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Background: The optimal management remains unknown after nucleos(t)ide analogue (NA) discontinuation in patients with chronic hepatitis B (CHB). This prospective study investigated the role of off-treatment viral kinetics in predicting relapse after discontinuation of NA therapy.Methods: A total of 82 noncirrhotic Asian patients with CHB who discontinued NA therapy according to international guidelines were prospectively followed. Patients with a hepatitis B virus (HBV) DNA level of >2000 IU/mL and an alanine aminotransferase (ALT) level of >2 times the upper limit of normal (clinical relapse) were retreated.Results: Sixty patients were HBV envelope antigen (HBeAg) positive at the start of treatment, and 22 were HBeAg negative. Clinical relapse developed in 28 patients (2-year rates, 31% among HBeAg-positive patients and 53% among HBeAg-negative patients). Age of ≤35 years (hazard ratio [HR], 0.37; P = .026) and end-of-treatment HBsAg level of ≤200 IU/mL (HR, 0.39; P = .078) were independently associated with lower relapse rates. A high risk of biochemical relapse (defined as an ALT level of >2 times the upper limit of normal) was observed if the HBV DNA level was >200000 IU/mL when the level was initially elevated, compared with HBV DNA levels of >2000 to ≤200000 IU/mL (HR, 8.42; P < .001). The risk of biochemical relapse was also high in patients with persistent elevation in the HBV DNA level (confirmed to be >2000 IU/mL within 3 months), compared with the group with transient elevation (HR, 6.87; P < .001).Conclusions: After NA discontinuation, a lower relapse rate was observed in younger patients and in those with low end-of-treatment HBsAg levels. The level and persistence of off-treatment elevated HBV DNA levels were useful in the prediction of a subsequent biochemical relapse and may thus be used to guide off-treatment management. [ABSTRACT FROM AUTHOR]

Direct-conversion receivers (DCRs) have been widely used in recent years due to their small size and low power consumption. However, the mismatch between the in-phase (I) and the quadrature (Q) branches will seriously affect the performance of the DCRs. This paper proposes a novel blind compensation method to suppress the interference introduced by IQ mismatch. Based on the Hilbert transform, our proposed method can obtain the orthogonal signal of the I-channel signal by utilizing the Weaver architecture. Compared with traditional compensation methods, the main difference of the proposed method is that it ignores prior information, training sequences, and additional hardware circuits. Furthermore, the complexity of the proposed blind compensation method is low because no iterative operations are involved in the compensation process. The simulation results show that the proposed method has an excellent compensation performance, especially in wideband applications. [ABSTRACT FROM AUTHOR]

We report the observation of optically pumped continuous wave lasing in a self-rolled-up InGaAs/GaAs quantum dot microtube at room temperature. Single layer of InAs quantum dots (~ 2.6 ML coverage) in a GaAs well sandwiched by two AlGaAs barriers are incorporated into the tube wall as the gain media. As-fabricated microtube is supported by a 300-nm-thick Au pad, aiming to separate the tube from GaAs substrate and thus to decrease the substrate loss, which finally enables lasing with ultralow threshold power (~ 4 µW) from an microtube ring resonator. [ABSTRACT FROM AUTHOR]

This paper presents herein pertains the experimental and numerical investigations on axial compressive behavior of square concrete-filled stainless steel tube (CFSST) columns after high-temperature sliding. A total of 117 CFSST specimens were tested under axial compression loading. The design variables included tube thickness, temperature, duration, and concrete compressive strength. Test results indicated that the initial stiffness of square CFSST short columns was degenerated due to high-temperature sliding. CFSST specimens exhibited a 62.7% lowest residual strength at 1000 °C. The influence of high-temperature duration on the residual strength of square CFSST short columns after high-temperature sliding was limited. The residual strength of specimens was positively correlated with the thickness and concrete strength. All square CFSST columns after high-temperature sliding experienced an outward local buckling under axial compression. Finite element models of square CFSST columns after high-temperature sliding are established and validated against the experimental results. In addition, the parameter formulae of residual strength for CFSST columns after high-temperature sliding were proposed, which achieved high accuracy. This research results could provide strengthening reference for the application of CFSST columns after high-temperature sliding. • Axial compressive behavior of square CFSST columns after high-temperature sliding were investigated in this paper. • The effects of tube thickness, temperature, duration, and concrete compressive strength are analyzed. • Finite element model (FEM) of square CFSST columns after high-temperature sliding were established. • Parameter formula was proposed to estimate residual strength for square CFSST columns after high-temperature sliding. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is the leading cause of cancer death for women worldwide. Most of the breast cancer death are due to disease recurrence and metastasis. Increasingly accumulating evidence indicates that mitochondria play key roles in cancer progression and metastasis. Our recent study revealed that transmembrane protein PRRG4 promotes the metastasis of breast cancer. However, it is not clear whether PRRG4 can affect the migration and invasion of breast cancer cells through regulating mitochondria function. Methods: RNA-seq analyses were performed on breast cancer cells expressing control and PRRG4 shRNAs. Quantitative PCR analysis and measurements of mitochondrial ATP content and oxygen consumption were carried out to explore the roles of PRRG4 in regulating mitochondrial function. Luciferase reporter plasmids containing different lengths of promoter fragments were constructed. Luciferase activities in breast cancer cells transiently transfected with these reporter plasmids were analyzed to examine the effects of PRRG4 overexpression on promoter activity. Transwell assays were performed to determine the effects of PRRG4-regulated pathway on migratory behaviors of breast cancer cells. Results: Analysis of the RNA-seq data revealed that PRRG4 knockdown decreased the transcript levels of all the mitochondrial protein-encoding genes. Subsequently, studies with PRRG4 knockdown and overexpression showed that PRRG4 expression increased mitochondrial DNA (mtDNA) content. Mechanistically, PRRG4 via Src activated STAT3 in breast cancer cells. Activated STAT3 in turn promoted the transcription of mtDNA polymerase POLG through a STAT3 DNA binding site present in the POLG promoter region, and increased mtDNA content as well as mitochondrial ATP production and oxygen consumption. In addition, PRRG4-mediated activation of STAT3 also enhanced filopodia formation, migration, and invasion of breast cancer cells. Moreover, PRRG4 elevated migratory behaviors and mitochondrial function of breast cancer cells through POLG. Conclusion: Our results indicate that PRRG4 via the Src-STAT3-POLG axis enhances mitochondrial function and promotes migratory behaviors of breast cancer cells. [ABSTRACT FROM AUTHOR]

In the past decade, in the context of the carbon peaking and carbon neutrality era, the rapid development of new energy vehicles has led to higher requirements for the performance of strike forces such as battery cycle life, energy density, and cost. Lithium-ion batteries have gradually become mainstream in electric vehicle power batteries due to their excellent energy density, rate performance, and cycle life. At present, the most widely used cathode materials for power batteries are lithium iron phosphate (LFP) and LixNiyMnzCo1−y−zO2 cathodes (NCM). However, these materials exhibit bottlenecks that limit the improvement and promotion of power battery performance. In this review, the performance characteristics, cycle life attenuation mechanism (including structural damage, gas generation, and active lithium loss, etc.), and improvement methods (including surface coating and element-doping modification) of LFP and NCM batteries are reviewed. Finally, the development prospects of this field are proposed. [ABSTRACT FROM AUTHOR]

Au modified TiO2/In2O3 hollow nanospheres were synthesized by the hydrolysis method using the carbon nanospheres as a sacrificial template. Compared to pure In2O3, pure TiO2, and TiO2/In2O3 based sensors, the Au/TiO2/In2O3 nanosphere-based chemiresistive-type sensor exhibited excellent sensing performances to formaldehyde at room temperature under ultraviolet light (UV-LED) activation. The response of the Au/TiO2/In2O3 nanocomposite-based sensor to 1 ppm formaldehyde was about 5.6, which is higher than that of In2O3 (1.6), TiO2 (2.1), and TiO2/In2O3 (3.8). The response time and recovery time of the Au/TiO2/In2O3 nanocomposite sensor were 18 s and 42 s, respectively. The detectable formaldehyde concentration could go down as low as 60 ppb. In situ diffuse reflectance Fourier transform infrared spectroscopy (DRIFTS) was used to analyze the chemical reactions on the surface of the sensor activated by UV light. The improvement in the sensing properties of the Au/TiO2/In2O3 nanocomposites could be attributed to the nanoheterojunctions and electronic/chemical sensitization of the Au nanoparticles. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer is one of the most aggressive malignancies without effective targeted therapies. MUC1 has emerged as a potential common target for cancer therapy because it is overexpressed in a variety of different cancers including the majority of pancreatic cancer. However, there are still no approved monoclonal antibody drugs targeting MUC1 have been reported. Recently, we generated a humanized MUC1 antibody (HzMUC1) specific to the interaction region between MUC1-N and MUC1-C. In this study, we generated the antibody drug conjugate (ADC) by conjugating HzMUC1 with monomethyl auristatin (MMAE), and examined the efficacy of HzMUC1-MMAE against the MUC1-positive pancreatic cancer in vitro and in vivo. Methods: Western blot and immunoprecipitation were used to detect MUC1 in pancreatic cancer cells. MUC1 localization in pancreatic cancer cells was determined by confocal microscopy. HzMUC1 was conjugated with the monomethyl auristatin (MMAE), generating the HzMUC1-MMAE ADC. Colony formation assay and flow cytometry were used to assess the effects of the HzMUC1-MMAE cell viability, cell cycle progression and apoptosis. Capan-2 and CFPAC-1 xenograft model were used to test the efficacy of HzMUC1-MMAE against pancreatic cancer. Results: HzMUC1 antibody binds to MUC1 on the cell surface of pancreatic cancer cells. HzMUC1-MMAE significantly inhibited cell growth by inducing G2/M cell cycle arrest and apoptosis in pancreatic cancer cells. Importantly, HzMUC1-MMAE significantly reduced the growth of pancreatic xenograft tumors by inhibiting cell proliferation and enhancing cell death. Conclusion: Our results indicate that HzMUC1-ADC is a promising novel targeted therapy for pancreatic cancer. HzMUC1-ADC should also be an effective drug for the treatment of different MUC1-positive cancers. [ABSTRACT FROM AUTHOR]

This manuscript proposed a new approach to manufacture SiBOC ceramic samples with complex structures via DLP 3D printing technique from ceramic precursors. High ceramic yield photosensitive SiBOC resin for 3D printing was synthesized based on the condensation reaction of boric acid and siloxanes. The stability of printed block samples significantly improved by increasing the content of diethoxydimethyl silane. And this strategy was applicable to most systems of UV cured ceramic precursors. The DLP-printed SiBOC ceramics maintained high ceramic yield (>76 %) and exhibited perfect 25 % isotropic shrinkage after pyrolysis at 1000 ℃. They experienced only a 0.5 % weight loss in an argon environment at 1450 ℃, and exhibited better mechanical properties at 1000 ℃ compared to room temperature. The results indicated that the DLP-printed SiBOC ceramics had excellent thermal stability and mechanical properties, which could significantly expand the application range of SiBOC ceramics. [ABSTRACT FROM AUTHOR]

Since the emergence of single-cell electroanalysis, the two-electrode system has become the predominant electrochemical system for real-time behavioral analysis of single-cell and multicellular populations. However, due to the transmembrane placement of the two electrodes, cellular activities can be interrupted by the transmembrane potentials, and the test results are susceptible to influences from factors such as intracellular solution, membrane, and bulk solution. These limitations impede the advancement of single-cell analysis. Here, we propose a highly miniaturized and integrated in situ self-referenced intracellular two-electrode system (IS-SRITES), wherein both the working and reference electrodes are positioned inside the cell. Additionally, we demonstrated the stability (0.28 mV/h) of the solid-contact in situ Ag/AgCl reference electrode and the ability of the system to conduct standard electrochemical testing in a wide pH range (pH 6.0–8.0). Cell experiments confirmed the non-destructive performance of the electrode system towards cells and its capacity for real-time monitoring of intra- and extracellular pH values. Moreover, through equivalent circuits, finite element simulations, and drug delivery experiments, we illustrated that the IS-SRITES can yield more accurate test results and exhibit enhanced resistance to interference from the extracellular environment. Our proposed system holds the potential to enable the precise detection of intracellular substances and optimize the existing model of the electrode system for intracellular signal detection, thereby spearheading advancements in single-cell analysis. [ABSTRACT FROM AUTHOR]

• The spray properties of liquid ammonia is studied in a constant pressure vessel at an injection pressure level up to 800 bar. • A slower initial penetratration and shorter quasi-steady liquid length of ammonia is observed compared to diesel. • Parametric trends are similar to diesel when changing ambient density, temperature, injection pressure and nozzle diameter. • 1D spray model results suggest the adequacy of mixing-controlled spray hypotheses for ammonia under non-reacting conditions. Ammonia is seen as a promising fuel to replace fossil fuels internal combustion engines, given the advantages of zero carbon emission and extensive experience in its synthesis at large scale. The ignition of ammonia in direct injection engine is still a challenge due to its unfavorable combustion characteristics, but the investigation of ammonia spray characteristics is an important step to shed light on the optimum combustion strategy. In this paper, the evolution of direct injection ammonia sprays was measured at engine-like conditions generated in a constant pressure facility by means of diffused back-illumination imaging and schlieren. In a first step, ammonia spray behavior is compared against that of Diesel fuel. Experimental results show a slower penetration of ammonia mainly due to a lagging starting penetration phase, which cannot be later recovered. In terms of liquid length, initial stages show the same pattern as for ammonia, while a shorter stabilized liquid length can be observed. Parametric trends over different operating conditions show a similar behavior to Diesel against ambient density and temperature, as well as with injection pressure and nozzle diameter. Such results, backed up by the application of a 1D spray model developed for Diesel-like fuels, suggest that ammonia sprays under non-reacting conditions have a mixing-controlled evolution. [ABSTRACT FROM AUTHOR]

As one of the most popular synthetic fuels (E-fuels), Polyoxymethylene dimethyl ethers(PODE X) have garnered significant attention among researchers in the compression ignition engine field. This work aims to provide an exhaustive analysis of the combustion characteristics of PODE 3 , which typically constitutes the primary component of PODE X. This research seeks to deepen our understanding of the flame structure of PODE 3 , particularly in relation to ambient temperature variation, and unravel the underlying mechanisms driving the observed trends. To achieve this aim, a range of optical techniques was employed within a high-temperature high-pressure combustion vessel to quantify various general combustion parameters and assess OH* chemiluminescence, formaldehyde, and soot distribution. Two additional reference fuels, pure n-dodecane and a blend of 50 % vol n-dodecane and 50 % vol PODE 3 were also tested. Additionally, some analysis from chemical kinetics and 1D spray model calculations were used to substantiate the experimental observations. The findings reveal that the flame structure of PODE 3 differs significantly from traditional diffusion flames associated with diesel-like sprays. The flame lift-off length (LOL) of PODE 3 aligns closely with that of n-dodecane, and maintains the two-lobe structure under high-temperature conditions. In contrast, under low ambient temperatures, the LOL of PODE 3 significantly extends, accompanied by a concentration of OH* radicals at the spray center. The notable sensitivity of PODE 3 flames to temperature variation is related to the chemical kinetics of formaldehyde and CO. As a result of the analysis, conceptual models of PODE 3 flames under varying temperatures were proposed in the end. [ABSTRACT FROM AUTHOR]

[Display omitted] • Celastrol significantly ameliorated renal function and decreased renal pathological injury in db/db mice. • Celastrol treatment alleviated podocyte injury by up-regulating SIRT1 expression and suppressing EZH2 levels. • Celastrol treatment alleviated podocyte injury was related to inhibiting wnt/β-catenin signaling pathway. • This study provides new insights into celastrol use as a potential therapeutic agent against diabetic nephropathy. Proteinuria is an independent risk factor for the progression of diabetic nephropathy (DN) and an imbalance in podocyte function aggravates proteinuria. Celastrol is the primary active ingredient of T. wilfordii, effective in treating DN renal injury; however, the mechanisms underlying its effect are unclear. We explored how celastrol prevents DN podocyte damage using in vivo and in vitro experiments. We randomly divided 24 male C57BLKS/J mice into three groups: db/m (n = 8), db/db (n = 8), and celastrol groups (db/db + celastrol, 1 mg/kg/d, gavage administration, n = 8). In vivo experiments lasted 12 weeks and intervention lasted ten weeks. Serum samples and kidney tissues were collected for biochemical tests, pathological staining, transmission electron microscopy, fluorescence quantitation polymerase chain reaction, and western blotting analysis. In vitro experiments to elaborate the mechanism of celastrol protection were performed on high glucose (HG)-induced podocyte injury. Celastrol reduced blood glucose levels and renal function index in db/db mice, attenuated renal histomorphological injury and glomerular podocyte foot injuries, and induced significant anti-inflammatory effects. Celastrol upregulated silent information regulator 2 related enzyme 1(SIRT1) expression and downregulated enhancer of zeste homolog (EZH2), inhibiting the wnt/β-catenin pathway-related molecules, such as wnt1, wnt7a, and β-catenin. SIRT1 repressed the promoter activity of EZH2, and was co-immunoprecipitated with EZH2 in mouse podocyte cells (MPC5). SIRT1 knockdown aggravated the protective effects of celastrol on MPC5 cells. Celastrol protected podocyte injury via SIRT1/EZH2, which participates in the wnt/β-catenin pathway. Overall, celastrol-mediated SIRT1 upregulation inhibited the EZH2-related wnt/β-catenin signaling pathway to attenuate DN and podocyte injury, providing a theoretical basis for celastrol clinical application. [ABSTRACT FROM AUTHOR]

Simultaneous imaging of OH ∗ chemiluminescence and Mie scattering of fuel spray have been performed under reacting conditions in a constant volume combustion chamber aimed for a second-generation biodiesel/diesel blended fuel. Mie scattering of 532 nm laser light technique was used for the liquid fuel measurement. In order to remove the interference signal from soot radial, filtered Mie scattered light from the fuel droplet was recorded with a charge coupled device (CCD) camera. The spray liquid length and the flame lift-off length for this high cetane-number fuel were investigated under different ambient gas conditions (temperature, density, oxygen concentration) and injection pressure. Experiments showed that the spray liquid length under the reacting condition was shorter than that under non-reacting condition. The flame lift-off length was significantly influenced by the ambient gas temperature, density, oxygen concentration and injection pressure, while the spray liquid length was slightly affected by the injection pressure and oxygen concentration. The overlap between liquid fuel and combustion flame easily happened at high temperature, high oxygen concentration, and low injection pressure conditions. [ABSTRACT FROM AUTHOR]

[Display omitted] • A sustainable solid waste mixture-solidifier was developed. • The mixture-solidifier can improve strength, brittleness, and impermeability. • The mixture-solidifier is beneficial to the transition of copper to stable states. • The leaching toxicity of contaminated soil is analyzed. • The microstructure and mechanism of the solidified soil are investigated. In this paper, two aspects of studies are carried out: (1) synthesis of solid waste-mixture solidifier by using red mud, calcium carbide residue, and phosphogypsum; (2) solidification behaviors of the solid waste-mixture in the presence of Cu2+ ion. The performance of solidified soil was assessed by performing mechanical, permeability, and microstructure tests on samples. The results show that solid waste-mixture can improve the strength, brittleness, and impermeability of the contaminated soil, while the effect of Cu2+ ion is completely opposite. Additionally, the dominant heavy metal form in the solid waste-mixture solidified soil is iron-manganese oxide. The addition of solid waste is more conducive to the transformation of heavy metals to a stable form. The leaching toxicity values of solid waste-mixture solidified soil all meet the relevant standard and the effect is better than that of cement. Besides, the heavy metal can be fastened in the solidified soil through the precipitation, absorption of calcium silicate hydrate (C-S-H), and ion exchange of ettringite (AFt). In sum, it implied that the solid waste mixture had a potential application for the solidification of Cu2+-contaminated soil. [ABSTRACT FROM AUTHOR]

Methanol has been considered as a promising alternative fuel for combustion engines. However, it is quite challenging to use it directly in compressed ignition engines because of its ignition issues, especially for low load conditions. In this research, methanol was blended with hydrogenated catalytic biodiesel (HCB) using n-octanol as co-solvent. A fundamental study on spray and combustion characteristics of two ternary blends (68% HCB+17% octanol+ 15% methanol by volume; 58% HCB+17% octanol+ 25% methanol by volume) and the pure HCB was carried out within a constant volume combustion chamber equipped with a single-hole injector. As in Part Ⅰ, the spray morphology, ignition delay, and flame lift-off length have been studied in detail. This part focuses on liquid length and in-flame soot formation of reacting sprays, which were quantified utilizing a diffused back-illumination extinction imaging technique. There is an overlapping area between the fuel liquid phase and flame for all three fuels under all operating points. The reduction on liquid length after ignition is more noticeable for pure HCB than other blends, because of its shorter lift-off length. The results show that the liquid length increases with increasing fraction of methanol in the mixtures, which is mainly governed by the high latent heat of vaporization of methanol. Furthermore, extra methanol addition brings a considerable reduction on in-flame soot production because of the leaner fuel combustion at longer flame lift-off length, as well as the more oxygen content within the blends. • Methanol was blended with hydrogenated catalytic biodiesel using n-octanol as co-solvent. • The liquid length and in-flame soot of the ternary blends were measured utilizing a DBI technique. • Liquid length increases with higher methanol fraction because of its high latent heat of vaporization. • Extra methanol addition brings a considerable reduction on in-flame soot production. [ABSTRACT FROM AUTHOR]

Remodeling the endogenous regenerative microenvironment in wounds is crucial for achieving scarless, functional tissue regeneration, especially the functional recovery of skin appendages such as sweat glands in burn patients. However, current approaches mostly rely on the use of exogenous materials or chemicals to stimulate cell proliferation and migration, while the remodeling of a pro-regenerative microenvironment remains challenging. Herein, we developed a flexible sono-piezo patch (fSPP) that aims to create an endogenous regenerative microenvironment to promote the repair of sweat glands in burn wounds. This patch, composed of multifunctional fibers with embedded piezoelectric nanoparticles, utilized low-intensity pulsed ultrasound (LIPUS) to activate electrical stimulation of the target tissue, resulting in enhanced pro-regenerative behaviors of niche tissues and cells, including peripheral nerves, fibroblasts, and vasculatures. We further demonstrated the effective wound healing and regeneration of functional sweat glands in burn injuries solely through such physical stimulation. This noninvasive and drug-free therapeutic approach holds significant potential for the clinical treatment of burn injuries.

Objectives: This study examined people's preference for the location to receive palliative care services and determined the associated factors. Methods: A questionnaire with reference to the Chinese version of the Hospice Attitude Scale and the Death Correspondence Scale was designed, piloted, revised, and distributed online and in person to collect data (N = 762). Binary logistic regression was used to analyze the effects of relevant factors. Results: The average age of the participants was 38.1, with a relatively even gender distribution. Over 90% of the participants were either single/never married (44.9%) or married with children (46.0%). 58.1% of the respondents (N = 428) indicated that they would like to receive palliative care at home, compared to 41.9% who preferred receiving such care in institutions or other places (N = 309). Each time people's attitudes toward death became one point more positive, they were 10.2% more likely to choose to receive palliative care services at home. People with a neutral attitude toward palliative care, single/never married or divorced with children, and having/had an occupation in health and social work had higher odds of preferring receiving palliative care at home. Those who had poor self-rated health or with an educational background of primary school or lower or some college had lower odds of preferring receiving palliative care at home. Conclusions: The research showed that attitudes toward death and other factors were associated with people's preferences for palliative care locations. More accessible and affordable community-based and home-based palliative care services should be further explored and provided., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Since the origin of the Successful Aging (SA) model by Rowe and Kahn, scholars have been working on enriching the content of SA and taking actions to promote this concept worldwide. While most studies primarily focus on older individuals, only a few scholars have considered the environmental aspect of SA. However, the environment, directly and indirectly, enhances older adults' abilities to achieve SA. To measure SA comprehensively and address inequalities among older adults, this theoretical article aims to challenge current SA models by incorporating both individual and environmental aspects and proposing four measurement dimensions: inclusivity of disadvantaged groups, culture-specific adaptation, balance between physical and social environments, and dynamics of the whole lifecycle. Moreover, this article provides examples to illustrate how environment can support older adults especially those who would be defined as "unsuccessful" under the original SA model. Our proposed model would provide theoretical guidance for future research and spark new ideas for policies and programs that support every older adult in achieving SA., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Aortic aneurysm is a life-threatening disease with limited interventions that is closely related to vascular smooth muscle cell (VSMC) phenotypic switching. SLC44A2, a member of the solute carrier series 44 (SLC44) family, remains undercharacterized in the context of cardiovascular diseases. Venn diagram analysis based on microarray and single-cell RNA sequencing identified SLC44A2 as a major regulator of VSMC phenotypic switching in aortic aneurysm. Screening for Slc44a2 among aortic cell lineages demonstrated its predominant location in VSMCs. Elevated levels of SLC44A2 were evident in the aorta of both patients with abdominal aortic aneurysm and angiotensin II-infused (Ang II-infused) Apoe-/- mice. In vitro, SLC44A2 silencing promoted VSMCs toward a synthetic phenotype, while SLC44A2 overexpression attenuated VSMC phenotypic switching. VSMC-specific SLC44A2-knockout mice were more susceptible to aortic aneurysm under Ang II infusion, while SLC44A2 overexpression showed protective effects. Mechanistically, SLC44A2's interaction with NRP1 and ITGB3 activates TGF-β/SMAD signaling, thereby promoting contractile gene expression. Elevated SLC44A2 in aortic aneurysm is associated with upregulated runt-related transcription factor 1 (RUNX1). Furthermore, low-dose lenalidomide (LEN; 20 mg/kg/day) suppressed aortic aneurysm progression by enhancing SLC44A2 expression. These findings reveal that the SLC44A2-NRP1-ITGB3 complex is a major regulator of VSMC phenotypic switching and provide a potential therapeutic approach (LEN) for aortic aneurysm treatment.

The Chinese hamster ovarian (CHO) cells serve as a common choice in biopharmaceutical production, traditionally cultivated in stirred tank bioreactors (STRs). Nevertheless, the pursuit of improved protein quality and production output for commercial purposes demand exploration into new bioreactor types. In this context, inverted frustoconical shaking bioreactors (IFSB) present unique physical properties distinct from STRs. This study aims to compare the production processes of an antibody-based biotherapeutic in both bioreactor types, to enhance production flexibility. The findings indicate that, when compared to STRs, IFSB demonstrates the capability to produce an antibody-based biotherapeutic with either comparable or enhanced bioprocess performance and product quality. IFSB reduces shear damage to cells, enhances viable cell density (VCD), and improves cell state at a 5-L scale. Consequently, this leads to increased protein expression (3.70 g/L vs 2.56 g/L) and improved protein quality, as evidenced by a reduction in acidic variants from 27.0% to 21.5%. Scaling up the culture utilizing the Froude constant and superficial gas velocity ensures stable operation, effective mixing, and gas transfer. The IFSB maintains a high VCD and cell viability at both 50-L and 500-L scales. Product expression levels range from 3.0 to 3.6 g/L, accompanied by an improved acidic variants attribute of 20.6%-22.7%. The IFSB exhibits superior productivity and product quality, underscoring its potential for incorporation into the manufacturing process for antibody-based biotherapeutics. These results establish the foundation for IFSB to become a viable option in producing antibody-based biotherapeutics for clinical and manufacturing applications., Competing Interests: Author QG was employed by Taizhou Mabtech Pharmaceuticals Co., Ltd. Authors ZL, JC, and HG were employed by Shanghai Zhangjiang Biotechnology Co., Ltd. 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., (Copyright © 2024 Wang, Xu, Guo, Li, Cao, Fu, Xu, Zhao, Wang, Zhang, Dong, Li, Qian, Hou, Ji, Zhang and Guo.)

Therapy-related leukemia carries a poor prognosis, and leukemia after chemotherapy is a growing risk in clinic, whose mechanism is still not well understood. Ikaros transcription factor is an important regulator in hematopoietic cells development and differentiation. In the absence of Ikaros, lymphoid cell differentiation is blocked at an extremely early stage, and myeloid cell differentiation is also significantly affected. In this work, we showed that chemotherapeutic drug etoposide reduced the protein levels of several isoforms of Ikaros including IK1, IK2 and IK4, but not IK6 or IK7, by accelerating protein degradation, in leukemic cells. To investigate the molecular mechanism of Ikaros degradation induced by etoposide, immunoprecipitation coupled with LC-MS/MS analysis was conducted to identify changes in protein interaction with Ikaros before and after etoposide treatment, which uncovered KCTD5 protein. Our further study demonstrates that KCTD5 is the key stabilizing factor of Ikaros and chemotherapeutic drug etoposide induces Ikaros protein degradation through decreasing the interaction of Ikaros with KCTD5. These results suggest that etoposide may induce leukemic transformation by downregulating Ikaros via KCTD5, and our work may provide insights to attenuate the negative impact of chemotherapy on hematopoiesis., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Background: Neuropathic pain is chronic and affects the patient's life. Studies have shown that IRF5 and CXCL13/CXCR5 are involved in neuropathic pain; however, their interactions are unknown., Objective: In this study, a rat neuropathic pain model was constructed by inducing chronic compression injury (CCI). IRF5 recombinant lentiviral vector and CXCL13 neutralizing antibody were administered to investigate their action mechanisms in neuropathic pain. Consequently, the new strategies for disease treatment could be evolved., Methods: The CCI rats were intrathecally injected with recombinant lentivirus plasmid LV-IRF5 (overexpression), LV-SH-IRF5 (silencing), and CXCL13 neutralizing antibody. Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured. The tumor necrosis factor (TNF)-alpha, interleukin (IL)-1β, and IL-6 levels were recorded via the enzyme-linked immunosorbent assay (ELISA). The spinal cord was stained using hematoxylin-eosin (HE). The binding of IRF5 to CXCL13 was analyzed by chromatin immunoprecipitation (ChIP) and dual luciferase reporter assay. The IRF5, neuronal nuclei (NeuN), CXCL13, and CXCR5 expressions were detected through quantitative real-time polymerase chain reaction and Western blot., Results: The MWT and TWL values in the CCI group were lower than in the Sham group. The expressions of CXCL13, CXCR5, and IRF5 in CCI rats were gradually increased with the modeling time. IRF5 silencing suppressed the expression of NeuN and lumbar enlargement in CCI rats and promoted MWT and TWL. Moreover, IRF5 silencing inhibited the expressions of CXCR5 and CXCL13 genes and down-regulated the expression levels of inflammatory factors. IRF5 was directly and specifically bound with the endogenous CXCL13 promoter and thus regulated it. IRF5 overexpression exacerbated the disease phenotype of CCI-induced neuropathic pain in rats. Administration of CXCL13 neutralizing antibodies reversed the IRF5 overexpression effects., Conclusion: The IRF5 silencing alleviated neuropathic pain in CCI rats by downregulating the pain threshold, inflammatory cytokine levels, and CXCL13/CXCR5 signaling. IRF5 overexpression exacerbated the disease parameters of CCI-induced neuropathic pain in rats; however, they were reversed by neutralizing antibodies against CXCL13., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

This research investigates the impact of climate challenges on financial markets by introducing an innovative approach to measure climate risk, specifically the aggregate climate change concern (ACCC) index. The study aims to assess and quantify the potential influence of climate change and risk-related factors on the performance and dynamics of financial markets. In this paper, concern is defined as the attention paid to the risk of climate change and the associated negative consequences. The findings demonstrate that the aggregate index exhibits robust predictability of market risk premiums, both within the sample and out-of-sample. By comparison, the index contains additional information beyond 14 economic predictors and 12 risk/uncertainty indexes in forecasting stock market return. In addition, the index proves valuable for mean-variance investors in asset allocation, leading to significant economic gains. The study identifies the index's ability to capture the reversal of temporary price crashes caused by overreactions to climate change risk. Furthermore, it exhibits stronger return forecasting capability for green stocks, non-state-owned enterprise (non-SOE) stocks, and stocks in regions with low air pollution. Particularly during periods of low air pollution and relaxed regulation, the index displays an enhanced ability to forecast returns. The study's findings provide valuable insights for policymakers and financial institutions as they address 21st-century environmental challenges. Moreover, these findings can inform the design of adaptive measures and interventions aimed at mitigating ecological risks and promoting sustainable economic growth., (© 2023 Society for Risk Analysis.)

Perioperative cerebral hypoxia and neonatal hypoxia-ischemic encephalopathy are the main triggers that lead to temporary or permanent brain dysfunction. The pathogenesis is intimately correlated to neural activities and the pH of the microenvironment, which calls for a high demand for in situ multitype physiological signal acquisition in the brain. However, conventional pH sensing neural interfaces cannot obtain the characteristics of multimodes, multichannels, and high spatial resolution of physiological signals simultaneously. Here, we report a multifunctional implantable iridium oxide (IrOx) neural probe (MIIONP) combined with electrophysiology recording, in situ pH sensing, and neural stimulation for real-time dynamic brain hypoxia evaluation. The neural probe modified with IrOx films exhibits outstanding electrophysiology recording and neural stimulation performance and long-term stable high spatial pH sensing resolution of about 100 μm, and the cytotoxicity of IrOx microelectrodes was investigated as well. In addition, 4 weeks' tracking of the same neuron firing and instantaneous population spike captured during electrical stimulation was achieved by MIIONP. Finally, in a mouse brain hypoxia model, the MIIONP has demonstrated the capability of synchronous in situ recording of the pH and neural firing changes in the brain, which has a valuable application in dynamic brain disease evaluation through real-time acquisition of multiple physiological signals.

Introduction: The oil palm kernel (OPK) expeller is the main byproduct of palm oil, but its utilization is limited. Methods: To obtain angiotensin-I-converting enzyme (ACE) inhibition peptides with Zn-chelating capacity, defatted oil palm kernel globulin hydrolysates (DOPKGH) were subjected to Sephadex G-15 gel electrophoresis, reverse-phase high liquid performance chromatography, and UPLC-ESI-MS/MS analysis. Results and discussion: Five representative oligopeptides, including Gln-Arg-Leu-Asp-Arg-Cys-Lys (QRLERCK), Leu-Leu-Leu-Gly-Val-Ala-Asn-Tyr-Arg (LLLGVANYR), Arg-Ala-Asp-Val-Phe-Asn-Pro-Arg (RADVFNPR), Arg-Val-Ile-Lys-Tyr-Asn-Gly-Gly-Gly-Ser-Gly (RVIKYNGGGSG), and Glu-Val-Pro-Gln-Ala-Tyr-Ile-Pro (EVPQAYIP), without potential toxicity and allergenicity, were identified in DOPKGH. Of these, only EVPQAYIP showed both ACE-inhibitory activity (IC 50 : 102.75 μmol/L) and Zn-chelating capacity (11.69 mg/g). Molecular docking and inhibition kinetics showed that EVPQAYIP was a competitive inhibitor of ACE because it could bind to Glu384, Lys511, and Gln281 (belonging to the central S1 and S2 pockets, respectively) of ACE. Moreover, EVPQAYIP affects zinc tetrahedral coordination in ACE by binding to Glu411; the amino and carboxyl groups of EVPQAYIP chelate with zinc ions. During gastrointestinal digestion, the ACE inhibitory activity of EVPQAYIP was relatively stable. Additionally, EVPQAYIP enhanced zinc stability in the intestine and exerted antihypertensive effects in spontaneous hypertensive rats. These results suggest the potential application of OPK peptides as ingredients in antihypertensive agents or zinc fortification., 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 © 2023 Zhang, Pan, Shao, Zheng, Hao, Kan, Cao, Yu and Liu.)

Genetic information is generally transferred from RNA to protein according to the classic "Central Dogma". Here, we made a striking discovery that post-translational modification of a protein specifically regulates the editing of its own mRNA. We show that S-nitrosylation of cathepsin B (CTSB) exclusively alters the adenosine-to-inosine (A-to-I) editing of its own mRNA. Mechanistically, CTSB S-nitrosylation promotes the dephosphorylation and nuclear translocation of ADD1, leading to the recruitment of MATR3 and ADAR1 to CTSB mRNA. ADAR1-mediated A-to-I RNA editing enables the binding of HuR to CTSB mRNA, resulting in increased CTSB mRNA stability and subsequently higher steady-state levels of CTSB protein. Together, we uncovered a unique feedforward mechanism of protein expression regulation mediated by the ADD1/MATR3/ADAR1 regulatory axis. Our study demonstrates a novel reverse flow of information from the post-translational modification of a protein back to the post-transcriptional regulation of its own mRNA precursor. We coined this process as "Protein-directed EDiting of its Own mRNA by ADAR1 (PEDORA)" and suggest that this constitutes an additional layer of protein expression control. "PEDORA" could represent a currently hidden mechanism in eukaryotic gene expression regulation., (© 2023. The Author(s) under exclusive licence to Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences.)

A positively charged nanofiltration (NF) membrane is known to have exceptional separation performance for bivalent cations in aqueous solutions. In this study, a new NF activity layer was created using interfacial polymerization (IP) on a polysulfone (PSF) ultrafiltration substrate membrane. The aqueous phase combines the two monomers of polyethyleneimine (PEI) and phthalimide, while successfully producing a highly efficient and accurate NF membrane. The conditions of the NF membrane were studied and further optimized. The aqueous phase crosslinking process enhances the polymer interaction, resulting in an excellent pure water flux of 7.09 L·m -2 ·h -1 ·bar -1 under a pressure of 0.4 MPa. Additionally, the NF membrane shows excellent selectivity toward inorganic salts, with a rejection order of MgCl 2 > CaCl 2 > MgSO 4 > Na 2 SO 4 > NaCl. Under optimal conditions, the membrane was able to reject up to 94.33% of 1,000 mg/L of MgCl 2 solution at an ambient temperature. Further to assess the antifouling properties of the membrane with bovine serum albumin (BSA), the flux recovery ratio (FRR) was calculated to be 81.64% after 6 h of filtration. This paper presents an efficient and straightforward approach to customize a positively charged NF membrane. We achieve this by introducing phthalimide, which enhances the membrane's stability and rejection performance.

A series of 3DOM cerium-based perovskite catalysts with different B-site elements were prepared by the colloidal crystal template method and excess impregnation method with Cr, Ni, and Mn as the B-site elements. The physical and chemical properties of the catalysts were investigated by X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), hydrogen temperature-programmed reduction (H 2 -TPR), and oxygen temperature-programmed desorption (O 2 -TPD) characterization techniques. The results showed that the catalyst with Mn as the B-site element had a high-quality macropore structure (pore size 200-250 nm), large specific surface area (45.26 m 2 /g), and abundant surface adsorbed oxygen content (O ads /O latt = 0.46). The addition of manganese enhanced the low-temperature reducibility, and the main reduction peak was below 400 °C. The O 2 -TPD results showed that 3DOM CeMnO 3 expressed the highest adsorption oxygen content. The 3DOM CeMnO 3 possessed the best catalytic performance with T 50% = 102 °C and T 90% = 203 °C during the catalytic oxidation of toluene. Intermediate product study hinted that toluene was first converted into benzoic acid and benzaldehyde and then further degraded into small molecules. The catalyst with the best activity also exhibited good stability, and toluene degradation rate remained above 85% at 200°C for more than 20 h of continuous experiments.

Breast cancer is the most common malignant cancer in women. Triple-negative breast cancer (TNBC) has a poorer prognosis than other subtypes and is challenging to treat. MUC1 is a therapeutic target in breast and pancreatic cancer. We developed a novel humanized antibody that specifically binds MUC1 expressed in breast cancer cells and conjugated a humanized MUC1 (HzMUC1) antibody to monomethyl auristatin (MMAE). HzMUC1-MMAE showed an anti-proliferative effect on HER2 positive trastuzumab-resistant breast cancer. Immunoprecipitation indicated that HzMUC1 recognized native MUC1 in TNBC cells. Confocal microscopy showed that HzMUC1 bound MUC1 on the surface of TNBC cells, and the conjugates exhibited the same binding ability to HCC70 as unconjugated HzMUC1 by cell-based ELISA. Treatment of TNBC cells with HzMUC1-MMAE reduced growth of MUC1-positive cells and induced G2/M cell cycle arrest and apoptosis. In a mouse model of breast cancer, HzMUC1-MMAE significantly reduced the growth of tumors established by subcutaneous injection of HCC70 TNBC cells. Therefore, HzMUC1-ADC has therapeutic potential for TNBC., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors.)

Aims: Ferroptosis plays important roles in tumorigenesis and cancer therapy. Zoledronic acid is known to inhibit the activity of farnesyl pyrophosphate synthase, a key enzyme in the mevalonate pathway. We examined whether zoledronic acid can inhibit the growth of osteosarcoma cells by inducing ferroptosis. Methods : Cell viability was analyzed by using CCK8 reagent and counting cells with trypan blue exclusion. Ferroptosis markers including lipid peroxide and PTGS2 expression were examined by flow cytometry, western blot, and quantitative PCR analyses. Cellular ubiquinone content was determined using high performance liquid chromatography. Ferrostatin-1 and RSL3 were used as the ferroptosis inhibitor and inducer respectively. Results : Zoledronic acid treatment decreased cell viability and promoted the increase in lipid peroxide content and PTGS2 expression. Addition of ferrostatin-1 reverted these effects of zoledronic acid on osteosarcoma cells, supporting a role of zoledronic acid in inducing ferroptosis. Mechanistically, zoledronic acid significantly decreased ubiquinone, a metabolite of the mevalonate pathway. Treating cells with exogenous ubiquinone prevented zoledronic acid-induced ferroptosis and decrease in the growth of osteosarcoma cells. In addition, zoledronic acid enhanced the expression of HMOX1, whereas knockdown of HMOX1 inhibited the zoledronic acid-induced increase in lipid peroxide level and decrease in cell growth. Finally, zoledronic acid together with RSL3 significantly enhanced the inhibitory effect on the growth of osteosarcoma cells. Conclusion: Our results indicate that zoledronic acid induces ferroptosis by decreasing ubiquinone content and promoting HMOX1 expression in osteosarcoma cells. Zoledronic acid together with ferroptosis inducer may be a promising new strategy for the treatment of osteosarcoma., 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 © 2023 Ren, Huang, Sun, Wang, Wu, Jiang, Lv, Wu, Cao, Liu and Gu.)

In this work, monolithic catalysts with single coating Ce 0.75 Zr 0.25 O 2 , Al 2 O 3 and composite coating Ce 0.75 Zr 0.25 O 2 -Al 2 O 3 were prepared by PMMA hard template-excessive impregnation method with 3DOM La 0.7 Ce 0.3 CoO 3 as the active component and cordierite as the carrier, and characterized by SEM, XRD, BET, H 2 -TPR, and XPS, and the catalytic performance for toluene was tested. The results showed that the active components of 3DOM La 0.7 Ce 0.3 CoO 3 /Ce 0.75 Zr 0.25 O 2 -Al 2 O 3 /cordierite catalyst were highly dispersed, forming a complete macroporous structure with the largest specific surface area (10.57 m 2 ·g -1 ), high surface adsorbed oxygen concentration, and good low-temperature reducibility. Its catalytic activity (T 50%  = 103℃, T 90%  = 218℃) for toluene was obviously better than the others. According to the comprehensive analysis, the improvement of the performance of the catalyst may benefit from the excellent physicochemical properties and the synergistic effect between Ce 0.75 Zr 0.25 O 2 -Al 2 O 3 composite coating and active components., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Globally, lung adenocarcinoma (LUAD) is the leading cause of cancer-related deaths. It is a progressive disorder that arises from multiple genetic and environmental factors. Dysregulated expression of vesicle-mediated transport-related genes (VMTRGs) have been reported in several cancers. However, the prognostic significance of VMTRGs in LUAD has yet to be established., Methods: The VMTRG profiling data for 482 LUAD patients and 59 normal controls were downloaded from The Cancer Genome Altas (TCGA). Univariate Cox regression and Least Absolute Shrinkage and Selection Operator (LASSO) regression analyses were performed to construct and optimize the risk model. Several GEO datasets were used to validate the risk model. The roles of these genes were investigated via the Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) enrichment analyses. Differences in immune cell infiltrations between risk groups were evaluated using five algorithms. "pRRophetic" was used to investigate anti-cancer drug sensitivities in two groups. Expression of these five genes in LUAD samples and adjacent normal tissues were evaluated by qRT-PCR. Colony formation and wound healing assays were performed to assess the significance of CNIH1 and AP3S1 in LUAD cells., Results: We identified 85 prognosis-associated VMTRGs that could be constructed a risk model for LUAD patients, indicating their potential importance in LUAD development. The risk model including the five VMTRGs (CNIH1, KIF20A, GALNT2, GRIA1, and AP3S1) was associated with clinical outcomes. Tumor stage and risk score were found to be independent prognostic factors for LUAD patients. The five VMTRGs were also correlated with activation of the Notch and p53 signaling pathways. The risk model was significantly associated with immune responses and with high-level expression of immune checkpoints. High-risk group patients were more sensitive to several chemotherapeutic drugs and Lapatinib. Furthermore, CNIH1 and AP3S1 promoted LUAD cell growth and migration in vitro ., Conclusion: We constructed a VMTRG-based risk model for effective prediction of prognostic outcomes for LUAD patients. The risk model was associated with immune infiltration levels. These five hub genes are potential targets for immune therapy combined with chemotherapy in LUAD., 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 Qian, Jiang, Zhou, Wu, Zhang, Huang, Ouyang, Dong, Wu and Cao.)

Objective: This study investigates gender differences in the correlation between body mass index (BMI) and cognitive impairment among Chinese community-dwelling oldest-old., Setting: Twenty-three provinces in China. Participants' mini-mental state examination (MMSE) scores <24 were considered cognitive impairment. Furthermore, the assessment standards of BMI status were classified into four categories: obese (BMI >30), overweight (25≤BMI≤30), normal (18.5≤BMI<25) and underweight (BMI <18.5)., Participants: A total of 9218 older adults (age 80+) were included from the 2018 wave of Chinese Longitudinal Healthy Longevity Study., Methods: Cognitive impairment, BMI and other covariates consisted of the sociodemographic variables, health behaviours and health status were collected. Cognitive impairment was assessed by the MMSE. Inverse probability weighting procedure was adopted to deal with bias due to dropout.Logistic regression was conducted to examine the correlation between BMI and cognitive impairment., Results: Among 9218 respondents, 3837 were males. Overall, the percentage of participants with cognitive impairment was 44.7%, with 32.1% among males and 53.7% among females. After controlling for other variables, males who were either overweight or underweight and females who were underweight were found to have higher risk of cognitive impairment among the oldest-old. Age, education, economic status, physical activity, activities of daily living, hypertension as well as heart disease were the predicting factors of cognitive impairment., Conclusions: The relationship between BMI and cognitive impairment differs between male and female oldest-old, suggesting that we should pay attention to different BMI groups and adopt precise prevention strategies based on gender., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

A well-performing machine learning (ML) model is obtained by using proper descriptors and artificial neural network (ANN) algorithms, which can quickly and accurately predict activation free energy in hydrogen atom transfer (HAT)-based sp 3 C-H activation. Density functional theory calculations (UωB97X-D) are used to establish the reaction system data sets of methoxyl (CH 3 O·), trifluoroethoxyl (CF 3 CH 2 O·), tert -butoxyl (tBuO·), and cumyloxyl (CumO·) radicals. The simplified Roberts' equation proposed in our recent study works here [ R 2 = 0.84, mean absolute error (MAE) = 0.85 kcal/mol]. Its performance is comparable with univariate Mulliken-type electronegativity (χ) with the ANN model. The ANN model with bond dissociation free energy, χ, α-unsaturation, and Nolan buried volume (% V buried ) successively improves R 2 and MAE to 0.93 and 0.54 kcal/mol, respectively. It reproduces the test sets of trichloroethoxyl (CCl 3 CH 2 O·) with R 2 = 0.87 and MAE = 0.89 kcal/mol and accurately predicts the relative experimental barrier of the HAT reactions with CumO· and the site selectivity of CH 3 O·., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)