges for designing rational pH-responsive peptide assemblies. In our study, we introduce a novel approach by incorporating a library of non-natural amino acids featuring chemically diverse tertiary amine side chains. Hydrophobic and ionic properties of these non-natural amino acids facilitate their incorporation into the assembly domain when uncharged, and electrostatic repulsion promotes disassembly under lower pH conditions. Furthermore, we observed a direct relationship between the number of substitutions and the hydrophobicity of these amino acids, influencing their pH-responsive properties and enabling rational design based on desired transitional pH ranges. The structure-activity relationship of these pH-responsive peptides was evaluated by assessing their antimicrobial properties, as their antimicrobial activity is triggered by the disassembly of peptides to release active monomers. This approach not only enhances the specificity and controllability of pH responsiveness but also broadens the scope of peptide materials in biomedical and technological applications., (© 2024 Wiley‐VCH GmbH.)

Unlike most other picornaviruses, foot-and-mouth disease (FMD) intact virions (146S) dissociate easily into small pentameric subunits (12S). This causes a dramatically decreased immunogenicity by a mechanism that remains elusive. Here, we present the high-resolution structures of 12S (3.2 Å) and its immune complex of a single-domain antibody (VHH) targeting the particle interior (3.2 Å), as well as two 146S-specific VHHs complexed to distinct sites on the 146S capsid surface (3.6 Å and 2.9 Å). The antigenic landscape of 146S is depicted using 13 known FMD virus-antibody complexes. Comparison of the immunogenicity of 146S and 12S in pigs, focusing on the resulting antigenic sites and incorporating structural analysis, reveals that dissociation of 146S leads to structural alteration and destruction of multiple epitopes, resulting in significant differences in antibody profiles/lineages induced by 12S and 146S. Furthermore, 146S generates higher synergistic neutralizing antibody titers compared to 12S, whereas both particles induce similar total FMD virus specific antibody titers. This study can guide the structure-based rational design of novel multivalent and broad-spectrum recombinant vaccines for protection against FMD., (© 2024. The Author(s).)