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Sulfate-reducing bacteria (SRB) are known to alter methylmercury (MeHg) production in paddy soil, but the effect of SRB on MeHg dynamics in rhizosphere and rice plants remains to be fully elucidated. The present study investigated the impact of SRB on MeHg levels in unsterilized and γ-sterilized mercury-polluted paddy soils, with the aim to close this knowledge gap. Results showed that the presence of SRB reduced MeHg production by ∼22 % and ∼17 % in the two soils, but elevated MeHg contents by approximately 55 % and 99 % in rice grains, respectively. Similar trend at smaller scales were seen in roots and shoots. SRB inoculation exerted the most profound impact on amino acid metabolism in roots, with the relative response of L-arginine positively linking to MeHg concentrations in rhizosphere. The SRB-induced enrichment of MeHg in rice plants may be interpreted by the stronger presence of endophytic nitrogen-related microbes (e.g. Methylocaldum, Hyphomicrobium and Methylocystis) and TGA transcription factors interacting with glutathione metabolism and calmodulin. Our study provides valuable insights into the complex effects of SRB inoculation on MeHg dynamics in rice ecosystems, and may help to develop strategies to effectively control MeHg accumulation in rice grains., 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 presented a case of a 34-year-old male with postoperative brainstem cavernous malformations complicated with LGI1 encephalitis and secondary hypertrophic olivary degeneration (HOD). Due to recurrent dizziness and headache, the patient was diagnosed as brainstem cavernous malformations with recurrent hemorrhage and underwent resection. He subsequently developed unexplained abnormal mental behavior 1 month after the surgery, and diagnosed with LGI1 encephalitis. Six months later, cranial MRI showed HOD. This condition is rare in clinical practice,and a complex mechanism underlies the occurrence., Competing Interests: Declaration of Competing Interest All authors declare no competing interests, (Copyright © 2024 Elsevier B.V. All rights reserved.)

Acute myocardial infarction (AMI) is a life-threatening disease with a short course and a high mortality rate. However, it is still a great challenge to achieve the on-site diagnosis of this disease within minutes, meaning there is an urgent need to develop an efficient technology for realizing the rapid diagnosis and early warning of AMI in clinical emergencies. In this study, an ultrasensitive electrochemical aptasensor based on an extended-gate ion-sensitive field-effect transistor (EGISFET) was designed to achieve the quantitative assay of cardiac troponin I (cTnI), which is a highly sensitive and specific biomarker of AMI, within only 5 min. The EGISFET exhibits extremely high detection sensitivity due to its separated structure with a large sensing area and the surface-modified Prussian blue-gold nanoparticles (PB-AuNPs) composite, which serves as a signal magnifier and DNA loading platform for good electrocatalytic ability with a large specific area. Additionally, a target-induced strand-release strategy is proposed to shorten the recognition time of cTnI using a particular DNA strand. Under optimal conditions, the as-prepared aptasensor exhibits a wide linear range of 1-1000 pg/mL, an ultralow detection limit of 0.3 pg/mL, and reliable detection results in real serum samples. It is highly anticipated that this EGISFET-based aptasensor will have broad applications in the early warning and rapid diagnosis of AMI and other acute diseases in emergency 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 Elsevier B.V. All rights reserved.)

In recent years, the prevalence and danger of organophosphorus flame retardants (OPFRs) have drawn attention from all around the world. This study examined twenty-five OPFRs observed in water and sediment samples from the Qiantang River in eastern China, as well as their occurrence, spatial distribution, possible origins, and ecological hazards. All the 25 OPFRs were detected in water and sediment samples. The levels of Σ 25 OPFRs in water and sediment were 35.5-192 ng/L and 8.84-48.5 ng/g dw, respectively. Chlorinated OPFRs were the main contributions in water, whereas alkyl-OPFRs were the most common congeners found in sediment. Spatial analysis revealed that sample locations in neighboring cities had somewhat higher water concentrations of OPFRs. Slowing down the river current and making the reservoir the main sink of OPFRs, the dam can prevent OPFRs from moving via the Qiantang River. Positive matrix factorization indicated that plasticizer in polyvinyl chloride, polyester resins, and polyurethane foam made the greatest contributions in water, whereas polyurethane foam and textile were the predominant source in sediment. Analysis of sediment-water exchange of OPFRs showed that twelve OPFRs in sediments can re-enter into the water body. The risk quotients showed the ecological risk was low to medium, but trixylyl phosphate exposures posed high ecological risk to aquatic organisms., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Land use plays a critical role in managing water quality in a watershed, as it governs the import and distribution of nutrients. In addition to the land use, some rivers in Southwest China are encountering a new environmental stressor of damming, which is being driven by the national strategy of hydropower development. However, the coupling effect of land use and dams on nutrients remains poorly understood, challenging the effective management of riverine water quality. Therefore, this study examined the nutrients in the Nu, Yarlung Tsangpo (YT), and Lancang (LC) Rivers, which have no dam, 1 dam, and 11 dams, respectively, during different regulatory periods (spring and fall) to identify variations in nutrient control patterns influenced by land use and dams. The findings suggested that an increase in hydropower development contributed to a notable shift in nutrient patterns from land use regulation towards dam regulation and coupling effects. Land use dominated the nutrient variations of the Nu (27.4 %-32.8 %) and low hydropower development YT (25.2 %-30.9 %) Rivers during both seasons, but the primary contributors to the nutrient variations of the high hydropower development LC River were dams (17.9 %-41.6 %) and coupling effects (16.5 %-29.0 %). Dams transform nutrient levels and compositions through internal reservoir cycling, decoupling land use and nutrients. Partial least-squares structural equation model analysis further suggested that the coupling effects of the LC River were seasonal-specific, which was primarily attributed to hydrological variations that affected their interactions. During spring, the reservoir underwent a drainage mode characterized by high-level nutrients in the bottom water. Combined with the import of riverine nutrients, it exacerbated the increase of nutrients (synergistic effect). In contrast, the reservoir transitioned into a storage mode where it intercepted nutrients from the upstream and watershed during the fall, leading to a reduction in the previously observed increasing trend and an increase in nutrient variability (antagonism effect)., 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.)

Bark beetles, major pests that bore into forest stems, cause significant economic damage to forests globally. (+)-α-Pinene is the precursor to (+)- cis -verbenol, a crucial component of the aggregation pheromones produced by bark beetles. This paper describes the de novo synthesis of (+)- cis -verbenol in Escherichia coli . Initially, the truncation position of (+)-α-pinene synthase ( Pt PS30 from Pinus taeda ) and monoterpene precursor (geranyl diphosphate/neryl diphosphate) synthases were evaluated. Neryl diphosphate synthase from Solanum lycopersicum ( Sl NPPS1) and truncated (+)-α-pinene synthase ( Pt PS30-39) were selected as promising candidates. Subsequently, the titer of (+)-α-pinene was significantly increased 8.9-fold by using the fusion tag CM29, which enhanced the solubility of Pt PS30-39. In addition, by optimizing expression elements (ribosomal binding sites, linkers, and up elements) and overexpressing CM29* Pt PS30-39, a yield of 134.12 mg/L (+)-α-pinene was achieved. Finally, the first de novo synthesis of enantiopure (+)- cis -verbenol was achieved by introducing a cytochrome P450 mutant from Pseudomonas putida (P450 cam F89W,Y98F,L246A ), resulting in a yield of 11.13 mg/L. This study lays the groundwork for developing verbenol-based trapping technology for controlling bark beetles.

Background: Omicron variant impacts populations with its rapid contagiousness, and part of patients suffered from persistent symptoms termed as long COVID. The molecular and immune mechanisms of this currently dominant global variant leading to long COVID remain unclear, due to long COVID heterogeneity across populations., Methods: We recruited 66 participants in total, 22 out of 66 were healthy control without COVID-19 infection history, and 22 complaining about long COVID symptoms 6 months after first infection of Omicron, referred as long COVID (LC) Group. The left ones were defined as non-long COVID (NLC) Group. We profiled them via plasma neutralizing antibody titer, SARS-CoV-2 viral load, transcriptomic and proteomics screening, and machine learning., Results: No serum residual SARS-CoV-2 was observed in the participants 6 months post COVID-19 infection. No significant difference in neutralizing antibody titers was found between the long COVID (LC) Group and the non-long COVID (NLC) Group. Transcriptomic and proteomic profiling allow the stratification of long COVID into neutrophil function upregulated (NU-LC) and downregulated types (ND-LC). The NU-LC, identifiable through a refined set of 5 blood gene markers (ABCA13, CEACAM6, CRISP3, CTSG and BPI), displays evidence of relatively higher neutrophil counts and function of degranulation than the ND-LC at 6 months after infection, while recovered at 12 months post COVID-19., Conclusion: The transcriptomic and proteomic profiling revealed heterogeneity among long COVID patients. We discovered a subgroup of long COVID population characterized by neutrophil activation, which might associate with the development of psychiatric symptoms and indicate a higher inflammatory state. Meanwhile, a cluster of 5 genes was manually curated as the most potent discriminators of NU-LC from long COVID population. This study can serve as a foundational exploration of the heterogeneity in the pathogenesis of long COVID and assist in therapeutic targeting and detailed epidemiological investigation of long COVID., (© 2024. The Author(s).)

The incorporation of multiple immiscible metals in high-entropy oxides can create the unconventional coordination environment of catalytic active sites, while the high formation temperature of high-entropy oxides results in bulk materials with low specific surface areas. Here we develop the high-entropy LaMnO 3 -type perovskite-polyoxometalate subnanowire heterostructures with periodically aligned high-entropy LaMnO 3 oxides and polyoxometalate under a significantly reduced temperature of 100  o C, which is much lower than the temperature required by state-of-the-art calcination methods for synthesizing high-entropy oxides. The high-entropy LaMnO 3 -polyoxometalate subnanowires exhibit excellent catalytic activity for the photoelectrochemical coupling of methane into acetic acid under mild conditions (1 bar, 25  o C), with a high productivity (up to 4.45 mmol g ‒1 cat h ‒1 ) and selectivity ( > 99%). Due to the electron delocalization at the subnanometer scale, the contiguous active sites of high-entropy LaMnO 3 and polyoxometalate in the heterostructure can efficiently activate C - H bonds and stabilize the resulted *COOH intermediates, which benefits the in situ coupling of *CH 3 and *COOH into acetic acid., (© 2024. The Author(s).)

A rapid in situ synthesis of electrochromic covalent organic frameworks (EC-COFs) was proposed by using green electrochemical interface polymerization of N,N,N',N'-tetrakis(p-aminophenyl)p-phenylenediamine (TPDA) and 2,5-dihydroxy-p-phenylenedicarboxaldehyde (DHBD). The synthetized TPDA-DHBD films exhibit stable polymorphic colour variations under different applied potentials, which can be attributed to the redox state changes of bis(triphenylamine) and imine electroactive functional groups within the COFs skeleton. TPDA-DHBD represents markedly different electrochromisms from red to cyan due to the steric hindrance effect caused by the presence of UO22+, demonstrating the unique tunability of COFs materials. This work offers a new feasible idea for rapid EC-COFs synthesis and tunable EC-COFs realization., (© 2024 Wiley‐VCH GmbH.)

Adhesion between epithelial cells enables the remarkable mechanical behavior of epithelial tissues during morphogenesis. However, it remains unclear how cell-cell adhesion influences mechanics in both static and dynamically flowing confluent epithelial tissues. Here, we systematically modulate E-cadherin-mediated adhesion in the Drosophila embryo and study the effects on the mechanical behavior of the germband epithelium before and during dramatic tissue remodeling and flow associated with body axis elongation. Before axis elongation, we find that increasing E-cadherin levels produces tissue comprising more elongated cells and predicted to be more fluid-like, providing reduced resistance to tissue flow. During axis elongation, we find that the dominant effect of E-cadherin is tuning the speed at which cells proceed through rearrangement events. Before and during axis elongation, E-cadherin levels influence patterns of actomyosin-dependent forces, supporting the notion that E-cadherin tunes tissue mechanics in part through effects on actomyosin. Notably, the effects of ∼4-fold changes in E-cadherin levels on overall tissue structure and flow are relatively weak, suggesting that the system is tolerant to changes in absolute E-cadherin levels over this range where an intact tissue is formed. Taken together, these findings reveal dual-and sometimes opposing-roles for E-cadherin-mediated adhesion in controlling tissue structure and dynamics in vivo, which result in unexpected relationships between adhesion and flow in confluent tissues., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Effective treatments for the alveolar bone defect remain a major concern in dental therapy. The objectives of this study were to develop a fibrin and konjac glucomannan (KGM) composite hydrogel as scaffolds for the osteogenesis of nasal mucosa-derived ectodermal mesenchymal stem cells (EMSCs) for the regeneration of alveolar bone defect, and to investigate the osteogenesis-accelerating effects of black phosphorus nanoparticles (BPNs) embedded in the hydrogels., Methods: Primary EMSCs were isolated from rat nasal mucosa and used for the alveolar bone recovery. Fibrin and KGM were prepared in different ratios for osteomimetic hydrogel scaffolds, and the optimal ratio was determined by mechanical properties and biocompatibility analysis. Then, the optimal hydrogels were integrated with BPNs to obtain BPNs/fibrin-KGM hydrogels, and the effects on osteogenic EMSCs in vitro were evaluated. To explore the osteogenesis-enhancing effects of hydrogels in vivo, the BPNs/fibrin-KGM scaffolds combined with EMSCs were implanted to a rat model of alveolar bone defect. Micro-computed tomography (CT), histological examination, real-time quantitative polymerase chain reaction (RT-qPCR) and western blot were conducted to evaluate the bone morphology and expression of osteogenesis-related genes of the bone regeneration., Results: The addition of KGM improved the mechanical properties and biodegradation characteristics of the fibrin hydrogels. In vitro, the BPNs-containing compound hydrogel was proved to be biocompatible and capable of enhancing the osteogenesis of EMSCs by upregulating the mineralization and the activity of alkaline phosphatase. In vivo, the micro-CT analysis and histological evaluation demonstrated that rats implanted EMSCs-BPNs/fibrin-KGM hydrogels exhibited the best bone reconstruction. And compared to the model group, the expression of osteogenesis genes including osteopontin (Opn, p < 0.0001), osteocalcin (Ocn, p < 0.0001), type collagen (Col , p < 0.0001), bone morphogenetic protein-2 (Bmp2, p < 0.0001), Smad1 (p = 0.0006), and runt-related transcription factor 2 (Runx2, p < 0.0001) were all significantly upregulated., Conclusions: EMSCs/BPNs-containing fibrin-KGM hydrogels accelerated the recovery of the alveolar bone defect in rats by effectively up-regulating the expression of osteogenesis-related genes, promoting the formation and mineralisation of bone matrix., (© 2024. The Author(s).)

Due to their identical building blocks and high surface-to-volume ratio, subnanomaterials exhibit significant properties compared to their bulk nanomaterial counterparts. The interactions between these building blocks can result in either equal or unequal sharing of electrons, leading to electron transfer in heterojunctions or electron delocalization within symmetric structures. Clusters, possessing electronic properties akin to atoms, can serve as reservoirs of electrons to stabilize crucial intermediates in catalytic reactions. This perspective provides a novel understanding of well-defined subnanomaterials with distinct architectures, such as cluster-based constructions and co-assembled heterojunctions, emphasizing the relationship between electronic structures and catalytic properties. The objective is to provide novel perspectives on the realm of subnanomaterials and cluster-based architectures., (© 2023 Wiley‐VCH GmbH.)

Bee venom serves as an essential defensive weapon for bees and also finds application as a medicinal drug. MicroRNAs (miRNAs) serve as critical regulators and have been demonstrated to perform a variety of biological functions. However, the presence of miRNAs in bee venom needs to be confirmed. Therefore, we conducted small RNA sequencing and identified 158 known miRNAs, 15 conserved miRNAs and 4 novel miRNAs. It is noteworthy that ame-miR-1-3p, the most abundant among them, accounted for over a quarter of all miRNA reads. To validate the function of ame-miR-1-3p, we screened 28 candidate target genes using transcriptome sequencing and three target gene prediction software (miRanda, PITA and TargetScan) for ame-miR-1-3p. Subsequently, we employed real-time quantitative reverse transcription PCR (qRT-PCR), Western blot and other technologies to confirm that ame-miR-1-3p inhibits the relative expression of antizyme inhibitor 1 (AZIN1) by targeting the 3' untranslated region (UTR) of AZIN1. This, in turn, caused ODC antizyme 1 (OAZ1) to bind to ornithine decarboxylase 1 (ODC1) and mark ODC1 for proteolytic destruction. The reduction in functional ODC1 ultimately resulted in a decrease in polyamine biosynthesis. Furthermore, we determined that ame-miR-1-3p accelerates cell death through the AZIN1/OAZ1-ODC1-polyamines pathway. Our studies demonstrate that ame-miR-1-3p diminishes cell viability and it may collaborate with sPLA2 to enhance the defence capabilities of honeybees (Apis mellifera L.). Collectively, these data further elucidate the defence mechanism of bee venom and expand the potential applications of bee venom in medical treatment., (© 2024 The Royal Entomological Society.)

Background and Aims: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. In this study, we aimed to investigate the role and regulatory mechanism of Annexin A2 (ANXA2) in the pathogenesis of NAFLD., Methods: Histological analyses and ELISA were used to illuminate the expression of ANXA2 in NAFLD and healthy subjects. The role of ANXA2 was evaluated using high-fat diet (HFD)-fed mice via vein injection of adeno-associated viruses (AAV) knocking down ANXA2 or non-targeting control (NC) shRNAs. Moreover, HepG2 and LO2 cells were employed as in vitro hepatocyte models to investigate the expression and function of ANXA2., Results: ANXA2 was confirmed to be one of three hub genes in liver injury, and its expression was positively correlated with NAFLD activity score (NAS) and macrophage infiltration in NAFLD. Moreover, ANXA2 was significantly upregulated in NAFLD patients and HFD-fed mice. LPS/TLR4 pathway strongly upregulated ANXA2 expression, which is mediated by direct ANXA2 promoter binding by TLR4 downstream NF-κB p65 and c-Jun transcription factors. Increased ANXA2 expression was correlated with decreased autophagy flux and autophagy was activated by the depletion of ANXA2 in the models of NAFLD. Furthermore, ANXA2 interference led to the activation of AMPK/mTOR signaling axis, which may play a causal role in autophagy flux and the amelioration of steatosis., Conclusions: ANXA2 is a pathological predictor and promising therapeutic target for NAFLD. ANXA2 plays a crucial role in linking inflammation to hepatic metabolic disorder and injury, mainly through the blockage of AMPK/mTOR-mediated lipophagy., (© 2024. Asian Pacific Association for the Study of the Liver.)

Background: Excessive visceral adipose tissue (VAT) is associated with a spectrum of diseases, including diabetes, cancer, and cardiovascular diseases. Remnant cholesterol (RC), denoting cholesterol within triglyceride-rich lipoproteins and their metabolic byproducts, has been identified as a key contributor to cardiovascular diseases and related mortality. However, the association between the VAT and RC remains unclear. In this study, the objective is to provide new evidence regarding the association between VAT and RC concentrations., Methods: 4727 individuals aged 18-59 were selected from the National Health and Nutrition Examination Survey conducted between 2011 and 2018 as study participants. This study utilized several weighted linear regression models and a restricted cubic spline (RCS) to explore the association and potential nonlinearities between VAT and RC. Subgroup analyses were performed to determine the consistency of findings., Results: The mean VAT value was 103.82 ± 1.42 cm 2 , and the median RC value was 18 mg/dl. VAT demonstrated a positive association with RC in a fully adjusted model, with a β and 95% confidence interval (CI) of 0.09 (0.08, 0.11) after adjustment for potential confounders. Analysis using RCS revealed a nonlinear association between the VAT area and RC (P < 0.001 for nonlinearity). Adjusted two-piecewise regression models demonstrated β coefficients of 0.13 (95%CI: 0.11 ~ 0.16, P < 0.001) for RC in individuals with VAT < 143 cm 2 , and 0.02 (95%CI: -0.01 ~ 0.06, P = 0.15) for those with VAT ≥ 143 cm 2 . Interactions were observed among the body mass index (BMI) subgroup; the β coefficients for RC were 0.14 (95%CI: 0.12 ~ 0.16) in those with BMI < 30 kg/m 2 and 0.05 (95%CI:0.04 ~ 0.07) in those with BMI ≥ 30 kg/m 2 , with a P-value of < 0.001 for interaction., Conclusions: This study identified a nonlinear association between VAT and RC in American adults. Reducing the VAT area may be beneficial in lowering RC concentration, particularly when VAT is < 143 cm 2 and those with a BMI < 30 kg/m 2 ., (© 2024. The Author(s).)

Plastic debris has recently been proposed as a novel habitat for bacterial colonization, which can raise perturbations in bacterial ecology after burial in riverine sediments. However, community coalescence, as a prevalent process involving the interrelationships of multiple communities and their surrounding environments, has been rarely discussed to reveal the impact of the plastisphere on sedimentary bacterial community. This study analyzed the bacterial community in plastic debris and sediment along the Nujiang River, elucidating the role of the plastisphere in mediating community coalescence in sediments. Our results demonstrated that the plastisphere and sedimentary bacterial communities exhibited distinct biogeography along the river (r = 0.694, p < 0.01). Based on overlapped taxa and SourceTracker, the extent of coalescence between adjacent communities was in following orders: plastic-plastic (0.589) > plastic-sediment (0.561) > sediment-sediment (0.496), indicating the plastisphere promoted bacterial community coalescence along the river. Flow velocity and geographic distance were the major factors driving the plastisphere changes, suggesting that the plastisphere were vulnerable to dispersal. The null model and the neutral model provided additional support for the higher immigration ability of the plastisphere to overcome dispersal limitation, highlighting the potential importance of the plastisphere in community coalescence. Network analysis indicated the critical role of keystone species (Proteobacteria, Bacteroidetes, and Gemmatimonadetes) in mediating the coalescence between sedimentary bacterial community and the plastisphere. In summary, the plastisphere could mediate the coalescence of bacterial communities by overcoming dispersal limitation, which provides new perspectives on the plastisphere altering bacterial ecology in riverine sediments., 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.)

Using bone regeneration scaffolds to repair craniomaxillofacial bone defects is a promising strategy. However, most bone regeneration scaffolds still exist some issues such as a lack of barrier structure, inability to precisely match bone defects, and necessity to incorporate biological components to enhance efficacy. Herein, inspired by a periosteum-bone complex, a class of multifunctional hierarchical porous poly(lactic-co-glycolic acid)/baicalein scaffolds is facilely prepared by the union of personalized negative mold technique and phase separation strategy and demonstrated to precisely fit intricate bone defect cavity. The dense up-surface of the scaffold can prevent soft tissue cell penetration, while the loose bottom-surface can promote protein adsorption, cell adhesion, and cell infiltration. The interior macropores of the scaffold and the loaded baicalein can synergistically promote cell differentiation, angiogenesis, and osteogenesis. These findings can open an appealing avenue for the development of personalized multifunctional hierarchical materials for bone repair., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Stapled hemorrhoidopexy has been used for years to treat hemorrhoids. Despite numerous systematic reviews and meta-analyses on the topic, inconsistent conclusions have left people uncertain about its effectiveness and raised doubts about the quality of these reviews.In order to provide reliable evidence for clinical practice, it is crucial to conduct an overview to assess the quality of MAs/SRs regarding the efficacy and complications of SH.A comprehensive search was performed across seven databases to identify MAs/SRs on the efficacy and complications of SH from inception to October 2023. The selected MAs/SRs were then assessed using three well-established tools: AMSTAR-2, PRISMA 2020and GRADE. These assessments provide a robust evaluation of the quality and reliability of the included MAs/SRs.We removed overlapping randomized controlled trials (RCTs) and conducted a new meta-analysis of the outcomes. The overview included 23 meta-analyses.In AMSTAR-2, three reviews were deemed moderate quality, nine reviews were classified as low quality, and eleven reviews were evaluated as critically low quality.In PRISMA 2020,certain deficiencies were exhibited, such as abstracts (0/23:0 %),final retrieval date (0/23:0 %), sensitivity analysis (6/23:26.09 %),publication bias assessment (11/23:47.83 %), the quality of evidence (2/23:8.70 %) and so on.In GRADE,twenty-six items were rated as moderate quality (27.96 %),forty-one items were rated as low quality (44.09 %) and twenty-six items were rated as critically low quality (27.96 %).SH has been found to be an effective intervention for reducing postoperative pain, shortening procedure time, and promoting wound healing. The re-analysis indicated that SH can reduce postoperative pain in hemorrhoid patients (odds ratio = 0.28, 95 % confidence interval [0.15,0.55], p = 0.0002; I2 = 74 %, p < 0.00001). But SH is associated with a higher risk of postoperative bleeding and recurrence of prolapse.Given that the reviews included in this overview were rated as low quality, caution should be exercised when interpreting the findings., (Copyright © 2024 Asian Surgical Association and Taiwan Society of Coloproctology. Published by Elsevier B.V. All rights reserved.)

Increased selenium (Se) content in fruits can supply Se in human body, but the effects of teas on the Se uptake in fruit trees are unknown. The effects of infusions of four teas (green, black, dark, and white) on the Se uptake of grapevine were studied to promote the Se uptake in fruit trees in this study. However, only black tea infusion increased the biomass, photosynthetic pigment content, superoxide dismutase (SOD) activity, peroxidase (POD) activity, and soluble protein content of grapevine. Except for white tea infusion, other tea infusions also increased the catalase (CAT) activity of grapevine. Furthermore, the tea infusions increased the activities of adenosine triphosphate sulfurase (ATPS) and adenosine 5'-phosphosulfate reductase (APR), and decreased the activities of serine acetyltransferase (SAT) and selenocysteine methyltransferase (SMT). Only the dark and white tea infusions increased the shoot total Se content by 86.53% and 23.32%, respectively (compared with the control), and also increased the shoot inorganic Se content and shoot organic Se content. Notably, four tea infusions decreased the organic Se proportion and increased the inorganic Se proportion in grapevine. Correlation and grey relational analyses showed that the root total Se content, ATPS activity, and ARP activity were closely associated with the shoot total Se content. The principal component and cluster analyses also showed that the ATPS activity, APR activity, root total Se content, and shoot total Se content were classified into one category. These findings show that black tea infusion can promote grapevine growth, while dark and white tea infusions can promote the Se uptake in grapevine., (© 2024. The Author(s).)

Autophagy could play suppressing role in cancer therapy by facilitating release of tumor antigens from dying cells and inducing immunogenic cell death (ICD). Therefore, discovery and rational design of more effective inducers of cytotoxic autophagy is expected to develop new strategies for finding innovative drugs for precise and successful cancer treatment. Herein, we develop MoO 3-x nanowires (MoO 3-x NWs) with high oxygen vacancy and strong photothermal responsivity to ablate tumors through hyperthermia, thus promote the induction of cytotoxic autophagy and severe ICD. As expected, the combination of MoO 3-x NWs and photothermal therapy (PTT) effectively induces autophagy to promote the release of tumor antigens from the ablated cells, and induces the maturation and antigen presentation of dendritic cells (DCs), subsequently activates cytotoxic T lymphocytes (CTLs)-mediated adaptive immunity. Furthermore, the combination treatment of MoO 3-x NWs with immune checkpoint blockade of PD-1 could promote the tumor-associated macrophages (TAMs) polarization into tumor-killing M1 macrophages, inhibit infiltration of Treg cells at tumor sites, and alleviate immunosuppression in the tumor microenvironment, finally intensify the anti-tumor activity in vivo. This study provides a strategy and preliminary elucidation of the mechanism of using MoO 3-x nanowires with high oxygen vacancy to induce autophagy and thus enhance photothermal immunotherapy., (© 2024 Wiley-VCH GmbH.)

Primary familial brain calcification (PFBC), also known as Fahr's disease, is a central nervous system calcium deposition disorder with symmetrical basal ganglia calcification. Most PFBC cases are caused by SLC20A2 gene variant. We report a Chinese female patient with PFBC and dopamine-responsive parkinsonism who had motor fluctuations and dyskinesia and recovered effectively after symptomatic medication adjustment. A novel heterozygous missense variant was found by whole-exome sequencing and proven harmful by family validation and genetic analysis. This example expands the phenotype of SLC20A2 -associated PFBC patients and shows the clinical efficacy of dopaminergic replacement treatment., 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 Sun, Wang, Wang, Wang, Zhu, Xia, Zhang and Wang.)

Background: At present, shoulder arthroscopy is usually used for treatment of rotator cuff injuries. There is still debate over the precise technique of using shoulder arthroscopy to treat partial articular-sided supraspinatus tendon injuries., Objective: To compare the clinical efficacy of the arthroscopic transtendon repair method and the arthroscopic full-thickness repair method in the treatment of patients with Ellman III partial articular-sided supraspinatus tendon tears and to analyze the influencing factors of postoperative efficacy., Study Design: Cohort study; level of evidence,4., Methods: A total of 84 partial-thickness rotator cuff tear (PTRCT) patients with Ellman III injuries who underwent surgical treatment in our hospital between January 2017 and January 2020 were selected and divided into the arthroscopic trans-tenon repair group (32 cases) and the arthroscopic full-thickness repair group (52 cases). Shoulder joint pain and functional status were assessed by the Constant score, ASES score and VAS score; shoulder mobility was assessed by measuring shoulder ROM. The clinical outcomes of the two groups of patients were compared, and the factors affecting the postoperative efficacy of the patients were investigated., Results: All patients were followed up for at least 2 years. The Constant score, ASES score, and VAS score of the two groups of patients were all improved compared with those before surgery, and the differences were statistically significant (P < 0.05). There were no significant differences in the Constant score, ASES score, or VAS score between the two groups (P > 0.05). The results of binary logistic regression analysis showed that the preoperative ASES score and whether biceps tenotomy was performed were independent risk factors for satisfactory postoperative efficacy (P < 0.05)., Conclusion: For patients with Ellman III partial articular-sided supraspinatus tendon tears, the arthroscopic transtendon repair method and the arthroscopic full-thickness repair method can both significantly improve the shoulder pain and function of the patient, but there is no significant difference between the efficacy of the two surgical methods. The preoperative ASES score and whether biceps tenotomy was performed were independent risk factors for satisfactory postoperative efficacy in PTRCT patients with Ellman III injury., (© 2024. The Author(s).)

Integration of inherently incompatible elements into a single sublattice, resulting in the formation of monophasic metal oxide, holds great scientific promise; it unveils that the overlooked surface entropy in subnanometer materials can thermodynamically facilitate the formation of homogeneous single-phase structures. Here a facile approach is proposed for synthesizing multimetallic oxide subnanometer nanobelts (MMO-PMA SNBs) by harnessing the potential of phosphomolybdic acid (PMA) clusters to capture inorganic nuclei and inhibiting their subsequent growth in solvothermal reactions. Experimental and theoretical analyses show that PMA in MMO-PMA SNBs not only aids subnanometer structure formation but also induces in situ modifications to catalytic sites. The electron transfer from PMA, coupled with the loss of elemental identity of transition metals, leads to electron delocalization, jointly activating the reaction sites. The unique structure makes pentametallic oxide (PMO-PMA SNBs) achieve a current density of 10 mA cm -2 at a low potential of 1.34 V and remain stable for 24 h at 10 mA cm -2 on urea oxidation reaction (UOR). The exceptional UOR catalytic activity suggests a potential for utilizing multimetallic subnanometer nanostructures in energy conversion and environmental remediation., (© 2024 Wiley‐VCH GmbH.)

Parabens can particularly raise significant concerns regarding the disruption of microbial ecology due to their antimicrobial properties. However, the responses of biofilm bacteria to diverse parabens with different alkyl-chain length remains unclear. Here, theoretical calculations and bioinformatic analysis were performed to decipher the influence of parabens varying alkyl-chain lengths on the biofilm bacteria. Our results showed that the disturbances in bacterial community did not linearly response to the alkyl-chain length of parabens, and propylparaben (PrP), with median chain length, had more severe impact on bacterial community. Despite the fact that paraben lethality linearly increased with chain length, the PrP had a higher chemical reactions potential than parabens with shorter or longer alkyl-chain. The chemical reactions potential was critical in the nonlinear responses of bacterial community to alkyl-chain length of parabens. PrP could impose selective pressure to disturb the bacterial community, because it had a more profound contribution to deterministic assembly process. Furthermore, N-acyl-homoserine lactones was also significantly promoted under PrP exposure, confirming that PrP could affect the bacterial community by influencing the quorum-sensing system. Overall, our study reveals the nonlinear responses of bacterial communities to the alkyl-chain lengths of parabens and provides insightful perspectives for the better regulation of parabens. ENVIRONMENTAL IMPLICATION: Parabens are recognized as emerging organic pollutants, which specially raise great concerns due to their antimicrobial properties disturbing microbial ecology. However, few study have addressed the relationship between bacterial community responses and the molecular structural features of parabens with different alkyl-chain length. This investigation revealed nonlinear responses of the bacterial community to the alkyl-chain length of parabens through DFT calculation and bioinformatic analysis and identified the critical roles of chemical reactions potential in nonlinear responses of bacterial community. Our results benefit the precise evaluation of ecological hazards posed by parabens and provide useful insights for better regulation of parabens., 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.)

Cluster aggregation states are thermodynamically favored at the subnanoscale, for which an inverse growth from nanoparticles to clusters may be realized on subnanometer supports. Herein, we develop Au-polyoxometalate-layered double hydroxide (Au-POM-LDH) sub-1 nm nanosheets (Sub-APL) based on the above strategy, where sub-1 nm Au clusters with negative valence are generated by the in situ disintegration of Au nanoparticles on POM-LDH supports. Sub-1 nm Au clusters with ultrahigh surface atom ratios exhibit remarkable efficiency for glutathione (GSH) depletion. The closely connected sub-1 nm Au with negative valence and POM hetero-units can promote the separation of hole-electrons, resulting in the enhanced reactive oxygen species (ROS) generation under ultrasound (US). Besides, the reversible redox of Mo in POM is able to deplete GSH and trigger chemodynamic therapy (CDT) simultaneously, further enhancing the oxidative stress. Consequently, the Sub-APL present 2-fold ROS generation under US and 7-fold GSH depletion compared to the discrete Au and POM-LDH mixture. Therefore, the serious imbalance of redox in the TME caused by the sharp increase of ROS and rapid decrease of GSH leads to death of tumor ultimately., (© 2024 Wiley-VCH GmbH.)

Aim: To investigate the association of floor area ratio (FAR), an indicator of built environments, and myopia onset., Methods: This prospective cohort study recruited 136 753 children aged 6-10 years from 108 schools in Shenzhen, China at baseline (2016-2017). Refractive power was measured with non-cycloplegic autorefraction over a 2-year follow-up period. FAR was objectively evaluated using geographical information system technology. Mixed-effects logistic regression models were constructed to examine the association of FAR with a 2-year cumulative incidence of myopia among individuals without baseline myopia; multiple linear regression model, with a 2-year cumulative incidence rate of myopia at each school., Results: Of 101 624 non-myopic children (56.3% boys; mean (SE) age, 7.657±1.182 years) included in the study, 26 391 (26.0%) of them developed myopia after 2 years. In the individual-level analysis adjusting for demographic, socioeconomic and greenness factors, an IQR in FAR was associated with a decreased risk of 2-year myopia incidence (OR 0.898, 95% CI 0.866 to 0.932, p<0.001). Similar findings were observed in the analysis additionally adjusted for genetic and behavioural factors (OR 0.821, 95% CI 0.766 to 0.880, p<0.001). In the school-level, an IQR increase in FAR was found to be associated with a 2.0% reduction in the 2-year incidence rate of myopia (95% CI 1.3% to 2.6%, p<0.001)., Conclusions: Exposure to higher FAR was associated with a decreased myopia incidence, providing insights into myopia prevention through school built environments in China., 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.)

Intelligent predictive models for autistic symptoms based on neuroimaging datasets were beneficial for the precise intervention of patients with ASD. The goals of this study were twofold: investigating predictive models for autistic symptoms and discovering the brain connectivity patterns for ASD-related behaviors. To achieve these goals, we obtained a cohort of patients with ASD from the ABIDE project. The autistic symptoms were measured using the Autism Diagnostic Observation Schedule (ADOS). The anatomical MRI datasets were preprocessed using the Freesurfer package, resulting in regional morphological features. For each individual, the interregional morphological network was constructed using a novel feature distance-based method. The predictive models for autistic symptoms were built using the support vector regression (SVR) algorithm with feature selection method. The predicted autistic symptoms (i.e., ADOS social score, ADOS behavior) were significantly correlated to the original measures. The most predictive features for ADOS social scores were located in the bilateral fusiform. The most predictive features for ADOS behavior scores were located in the temporal pole and the lingual gyrus. In summary, the autistic symptoms could be predicted using the interregional morphological connectivity and machine learning. The interregional morphological connectivity could be a potential biomarker for autistic symptoms., Competing Interests: Declaration of competing interest There is no conflicts of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

We conducted this study to investigate the radioprotective effects of recombinant human thrombopoietin (rhTPO) on beagle dogs irradiated with 3.0 Gy 60Co gamma rays. Fifteen healthy adult beagles were randomly assigned to a control group with alleviating care, and 5 and 10 μg/kg rhTPO treatment group. All animals received total-body irradiation using 60Co γ-ray source at a dose of 3.0 Gy (dose rate was 69.1 cGy/min). The treatment group received intramuscular injection of rhTPO 5 and 10 μg/kg at 2 h postirradiation, and the control group was administrated the same volume of normal saline. The survival rate, clinical signs, peripheral hemogram, serum biochemistry, and histopathological examination of animals in each group were assessed. Single administration of 10 μg/kg rhTPO at 2 h postirradiation promoted the recovery of multilineage hematopoiesis and improved the survival rate of beagles irradiated with 3 Gy 60Co γ rays. The administration of 10 μg/kg rhTPO alleviated fever and bleeding, reduced the requirement for supportive care, and may have mitigated multiple organ damage., (© 2024 by Radiation Research Society. All rights of reproduction in any form reserved.)

Salt stress is a critical limiting factor for fruit yield and quality of apples. Brassinosteroids (BRs) play an important role in response to abiotic stresses. In the present study, application of 2,4- Epicastasterone on seedlings of Malus 'M9T337' and Malus domestica 'Gala3' alleviated the physiological effects, such as growth inhibition and leaf yellowing, induced by salt stress. Further analysis revealed that treatment with NaCl induced expression of genes involved in BR biosynthesis in 'M9T337' and 'Gala3'. Among which, the expression of BR biosynthetic gene MdBR6OX2 showed a three-fold upregulation upon salt treatment, suggesting its potential role in response to salt stress in apple. MdBR6OX2, belonging to the CYP450 family, contains a signal peptide region and a P450 domain. Expression patterns analysis showed that the expression of MdBR6OX2 can be significantly induced by different abiotic stresses. Overexpressing MdBR6OX2 enhanced the tolerance of apple callis to salt stress, and the contents of endogenous BR-related compounds, such as Typhastero (TY), Castasterone (CS) and Brassinolide (BL) were significantly increased in transgenic calli compared with that of wild-type. Extopic expression of MdBR6OX2 enhanced tolerance to salt stress in Arabidopsis. Genes associated with salt stress were significantly up-regulated, and the contents of BR-related compounds were significantly elevated under salt stress. Our data revealed that BR-biosynthetic gene MdBR6OX2 positively regulates salt stress tolerance in both apple calli and Arabidopsis., 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.)

Grain size is one of the key microstructural factors affecting the mechanical properties of polycrystalline metal materials. In this study, a novel method for grain size evaluation using ultrasonic coda waves is proposed. Different from conventional bulk wave methods that require a point-by-point scanning of the structure, the proposed method allows for a rapid evaluation of the average grain size of the whole part from a single inspection location using one-pass testing data. A piecewise energy attenuation function dealing with different attenuation mechanisms is proposed to obtain the effective attenuation coefficient of coda waves. A power-law model is constructed to correlate the effective attenuation coefficient with the average grain size. Ultrasonic testing on nickel-based superalloy plate specimens with different average grain sizes is performed for model calibration and method verification. The applicability and robustness of the proposed method are further validated using a realistic turbine disk specimen with an irregular shape and non-uniform grain sizes. Results show that the proposed method yields a reliable and accurate estimation of the average grain size with a maximum relative error less than 20 %., 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.)

Purpose: To explore the factors related to the diagnosis yield of syndromic congenital cataracts and describe the phenotype-genotype correlation in congenital cataract patients., Design: Prospective cohort study., Methods: Setting: the participants from underwent clinical examinations between 2021 and 2022. Facial and anterior eye segment photographs, pre- and postoperative ocular parameters, and medical and family histories were recorded. Bioinformatics analysis was performed using whole-exome sequencing data. Statistical and correlation analyses were performed using the basic characteristics, deep phenotype, and genotype data., Participants: 115 patients with unrelated congenital cataract., Interventions: performing clinical examinations, whole-exome sequencing, and bioinformatics analysis for all participants., Main Outcomes and Measures: factors related to the genetic diagnosis yield of syndromic congenital cataracts., Results: Bilaterally asymmetrical cataracts were identified to be associated with syndromic congenital cataracts. The overall genetic diagnostic yield in the cohort was 72.2%. In total, 34.8% of the probands were early diagnosed with various syndromes with the help of genetic information. A phenotype-genotype correlation was detected for some genes and deep phenotypes., Conclusions: We highlight the importance of screening syndromic diseases in the patients with asymmetrical congenital cataracts. Application of whole-exome sequencing helps provide early diagnosis and treatment for the patients with syndromic congenital cataracts. This study also achieved a high genetic diagnostic yield, expanded the genotypic spectrum, and found phenotype-genotype correlations. A comprehensive analysis of cataract symmetricity, family history, and deep phenotypes makes the genotype prediction of some congenital cataract patients possible., (Copyright © 2023 Elsevier Inc. All rights reserved.)

There is no universally accepted method for evaluating lymph node metastasis (LNM) in non-small cell lung cancer (NSCLC) after neoadjuvant chemoimmunotherapy. Different protocols recommend evaluating the percentage of residual viable tumor (RVT%) and metastatic tumor size (MTS). Our aim was to determine the prognostic significance of RVT% and MTS, and identify the more effective parameter for pathological evaluating LNM. Two independent cohorts were collected (derivation, n = 84; external validation, n = 42). All patients exhibited metastatic cancer or treatment response in lymph nodes post-surgery. In the derivation cohort, we assessed the mean and largest values of MTS and RVT% in LNM, estimating their optimal cutoffs for event-free survival (EFS) using maximally selected rank statistics. Validation was subsequently conducted in the external validation cohort. The quality of prognostic factors was evaluated using the Area Under Curve (AUC). A positive association was identified between RVT% and MTS, but an absolute association could not be conclusively established. In the derivation cohort, neither the largest MTS (cutoff = 6 mm, p = 0.28), largest RVT% (cutoff = 75%, p = 0.23), nor mean RVT% (cutoff = 55%, p = 0.06) were associated with EFS. However, mean MTS (cutoff = 4.5 mm) in lymph nodes was statistically associated with EFS (p = 0.018), validated by the external cohort (p = 0.017). The prognostic value of MTS exceeded that of ypN staging in both cohorts, as evidenced by higher AUC values. The mean value of MTS can effectively serve as a parameter for the pathological evaluation of lymph nodes, with a threshold of 4.5 mm, closely linked to EFS. Its prognostic value outperforms that of ypN staging., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Our work reveals for the first time that directly calcined bismuth nitrate derivatives (BNDs) possess significant photocatalytic activity towards rhodamine B (RhB). As the calcination temperature increased, the Bi(NO 3 ) 3 ·5H 2 O powder gradually ruptured and transformed into different bismuth nitrate products and their mixtures, finally into stable α-Bi 2 O 3 at 500 °C. Among them, BNDs-100 could achieve 100 % photocatalytic degradation of 10 mg/L RhB solution under UV irradiation for 6 min. The ImageJ-led paper microzones (PMZs) method is introduced for the first time into the performance evaluation process of photocatalysts, which can achieve the green chemistry pathway and the rapid evaluation of different catalysts. The accuracy of the results of the PMZs method relative to the spectrophotometric method was up to 91.14 %, which has a better reliability and is suitable for qualitative analysis, and a certain ability when used for quantitative analysis. The results showed that the PMZs method was used to assess the photocatalytic degradation of rhodamine B by bismuth nitrate-derived materials at different calcination temperatures with well reliability, and the preparation of BNDs by direct calcination was a simple and effective strategy., 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.)

Myocardial ischemia-reperfusion (I/R) injury is a prevalent cause of myocardial injury, involving a series of interconnected pathophysiological processes. However, there is currently no clinical therapy for effectively mitigating myocardial I/R injury. Here, we show that p85α protein levels increase in response to I/R injury through a comprehensive analysis of cardiac proteomics, and confirm this in the I/R-injured murine heart and failing human myocardium. Genetic inhibition of p85α in mice activates the Akt-GSK3β/Bcl-x(L) signaling pathway and ameliorates I/R-induced cardiac dysfunction, apoptosis, inflammation, and mitochondrial dysfunction. p85α silencing in cardiomyocytes alleviates hypoxia-reoxygenation (H/R) injury through activating the Akt-GSK3β/Bcl-x(L) signaling pathway, while its overexpression exacerbates the damage. Mechanistically, the interaction between MG53 and p85α triggers the ubiquitination and degradation of p85α, consequently enhancing Akt phosphorylation and ultimately having cardioprotective effects. Collectively, our findings reveal that substantial reduction of p85α and subsequently activated Akt signaling have a protective effect against cardiac I/R injury, representing an important therapeutic strategy for mitigating myocardial damage., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Volatile compounds are important determinants affecting fruit flavor. Previous study has identified a bud mutant of 'Ehime 38' ( Citrus reticulata ) with different volatile profile. However, the volatile changes between WT and MT during fruit development and underlying mechanism remain elusive. In this study, a total of 35 volatile compounds were identified in the pulps of WT and MT at five developmental stages. Both varieties accumulated similar and the highest levels of volatiles at stage S1, and showed a downward trend as the fruit develops. However, the total volatile contents in the pulps of MT were 1.4-2.5 folds higher than those in WT at stages S2-S5, which was mainly due to the increase in the content of d-limonene. Transcriptomic and RT-qPCR analysis revealed that most genes in MEP pathway were positively correlated with the volatile contents, of which DXS1 might mainly contribute to the elevated volatiles accumulation in MT by increasing the flux into the MEP pathway. Moreover, temporal expression analysis indicated that these MEP pathway genes functioned at different developmental stages. This study provided comprehensive volatile metabolomics and transcriptomics characterizations of a citrus mutant during fruit development, which is valuable for fruit flavor improvement in citrus., 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 He, Qin, Liu, Li, Kou, Jin, He, Hong, Xiong, Liao, Sun, He, Zhang, Liang, Lv, Wang and Wang.)

Indoleamine 2,3-dioxygenase (IDO), highly expressed in hepatocellular carcinoma (HCC), plays a pivotal role in creating an immune-suppressive tumor microenvironment. Inhibiting IDO activity has emerged as a promising immunotherapeutic strategy; however, the delivery of IDO inhibitors to the tumor site is constrained, limiting their therapeutic efficacy. In this study, we developed a magnetic vortex nanodelivery system for the targeted delivery of the IDO inhibitor NLG919, integrated with magnetic hyperthermia therapy to reverse the immune-suppressive microenvironment of liver cancer and inhibit tumor growth. This system comprises thermoresponsive polyethylenimine-coated ferrimagnetic vortex-domain iron oxide nanorings (PI-FVIOs) loaded with NLG919 (NLG919/PI-FVIOs). Under thermal effects, NLG919 can be precisely released from the delivery system, counteracting IDO-mediated immune suppression and synergizing with NLG919/PI-FVIOs-mediated magnetothermodynamic (MTD) therapy-induced immunogenic cell death (ICD), resulting in effective HCC suppression. In vivo studies demonstrate that this combination therapy significantly inhibits tumor growth and metastasis by enhancing the accumulation of cytotoxic T lymphocytes and suppressing regulatory T cells within the tumor. Overall, our findings reveal that NLG919/PI-FVIOs can induce a potent antitumor immune response by disrupting the IDO pathway and activating the ICD, offering a promising therapeutic avenue for HCC treatment.

Both g-C 3 N 4 and Bi 2 O 2 CO 3 are good photocatalysts for the removal of antibiotic pollutants, but their morphological modulation and catalytic performance need to be further improved. In this study, the calcination-hydrothermal method is used to prepare a O-g-C 3 N 4 @Bi 2 O 2 CO 3 (CN@BCO) composite photocatalyst from dicyandiamide and bismuth nitrate. The prepared catalyst is characterized through various methods, including X-ray diffraction (XRD) and transmission electron microscopy (TEM). Further, the effects of different parameters, such as catalyst concentration and initial pH of the reaction solution, on its photocatalytic activity are investigated. The results show that the CN@BCO sample achieves an optimal degradation rate of 98.1% for tetracycline hydrochloride (TCH) with a concentration of 20 mg/L and a removal rate of 69.4% for total organic carbon (TOC) at 40 min. The quenching experiments show that ·O 2 - , h + , and ·OH participate in the photocatalytic process, with ·O 2 - being the most dominant active species. The toxicity of the predicted TCH degradation intermediates is analyzed using Toxicity Estimation Software Tool (TEST). Overall, the CN@BCO composite exhibits excellent photocatalytic performance, making it a promising candidate for environmental purification and wastewater 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 Elsevier Inc. All rights reserved.)

Background: Low-frequency intrahost single-nucleotide variants of SARS-CoV-2 have been recognized as predictive indicators of selection. However, the impact of vaccination on the intrahost evolution of SARS-CoV-2 remains uncertain at present., Methods: We investigated the genetic variation of SARS-CoV-2 in individuals who were unvaccinated, partially vaccinated, or fully vaccinated during Shanghai's Omicron BA.2.2 wave. We substantiated the connection between particular amino acid substitutions and immune-mediated selection through a pseudovirus neutralization assay or by cross-verification with the human leukocyte antigen-associated T-cell epitopes., Results: In contrast to those with immunologic naivety or partial vaccination, participants who were fully vaccinated had intrahost variant spectra characterized by reduced diversity. Nevertheless, the distribution of mutations in the fully vaccinated group was enriched in the spike protein. The distribution of intrahost single-nucleotide variants in individuals who were immunocompetent did not demonstrate notable signs of positive selection, in contrast to the observed adaptation in 2 participants who were immunocompromised who had an extended period of viral shedding., Conclusions: In SARS-CoV-2 infections, vaccine-induced immunity was associated with decreased diversity of within-host variant spectra, with milder inflammatory pathophysiology. The enrichment of mutations in the spike protein gene indicates selection pressure exerted by vaccination on the evolution of SARS-CoV-2., Competing Interests: Potential conflicts of interest All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Mitochondria are critical for proper organ function and mechanisms to promote mitochondrial health during regeneration would benefit tissue homeostasis. We report that during liver regeneration, proliferation is suppressed in electron transport chain (ETC)-dysfunctional hepatocytes due to an inability to generate acetyl-CoA from peripheral fatty acids through mitochondrial β-oxidation. Alternative modes for acetyl-CoA production from pyruvate or acetate are suppressed in the setting of ETC dysfunction. This metabolic inflexibility forces a dependence on ETC-functional mitochondria and restoring acetyl-CoA production from pyruvate is sufficient to allow ETC-dysfunctional hepatocytes to proliferate. We propose that metabolic inflexibility within hepatocytes can be advantageous by limiting the expansion of ETC-dysfunctional cells.

It is unknown which posttranscriptional regulatory mechanisms are required for oncogenic competence. Here, we show that the LIN28 family of RNA-binding proteins (RBPs), which facilitate posttranscriptional RNA metabolism within ribonucleoprotein networks, is essential for the initiation of diverse oncotypes of hepatocellular carcinoma (HCC). In HCC models driven by NRASG12V/Tp53, CTNNB1/YAP/Tp53, or AKT/Tp53, mice without Lin28a and Lin28b were markedly impaired in cancer initiation. We biochemically defined an oncofetal regulon of 15 factors connected to LIN28 through direct mRNA and protein interactions. Interestingly, all were RBPs and only 1 of 15 was a Let-7 target. Polysome profiling and reporter assays showed that LIN28B directly increased the translation of 8 of these 15 RBPs. As expected, overexpression of LIN28B and IGFBP1-3 was able to genetically rescue cancer initiation. Using this platform to probe components downstream of LIN28, we found that 8 target RBPs were able to restore NRASG12V/Tp53 cancer formation in Lin28a/Lin28b-deficient mice. Furthermore, these LIN28B targets promote cancer initiation through an increase in protein synthesis. LIN28B, central to an RNP regulon that increases translation of RBPs, is important for tumor initiation in the liver.

Protein-protein interactions are the basis of many protein functions, and understanding the contact and conformational changes of protein-protein interactions is crucial for linking the protein structure to biological function. Although difficult to detect experimentally, molecular dynamics (MD) simulations are widely used to study the conformational ensembles and dynamics of protein-protein complexes, but there are significant limitations in sampling efficiency and computational costs. In this study, a generative neural network was trained on protein-protein complex conformations obtained from molecular simulations to directly generate novel conformations with physical realism. We demonstrated the use of a deep learning model based on the transformer architecture to explore the conformational ensembles of protein-protein complexes through MD simulations. The results showed that the learned latent space can be used to generate unsampled conformations of protein-protein complexes for obtaining new conformations complementing pre-existing ones, which can be used as an exploratory tool for the analysis and enhancement of molecular simulations of protein-protein complexes.

The effects of rootstocks tomato ( Solanum lycopersicum L.), eggplant ( Solanum melongena L.), and nightshade ( Solanum nigrum L.) grafting on the growth and selenium (Se) accumulation of Cyphomandra betacea Sendt. seedlings were studied to identify the most suitable rootstock for increasing Se uptake of fruit trees grown in Se-contaminated soil. The rootstocks of tomato, eggplant, and nightshade grafting increased the scion biomass of C. betacea seedlings by 146.1%, 23.2%, and 94.5%, respectively, compared with the un-grafted seedlings. Moreover, tomato, eggplant, and nightshade rootstocks grafting increased the photosynthesis, superoxide dismutase activity, and peroxidase activity, while reducing the catalase activity and soluble protein content of C. betacea seedlings. Although all three rootstocks grafting decreased Se contents in rootstock roots and stems, only nightshade rootstock grafting increased Se content in the scions of C. betacea seedlings. Notably, root biomass, catalase activity, soluble protein content, rootstock root Se content, and rootstock stem Se content were closely related to the scion Se content. These findings suggest that only grafting onto nightshade rootstock significantly enhances Se uptake in C. betacea , whereas tomato and eggplant rootstocks grafting have no effect on Se uptake.

Unlike other poultry, parent pigeons produce "pigeon milk" in their crops to nurture their squabs, which is mainly controlled by prolactin (PRL). Exception for PRL, the pituitary gland may also release various other peptide and protein hormones. However, whether these hormones change during pigeon crop lactation and their potential physiological functions remain unclear. Here, to identify potential peptide or protein hormone genes that regulate crop lactation, we conducted transcriptome analysis of pigeon pituitary glands at 3 different breeding stages (the ceased stage-nonincubation and non-nurturing stage, the 11th d of the incubation, and the 1st d of the nurturing stage) using RNA sequencing (RNA-Seq). Our analysis identified a total of 15,191 mRNAs and screened out 297 differentially expressed genes (DEG), including PRL, VIP, etc. The expression abundance of PRL mRNA on the 1st d of the nurturing stage was respectively 4.93 and 3.62 folds higher when compared to the ceased stage and the 11th d of the incubation stage. Additionally, the expression abundance of VIP is higher in the 1st d of the nurturing stage than in the ceased stage. Protein-protein interaction (PPI) network and Molecular Complex Detection (MCODE) analysis identified several vital DEGs (e.g., GHRHR, VIP, etc.), being closely linked with hormone and enriched in neuropeptide signaling pathway and response to the hormone. Expression pattern analysis revealed that these DEGs exhibited 4 distinct expression patterns (profile 10, 16, 18, 19). Genes in profile 10 and 19 presented a trend with the highest expression level on 1st d of the nurturing stage, and functional enrichment analysis indicated that these genes are involved in neuropeptide hormone activity, receptor-ligand activity, and the extracellular matrix, etc. Taken together, being consistent with PRL, some genes encoding peptide and protein hormones (e.g., VIP) presented differentially expressed in different breeding stages. It suggests that these hormones may be involved in regulation of the crop lactation process or corresponding behavior in domestic pigeons. The results of this study help to gain new insights into the role of pituitary gland in regulating pigeon lactation., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives-This report examines changes in telemedicine use among U.S. adults between 2021 and 2022 by selected sociodemographic and geographic characteristics. Methods-Data from the 2021 and 2022 National Health Interview Survey were used to assess changes between these 2 years in the percentage of adults who used telemedicine in the previous 12 months, by sex, age, race and Hispanic origin, family income, education, region of residence, urbanization level, and health insurance coverage. Results-Overall, the percentage of adults who used telemedicine in the past 12 months decreased from 37.0% in 2021 to 30.1% in 2022. This pattern was observed across several sociodemographic and geographic characteristics, such as sex, family income, education, region, and urbanization level. Women, adults with a college degree or higher, and adults living in more urban areas were all more likely to use telemedicine in 2022. In 2021 and 2022, uninsured adults ages 18-64 were less likely to use telemedicine compared with those who had private or public insurance, while adults age 65 and older who had Medicare only were less likely to use telemedicine compared with those with other types of insurance. However, for both age groups, telemedicine use decreased from 2021 to 2022 for all insurance types except public coverage for adults ages 18-64. Summary-National Health Interview Survey data may be used to monitor national trends and understand patterns of telemedicine use by sociodemographic and geographic characteristics as the transition forward from the global COVID-19 pandemic continues., (All material appearing in this report is in the public domain and may be reproduced or copied without permission; citation as to source, however, is appreciated.)

Displaying antibodies on carrier surfaces facilitates precise targeting and delivery of drugs to diseased cells. Here, we report the synthesis of antibody-lipid conjugates (ALCs) through site-selective acetylation of Lys 248 in human Immunoglobulin G (IgG) and the development of antibody-functionalized red blood cells (immunoRBC) for targeted drug delivery. ImmunoRBC with the HER2-selective antibody trastuzumab displayed on the surface (called Tras-RBC) was constructed following a three-step procedure. First, a peptide-guided, proximity-induced reaction transferred an azidoacetyl group to the ε-amino group of Lys 248 in the Fc domain. Second, the azide-modified IgG was subsequently conjugated with dibenzocyclooctyne (DBCO)-functionalized lipids via strain-promoted azide-alkyne cycloaddition (SPAAC) to result in ALCs. Third, the lipid portion of ALCs was then inserted into the cell membranes, and IgGs were displayed on red blood cells (RBCs) to construct immunoRBCs. We then loaded Tras-RBC with a photosensitizer (PS), Zinc phthalocyanine (ZnPc), to selectively target HER2-overexpressing cells, release ZnPc into cancer cells following photolysis, and induce photodynamic cytotoxicity in the cancer cells. This work showcases assembling immunoRBCs following site-selective lipid conjugation on therapeutic antibodies and the targeted introduction of PS into cancer cells. This method could apply to the surface functionalization of other membrane-bound vesicles or lipid nanoparticles for antibody-directed drug delivery., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Sorafenib, a first-line drug for advanced hepatocellular carcinoma (HCC), unfortunately encounters resistance in most patients, leading to disease progression. Traditional approaches to counteract this resistance, particularly those targeting the RAF-MEK-ERK pathway, often face clinical feasibility limitations. Magnetic hyperthermia (MH), unlike conventional thermal therapies, emerges as a promising alternative. It uniquely combines magnetothermal effects with an increase in reactive oxygen species (ROS). This study found the potential of intracellular MH enhanced the efficacy of sorafenib, increased cellular sensitivity to sorafenib, and reversed sorafenib resistance by inhibiting the RAF-MEK-ERK pathway in an ROS-dependent manner in a sorafenib-resistant HCC cell. Further, in a sorafenib-resistant HCC mouse model, MH significantly sensitized tumors to sorafenib therapy, resulting in inhibited tumor growth and improved survival rates. This presents a promising strategy to overcome sorafenib resistance in HCC, potentially enhancing therapeutic outcomes for patients with this challenging condition., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Mitogen-activated protein kinase (MAPK) signalling cascades are functionally important signalling modules in eukaryotes. Transcriptome reprogramming of immune-related genes is a key process in plant immunity. Emerging evidence shows that plant MAPK cascade is associated with processing (P)-body components and contributes to transcriptome reprogramming of immune-related genes. However, it remains largely unknown how this process is regulated. Here, we show that OsMPK12, which is induced by Magnaporthe oryzae infection, positively regulates rice blast resistance. Further analysis revealed that OsMPK12 directly interacts with enhancer of mRNA decapping protein 4 (OsEDC4), a P-body-located protein, and recruits OsEDC4 to where OsMPK12 is enriched. Importantly, OsEDC4 directly interacts with two decapping complex members OsDCP1 and OsDCP2, indicating that OsEDC4 is a subunit of the mRNA decapping complex. Additionally, we found that OsEDC4 positively regulates rice blast resistance by regulating expression of immune-related genes and maintaining proper mRNA levels of some negatively-regulated genes. And OsMPK12 and OsEDC4 are also involved in rice growth and development regulation. Taken together, our data demonstrate that OsMPK12 positively regulates rice blast resistance via OsEDC4-mediated mRNA decay of immune-related genes, providing new insight into not only the new role of the MAPK signalling cascade, but also posttranscriptional regulation of immune-related genes., (© 2024 John Wiley & Sons Ltd.)

To enhance physical capabilities of workers who regularly perform physically demanding tasks involving heavy lifting and awkward postures, various tools and occupational exoskeletons can be used. Most of the studies aiming to explore the efficiency of these tools and exoskeletons have been performed in confined and controlled laboratory spaces, which do not represent the real-world work environment. This study aimed to compare the outcome of biomechanical assessment of using a back support exoskeleton and assistive tools (Lever and Jake) in the procedure of a high demanding manual material handling task versus the results found by performing the same task in a laboratory. Ten able-bodied participants and ten able-bodied utility workers performed the same manhole removal task in-lab and in-field, respectively, with the aid of an exoskeleton and Lever and Jake tools. Muscle activity and Rapid Entire Body Assessment (REBA) scores were recorded using surface electromyography and inertial measurement units, respectively and compared between in-lab and in-field trials. The field experiments indicated significant differences ( p < 0.05) in normalized muscle activity across most muscles when compared to laboratory data. These results revealed how muscle activity is affected by the controlled lab setting compared to real-world field conditions. However, REBA scores indicate similar ergonomic implications regardless of the utilization of exoskeletons or tools. These findings underscore that real-world field assessments are crucial for evaluating ergonomic risks and effects of occupational exoskeletons and tools to account for environmental factors and workers' skills in ergonomic evaluations of this nature., Competing Interests: Author AG was employed by EWI Works Inc. Author SK was employed by EPCOR Utilities Inc. The remaining 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Shakourisalim, Wang, Beltran Martinez, Golabchi, Krell, Tavakoli and Rouhani.)