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Capsules were widely used in clinical settings for the oral delivery of various drugs, although it remains challenging to trace real-time drug release behavior and adjust dosages based on the therapeutic effect. To address these issues, we developed theranostic capsules that loaded two kinds of fluorescence nanoparticles, H 2 O 2 -responsive Janus Ag/Ag 2 S nanoparticles (Ag/Ag 2 S JNPs) and the downconversion nanoparticles (DCNPs), and the dexamethasone (Dex) drug. The Ag/Ag 2 S JNPs exhibit a highly sensitive fluorescence (FL) signal at 1250 nm in response to H 2 O 2 , while the FL signal from the DCNPs at 1550 nm remains stable under physiological conditions. The ratio of these two FL signals formed the ratiometric FL signal, which shows correlation with the H 2 O 2 concentration with a detection limit of 1.7 μM. Moreover, the capsules can be precisely delivered into the intestine, where they release the JNPs and DCNPs simultaneously. The H 2 O 2 -triggered ratiometric FL signals and images can diagnose inflammation and indicate its location. Meanwhile, the encapsulated Dex is released in the disease region, with ratiometric imaging allowing for real-time tracking of therapeutic efficacy and providing guidance for ongoing treatment. The theranostic capsule system provides an approach for quantitative detection of disease biomarkers and further localized release of therapeutics, thereby avoiding overdose and reducing side effects.

The injectable hydrogels can deliver the loads directly to the predetermined sites and form reservoirs to increase the enrichment and retention of the loads in the target areas. The preparation and injection of injectable hydrogels involve the sol-gel transformation of hydrogels, which is affected by factors such as temperature, ions, enzymes, light, mechanics (self-healing property), and pH. However, tracing the injection, degradation, and drug release from hydrogels based on different ways of gelation is a major concern. To solve this problem, contrast agents are introduced into injectable hydrogels, enabling the hydrogels to be imaged under techniques such as fluorescence imaging, photoacoustic imaging, magnetic resonance imaging, and radionuclide imaging. This review details methods for causing the gelation of imageable hydrogels; discusses the application of injectable hydrogels containing contrast agents in various imaging techniques, and finally explores the potential and challenges of imageable hydrogels based on different modes of gelation., (© 2024 Wiley‐VCH GmbH.)

Background: Bevacizumab and sintilimab combined interventional treatment (BeSiIT) and L envatinib and sintilimab combined interventional treatment (LeSiIT) are two commonly used therapeutic regimens for intermediate-advanced hepatocellular carcinoma (HCC) in clinical practice., Aim: To compare the clinical efficacy and safety of BeSiIT and LeSiIT for the treatment of intermediate and advanced HCC., Methods: Patients diagnosed with intermediate-advanced HCC and initially treated with BeSiIT or LeSiIT in the Tianjin Medical University Cancer Institute and Hospital between February 2020 and July 2021 were included. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), conversion rate, and treatment-related adverse events., Results: Total 127 patients met the inclusion criteria and were divided into BeSiIT and LeSiIT groups. Twenty-eight and fifty patients in the BeSiIT and LeSiIT groups, respectively, were assessed after 1:2 propensity score matching. PFS and OS rates were not significantly different between the two groups. No significant variations were noted in ORRs or DCRs according to the Response Evaluation Criteria in Solid Tumors (RECIST), and modified RECIST. BeSiIT group showed a better conversion rate than the LeSiIT group ( P = 0.043). Both groups showed manageable toxicity profiles. Multivariate analysis showed that the independent factors associated with PFS were alpha-fetoprotein levels and carcinoembryonic antigen score., Conclusion: In intermediate-to-advanced HCC, the BeSiIT and LeSiIT groups exhibited acceptable toxicities and comparable PFS, OS, and ORR., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Cerium and lanthanum dialkyl complexes [η 5 -1,2,4-(Me 3 C) 3 C 5 H 2 ]Ln(CH 2 C 6 H 4 - o -NMe 2 ) 2 (Ln = Ce 1 and La 2 ), supported by a tri -tert -butylcyclopentadienyl ligand, have been successfully synthesized. Studies demonstrate that these complexes possess diverse reactivity toward various small molecules. For example, the reaction of complexes 1 and 2 with diphenyl dichalcogenides PhEEPh (E = S, Se) results in the formation of lanthanide thiolates [(η 5 -1,2,4-(Me 3 C) 3 C 5 H 2 )Ln(SPh)(μ-SPh)] 2 (Ln = Ce 3 and La 4 ) and selenolates [(η 5 -1,2,4-(Me 3 C) 3 C 5 H 2 )Ln(SePh)(μ-SePh)] 2 (Ln = Ce 5 and La 6 ), concomitantly releasing PhE(CH 2 C 6 H 4 - o -NMe 2 ). Furthermore, complexes 1 and 2 , upon reaction with dibenzyl disulfide, yield tetranuclear rare-earth metallomacrocyclic compounds {[(η 5 -1,2,4-(Me 3 C) 3 C 5 H 2 )Ln(μ - SCH 2 C 6 H 5 )] 2 (μ-η 3 :η 3 -SCHC 6 H 5 )} 2 (Ln = Ce 7 and La 8 ). This reaction may involve a process of σ-bond metathesis and C-H activation. While the reaction of 1 and 2 with dibenzyl diselenide in the presence of LiCH 2 C 6 H 4 -o-NMe 2 leads to the formation of lanthanide-lithium selenido clusters [(η 5 -1,2,4-(Me 3 C) 3 C 5 H 2 )La(μ-SeCH 2 C 6 H 5 )] 3 (μ 3 -Se)[μ 3 -SeLi(THF) 3 ] (Ln = Ce 9 and La 10 ). Meanwhile, lanthanide selenido clusters [(η 5 -1,2,4-(Me 3 C) 3 C 5 H 2 )La(μ-SeCH 2 C 6 H 4 - o -NMe 2 )] 4 (μ 3 -Se) 2 (Ln = Ce 11 and La 12 ) can be obtained by treating 1 and 2 with elemental selenium in a 1:2 molar ratio. Additionally, the treatment of 1 and 2 with benzoxazole generates ring-opening/C-C coupling/C-N coupling products {(η 5 -1,2,4-(Me 3 C) 3 C 5 H 2 )La[μ-OC 6 H 4 - o -N═CHN(CH(CH 2 C 6 H 4 - o -NMe 2 ) 2 C 6 H 4 - o -O]} 2 (Ln = Ce 13 and La 14 ). All new compounds were characterized by various spectroscopic methods, and their solid-state structures were confirmed by single-crystal X-ray diffraction analyses.

ADP-ribosylation is an ancient posttranslational modification with exceptional versatility in terms of breadth of modification targets including at least seven different amino acid side chains, various moieties on nucleic acids, and a variety of small chemical compounds. The spatiotemporal signaling dynamic of the different modification variations is tightly regulated and depends on the writers, erases, and readers of each type. Among these, tyrosine ADP-ribosylation (Tyr-ADPr) has been consistently detected as a novel modification type, but systematic analysis of its potential physiological role, modification establishment, and reversal are still lacking. Here we present a re-analysis of recent ADP-ribosylome data and show that Tyr-ADPr sites are conserved and enriched among ribosome biogenesis and mRNA processing proteins and that these sites are affected by the status of the (ADP-ribosyl)hydrolase ARH3. To facilitate the study of Tyr-ADPr, we establish methodologies for the synthesis of well-defined Tyr-ADPr peptides and with these could show that Tyr-ADPr is reversed both by ARH3 and PARG enzymes. Together, our work lays the foundation for the future exploration of the Tyr-ADPr., Competing Interests: Conflict of interest E. P. is an employee of Vertex Pharmaceuticals and may own stock or stock options in that company., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

In the quest for sustainable energy solutions, solid oxide electrolysis cell (SOEC) emerges as a key technology for converting CO 2 into fuels and valuable chemicals. This work focuses on pure ceramic Fe x Sm 0.2 Ce 0.8 O 2- δ (xFe-SDC) as the fuel electrodes, and Sr-free ceria-based ceramic electrodes can be successfully constructed for x ≤ 0.05. The incorporation of Fe into the ceria lattice increases the oxygen vacancy concentration and promotes the formation of catalytic sites crucial for the CO 2 reduction reaction (CO 2 RR). Density functional theory calculations indicate that Fe enhances electrochemical performance by decreasing the CO 2 RR energy barrier and facilitating oxygen ion diffusion. At 800 °C and 1.5 V, single cells with 0.05Fe-SDC cathodes manifest attractive performance, attaining current densities of -1.98 and -2.26 A cm -2 under 50% CO 2 /CO and pure CO 2 atmospheres, respectively. These results suggest the great potential of xFe-SDC electrodes as promising avenues for high-performance fuel electrodes in SOEC., (© 2024 Wiley‐VCH GmbH.)

The recent discovery of non-proteinaceous ubiquitylation substrates broadened our understanding of this modification beyond conventional protein targets. However, the existence of additional types of substrates remains elusive. Here, we present evidence that nucleic acids can also be directly ubiquitylated via ester bond formation. DTX3L, a member of the DELTEX family E3 ubiquitin ligases, ubiquitylates DNA and RNA in vitro and that this activity is shared with DTX3, but not with the other DELTEX family members DTX1, DTX2 and DTX4. DTX3L shows preference for the 3'-terminal adenosine over other nucleotides. In addition, we demonstrate that ubiquitylation of nucleic acids is reversible by DUBs such as USP2, JOSD1 and SARS-CoV-2 PLpro. Overall, our study proposes reversible ubiquitylation of nucleic acids in vitro and discusses its potential functional implications., (© 2024. The Author(s).)

Background: Surgical resection and liver transplantation (LT) are the most effective curative options for hepatocellular carcinoma (HCC). However, few patients with huge HCC (> 10 cm in diameter), especially those with portal vein tumor thrombus (PVTT), can receive these treatments. Selective internal radiation therapy (SIRT) can be used as a conversion therapy for them because it has the dual benefit of shrinking tumors and increasing residual hepatic volume. However, in patients with huge HCC, high lung absorbed dose often prevents them from receiving SIRT., Case Summary: A 35-year-old man was admitted because of emaciation and pain in the hepatic region for about 1 month. The computed tomography scan showed a 20.2 cm × 19.8 cm tumor located in the right lobe-left medial lobes with right portal vein and right hepatic vein invasion. After the pathological type of HCC was confirmed by biopsy, two conversions were presented. The first one was drug-eluting bead transarterial chemoembolization plus hepatic arterial infusion chemotherapy and lenvatinib and sintilimab, converted to SIRT, and the second one was sequential SIRT with continued systemic treatment. The tumor size significantly decreased from 20.2 cm × 19.8 cm to 16.2 cm × 13.8 cm, then sequentially to 7.8 cm × 6.8 cm. In the meantime, the ratio of spared volume to total liver volume increased gradually from 34.4% to 55.7%, then to 62.9%. Furthermore, there was visualization of the portal vein, indicating regression of the tumor thrombus. Finally, owing to the new tumor in the left lateral lobe, the patient underwent LT instead of resection without major complications., Conclusion: Patients with inoperable huge HCC with PVTT could be converted to SIRT first and accept surgery sequentially., Competing Interests: Conflict-of-interest statement: All the authors have no relevant conflicts of interest to declare for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Water, being abundant and readily accessible, gains widespread usage as proton source in many catalysis and energy conversion technologies, including applications like reversible protonic ceramic cells (R-PCCs). Revealing the influence of water on the electrode surface and reaction kinetics is critical for further improving their electrochemical performance. Herein, a hydrophilic air-electrode PrBa 0.875 Cs 0.125 Co 2 O 5+δ is developed for R-PCC, which demonstrates a remarkable peak power density of 1058 mW cm -2 in fuel cell mode and a current density of 1354 mA cm -2 under 1.3 V in electrolyzing steam at 650 °C. For the first time on R-PCC, surface protons' behavior in response to external voltages is captured using in situ FTIR characterizations. Further, it is shown that contrary to the bulk proton uptake process that is thought to follow hydrogenation reactions and lead to cation reductions. The air-electrode presents enriched surface protons occurring through oxidizing surface cations, as confirmed by depth-profiling XPS results. H/D isotope exchange experiments and subsequent electrochemical characterization analyses reveal that the presence of protons enhances surface reactions. This study fills the knowledge gap between water-containing atmospheres and electrochemical performance by providing insights into the surface properties of the material. These new findings provide guidance for future electrode design and optimization., (© 2024 Wiley‐VCH GmbH.)

Background: Osteoporosis, a metabolic bone disorder, markedly elevates fracture risks, with vertebral compression fractures being predominant. Antiosteoporotic treatments for patients with osteoporotic vertebral compression fractures (OVCF) lessen both the occurrence of subsequent fractures and associated pain. Thus, diagnosing osteoporosis in OVCF patients is vital., Purpose: The aim of this study was to develop a predictive radiographic model using T1 sequence MRI images to accurately determine whether patients with lumbar spine compression fractures also have osteoporosis., Study Design: Retrospective cohort study., Patient Sample: Patients over 45 years of age diagnosed with a fresh lumbar compression fracture., Outcome Measures: Diagnostic accuracy of the model (area under the ROC curve)., Methods: The study retrospectively collected clinical and imaging data (MRI and DEXA) from hospitalized lumbar compression fracture patients (L1-L4) aged 45 years or older between January 2021 and June 2023. Using the pyradiomics package in Python, features from the lumbar compression fracture vertebral region of interest (ROI) were extracted. Downscaling of the extracted features was performed using the Mann-Whitney U test and the least absolute shrinkage selection operator (LASSO) algorithm. Subsequently, six machine learning models (Naive Bayes, Support Vector Machine [SVM], Decision Tree, Random Forest, Extreme Gradient Boosting [XGBoost], and Light Gradient Boosting Machine [LightGBM]) were employed to train and validate these features in predicting osteoporosis comorbidity in OVCF patients., Results: A total of 128 participants, 79 in the osteoporotic group and 49 in the nonosteoporotic group, met the study's inclusion and exclusion criteria. From the T1 sequence MRI images, 1906 imaging features were extracted in both groups. Utilizing the Mann-Whitney U test, 365 radiologic features were selected out of the initial 1,906. Ultimately, the lasso algorithm identified 14 significant radiological features. These features, incorporated into six conventional machine learning algorithms, demonstrated successful prediction of osteoporosis in the validation set. The NaiveBayes model yielded an area under the receiver operating characteristic curve (AUC) of 0.84, sensitivity of 0.87, specificity of 0.70, and accuracy of 0.81., Conclusions: A NaiveBayes machine learning algorithm can predict osteoporosis in OVCF patients using t1-sequence MRI images of lumbar compression fractures. This approach aims to obviate the necessity for further osteoporosis assessments, diminish patient exposure to radiation, and bolster the clinical care of patients with OVCF., 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.)

Low-cost, highly efficient thermoelectric thin-film materials are becoming increasingly popular as miniaturization progresses. Mg 3 Sb 2 has great potential due to its low cost and high performance. However, the fabrication of Mg 3 Sb 2 thin films with high power factors (PFs) poses a certain challenge. In this work, we propose a general approach to prepare Mg 3 Sb 2 thin films with excellent thermoelectric properties. Using a two-step thermal evaporation and rapid annealing process, (001)-oriented Mg 3 Sb 2 thin films are fabricated on c -plane-oriented Al 2 O 3 substrates. The structure of the film orientation is optimized by controlling the film thickness, which modulates the thermoelectric performance. The PF of the Mg 3 Sb 2 at 500 nm (14 μ W·m -1 ·K -2 ) would increase to 169 μ W·m -1 ·K -2 with Ag doping (Mg 3 Ag 0.02 Sb 2 ) at room temperature. This work provides a new strategy for the development of high-performance thermoelectric thin films at room temperature., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

The positive electrode|electrolyte interface plays an important role in all-solid-state Li batteries (ASSLBs) based on garnet-type solid-state electrolytes (SSEs) like Li 6.4 La 3 Zr 1.4 Ta 0.6 O 12 (LLZTO). However, the trade-off between solid-solid contact and chemical stability leads to a poor positive electrode|electrolyte interface and cycle performance. In this study, we achieve thermodynamic compatibility and adequate physical contact between high-entropy cationic disordered rock salt positive electrodes (HE-DRXs) and LLZTO through ultrafast high-temperature sintering (UHS). This approach constructs a highly stable positive electrode|electrolyte interface, reducing the interface resistance to 31.6 Ω·cm 2 at 25 °C, making a 700 times reduction compared to the LiCoO 2  | LLZTO interface. Moreover, the conformal and tight HE-DRX | LLZTO solid-state interface avoids the transition metal migration issue observed with HE-DRX in liquid electrolytes. At 150 °C, HE-DRXs in ASSLBs (Li|LLZTO | HE-DRXs) exhibit an average specific capacity of 239.7 ± 2 mAh/g at 25 mA/g, with a capacity retention of 95% after 100 cycles relative to the initial cycle-a stark contrast to the 76% retention after 20 cycles at 25 °C in conventional liquid batteries. Our strategy, which considers the principles of thermodynamics and kinetics, may open avenues for tackling the positive electrode|electrolyte interface issue in ASSLBs based on garnet-type SSEs., (© 2024. The Author(s).)

PARP-catalysed ADP-ribosylation (ADPr) is important in regulating various cellular pathways. Until recently, PARP-dependent mono-ADP-ribosylation has been poorly understood due to the lack of sensitive detection methods. Here, we utilised an improved antibody to detect mono-ADP-ribosylation. We visualised endogenous interferon (IFN)-induced ADP-ribosylation and show that PARP14 is a major enzyme responsible for this modification. Fittingly, this signalling is reversed by the macrodomain from SARS-CoV-2 (Mac1), providing a possible mechanism by which Mac1 counteracts the activity of antiviral PARPs. Our data also elucidate a major role of PARP9 and its binding partner, the E3 ubiquitin ligase DTX3L, in regulating PARP14 activity through protein-protein interactions and by the hydrolytic activity of PARP9 macrodomain 1. Finally, we also present the first visualisation of ADPr-dependent ubiquitylation in the IFN response. These approaches should further advance our understanding of IFN-induced ADPr and ubiquitin signalling processes and could shed light on how different pathogens avoid such defence pathways., (© 2024. The Author(s).)

A novel construction strategy is introduced for an ultrasensitive dynamic light scattering (DLS) immunosensor targeting alpha fetoprotein (AFP). This approach relies on a self-assembled heptamer fusion protein (A1-C4bpα), incorporating the dual functions of multivalent recognition and crosslinking aggregation amplification due to the presence of seven AFP-specific A1 nanobodies on the A1-C4bpα heptamer. Leveraging antibody-functionalized magnetic nanoparticles for target AFP capture and DLS signal output, the proposed heptamer-assisted DLS immunosensor offers high sensitivity, strong specificity, and ease of operation. Under the optimized conditions, the designed DLS immunosensor demonstrates excellent linear detection of AFP in the concentration range 0.06 ng mL -1 to 512 ng mL -1 , with a detection limit of 15 pg mL -1 . The selectivity, accuracy, precision, practicability, and reliability of this newly developed method were further validated through an assay of AFP levels in spiked and actual human serum samples. This work introduces a novel approach for constructing ultrasensitive DLS immunosensors, easily extendable to the sensitive determination of other targets via simply replacing the nanobody sequence, holding great promise in various applications, particularly in disease diagnosis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background: The role of transarterial chemoembolization (TACE) in the treatment of advanced hepatocellular carcinoma (HCC) is unconfirmed. This study aimed to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) plus anti-vascular endothelial growth factor (anti-VEGF) antibody/tyrosine kinase inhibitors (TKIs) with or without TACE as first-line treatment for advanced HCC., Methods: This nationwide, multicenter, retrospective cohort study included advanced HCC patients receiving either TACE with ICIs plus anti-VEGF antibody/TKIs (TACE-ICI-VEGF) or only ICIs plus anti-VEGF antibody/TKIs (ICI-VEGF) from January 2018 to December 2022. The study design followed the target trial emulation framework with stabilized inverse probability of treatment weighting (sIPTW) to minimize biases. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and safety. The study is registered with ClinicalTrials.gov, NCT05332821., Findings: Among 1244 patients included in the analysis, 802 (64.5%) patients received TACE-ICI-VEGF treatment, and 442 (35.5%) patients received ICI-VEGF treatment. The median follow-up time was 21.1 months and 20.6 months, respectively. Post-application of sIPTW, baseline characteristics were well-balanced between the two groups. TACE-ICI-VEGF group exhibited a significantly improved median OS (22.6 months [95% CI: 21.2-23.9] vs 15.9 months [14.9-17.8]; P < 0.0001; adjusted hazard ratio [aHR] 0.63 [95% CI: 0.53-0.75]). Median PFS was also longer in TACE-ICI-VEGF group (9.9 months [9.1-10.6] vs 7.4 months [6.7-8.5]; P < 0.0001; aHR 0.74 [0.65-0.85]) per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. A higher ORR was observed in TACE-ICI-VEGF group, by either RECIST v1.1 or modified RECIST (41.2% vs 22.9%, P < 0.0001; 47.3% vs 29.7%, P < 0.0001). Grade ≥3 adverse events occurred in 178 patients (22.2%) in TACE-ICI-VEGF group and 80 patients (18.1%) in ICI-VEGF group., Interpretation: This multicenter study supports the use of TACE combined with ICIs and anti-VEGF antibody/TKIs as first-line treatment for advanced HCC, demonstrating an acceptable safety profile., Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Jiangsu Provincial Medical Innovation Center, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and Nanjing Life Health Science and Technology Project., Competing Interests: We declare no competing interests., (© 2024 Published by Elsevier Ltd.)

Competing Interests: Competing interests statement:The authors declare no competing interest.

The permeability of the highly selective blood-brain barrier (BBB) to anticancer drugs and the difficulties in defining deep tumor boundaries often reduce the effectiveness of glioma treatment. Thus, exploring the combination of multiple treatment modalities under the guidance of second-generation near-infrared (NIR-II) window fluorescence (FL) imaging is considered a strategic approach in glioma theranostics. Herein, a hybrid X-ray-activated nanoprodrug was developed to precisely visualize the structural features of glioma microvasculature and delineate the boundary of glioma for synergistic chemo-radiotherapy. The nanoprodrug comprised down-converted nanoparticle (DCNP) coated with X-ray sensitive poly(Se-Se/DOX- co -acrylic acid) and targeted Angiopep-2 peptide (DCNP@P(Se-DOX)@ANG). Because of its ultrasmall size and the presence of DOX, the nanoprodrug could easily cross BBB to precisely monitor and localize glioblastoma via intracranial NIR-II FL imaging and synergistically administer antiglioblastoma chemo-radiotherapy through specific X-ray-induced DOX release and radiosensitization. This study provides a novel and effective strategy for glioblastoma imaging and chemo-radiotherapy.

Lei's formula (LSF), a traditional Chinese herbal remedy, is recognized for its remarkable clinical effectiveness in treating osteoarthritis (OA). Despite its therapeutic potential, the exact molecular mechanisms underlying LSF's action in OA have remained enigmatic. Existing research has shed light on the role of the mTOR signaling pathway in promoting chondrocyte senescence, a central factor in OA-related cartilage degeneration. Consequently, targeting mTOR to mitigate chondrocyte senescence presents a promising avenue for OA treatment. The primary objective of this study is to establish LSF's chondroprotective potential and confirm its anti-osteoarthritic efficacy through mTOR inhibition. In vivo assessments using an OA mouse model reveal substantial articular cartilage degeneration. However, LSF serves as an effective guardian of articular cartilage, evidenced by reduced subchondral osteosclerosis, increased cartilage thickness, improved surface smoothness, decreased OARSI scores, elevated expression of cartilage anabolic markers (Col2 and Aggrecan), reduced expression of catabolic markers (Adamts5 and MMP13), increased expression of the chondrocyte hypertrophy marker (Col10), and decreased expression of chondrocyte senescence markers (P16 and P21). In vitro findings demonstrate that LSF shields chondrocytes from H 2 O 2 -induced apoptosis, inhibits senescence, enhances chondrocyte differentiation, promotes the synthesis of type II collagen and proteoglycans, and reduces cartilage degradation. Mechanistically, LSF suppresses chondrocyte senescence through the mTOR axis, orchestrating the equilibrium between chondrocyte anabolism and catabolism, ultimately leading to reduced apoptosis and decelerated OA cartilage degradation. LSF holds significant promise as a therapeutic approach for OA treatment, offering new insights into potential treatments for this prevalent age-related condition.

Protonic ceramic cells merit extensive exploration, attributed to their innate capabilities for potent and environmentally benign energy conversion. In this work, a temperature-induced exsolution methodology to synthesize SrCo 0.5 Nb 0.5 O 3-δ (SCN) nanoparticles (NPs) with notably elevated activity on the surface of PrSrCo 1.8 Nb 0.2 O 6-δ (PSCN) is proposed, directly addressing the extant challenge of restrained catalytic activity prevalent in air electrode materials. In situ assessments reveal that SCN NPs commence exsolution from the matrix at temperatures surpassing 900 °C during straightforward calcination processes and maintain stability throughout annealing. Notably, the resultant SCN-PSCN interface facilitates vapor adsorption and protonation processes, which are poised to enhance surface reaction kinetics pertaining to the proton-involved oxygen reduction and evolution reaction (P-ORR and P-OER). A fuel-electrode-supported protonic ceramic cell leveraging SCN-PSCN as the air electrode manifests compelling performance, attaining a peak power density of 1.30 W·cm -2 in the fuel cell modality and a current density of 1.91 A·cm -2 at 1.3 V in the electrolysis mode, recorded at 650 °C. Furthermore, density functional theory calculations validate that the introduction of SCN NPs onto the PSCN surface conspicuously accelerates electrode reaction rates correlated with P-ORR and P-OER, by significantly mitigating energy barriers associated with surface oxygen and vapor dissociation.

Ionic thermoelectric (i-TE) liquid cells offer an environmentally friendly, cost effective, and easy-operation route to low-grade heat recovery. However, the lowest temperature is limited by the freezing temperature of the aqueous electrolyte. Applying a eutectic solvent strategy, we fabricate a high-performance cryo-temperature i-TE liquid cell. Formamide is used as a chaotic organic solvent that destroys the hydrogen bond network between water molecules, forming a deep eutectic solvent that enables the cell to operate near cryo temperatures (down to -35 °C). After synergistic optimization of the electrode and cell structure, the as-fabricated liquid i-TE cell with cold (-35 °C) and hot (70 °C) ends achieve a high power density (17.5 W m -2 ) and a large two-hour energy density (27 kJ m -2 ). In a prototype 25-cell module, the open-circuit voltage and short-circuit current are 6.9 V and 68 mA, respectively, and the maximum power is 131 mW. The anti-freezing ability and high output performance of the as-fabricated i-TE liquid cell system are requisites for applications in frigid regions., (© 2024. The Author(s).)

Dynamic variations in the concentration and abnormal distribution of endogenous biomarkers are strongly associated with multiple physiological and pathological states. Therefore, it is crucial to design imaging systems capable of real-time detection of dynamic changes in biomarkers for the accurate diagnosis and effective treatment of diseases. Recently, ratiometric imaging has emerged as a widely used technique for sensing and imaging of biomarkers due to its advantage of circumventing the limitations inherent to conventional intensity-dependent signal readout methods while also providing built-in self-calibration for signal correction. Here, the recent progress of ratiometric probes and their applications in sensing and imaging of biomarkers are outlined. Ratiometric probes are classified according to their imaging mechanisms, and ratiometric photoacoustic imaging, ratiometric optical imaging including photoluminescence imaging and self-luminescence imaging, ratiometric magnetic resonance imaging, and dual-modal ratiometric imaging are discussed. The applications of ratiometric probes in the sensing and imaging of biomarkers such as pH, reactive oxygen species (ROS), reactive nitrogen species (RNS), glutathione (GSH), gas molecules, enzymes, metal ions, and hypoxia are discussed in detail. Additionally, this Review presents an overview of challenges faced in this field along with future research directions.

Hepatocellular carcinoma (HCC) is one of the most common malignancies and the third leading cause of cancer-related deaths globally. Hepatic arterial infusion chemotherapy (HAIC) treatment is widely accepted as one of the alternative therapeutic modalities for HCC owing to its local control effect and low systemic toxicity. Nevertheless, although accumulating high-quality evidence has displayed the superior survival advantages of HAIC of oxaliplatin, fluorouracil, and leucovorin (HAIC-FOLFOX) compared with standard first-line treatment in different scenarios, the lack of standardization for HAIC procedure and remained controversy limited the proper and safe performance of HAIC treatment in HCC. Therefore, an expert consensus conference was held on March 2023 in Guangzhou, China to review current practices regarding HAIC treatment in patients with HCC and develop widely accepted statements and recommendations. In this article, the latest evidence of HAIC was systematically summarized and the final 22 expert recommendations were proposed, which incorporate the assessment of candidates for HAIC treatment, procedural technique details, therapeutic outcomes, the HAIC-related complications and corresponding treatments, and therapeutic scheme management., (© 2023. Asian Pacific Association for the Study of the Liver.)

Aiming at the problems of long reaction time and the risk of explosion polymerization of acrylate resin, a small amount of ferrocene (Fc) is added to the existing dibenzoyl peroxide (BPO)/N,N-dimethylaniline (DMA) initiators, and the compound redox initiators (BPO/DMA/ (Fc)) are proposed for acrylate resin polymerization at room temperature. The effect of the content of Fc in the resin on the reaction efficiency and the molding quality of products is researched, and the initiation mechanism of the compound redox initiators is analyzed. It is found that with the addition of Fc, the reaction time of the resin can be shortened by 68% at maximum, the heat release temperature of the resin can be reduced by 40% at maximum, the molecular weight of the reaction products can be increased by 74% at maximum, the tensile and bending properties of the resin castings are increased by 23% and 35% at maximum, respectively, and the bending strength and bending modulus are increased by 57% and 27% at maximum, respectively. The compound redox initiators proposed in this paper can improve the molding efficiency and quality of the product, lay a foundation for the application of acrylic resin in the field of pultrusion molding, perfusion molding, and other in situ molding of thermoplastic composites., (© 2023 Wiley-VCH GmbH.)

Ceria-based oxides, such as samaria-doped ceria (SDC), are potential electrolytes for low-to-intermediate-temperature solid oxide fuel cells (SOFCs). The sinterability of these materials can be improved by adding iron as the sintering aid. This work reveals that Fe is soluble in SDC, forming an Fe-doped SDC solid solution. It is found that the solubility is affected by the sintering temperature. Fe doping has obvious effects on electrolyte properties, including sintering characteristics, thermal expansion behaviors, and electrical conductivities in both air and hydrogen atmospheres. The conductivity obviously increases while the activation energy decreases by doping Fe. Compared with that of the bare SDC electrolyte, the performance of the single cell with the Fe-doped SDC is enhanced; for example, the peak power density is increased by 52.8% to 0.726 W cm -2 at 600 °C when humidified hydrogen is used as the fuel and ambient air is used as the oxidant. The single cell showed stable operation at 600 °C under a constant current density of 0.3 A cm -2 for 150 h. Therefore, the Fe-doped SDC solid solution shows promise as a potential electrolyte for low-to-intermediate-temperature SOFCs.

Although ubiquitylation had traditionally been considered limited to proteins, the discovery of non-proteinaceous substrates (e.g. lipopolysaccharides and adenosine diphosphate ribose (ADPr)) challenged this perspective. Our recent study showed that DTX2 E3 ligase efficiently ubiquitylates ADPr. Here, we show that the ADPr ubiquitylation activity is also present in another DELTEX family member, DTX3L, analysed both as an isolated catalytic fragment and the full-length PARP9:DTX3L complex, suggesting that it is a general feature of the DELTEX family. Since structural predictions show that DTX3L possesses single-stranded nucleic acids binding ability and given the fact that nucleic acids have recently emerged as substrates for ADP-ribosylation, we asked whether DELTEX E3s might catalyse ubiquitylation of an ADPr moiety linked to nucleic acids. Indeed, we show that DTX3L and DTX2 are capable of ubiquitylating ADP-ribosylated DNA and RNA synthesized by PARPs, including PARP14. Furthermore, we demonstrate that the Ub-ADPr-nucleic acids conjugate can be reversed by two groups of hydrolases, which remove either the whole adduct (e.g. SARS-CoV-2 Mac1 or PARP14 macrodomain 1) or just the Ub (e.g. SARS-CoV-2 PLpro). Overall, this study reveals ADPr ubiquitylation as a general function of the DELTEX family E3s and presents the evidence of reversible ubiquitylation of ADP-ribosylated nucleic acids., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Understanding the pharmacokinetics of prodrugs in vivo necessitates quantitative, noninvasive, and real-time monitoring of drug release, despite its difficulty. Ratiometric photoacoustic (PA) imaging, a promising deep tissue imaging technology with a unique capacity for self-calibration, can aid in solving this problem. Here, for the first time, a methylamino-substituted Aza-BODIPY (BDP-N) and the chemotherapeutic drug camptothecin (CPT) are joined via a disulfide chain to produce the molecular theranostic prodrug (BSC) for real-time tumor mapping and quantitative visualization of intratumoral drug release using ratiometric PA imaging. Intact BSC has an extremely low toxicity, with a maximum absorption at ∼720 nm; however, endogenous glutathione (GSH), which is overexpressed in tumors, will cleave the disulfide bond and liberate CPT (with full toxicity) and BDP-N. This is accompanied by a significant redshift in absorption at ∼800 nm, resulting in the PA 800 /PA 720 ratio. In vitro , a linear relationship is successfully established between PA 800 /PA 720 values and CPT release rates, and subsequent experiments demonstrate that this relationship can also be applied to the quantitative detection of intratumoral CPT release in vivo . Notably, the novel ratiometric strategy eliminates nonresponsive interference and amplifies the multiples of the signal response to significantly improve the imaging contrast and detection precision. Therefore, this research offers a viable alternative for the design of molecular theranostic agents for the clinical diagnosis and treatment of tumors.

Optical imaging and photoacoustic (PA) imaging have become essential tools to investigate physiological or pathological processes at the molecular level in vivo . The detection of variations at the molecular level in vivo is particularly important owing to the rapid progression of diseases. However, most studies have mainly focused on plain qualitative molecular imaging and detection, which is characterized by the absence of a reference signal in one-channel responsive imaging. To overcome the limitation and quantitatively detect molecules in situ , this Account reviews the recent contributions of our group to the quantitative imaging field in the form of ratiometric optical and PA imaging in vivo in the second near-infrared window (NIR-II, 950-1700 nm).In this Account, we present recent advances that our group has made in ratiometric imaging probe design and biomedical applications by constructing probes based on ratiometric optical imaging and ratiometric PA imaging. First, we highlight the design strategies of ratiometric optical probes that were based on organic ratiometric molecular probes, radio-activated organic ratiometric probes, and hybrid organic-inorganic assembled ratiometric probes. Subsequently, the design strategies of the ratiometric NIR-II optical nanoprobes with activated bioluminescence resonance energy transfer (BRET), Förster resonance energy transfer (FRET), and nonradiative energy transfer (NRET) effects provide a reliable tool to achieve the ratiometric detection of endogenous signaling molecules and thereby apply it to the monitoring and evaluation of the efficacy of photodynamic therapy, radiotherapy, and immunotherapy to guide the treatment process. In addition, we systematically introduce the functional design principles of ratiometric PA imaging probes based on core-shell nanoprobes, core-satellite nanoprobes, and universal hybrid nanoprobes, where we have established that reference signal and sensing signal can be obtained from the random assortment of plasmonic components and organic semiconducting molecules using a phase separation strategy. On these insights, we discuss the rational and detailed biomedical applications of ratiometric PA imaging probes which include accurate quantitative detection of disease-related molecules in inflammation or tumors in real time. In these champion implementations of ratiometric PA imaging probes, different diagnostic modules have been linked through compound modification with activation characteristics (e.g., pH, redox, enzyme, hypoxia). Finally, we present the challenges and perspectives for ratiometric probes based on optical imaging and PA imaging for multitarget design and future clinical translation. We believe that the upcoming generations of ratiometric imaging probes would have promising potential applications in the precise diagnosis of diseases. Finally, this Account may stimulate innovative studies in the design of ratiometric imaging probes and exploration of their clinical applications.

Background: Transjugular intrahepatic portosystemic shunt (TIPS) has been extensively used to treat portal hypertension-associated complications, including cirrhosis. The prediction of post-TIPS prognosis is important for cirrhotic patients, as more aggressive liver transplantation is needed when the post-TIPS prognosis is poor., Aim: To construct a nutrition-based model that could predict the disease progression of cirrhotic patients after TIPS implantation in a sex-dependent manner., Methods: This study retrospectively recruited cirrhotic patients undergoing TIPS implantation for analysis. Muscle quality was assessed by measuring the skeletal muscle index (SMI) by computed tomography. Multivariate Cox proportional hazard models were utilized to determine the association between SMI and disease progression in cirrhotic patients after TIPS implantation., Results: This study eventually included 186 cirrhotic patients receiving TIPS who were followed up for 30.5 ± 18.8 mo. For male patients, the 30-mo survival rate was significantly lower and the probability of progressive events was higher (3.257-fold) in the low-level SMI group than in the high-level SMI group. According to the multivariate Cox analysis of male patients, SMI < 32.8 was an independent risk factor for long-term adverse outcomes after TIPS implantation. A model was constructed, which involved creatinine, plasma ammonia, SMI, and acute-on-chronic liver failure and hepatic encephalopathy occurring within half a year after surgery. This model had an area under the receiver operating characteristic curve of 0.852, sensitivity of 0.926, and specificity of 0.652. According to the results of the DeLong test, this model outperformed other models (Child-Turcotte-Pugh, Model for End-Stage Liver Disease, and Freiburg index of post-TIPS survival) ( P < 0.05)., Conclusion: SMI is strongly associated with poor long-term outcomes in male patients with cirrhosis who underwent TIPS implantation., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest to report., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Our previous study showed that miR-146a-3p was elevated in serum exosomes of allergic rhinitis (AR) patients, but the underlying mechanisms were unclarified. This study was to investigate the impact of exosome-derived miR-146a-3p on macrophage polarization in the pathology of AR., Method: We detected the expression of miR-146a-3p in nasal tissues of AR patients and healthy controls (HCs), and investigated its correlation with macrophage polarization markers. The impact of miR-146a-3p derived from AR serum exosomes on macrophage polarization was examined. Transcriptome sequencing was performed on macrophages treated with a miR-146a-3p inhibitor, and target genes of miR-146a-3p were explored through a combination of bioinformatics analysis and experimental validation., Results: The expressions of miR-146a-3p and macrophage polarization markers were increased in the AR nasal tissues, and a positive association was observed between the expressions of miR-146a-3p and the levels of CD163 and CD206. The AR serum exosomes could be uptake by macrophages, and promote M2 polarization and cytokine secretions. Mechanistically, miR-146a-3p regulation could impact both macrophage M2 polarization and cytokine secretion. Inhibition of miR-146a-3p altered the gene transcriptions within macrophages. Bioinformatics analysis and clinical pathological specimen research confirmed that VAV3 was a target gene of miR-146a-3p, and it exerted a detrimental effect on macrophage M2 polarization via the PI3K/AKT/mTOR pathway. Functional recovery experiments and dual-luciferase reporter gene assays confirmed that miR-146a-3p could selectively target and inhibit the expression of VAV3, thereby promoting macrophage M2 polarization through the PI3K/AKT/mTOR pathway., Conclusion: Serum exosome-derived miR-146a-3p facilitated macrophage M2 polarization in AR by targeting VAV3 through the PI3K/AKT/mTOR pathway. These findings implied that miR-146a-3p and VAV3 could serve as potential targets for the development of novel therapeutic strategies in AR management., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

In situ thermal desorption (ISTD) provides an efficient solution to remediation of soil and groundwater contaminated with nonaqueous phase liquids (NAPLs). Establishing a relationship between the subsurface temperature rise and NAPL removal is significant to reduce energy consumption of ISTD. However, the co-boiling phenomenon between NAPL and water poses a great challenge in developing this relationship due to the nonequilibrium heat and mass transport effects. We performed a systematic experimental investigation into the local temperature rise patterns at different distances from a NAPL pool and under different degrees of superheat by selecting four representative NAPLs (i.e., trichloroethylene, tetrachlorethylene, n -hexane, and n -octane) according to their density and boiling point relative to water. The patterns of temperature rise indicated that the underground temperature field can be divided into three zones: the zone of local thermal equilibrium, the nonequilibrium zone affected by co-boiling, and the zone unaffected by co-boiling. We developed a pattern-recognition-based approach, which considers the effects of local heat and mass transport to establish a qualitative correlation between the temperature rise and NAPL removal. Our results give deeper insights into the understanding of subsurface temperatures in ISTD practice, which can serve as the guideline for more accurate and sustainable remediation.

To evaluate the association of intracranial non-stenotic atherosclerotic plaque with cerebral small vessel disease (CSVD) imaging markers in a CSVD population using 3.0 T high-resolution magnetic resonance imaging (HRMRI), which was validated in embolic stroke of undetermined source (ESUS) cohort. We retrospectively recruited consecutive patients who were diagnosed with CSVD or ESUS from January 2015 to December 2019. All patients underwent intracranial HRMRI to assess intracranial non-stenotic atherosclerotic plaques. Baseline and imaging data were collected and were measured among all patients. Among 153 patients with CSVD, there were 59 with intracranial atherosclerotic plaque (IAP) and 94 with non-IAP, including 36 with intracranial atherosclerotic complicated plaque (IACP). Among 227 ESUS patients, there were 155 with IAP and 72 with non-IAP, including 127 with IACP. In the CSVD population, we found that: (1) CSVD burden was associated with IAP (p = 0.036) and IACP (p = 0.008); (2) IAP was associated with white matter hyperintensity (51% vs. 34%; P = 0.039), and IACP was associated with lacunes (69% vs. 35%; P = 0.009) and enlarge perivascular space (69% vs. 39%; P = 0.022). A similar association of CSVD imaging markers with IAP or IACP was found in the ESUS population. Furthermore, the association of unilateral IAP or IACP with CSVD imaging markers of ipsilateral hemisphere was identified in the two cohorts. This is the first report that intracranial non-stenotic atherosclerotic plaque, especially complicated plaque, is closely associated with CSVD imaging markers, which provide further evidence for the association of large artery atherosclerosis with CSVD., (© 2023. Springer Nature Limited.)

PARP14 is a mono-ADP-ribosyl transferase involved in the control of immunity, transcription, and DNA replication stress management. However, little is known about the ADP-ribosylation activity of PARP14, including its substrate specificity or how PARP14-dependent ADP-ribosylation is reversed. We show that PARP14 is a dual-function enzyme with both ADP-ribosyl transferase and hydrolase activity acting on both protein and nucleic acid substrates. In particular, we show that the PARP14 macrodomain 1 is an active ADP-ribosyl hydrolase. We also demonstrate hydrolytic activity for the first macrodomain of PARP9. We reveal that expression of a PARP14 mutant with the inactivated macrodomain 1 results in a marked increase in mono(ADP-ribosyl)ation of proteins in human cells, including PARP14 itself and antiviral PARP13, and displays specific cellular phenotypes. Moreover, we demonstrate that the closely related hydrolytically active macrodomain of SARS2 Nsp3, Mac1, efficiently reverses PARP14 ADP-ribosylation in vitro and in cells, supporting the evolution of viral macrodomains to counteract PARP14-mediated antiviral response.

AlphaFold2 and related computational tools have greatly aided studies of structural biology through their ability to accurately predict protein structures. In the present work, we explored AF2 structural models of the 17 canonical members of the human PARP protein family and supplemented this analysis with new experiments and an overview of recent published data. PARP proteins are typically involved in the modification of proteins and nucleic acids through mono or poly(ADP-ribosyl)ation, but this function can be modulated by the presence of various auxiliary protein domains. Our analysis provides a comprehensive view of the structured domains and long intrinsically disordered regions within human PARPs, offering a revised basis for understanding the function of these proteins. Among other functional insights, the study provides a model of PARP1 domain dynamics in the DNA-free and DNA-bound states and enhances the connection between ADP-ribosylation and RNA biology and between ADP-ribosylation and ubiquitin-like modifications by predicting putative RNA-binding domains and E2-related RWD domains in certain PARPs. In line with the bioinformatic analysis, we demonstrate for the first time PARP14's RNA-binding capability and RNA ADP-ribosylation activity in vitro. While our insights align with existing experimental data and are probably accurate, they need further validation through experiments., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Lipid homeostasis is essential for normal cellular functions and dysregulation of lipid metabolism is highly correlated with human diseases including neurodegenerative diseases. In the ubiquitin-dependent autophagic degradation pathway, Troyer syndrome-related protein Spartin activates and recruits HECT-type E3 Itch to lipid droplets (LDs) to regulate their turnover. In this study, we find that Spartin promotes the formation of Itch condensates independent of LDs. Spartin activates Itch through its multiple PPAY-motif platform generated by self-oligomerization, which targets the WW12 domains of Itch and releases the autoinhibition of the ligase. Spartin-induced activation and subsequent autoubiquitination of Itch lead to liquid-liquid phase separation (LLPS) of the poly-, but not oligo-, ubiquitinated Itch together with Spartin and E2 both in vitro and in living cells. LLPS-mediated condensation of the reaction components further accelerates the generation of polyubiquitin chains, thus forming a positive feedback loop. Such Itch-Spartin condensates actively promote the autophagy-dependent turnover of LDs. Moreover, we show that the catalytic HECT domain of Itch is sufficient to interact and phase separate with poly-, but not oligo-ubiquitin chains. HECT domains from other HECT E3 ligases also exhibit LLPS-mediated the promotion of ligase activity. Therefore, LLPS and ubiquitination are mutually interdependent and LLPS promotes the ligase activity of the HECT family E3 ligases.

Radiotherapy (RT) is an effective and widely applied cancer treatment strategy in clinic. However, it usually suffers from radioresistance of tumor cells and severs side effects of excessive radiation dose. Therefore, it is highly significant to improve radiotherapeutic performance and monitor real-time tumor response, achieving precise and safe RT. Herein, an X-ray responsive radio-pharmaceutical molecule containing chemical radiosensitizers of diselenide and nitroimidazole (BBT-IR/Se-MN) is reported. BBT-IR/Se-MN exhibits enhanced radiotherapeutic effect via a multifaceted mechanisms and self-monitoring ROS levels in tumors during RT. Under X-ray irradiation, the diselenide produces high levels of ROS, leading to enhanced DNA damage of cancer cell. Afterwards, the nitroimidazole in the molecule inhibits the damaged DNA repair, offering a synergetic radiosensitization effect of cancer. Moreover, the probe shows low and high NIR-II fluorescence ratios in the absence and presence of ROS, which is suitable for precise and quantitative monitoring of ROS during sensitized RT. The integrated system is successfully applied for radiosensitization and the early prediction of in vitro and in vivo RT efficacy., (© 2023 Wiley-VCH GmbH.)

To investigate the effects of biogas slurry return-to-field methods, the duration of biogas slurry return to field and the amount of heavy metals brought in from biogas slurry on the accumulation of heavy metals in soil-crop systems, and the importance of factors influencing heavy metal accumulation, 41 papers and 1972 pairs of data were integrated and analyzed. The results showed that the application of biogas slurry alone significantly increased the accumulation of As, Cd, Cr, Cu, and Zn in soil and As and Cr in crops by 20.5%, 15.2%, 25.6%, 18.7%, and 26.3% and 14.6% and 39.5%, respectively, and it had no significant effect on the accumulation of other heavy metals in crops. The combined application of biogas slurry and chemical fertilizers significantly increased the accumulation of soil Cr and Zn by 8.05% and 4.70% and decreased the accumulation of As by crops. Correlation analysis showed that the accumulation rates of soil As, Cd, and Cr were highly significantly and positively correlated ( P <0.01) with the duration of biogas slurry return to field and soil organic matter (SOM) content, with correlation coefficients of 0.30, 0.15, and 0.13 and 0.22, 0.27, and 0.22, respectively; they were highly significantly and negatively correlated ( P <0.01) with soil pH, with correlation coefficients of 0.16, 0.13, and 0.11, respectively. The heavy metals brought in by biogas slurry return to field promoted the accumulation of As, Cd, and Cr in soil and As, Cd, Cr, and Zn in crops, whereas the accumulation of Cd, Cu, and Zn in soil promoted the accumulation of Cd, Cu, and Zn in crops, with correlation coefficients of 0.45, 0.58, and 0.42, respectively. The main factors of heavy metal accumulation in the soil-crop systems were the duration of biogas slurry return to field, SOM, and soil pH.

The present work explored alkali-treated coconut petiole fibers (ACPFs) characterization and the effect of fiber loadings on the mechanical properties of poly (lactic acid) (PLA)/ACPF composites for the first time. The physical, mechanical, and interfacial properties, as well as the morphology of the ACPFs were reported. It was found that ACPFs with a density of 0.92 g/cm 3 have average tensile strength and tensile modulus equal to 355.77 MPa and 5212.36 MPa. The interfacial strength between ACPFs and PLA was high (14.06 MPa), attributed to the micro-sized holes on the fibers, as established from SEM micrographs. Then composites with varying fiber loadings were fabricated by melt-blending and compression molding. The mechanical (tensile, flexural, and impact) performance of composites was reported. Based on the high interfacial strength between fibers and PLA and the unique "spiral" structure of fibers, the composites reached a high impact strength of 8.2 kJ/m 2 and flexural modulus of 6959.70 MPa at 50 wt.%, representing 150% and 50% improvement relative to pure PLA.

Structurally complex genomic regions, such as centromeres, are inherently difficult to duplicate. The mechanism behind centromere inheritance is not well understood, and one of the key questions relates to the reassembly of centromeric chromatin following DNA replication. Here, we define ERCC6L2 as a key regulator of this process. ERCC6L2 accumulates at centromeres and promotes deposition of core centromeric factors. Interestingly, ERCC6L2 -/- cells show unrestrained replication of centromeric DNA, likely caused by the erosion of centromeric chromatin. Beyond centromeres, ERCC6L2 facilitates replication at genomic repeats and non-canonical DNA structures. Notably, ERCC6L2 interacts with the DNA-clamp PCNA through an atypical peptide, presented here in a co-crystal structure. Finally, ERCC6L2 also restricts DNA end resection, acting independently of the 53BP1-REV7-Shieldin complex. We propose a mechanistic model, which reconciles seemingly distinct functions of ERCC6L2 in DNA repair and DNA replication. These findings provide a molecular context for studies linking ERCC6L2 to human disease., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

In patients with stage IA non-small cell lung cancer (NSCLC), uniportal video-assisted thoracic surgery (U-VATS) anatomical segmentectomy removes the lung tumor while preserving lung function as much as possible, and it is therefore an alternative to lobectomy. Patients with stage IA NSCLC receiving U-VATS segmental resection at our institution from September 2017 to June 2019 were compared with patients receiving U-VATS lobectomy. A total of 47 patients received segmentectomy and 209 patients received U-VATS lobectomy in the same period. Propensity score matching was conducted to diminish bias. The final study cohort included 42 patients who received segmentectomy and 42 propensity score matching-matched patients who received lobectomy. Perioperative parameters and postoperative complications, length of hospital stay, postoperative forced expiratory volume in 1 s (FEV1), and forced vital capacity (FVC) were compared between the 2 groups. Surgery was successfully completed in all patients. The mean follow-up was for 8.2 months. The postoperative complication rate was comparable between the 2 groups: 31.0% in segmentectomy patients versus 35.7% in lobectomy patients (P = .643). At 1 month after surgery, FEV1% and FVC% were not significantly different between the 2 groups (P > .05). At 3 months after surgery, FEV1 and FVC were higher in segmentectomy patients than in lobectomy patients (FEV1, 82.79% ± 6.36% vs 78.55% ± 5.42%; FVC, 81.66% ± 6.09% vs 78.90% ± 5.58%, P < .05). Patients receiving segmentectomy suffer less pain and have better postoperative lung function and higher quality of life., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Lactoferrin (Lf) is a bioactive multifunctional glycoprotein that belongs to the transferrin family. As an important nutritional fortifier, Lf is one of the star nutrients in milk powder. Thus, the rapid and accurate quantitative detection of Lf content in milk powder is crucial to the evaluation of its quality. However, most reported immunoassay methods for Lf quantitation suffer from cumbersome sample pretreatment or lengthy testing time and do not meet the requirements for rapid Lf detection in milk powder. Herein, we report a novel method combining dynamic light scattering (DLS) immunosensing and boronate affinity recognition for the rapid and sensitive detection of Lf. Owing to the selective binding between a boronate ligand and the cis diol, the developed DLS immunosensor quantitatively detected Lf with saving one antibody, greatly reducing the need for matching antibodies, which are needed in traditional sandwich immunoassay for biomolecular detection. In addition, the DLS immunosensor exhibited high selectivity and sensitivity to Lf, with a detection limit of 1 ng/mL within ∼15 min through coupling with magnetic nanoparticle-assisted immunomagnetic separation and DLS signal transduction., 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 © 2022 Elsevier Ltd. All rights reserved.)

Plasmonic nanoparticles and their assemblies have been widely used in biosensing, optical imaging, and biomedicine over the past few decades. Especially in the field of radiotherapy, the physicochemical properties of high-Z plasmonic nanomaterials endow them with the ability to sensitize radiotherapy. Compared with single particles, the assembled structure with tunable properties leads to versatile applications in drug delivery and cancer treatment. In this review, we focus on plasmonic nanoparticles and their assemblies for cancer radiotherapy. First, the sensitization mechanism of plasmonic radiosensitizers is briefly introduced. Subsequently, the recent progress in cancer radiotherapy is systematically discussed according to the structure and shape classification. Finally, the current challenges and future perspectives in this field are also discussed in detail., 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 © 2023 Elsevier B.V. All rights reserved.)

Background: Targeted therapy combined with immune checkpoint inhibitors is considered a promising treatment for primary advanced hepatocellular carcinoma (HCC). Nevertheless, the difference between synchronous and asynchronous treatment of lenvatinib with programmed death receptor-1 (PD-1) inhibitor in advanced HCC is still unclear. The aim of this investigation is to evaluate the effectiveness of synchronous and asynchronous of lenvatinib and PD-1 inhibitor on the advanced HCC beyond oligometastasis., Methods: In this study, 213 patients from four institutions in China were involved. Patients were split into two collections: (1) lenvatinib plus PD-1 inhibitor were used synchronously (synchronous treatment group); (2) patients in asynchronous treatment group received PD-1 inhibitor after 3 months of lenvatinib treatment prior to tumour progression. To analyse progression-free survival (PFS), overall survival (OS), efficacy and safety of patients in both groups, we employed propensity score matching (PSM)., Results: The 6-, 12- and 24-month OS rates were 100%, 93.4% and 58.1% in the synchronous treatment group and 100%, 71.5% and 25.3% in the asynchronous treatment group, respectively. In contrast to the asynchronous treatment group, the group treated synchronously exhibited a substantially enhanced OS (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.30-0.66; p < .001). The 6-, 12- and 18-month PFS rates were 82.6%, 42.6% and 10.8% in the synchronous treatment group and 63.3%, 14.2% and 0% in the asynchronous treatment group, respectively. A significant difference was observed in the PFS rate (HR, 0.46; 95% CI, 0.33-0.63; p < .001) between the two collections., Conclusions: Patients with advanced HCC beyond oligometastasis, simultaneous administration of lenvatinib and PD-1 inhibitor led to significant improvements in survival., (© 2023 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Background: Sublingual immunotherapy (SLIT) is an effective treatment for allergic rhinitis (AR), but its efficacy is variable among individuals. This study aimed to characterize serum exosome-derived microRNAs (miRNAs) and evaluate their abilities in predicting the efficacy of SLIT in AR., Methods: RNA sequencing was performed to explore differentially expressed exosomal miRNAs in serum exosomes between AR patients and healthy controls (HCs). Sequencing analysis results were verified in an independent cohort, and the correlations between the levels of exosome-derived miRNAs and disease severity were evaluated. The most promising miRNAs were further tested in two AR cohorts treated with SLIT to assess their abilities in predicting short and long-term efficacy, respectively., Results: The exosome-derived miRNAs profiling in the AR group was significantly different from the HC group, and differentially expressed genes were enriched and clustered in pathways such as PI3K-Akt and ErbB signalling pathways. The top three most significant miRNAs were verified by reverse transcription-polymerase chain reaction (qRT-PCR), and results showed that miR-146a-3p levels were significantly elevated in the AR group and correlated with the total and specific gE levels, the visual analogue scale of the total nasal symptom score (all p < 0.05). Further data in the first validation cohort suggested that miR-146a-3p levels were significantly downregulated in the effective group, and logistic regression showed that miR-146a-3p levels were associated with the short-term efficacy of SLIT(p < 0.05). The receiver operating characteristic (ROC) curve showed that miR-146a-3p could early predict SLIT efficacy (AUC = 0.669, p = 0.047). In the second validation cohort, miR-146a-3p levels were also decreased in the effective group and the ROC curve further confirmed its reliable accuracy in predicting the long-term efficacy of SLIT in AR patients (AUC = 0.749, p < 0.001)., Conclusion: Serum exosome-derived miRNAs may be involved in the development of AR and associated with its disease severity. Serum exosome-derived miR-146a-3p seems to be a novel biomarker for predicting the short and long-term efficacies of SLIT in AR patients., 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 © 2023. Published by Elsevier B.V.)

Neijiang (NJ) and Yacha (YC) are two indigenous pig breeds in the Sichuan basin of China, displaying higher resistance to diseases, lower lean ratio, and slower growth rate than the commercial Western pig breed Yorkshire (YS). The molecular mechanisms underlying the differences in growth and development between these pig breeds are still unknown. In the present study, five pigs from NJ, YC, and YS breeds were subjected to the whole genome resequencing, and then the differential single-nucleotide polymorphisms (SNPs) were screened using a 10-kb window sliding in 1-kb step using the F st method. Finally, 48,924, 48,543, and 46,228 nonsynonymous single-nucleotide polymorphism loci (nsSNPs) were identified between NJ and YS, NJ and YC, and YC and YS, which highly or moderately affected 2,490, 800, and 444 genes, respectively. Moreover, three nsSNPs were detected in the genes of acetyl-CoA acetyltransferase 1 ( ACAT1 ) insulin-like growth factor 2 receptor ( IGF2R ), insulin-like growth factor 2 and mRNA-binding protein 3 ( IGF2BP3 ), which potentially affected the transformation of acetyl-CoA to acetoacetyl-CoA and the normal functions of the insulin signaling pathways. Moreover, serous determinations revealed significantly lower acetyl-CoA content in YC than in YS, supporting that ACAT1 might be a reason explaining the differences in growth and development between YC and YS breeds. Contents of phosphatidylcholine (PC) and phosphatidic acid (PA) significantly differed between the pig breeds, suggesting that glycerophospholipid metabolism might be another reason for the differences between Chinese and Western pig breeds. Overall, these results might contribute basic information to understand the genetic differences determining the phenotypical traits in pigs.

Background: Sudden chemosensory changes were considered an early predictor of COVID-19. Here, the effects of comorbidities on changes in taste and smell in COVID-19 patients were investigated based on a worldwide study., Methods: Data analyzed here were collected from the Global Consortium for Chemosensory Research (GCCR) core questionnaire, including questions regarding preexisting disease conditions. Overall, the final sample of 12,438 participants who were diagnosed with COVID-19 included patients with preexisting conditions. Mixed linear regression models were used to test our hypothesis, and the p -value of interaction was examined., Results: A total of 61,067 participants completed the GCCR questionnaire, including 16,016 participants had preexisting diseases. The multivariate regression analysis showed that individuals with high blood pressure, lung disease, or sinus problems, or neurological diseases exhibited worse self-reported smell loss ( p  < .05), but no apparent significant differences in the smell or taste recovery. COVID-19 patients with seasonal allergy/hay fever lost their olfactory ability more than patients who did not have it (with 11.90 [9.67, 14.13] vs. without 6.97 [6.04, 7.91], p  < .0001). The taste ability, smell loss and taste loss after COVID-19 recovery also decreased in the COVID-19 patients with seasonal allergy/hay fever ( p  < .001). Preexisting condition of diabetes did not worsen to chemosensory disorder but also had no obvious impact on the chemosensory recovery after acute infection. Preexisting diseases also affected the type of smell change in the COVID-19 patients with seasonal allergy/hay fever or sinus problems ( p  < .05)., Conclusions: COVID-19 patients with high blood pressure, lung disease, or sinus problems, or neurological diseases exhibited worse self-reported smell loss, but no differences in the smell or taste recovery. COVID-19 patients with seasonal allergy/hay fever had greater loss of smell and taste, poorer smell and taste recovery., Level of Evidence: 4., Competing Interests: The authors declare no competing financial interests concerning the work described., (© 2023 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

The SLC26A4 gene encodes the transmembrane protein pendrin, which is involved in the ion transport of chloride (Cl - ), iodide (I - ) or bicarbonate (HCO3 - ). Mutations in the SLC26A4 gene alter the structure and (or) function of pendrin, which are closely related to Pendred syndrome. What's more, researchers have demonstrated in vitro that mutations of SLC26A4 cause acidification of airway surface fluid (ASL), reduce airway defense, and increase the thickness of ASL. In the context of infection, it may lead to chronic inflammation, destruction of airway wall architecture and bronchiectasis. However, there is no case report of bronchiectasis caused by SLC26A4 gene mutations. Here, we describe the first case of Pendred syndrome and non-cystic fibrosis bronchiectasis in a child possibly caused by SLC26A4 mutations. We remind clinicians to pay attention to the possibility of bronchiectasis in patients with SLC26A4 gene mutations., 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., (© 2023 Zhu and Jin.)

KDM5C is a histone H3K4-specific demethylase, which has been shown to play a key role in biological disease and development. However, the role of KDM5C in trophoblasts at early pregnancy is currently unknown. Here, we showed that KDM5C was upregulated in placental trophoblasts from recurrent miscarriage (RM) patients compared with healthy controls (HCs). Trophoblast proliferation and invasion was inhibited by KDM5C overexpression and was promoted by KDM5C knockdown. Transcriptome sequencing revealed that elevated KDM5C exerted anti-proliferation and anti-invasion effects by repressing the expression of essential regulatory genes. The combination analysis of RNA-seq, ChIP-seq and CUT&Tag assay showed that KDM5C overexpression leads to the reduction of H3K4me3 on the promoters and the corresponding downregulation of expression of several regulatory genes in trophoblasts. Among these genes, TGFβ2 and RAGE are essential for the proliferation and invasion of trophoblasts. Importantly, overexpression of KDM5C by a systemically delivered KDM5C adenovirus vector (Ad-KDM5C) promoted embryo resorption rate in mouse. Our results support that KDM5C is an important regulator of the trophoblast function during early pregnancy, and suggesting that KDM5C activity could be responsible for epigenetic alterations seen RM disease., (© 2022. The Author(s).)

Attempted preparation of a low-valent Ca(I) complex by reduction of Ca iodide precursor [LCaI(THF)] 2 ( 1 ) (L = [CH 3 C(NAr)CHC(CH 3 )NCH 2 CH 2 N(CH 3 ) 2 ] - , Ar = 2,6- i Pr 2 C 6 H 3 ), with KC 8 led to isolation of a dinuclear calcium azaallyl complex {[H 2 CC(NAr)CHC(CH 3 )(NCH 2 CH 2 N(CH 3 ) 2 )]Ca(THF)} 2 ( 2 ). Alternatively, reaction of 1 with KC 8 in the presence of azobenzene gives an azobenzenyl calcium complex LCa(PhNNPh)(THF) ( 3 ). The electron paramagnetic resonance and UV-vis spectra of complex 3 suggest that the (PhNNPh) moiety should be regarded as a radical anion. Complex 3 can react with Me 3 SiN 3 , Me 3 SiCHN 2 , CS 2 , W(CO) 6 , elemental sulfur, and AgBr, resulting in the formation of the azido complex [LCaN 3 (THF)] 2 ( 5 ), isonitril complex {LCa[CNN(Si(CH 3 ) 3 )]} 2 ( 6 ), dimeric bis(thiolate) complex {[S 2 CC(CMe(NAr))C(Me)NCH 2 CH 2 NMe 2 ]Ca(DME)} 2 ( 7 ), metallocyclic carbene complex {[OC(W(CO) 5 )N(C 6 H 5 )]Ca(THF) 3 } 2 ( 8 ), bis(thiolate) complex {[S 2 C(CMe(NAr))C(Me)NCH 2 CH 2 NMe 2 ]Ca(THF)} 2 ( 9 ), and bromide complex [LCaBr(THF)] 2 ( 10 ). Additional insights on the reaction process resulting in the formation of complex 7 are provided by density-functional theory studies. These results demonstrate that the (PhNNPh) •- radical anion can serve as a very potent one-electron donor, and 3 acts as a low-valent calcium(I) synthon.

Aim: To explore the role of smell and taste changes in preventing and controlling the COVID-19 pandemic, we aimed to build a forecast model for trends in COVID-19 prediction based on Google Trends data for smell and taste loss., Methods: Data on confirmed COVID-19 cases from 6 January 2020 to 26 December 2021 were collected from the World Health Organization (WHO) website. The keywords "loss of smell" and "loss of taste" were used to search the Google Trends platform. We constructed a transfer function model for multivariate time-series analysis and to forecast confirmed cases., Results: From 6 January 2020 to 28 November 2021, a total of 99 weeks of data were analyzed. When the delay period was set from 1 to 3 weeks, the input sequence (Google Trends of loss of smell and taste data) and response sequence (number of new confirmed COVID-19 cases per week) were significantly correlated ( P < 0.01). The transfer function model showed that worldwide and in India, the absolute error of the model in predicting the number of newly diagnosed COVID-19 cases in the following 3 weeks ranged from 0.08 to 3.10 (maximum value 100; the same below). In the United States, the absolute error of forecasts for the following 3 weeks ranged from 9.19 to 16.99, and the forecast effect was relatively accurate. For global data, the results showed that when the last point of the response sequence was at the midpoint of the uptrend or downtrend (25 July 2021; 21 November 2021; 23 May 2021; and 12 September 2021), the absolute error of the model forecast value for the following 4 weeks ranged from 0.15 to 5.77. When the last point of the response sequence was at the extreme point (2 May 2021; 29 August 2021; 20 June 2021; and 17 October 2021), the model could accurately forecast the trend in the number of confirmed cases after the extreme points. Our developed model could successfully predict the development trends of COVID-19., Conclusion: Google Trends for loss of smell and taste could be used to accurately forecast the development trend of COVID-19 cases 1-3 weeks in advance., 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 © 2022 Chen, Mi, Fu, Zheng, Zhao, Yuan, Guo, Zhu, Zhang, Lyu, Zhang, She and Ren.)