Search

The development of environmentally responsive biodegradable polymers is a promising solution for balancing the stability and degradability of biodegradable plastics. In this study, a commercial biodegradable polyester, poly(butylene adipate-co-butylene terephthalate) (PBAT), was used as the substrate and was synthetically modified with a small amount of anionic sodium 1-3-isophthalate-5-sulfonate (SIPA) to obtain the ionized random poly(butylene adipate-co-butylene terephthalate-co-butylene 5-sodiosulfoisophthalate) (PBATS). The introduction of the sodium sulfonate ionic group enhanced the mechanical and heat-resistant properties of the material, while significantly improving the hydrophilicity and water absorption of the copolyesters of PBATSs and endowing them with special pH-responsive degradation properties. Compared with PBAT, PBATS copolyesters could accelerate degradation in acidic or alkaline buffer solutions and natural seawater, while degradation was inhibited in neutral buffer solutions at pH 7.2. Degradation experiments in simulated gastric, intestinal, and body fluids revealed that the copolyester showed specific and rapid degradation in acidic gastric fluids. This environmentally-responsive degradable material greatly expands the special applications of biodegradable polyesters in the fields of environmental remediation and medical applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Pollution fluxes from rivers into the sea are currently the main source of pollutants in nearshore areas. Based on the source-sink process of the basin-estuary-coastal waters system, the pollution fluxes into the sea and their spatiotemporal heterogeneity were estimated. A deep learning-based model was established to simplify the estimation of pollution fluxes into the sea, with socio-economic drivers and meteorological data as input variables. A method for estimating the contribution rate of pollution fluxes from different spatial gradient was proposed. In this study, we found that (1) the pollution fluxes into the sea of total nitrogen (TN) and total phosphorus (TP) from the Bohai Sea Rim Basin (BSRB) in 1980, 1990, 2000, 2010, and 2020 were 25.38 × 10 4 , 26.12 × 10 4 , 27.27 × 10 4 , 29.82 × 10 4 , 25.31 × 10 4 and 1.32 × 10 4 , 2.14 × 10 4 , 2.09 × 10 4 , 1.87 × 10 4 , 1.68 × 10 4 tons, respectively. (2) The proportion of rural life and livestock to the TN was the highest, accounting for 39.18 % and 21.19 %, respectively. The proportion of livestock to the TP was the highest, accounting for 39.20 %, followed by rural life, accounting for 24.72 %. The results indicated that the pollution fluxes in the BSRB were related to human economic activities and relevant environmental protection measures. (3) The deep learning-based model established to estimate runoff pollution fluxes into the sea had the accuracy of over 90 %. (4) As for contribution rate, in terms of the elevation, the range of 0-100 m had the highest proportion, accounting for 39.65 %. The range of 50-100 km from the coastline had the highest proportion, accounting for 18.11 %. In terms of the district, coastal area has the highest proportion, accounting for 38.00 %. This study revealed the changing trends and driving mechanisms of pollution fluxes into the sea over the past 40 years and established a simplified deep learning-based model for estimating pollution fluxes into the sea. Then, we identified regions with high pollution contribution rate. The results can provide scientific references for the adaptive management of the nearshore areas based on the ecosystem., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Presently, the exploration of novel inorganic lead-free perovskite scintillators has emerged as a prominent topic in the field of perovskite materials. Extensive attention has been garnered by materials such as Cs 3 Cu 2 I 5 due to their notable advantage in scintillation intensity, but the response time constants in the microsecond or even millisecond range severely constrain their potential applications in scintillators. In this study, large-sized (5-6 mm) CsAg 2 I 3 single crystals with an ultrafast warm-white light emission on a nanosecond time scale are presented. Specifically, upon X-ray excitation, the single crystal demonstrates a broad-spectrum white light emission with a color temperature as high as 5129 K, attributed to its self-trapped exciton emission. The 137 Cs energy spectrum reveals that CsAg 2 I 3 possesses an ultrafast response for γ rays with a time constant of 15 ns, which is significantly faster than that of Cs 3 Cu 2 I 5 . Furthermore, time-resolved photoluminescence unveils a subnanosecond component with a response time of 0.9 ns. The characteristics of ultrafast warm-white light emission exhibit the significant potential of CsAg 2 I 3 in radiation scintillation detection and its probability of playing a pivotal role in future radiation detection technology.

Phase engineering of two-dimensional (2D) transition metal dichalcogenides (TMDs) is an attractive avenue to construct new surface-enhanced Raman scattering (SERS) substrates. Herein, 2D WS 2 and MoS 2 monolayers with high-purity distorted octahedral phase (1T') are prepared for highly sensitive SERS detection of analytes (e.g., rhodamine 6G, rhodamine B and crystal violet). 1T'-WS 2 and 1T'-MoS 2 monolayers show the detection limits of 8.28 × 10 -12 and 8.57 × 10 -11 M for rhodamine 6G, with the enhancement factors of 4.6 × 10 8 and 3.9 × 10 7 , respectively, which are comparable to noble-metal substrates, outperforming semiconducting 2H-W(Mo)S 2 monolayers and most of the reported non-noble-metal substrates. First-principles density functional theory calculations show that their Raman enhancement effect is mainly ascribed to highly efficient interfacial charge transfer between the 1T'-W(Mo)S 2 monolayers and analytes. Our study reveals that 2D TMDs with semimetallic 1T' phase are promising as next-generation SERS substrates.

Background: A few sham-controlled studies have examined the efficacy, safety, and tolerability of low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) in adolescents with first-episode major depressive disorder (FE-MDD)., Methods: Forty adolescents (aged 13-17 years) with FE-MDD were randomly assigned to receive active rTMS (n = 20) or sham rTMS (n = 20) for 10 sessions over two weeks. The severity of baseline depressive symptoms and their improvement on the day immediately after the second, fourth, sixth, eighth, and tenth sessions were assessed with the 17-item Hamilton Depression Rating Scale (HAMD-17)., Results: After completing 10 rTMS treatment sessions, there was no significant difference in antidepressant response (70.0 % vs. 60.0 %, p > 0.05) and antidepressant remission (55.0 % vs. 35.0 %, p > 0.05) between rTMS groups. The linear mixed model analysis did not show a significant group-by-time interaction (F = 1.26; p > 0.05) in the HAMD-17 scores. There was a significant time main effect on the speed of processing (F = 13.61; p < 0.05), but this did not differ significantly between groups (p > 0.05). There were no other main effects and group-by-time interactions in the other MATRICS Consensus Cognitive Battery domains (all p > 0.05). All adverse event categories, such as fatigue and headache, were similar in the two groups (all p > 0.05)., Conclusions: In this study that compared a combination of LF-rTMS + medication with sham + medication, LF-rTMS had higher response and remission rates than a sham procedure in adolescents with FE-MDD, but the change was not statistically significant. LF-rTMS is generally safe, with mild adverse effects and no negative impact on neurocognitive performance for adolescents with FE-MDD., Registration Number: ChiCTR2000037878., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest in conducting this study or preparing the manuscript., (Copyright © 2024. Published by Elsevier B.V.)

In leader-follower multiagent systems (MASs), seeking an efficient scheme to select a set of agents as leaders is important for realizing the expected cooperative performance. In this article, the problem of minimal leader selection is investigated for impulsive general linear MASs with switching topologies. This study focuses on selecting a set of agents as leaders that receive information from a reference signal directly, while minimizing the number of leaders, subject to consensus tracking performance. First, adopting the average dwell time technique and a time-ratio constraint, an explicit criterion for consensus tracking is derived as prepreparation for leader selection. Second, applying the submodular optimization framework, leader selection metrics are established based on the derived criterion. Third, employing the greedy rule, an efficient leader selection scheme is presented according to the established metrics. The scheme comprises two polynomial-time algorithms that return selected leader sets within a logarithmic bound of the optimum. Finally, the effectiveness of the developed leader selection scheme is verified using an illustrative example.

Sterile inflammation occurs in various chronic diseases due to many nonmicrobe factors. Examples include endometrial hyperplasia (EH), endometriosis, endometrial cancer, and breast cancer, which are all sterile inflammation diseases induced by estrogen imbalances. However, how estrogen-induced sterile inflammation regulates EH remains unclear. Here, a single-cell RNA-Seq is used to show that SHP2 upregulation in endometrial endothelial cells promotes their inflammatory activation and subsequent transendothelial macrophage migration. Independent of the initial estrogen stimulation, IL1β and TNFα from macrophages then create a feedforward loop that enhances endothelial cell activation and IGF1 secretion. This endothelial cell-macrophage interaction sustains sterile endometrial inflammation and facilitates epithelial cell proliferation, even after estradiol withdrawal. The bulk RNA-Seq results and phosphoproteomic analysis show that endothelial SHP2 mechanistically enhances RIPK1 activity by dephosphorylating RIPK1 Tyr380 . This event activates downstream activator protein 1 (AP-1) and instigates the inflammation response. Furthermore, targeting SHP2 using SHP099 (an allosteric inhibitor) or endothelial-specific SHP2 deletion alleviates endothelial cell activation, macrophage infiltration, and EH progression in mice. Collectively, the findings demonstrate that SHP2 mediates the transition of endothelial activation from estradiol-driven acute inflammation to macrophage-amplified chronic inflammation. Targeting sterile inflammation mediated by endothelial cell activation is a promising strategy for nonhormonal intervention in estrogen-related diseases., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Clear cell renal cell carcinoma (ccRCC) represents a highly heterogeneous kidney malignancy associated with the poorest prognosis. The metastatic potential of advanced ccRCC tumors is notably high, posing significant clinical challenges. There is an urgent imperative to develop novel therapeutic approaches to address ccRCC metastasis. Recent investigations indicated a potential association between GBP2 and tumor immunity. However, the precise functional role of GBP2 in the progression of ccRCC remains poorly understood. The present study revealed a strong correlation between GBP2 and M2 macrophages. Specifically, our findings demonstrated that the inhibition of GBP2 significantly impedes the migratory and invasive capabilities of ccRCC cells. We observed that the presence of M2 macrophages can reverse the effects of GBP2 knockdown on tumor cell migration and invasion. Mechanistically, we demonstrated that M2 macrophages promote the expression of the GBP2/p-STAT3 and p-ERK axis in tumor cells through the secretion of interleukin-10 (IL-10) and transforming growth factor-β (TGF-β), thereby substantially enhancing the migratory and invasive capacities of the tumor cells. Simultaneously, we have identified that GBP2 promotes the polarization of macrophages to the M2 phenotype by stimulating the secretion of interleukin-18 (IL-18). In summary, our investigation anticipates that the GBP2/IL-18/M2 macrophages/IL-10 and the TGF-β/GBP2, p-STAT3, p-ERK loop plays a crucial role in ccRCC metastasis. The collective findings from our research underscore the significant role of GBP2 in tumor immunity and emphasize the potential for modulating GBP2 as a promising therapeutic strategy for targeting ccRCC metastasis., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Fire-retardant coatings represent a universal cost-effective approach to providing fire protection for various substrates without compromising substrates' bulk properties. However, it has been attractive yet highly challenging to create waterborne polymeric fire-retardant coatings combining high-efficiency, generally strong adhesion, and self-repairability due to a lack of rational design principles. Inspired by mussel's unique adhesive, self-healing, and char-forming mechanisms, herein, a "group synergy" design strategy is proposed to realize the combination of self-healing, strong adhesion, and high efficiency in a fully polymeric fire-retardant coating via multiple synergies between catechol, phosphonic, and hydroxyethyl groups. As-created fire-retardant coating exhibits a rapid room-temperature self-healing ability and strong adhesion to (non)polar substrates due to multiple dynamic non-covalent interactions enabled by these groups. Because these functional groups enable the formation of a robust structurally intact yet slightly expanded char layer upon exposure to flame, a 200 µm-thick such coating can make extremely flammable polystyrene foam very difficult to ignite and self-extinguishing, which far outperforms previous strategies. Moreover, this coating can provide universal exceptional fire protection for a variety of substrates from polymer foams, and timber, to fabric and steel. This work presents a promising material design principle to create next-generation sustainable high-performance fire-retardant coatings for general fire protection., (© 2024 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)

Designing robust catalysts for increasing the sluggish kinetics of the urea oxidation reaction (UOR) is challenging. Herein, the regulation of spin states for metal active sites by photoexcitation to facilitate the adsorption of urea and intermediates is demonstrated. Mo-doped nickel sulfide nanoribbon arrays (Mo-Ni 3 S 2 @NMF) with excellent light-trapping capacity are successfully prepared. Under AM 1.5G illumination, the activity of the Mo-Ni 3 S 2 @NMF exhibits a 50% improvement in the UOR current. Compared with those under dark conditions, Mo-Ni 3 S 2 @NMF achieve 10 mA cm -2 at 1.315 V RHE for UOR and 1.32 V cell for urea electrolysis, which are decreases of 15 and 80 mV, respectively. The electron spin resonance, in situ Fourier transform infrared spectroscopy analysis and density functional theory calculations reveal that illumination led to the formation of Ni 3+ active sites in a high-spin state, which strengthens the d-p orbital hybridization of Ni-N, hence facilitating the adsorption of urea. C─N cleavage of the * CONN intermediate is further inhibited, which promotes the oxidation of urea molecules via the active N 2 pathway, thereby accelerating the UOR rate., (© 2024 Wiley‐VCH GmbH.)

Background: Benzene exposure has been associated with increased risk of leukemia and other cancers; however, epidemiologic evidence is inconsistent for the latter, and confounding from smoking and alcohol was rarely adjusted., Methods: We investigated associations between occupational benzene exposure and risk of leukemia, lymphoma, myeloma, and lung, stomach, liver, and kidney cancers in a population-based cohort of 61,377 men, ages 40 to 74 years. A job-exposure matrix, constructed by industrial hygienists specifically for the study population, was used to derive cumulative benzene exposure from all jobs held. Cox regressions were performed to estimate adjusted HRs (aHR) and 95% confidence intervals (CI) for benzene-cancer risk associations with adjustment for potential confounders., Results: Over 15 years of follow-up, 1,145 lung cancer, 656 stomach cancer, 445 liver cancer, 243 kidney cancer, 100 leukemia, 124 lymphoma, and 46 myeloma cases were identified. Benzene exposure >550 mg/m3 was associated with an increased risk of leukemia (aHR = 2.3; 95% CI, 1.1-4.5), lung cancer (aHR = 1.2; 95% CI, 1.0-1.6), and stomach cancer (aHR = 1.4; 95% CI, 1.0-1.9); benzene exposure was associated with early cancer diagnosis age. The benzene-leukemia and benzene-stomach cancer associations followed a linear dose-response pattern (Plinear = 0.016 and 0.023), whereas the benzene-lung cancer association was evident at higher exposure levels (Pnonlinear = 0.027). Alcohol consumption modified the benzene-leukemia association (aHR = 3.0; 95% CI, 1.1-8.3 for drinkers and aHR = 0.9; 95% CI, 0.4-2.0 for nondrinkers, Pinteraction = 0.047)., Conclusions: Benzene exposure was associated with an increased risk of leukemia, stomach cancer, and lung cancer. Alcohol consumption may modify the benzene-leukemia association, although estimates are imprecise., Impact: Our study provides additional evidence that benzene exposure increases cancer risk beyond leukemia, information important for policymakers to develop programs to mitigate cancer risk among benzene-exposed workers., (©2024 American Association for Cancer Research.)

mRNA-4157 (V940) is an individualized neoantigen therapy targeting up to 34 patient-specific tumor neoantigens to induce T-cell responses and potentiate antitumor activity. We report mechanistic insights into the immunogenicity of mRNA-4157 via characterization of T-cell responses to neoantigens from the first-in-human, phase 1, KEYNOTE-603 study (NCT03313778) in patients with resected non-small cell lung cancer (Part A: 1-mg mRNA-4157, n = 4) or resected cutaneous melanoma (Part D: 1-mg mRNA-4157 + 200-mg pembrolizumab, n = 12). Safety, tolerability, and immunogenicity were assessed. All patients experienced ≥1 treatment-emergent adverse event; there were no grade 4/5 adverse events or dose-limiting toxicities. mRNA-4157 alone induced consistent de novo and strengthened preexisting T-cell responses to targeted neoantigens. Following combination therapy, sustained mRNA-4157-induced neoantigen-specific T-cell responses and expansion of cytotoxic CD8 and CD4 T cells were observed. These findings show the potential of a novel mRNA individualized neoantigen therapy approach in oncology. Significance: The safety and immunogenicity results from this phase 1 study of mRNA-4157 as adjuvant monotherapy or combination therapy with pembrolizumab show generation of de novo and enhancement of existing neoantigen-specific T-cell responses and provide mechanistic proof of concept to support further development of mRNA-4157 for patients with resected solid tumors. See related commentary by Berraondo et al., p. 2021., (©2024 American Association for Cancer Research.)

The corpus callosum is an oligodendrocyte-enriched brain region, replenished by newborn oligodendrocytes from oligodendrocyte progenitor cells (OPCs) in subventricular zone (SVZ). Lead (Pb) exposure has been associated with multiple sclerosis, a disease characterized by the loss of oligodendrocytes. This study aimed to investigate the effects of Pb exposure on oligodendrogenesis in SVZ and myelination in the corpus callosum. Adult female mice were used for a disproportionately higher prevalence of multiple sclerosis in females. Acute Pb exposure (one ip-injection of 27 mg Pb/kg as PbAc2 24 hr before sampling) caused mild Pb accumulation in the corpus callosum. Ex vivo assay using isolated SVZ tissues collected from acute Pb-exposed brains showed a diminished oligodendrogenesis in SVZ-derived neurospheres compared with controls. In vivo subchronic Pb exposure (13.5 mg Pb/kg by daily oral gavage 4 wk) revealed significantly decreased newborn BrdU+/MBP+ oligodendrocytes in the corpus callosum, suggesting demyelination. Mechanistic investigations indicated decreased Rictor in SVZ OPCs, defective self-defense pathways, and reactive gliosis in the corpus callosum. Given the interwined pathologies between multiple sclerosis and Alzheimer's disease, the effect of Pb on myelination was evaluated in AD-modeled APP/PS1 mice. Myelin MRI on mice following chronic exposure (1,000 ppm Pb in drinking water as PbAc2 for 20 wk) revealed a profound demyelination in the corpus callosum compared with controls. Immunostaining of the choroid plexus showed diminished signaling molecule (Klotho, OTX2) expressions in Pb-treated animals. These observations suggest that Pb caused demyelination in the corpus callosum, likely by disrupting oligodendrogenesis from SVZ OPCs. Pb-induced demyelination represents a crucial pathogenic pathway in Pb neurotoxicity, including multiple sclerosis., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Herein, a three-armed amphiphilic metallacycle-cored star supramolecular polymer (Por-MOM-PDMAEMA) has been designed and synthesized via highly efficient post-assembly polymerization. This star polymer is further self-assembled into nanoparticles of different sizes depending upon the experimental conditions. The gas-controlled morphology transformation and tunable antibacterial activities of Por-MOM-PDMAEMAis systematically investigated and compared with metallacycle (MOM). The superior antibacterial activity of Por-MOM-PDMAEMA against multidrug-resistant P. aeruginosa implies that the presence of photodynamic photosensitizer (Por) and cationic polymer chain will significantly enhance antibactericidal activity, which is mainly attributed to the synergistic effect of photosensitizer and polymer chain linked in one metallacycle core. By leveraging the unique properties of metallacycle and their dynamic response to gaseous stimuli, the antibacterial properties of the Por-MOM-PDMAEMA can be finely tuned in response to gas triggers., (© 2024 Wiley‐VCH GmbH.)

Background: Genome-wide association studies (GWAS) have identified more than 200 breast cancer risk-associated genetic loci, yet the causal genes and biological mechanisms for most loci remain elusive. Proteins, as final gene products, are pivotal in cellular function. In this study, we conducted a proteome-wide association study (PWAS) to identify proteins in breast tissue related to breast cancer risk., Methods: We profiled the proteome in fresh frozen breast tissue samples from 120 cancer-free European-ancestry women from the Susan G. Komen Tissue Bank (KTB). Protein expression levels were log2-transformed then normalized via quantile and inverse-rank transformations. GWAS data were also generated for these 120 samples. These data were used to build statistical models to predict protein expression levels via cis-genetic variants using the elastic net method. The prediction models were then applied to the GWAS summary statistics data of 133,384 breast cancer cases and 113,789 controls to assess the associations of genetically predicted protein expression levels with breast cancer risk overall and its subtypes using the S-PrediXcan method., Results: A total of 6388 proteins were detected in the normal breast tissue samples from 120 women with a high detection false discovery rate (FDR) p value < 0.01. Among the 5820 proteins detected in more than 80% of participants, prediction models were successfully built for 2060 proteins with R > 0.1 and P < 0.05. Among these 2060 proteins, five proteins were significantly associated with overall breast cancer risk at an FDR p value < 0.1. Among these five proteins, the corresponding genes for proteins COPG1, DCTN3, and DDX6 were located at least 1 Megabase away from the GWAS-identified breast cancer risk variants. COPG1 was associated with an increased risk of breast cancer with a p value of 8.54 × 10 -4 . Both DCTN3 and DDX6 were associated with a decreased risk of breast cancer with p values of 1.01 × 10 -3 and 3.25 × 10 -4 , respectively. The corresponding genes for the remaining two proteins, LSP1 and DNAJA3, were located in previously GWAS-identified breast cancer risk loci. After adjusting for GWAS-identified risk variants, the association for DNAJA3 was still significant (p value of 9.15 × 10 -5 and adjusted p value of 1.94 × 10 -4 ). However, the significance for LSP1 became weaker with a p value of 0.62. Stratification analyses by breast cancer subtypes identified three proteins, SMARCC1, LSP1, and NCKAP1L, associated with luminal A, luminal B, and ER-positive breast cancer. NCKAP1L was located at least 1Mb away from the GWAS-identified breast cancer risk variants. After adjusting for GWAS-identified breast cancer risk variants, the association for protein LSP1 was still significant (adjusted p value of 6.43 × 10 -3 for luminal B subtype)., Conclusion: We conducted the first breast-tissue-based PWAS and identified seven proteins associated with breast cancer, including five proteins not previously implicated. These findings help improve our understanding of the underlying genetic mechanism of breast cancer development., (© 2024. The Author(s).)

In order to understand the dispersion interactions between molecules and to provide information about the potential energy surface of geometry evolutions, NbN12- and N2·NbN12- complexes were investigated by using photoelectron spectroscopy and ab initio calculations. The experimental adiabatic detachment energy (ADE) and vertical detachment energy (VDE) of NbN12- were both measured to be 2.129 ± 0.030 eV. The experimental ADE and VDE of N2·NbN12- were measured to be 2.17 ± 0.05 and 2.23 ± 0.05 eV, respectively, which are slightly higher than those of NbN12-. The structures of NbN12-/0 were confirmed to be hexacoordinated octahedrons. The investigation of N2·NbN12- structures shows that it is stable for N2 to bind to the face or vertex site of octahedron NbN12-; the face-side-on structure has the lowest energy. The calculations based on symmetry-adapted perturbation theory suggest that the dispersion term is predominant and leads to the stability of N2·NbN12- complexes., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Cardiac remodeling and diastolic dysfunction in patients with aldosterone-producing adenomas (APA) can be improved after adrenalectomy. However, the effect of mineralocorticoid receptor antagonist (MRA) treatment remains unclear. The aim of this study is to evaluate the effect of MRA on cardiac remodeling and diastolic dysfunction in patients with PA. We prospectively enrolled patients with APA from 1993 to 2023, who either received medical treatment with MRAs or underwent adrenalectomy. Biochemical characteristics and echocardiographic findings were collected at baseline and one year after treatment. Propensity score matching was conducted based on baseline biochemical characteristics, left ventricular mass index (LVMI), and diastolic function. A total of 467 APA patients were enrolled in the study. After propensity score matching, 159 patients who underwent adrenalectomy were matched with 159 patients who received MRAs. After therapy, patients who received MRAs showed significant improvement in diastolic function after one year of treatment but not LVMI. Compared to the MRA group, the adrenalectomy group had greater improvement in systolic blood pressure, plasma aldosterone concentration, plasma renin activity, aldosterone-to-renin ratio, and LVMI. In multivariable regression analysis, pretreatment echocardiographic values were significantly associated with changes in both LVMI and E/e', while the treatment strategy showed a significant association with changes in LVMI. Thus, one year after therapy, both adrenalectomy and MRA are effective in improving diastolic function in patients with APA. However, adrenalectomy is more effective than MRA treatment in reversing cardiac remodeling in patients with APA., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

The advancement of rational nano drug delivery systems offers robust tools for achieving synergistic therapeutic outcomes in tumor treatment. In this study, we present the development of pH and near-infrared laser dual-responsive nanoparticles (DOX-CuS@CaCO 3 @PL-PEG, DCCP NPs) based on calcium carbonate, utilizing a one-pot gas diffusion reaction. These nanoparticles enable combined photothermal therapy (PTT), chemodynamic therapy (CDT), chemotherapy, and Ca 2+ -overloading synergistic therapy. Doxorubicin (DOX) and copper sulfide (CuS) NPs were co-loaded in CaCO 3 , followed by PEG surface functionalization. The presence of PEG enhanced the stability of DCCP NPs in aqueous environments. Controlled release of DOX, CuS NPs, and Ca 2+ occurs specifically in the acidic tumor microenvironment. Released DOX enhances chemotherapy efficiency, while CuS NPs, upon laser irradiation, induce thermal damage, promoting further drug release and cellular uptake. Additionally, CuS NPs in our system consume excess GSH and generate toxic hydroxyl radicals (·OH) through a Fenton-like reaction, contributing to CDT. These radicals not only directly eliminate tumor cells but also disrupt mitochondrial Ca 2+ buffering capacity. Furthermore, Ca 2+ released from CaCO 3 induces Ca 2+ -overloading, intensifying mitochondrial disruption and oxidative damage. The synergistic combination of PTT, CDT, chemotherapy, and Ca 2+ -overloading showcases significant therapeutic potential, indicating broad applications in tumor therapy. This multifaceted approach holds promise for advancing the field of tumor therapeutics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Recurrent preimplantation embryo developmental arrest (RPEA) is the most common phenotype in assisted reproductive technology treatment failure associated with identified genetic abnormalities. Currently known maternal genetic variants explain only a limited number of cases. Variants of the β-tubulin subunit gene, TUBB8 , cause oocyte meiotic arrest and RPEA through a broad spectrum of spindle defects. In contrast, α-tubulin subunit genes are poorly studied in the context of preimplantation embryonic development., Methods: Whole exome sequencing was performed on the PREA cohort. Functional characterisations of the identified candidate disease-causing variants were validated using Sanger sequencing, bioinformatics, in vitro functional analyses and single-cell RNA-sequencing of arrested embryos., Results: Four homozygous variants were identified in the PREA cohort: two of TUBA1C (p.Gln358Ter and p.Asp444Metfs*42) and two of TUBA4A (p.Arg339Cys and p.Tyr440Ter). These variants cause varying degrees of spindle assembly defects. Additionally, we characterised changes in the human arrested embryo transcriptome carrying TUBA4A variants, with a particular focus on spindle organisation, chromosome segregation and mRNA decay., Conclusion: Our findings identified TUBA1C as a novel genetic marker and expanded the genetic and phenotypic spectrum of TUBA4A in female infertility and RPEA, which altogether highlighted the importance of α-tubulin isotypes in preimplantation embryonic development., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: This study aimed to investigate the EEG microstate characteristics in patients with persistent Omicron-related Psychiatric Symptoms (ORPS) as well as their correlations with the severity of ORPS., Methods: This study included 31 patients with ORPS, and they were divided into remission group (n=19) and non-remission group (n=12) according to the decrease of Brief Psychiatric Rating Scale (BPRS) at discharge. Multivariate logistic models were applied to analyze the risk features associated with non-remission of ORPS at discharge, and the Spearman rank correlation was adopted to analyze the correlation between the occurrence of microstate class B and BPRS score at admission., Results: The analysis revealed that an increased occurrence of EEG microstate class B was significantly associated with a higher likelihood of non-remission of ORPS at discharge (p < 0.05). Furthermore, a moderate positive correlation was observed between the occurrence of microstate class B and BPRS scores at admission (r = 0.390, p = 0.030), indicating that patients with more frequent microstate class B tended to exhibit more severe psychiatric symptoms at onset., Conclusions: The findings suggest that an increased occurrence of EEG microstate class B is an independent risk factor for non-remission of ORPS at discharge. Additionally, the positive correlation between microstate class B and BPRS scores underscores the potential of microstate class B as a biomarker for the severity of psychiatric symptoms in ORPS patients., Significance: Identifying the increased occurrence of microstate class B at admission could serve as a novel marker for early assessment of ORPS severity and prognostic evaluation., Competing Interests: Declaration of Competing Interest None of the authors has any conflict of interest to disclose. We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines., (Copyright © 2024. Published by Elsevier Inc.)

Background: Ticks represent a significant vector for the transmission of infectious diseases, with the prevalence of tick-borne diseases becoming a prominent global health concern in recent decades. Anaplasma spp., Rickettsia spp., and Piroplasma have been identified as significant pathogens with the potential to impact human and animal health. However, there is a dearth of data concerning the prevalence of these pathogens in the eastern Tibetan Plateau, China., Methods: In this study, a total of 643 Dermacentor silvarum and 314 Haemaphysalis longicornis were identified through the application of morphological and molecular identification techniques on 957 ticks collected from yaks in Zoige County. The assessed of Anaplasma spp., Rickettsia spp., Theileria spp., and Babesia spp. was assessed in 957 ticks and 96 blood samples collected from yaks., Results: Significant discrepancies were observed in the positivity rates for the four pathogens among the tick species and sampling sites. The identification of different species within the four pathogens was based on the analysis of the 16S rRNA of Anaplasma spp., the ompA and ompB genes of Rickettsia spp., and the 18S rRNA of Theileria spp. and Babesia spp. The prevalence ranges of the four pathogens are 9.9-50.2%, 29.5-100%, 16.2-46.4%, and 14.5-58.4%, respectively., Conclusion: In view of the growing zoonotic risks, further investigations into the prevalence of additional pathogens in ticks and animals, including livestock, in the eastern Tibetan Plateau, China, are essential., Competing Interests: The authors declare that the research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xiang, He, Zhu, Xiao, Pan, Chen, Zheng, Yuan and Hao.)

Background: Atropine is an effective medicine for myopia prevention and control. This meta-analysis was conducted to investigate the effects of atropine on choroidal thickness (ChT) in children with myopia., Methods: Between its inception and 1 June 2023, Medline, Embase, and Web of Science were all searched, and only English literature was included. The choroidal thickness was the primary study outcome. Axial length, standardized equivalent refraction were examined as secondary outcomes. STATA 12.0 was used for data extraction and analysis., Results: A total of 307 eyes were involved in this study to evaluate the effect of atropine on ChT, axial length (AL) and standardized equivalent refraction (SER) in myopic children. Choroidal thickening was significantly higher in the atropine group than in the control group at 1 month (WMD, 6.87 mm, 95% CI, 0.04 to 13.10, P = 0.049), whereas it was significantly higher in the atropine group than in the control group at months 6 (WMD, 10.37 mm, 95% CI, -3.21 to 23.95, P = 0.135), 12 (WMD, 15.10 mm, 95% CI, -5.08 to 35.27, P = 0.143) and at final follow-up (WMD, 11.52 mm, 95% CI, -3.26 to 26.31, P = 0.127), the differences were not statistically significant. At months 1 (WMD, -0.03 mm, 95% CI, -0.04 to -0.01, P = 0.003), 6 (WMD, -0.07 mm, 95% CI, -0.01 to -0.03, P = 0.000), 12 (WMD, -0.13mm, 95% CI, -0.15 to -0.11, P = 0.843), and at final follow-up (WMD, -0.08 mm, 95% CI, -0.16 to -0.01, P = 0.127), atropine treatment was able to delay the axial elongation. At 1-month follow-up, there was no significant difference in the effect of atropine on SER in myopic children compared with the control group (WMD, 0.01D, 95% CI, -0.07 to 26.31, P = 0.127), whereas it was able to control the progression of refractive status at final follow-up (WMD, 11.52 mm, 95% CI, -3.26 to 26.31, P = 0.127)., Conclusion: Limited evidence suggests that 0.01% atropine causes choroidal thickening in myopic children at 1 month of treatment. In the short term, choroidal thickness may be a predictor of the effectiveness of atropine in controlling myopia in children. 0.01% atropine is effective in controlling myopic progression in terms of SER and AL., Systematic Review Registration: http://www.crd.york.ac.uk/prospero, identifier, CRD42022381195., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yang, Wei, Wang and Zheng.)

Objective: To explore the longitudinal association between blood count-derived immunoinflammatory markers and the risk of epilepsy in a large population cohort., Methods: We used data from the UK Biobank (UKB) to investigate the association between pre-diagnostic peripheral immunoinflammatory cells and their derived ratios, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), and the risk of epilepsy. This was a longitudinal cohort study in which multivariate Cox proportional hazards models and a series of sensitivity and subgroup analyses were performed to explore the nature of these associations., Results: We examined these associations in a prospective UKB cohort of 497,291 participants. During a median follow-up of 12.43 years, 2,715 participants developed epilepsy. After adjusting for all covariates, the results showed that higher monocyte counts and some blood count-derived immunoinflammatory metrics (monocyte counts, hazard ratio [HR]=1.093, 95 % confidence interval [CI] 1.052-1.136, P<0.001; NLR, HR=1.062, 95 % CI 1.022-1.103, P=0.002; PLR, HR=1.096, 95 % CI 1.055-1.139, P<0.001; SII, HR=1.041, 95 % CI 1.003-1.082, P=0.036) were associated with an increased risk of epilepsy. Conversely, we found that higher lymphocyte counts and LMR were negatively associated with the risk of epilepsy (lymphocyte count, HR=0.889, 95 % CI 0.856-0.923, P < 0.001; LMR, HR=0.85, 95 % CI 0.82-0.881, P < 0.001)., Conclusions: Monocyte count, NLR, PLR, and SII increased the risk of epilepsy, whereas lymphocyte count and LMR decreased it. Further studies will help translate these findings into clinical practice or targeted treatments., Competing Interests: Declaration of competing interest None of the authors has any conflict of interest to disclose. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines., (Copyright © 2024 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

The low cultivability of environmental bacteria has been widely acknowledged, but most previous estimates focused on the proportion of cultivable cells rather than cultivable taxa. Here, we estimate the proportions of cultivable cells and cultivable taxa for two sample types (soil and activated sludge) using cell counting, 16S rRNA gene amplicon sequencing, metagenomics, and cultivation on agar plates under various conditions. We find that the proportion of cultivable taxa exceeds that of cultivable cells at the sample level. A large proportion of cultivable taxa are taxonomically novel but tend to be present at very low abundance on agar plates, forming microcolonies, and some of them cease to grow during subculture. Compared with uncultivable taxa (under the conditions used in our study), cultivatable taxa tend to display higher metabolic activity as inferred by measuring rRNA copies per cell. Finally, we use the generated taxonomic and genomic information as a guide to isolate a strain representing a yet-uncultured class within the Bacteroidota and to enhance the cultivable diversity of Burkholderiales from activated sludge., (© 2024. The Author(s).)

Utidelone is an ebomycin derivative chemotherapeutic drug, which can promote tubulin polymerization and stabilize microtubule structure, so as to induce apoptosis. The drug is an innovative drug independently developed by China with independent intellectual property rights. Phase II clinical trials for advanced breast cancer are being approved by National Medical Products Administration for the treatment of advanced breast cancer. However, there is no report on the application in non-small cell lung cancer (NSCLC) patients with the epidermal growth factor receptor (EGFR) mutation. This case is a patient with EGFR mutant stage IV NSCLC who has progressed after third-line targeted therapy. The fourth line was treated with utidelone combined with pabolizumab. The patient had progressed after targeted therapy with oxitinib, ametinib, and vometinib. Due to the patient's physical reasons, the traditional platinum drugs were not suitable, so the patient was treated with utidelone combined with pabolizumab. The curative effect was evaluated as SD after two cycles and progesterone receptor after four cycles. At present, it is still in the maintenance of reduction of utidelone combined with pabolizumab, and the tumor continues to shrink. Although peripheral neurotoxicity occurred during treatment, it improved after symptomatic treatment. The treatment of EGFR mutant stage IV NSCLC with utidelone combined with pabolizumab has good effect and mild adverse reactions., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Exchangeable aluminum (Al) ions released from acidic soils with pH < 5.5 inhibit root elongation of crops, ultimately leading to yield reduced. It is necessary to identify the quantitative trait locus (QTLs) and candidate genes that confer toxicity resistance to understand the mechanism and improve tolerance of rapeseed. In this study, an F 2 segregating population was derived from a cross between Al-tolerance inbred line FDH188 (R178) and -sensitive inbred line FDH152 (S169), and the F 2:3 were used as materials to map QTLs associated with the relative elongation of taproot (RET) under Al toxicity stress. Based on bulked segregant analysis sequencing (BSA-seq), three QTLs ( qAT-A07-1 , qAT-A07-2 , and qAT-A09-1 ) were detected as significantly associated with RET, and 656 candidate genes were screened. By combined BSA and RNA-seq analysis, 55 candidate genes showed differentially expressed, including genes encoding ABC transporter G (ABCG), zinc finger protein, NAC, ethylene-responsive transcription factor (ERF), etc. These genes were probably positive factors in coping with Al toxicity stress in rapeseed. This study provides new insight into exploring the QTLs and candidate genes' response to Al toxicity stress by combined BSA-seq and RNA-seq and is helpful to further research on the mechanism of Al resistance in rapeseed.

We investigate the structures and properties of Ge 4 C -/0 and Ge 4 CH -/0 clusters using anion photoelectron spectroscopy and theoretical calculations. Our calculations show that the first two low-lying isomers coexist in the experiments of Ge 4 C - and Ge 4 CH - . The first two low-lying isomers of Ge 4 C - have trigonal bipyramidal structures with the C atom on the equatorial plane and the top vertex, respectively. It is found that the first two low-lying isomers of Ge 4 CH - can be obtained by adding an H atom to the top and equatorial C atoms of Ge 4 C - , respectively. The AdNDP analyses reveal that the C atom in Ge 4 C forms one 4c-2e σ bond, two 4c-2e π bonds, and one 5c-2e σ bond with Ge atoms. The C atom in Ge 4 C interacts with an H - forming a C-H σ bond in Ge 4 CH - . AIMD simulation results indicate high dynamic stabilities of Ge 4 C and Ge 4 CH - at 300 and 500 K. Our results show that the structures and chemical bonding of Ge 4 B - and Ge 4 N + are similar to those of Ge 4 C, while those of Ge 4 BH 2- and Ge 4 NH resemble those of Ge 4 CH - .

Material stability is the focus on both experiments and calculations, which includes the energetic stability at the static state and the thermodynamic stability at the kinetic state. To show whether energetics or kinetics dominates on material stability, this study focuses on the Pd 13 clusters, because of their observable magnetic moment in experiment. Energetically, the CALYPSO searching method and first-principles calculations find that Pd 13 (C 2 ) is the ground state at 0 K while the static frequency calculations demonstrate that the icosahedron Pd 13 (I h ) becomes more favorable on free energy as temperature increases. However, their magnetic moments (8 μ B ) are not in agreement with the experimental value (<5.2 μ B ). Kinetically, ab initio molecular dynamics simulations reveal that Pd 13 (C 3v ) (6 μ B ) has supreme isomerization temperature and the other 11 low-lying isomers transform to Pd 13 (C 3v ) directly or indirectly, demonstrating that Pd 13 (C 3v ) has the maximum probability to be observed in experiment. The magnetic moment difference between experiment (<5.2 μ B ) and this calculation (6 μ B ) may be due to the spin multiplicities. Our result suggests that the magnetic moment disparity between theory and experiment (in Pd 13 clusters) originates from the kinetic stability.

Understanding the emergence and evolution of collective dynamics in large-scale neural networks remains a complex challenge. This paper seeks to address this gap by applying dynamical systems theory, with a particular focus on tipping mechanisms. First, we introduce a novel (n+mn)-scale radial-ring neural network and employ Coates' flow graph topological approach to derive the characteristic equation of the linearized network. Second, through deriving stability conditions and predicting the tipping point using an algebraic approach based on the integral element concept, we identify critical factors such as the synaptic transmission delay, the self-feedback coefficient, and the network topology. Finally, we validate the methodology's effectiveness in predicting the tipping point. The findings reveal that increased synaptic transmission delay can induce and amplify periodic oscillations. Additionally, the self-feedback coefficient and the network topology influence the onset of tipping points. Moreover, the selection of activation function impacts both the number of equilibrium solutions and the convergence speed of the neural network. Lastly, we demonstrate that the proposed large-scale radial-ring neural network exhibits stronger robustness compared to lower-scale networks with a single topology. The results provide a comprehensive depiction of the dynamics observed in large-scale neural networks under the influence of various factor combinations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Biliary tract cancer (BTC) is potentially influenced by metabolic dysregulation yet previous metabolomic evaluations are limited. To address this gap, we prospectively investigated associations of blood metabolites and BTC risk in the UK biobank cohort study. We used Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) between 249 plasma metabolites per standard deviation and BTC risk in 232,781 participants. We implemented exploratory factor analyses and evaluated associations between factors and BTC risk. Associations at p-value<0.001 were considered statistically significant after multiple comparison adjustments. In a median follow-up of 11.8 years, we identified 268 first primary incident BTC cases. Of 49 biomarkers significantly associated with BTC risk, 12% were fatty acids, and 49%, 31%, and 8% were cholesterol, triglyceride, and phospholipid to total lipids ratios, respectively. Multiple cholesterol ratios were inversely associated with BTC with HRs (95% CIs) of 0.74 (0.65-0.84), p<6.0x10-6. Conversely, a triglyceride ratio was positively associated with BTC with an HR (95% CI) of 1.40 (1.22-1.61), p=2.5x10-6. Congruently, a factor high in cholesterol measures and low in triglyceride measures was inversely associated with BTC. Multiple metabolite biomarkers were associated with BTC risk, suggesting metabolism has a substantial role in BTC etiology., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Asymptomatic intracranial atherosclerotic stenosis (aICAS) is a major risk factor for cerebrovascular events. The study aims to construct and validate a nomogram for predicting the risk of aICAS. Participants who underwent health examinations at our center from September 2019 to August 2023 were retrospectively enrolled. The participants were randomly divided into a training set and a testing set in a 7:3 ratio. Firstly, in the training set, least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression were performed to select variables that were used to establish a nomogram. Then, the receiver operating curves (ROC) and calibration curves were plotted to assess the model's discriminative ability and performance. A total of 2563 neurologically healthy participants were enrolled. According to LASSO-Logistic regression analysis, age, fasting blood glucose (FBG), systolic blood pressure (SBP), hypertension, and carotid atherosclerosis (CAS) were significantly associated with aICAS in the multivariable model (adjusted P < 0.005). The area under the ROC of the training and testing sets was, respectively, 0.78 (95% CI: 0.73-0.82) and 0.65 (95% CI: 0.56-0.73). The calibration curves showed good homogeneity between the predicted and actual values. The nomogram, consisting of age, FBG, SBP, hypertension, and CAS, can accurately predict aICAS risk in a neurologically healthy population., (© 2024. The Author(s).)

The relevant mechanism of tumor-associated macrophages (TAMs) in the treatment of colorectal cancer patients with immune checkpoint inhibitors (ICIs) is discussed, and the application prospects of TAMs in reversing the treatment tolerance of ICIs are discussed to provide a reference for related studies. As a class of drugs widely used in clinical tumor immunotherapy, ICIs can act on regulatory molecules on cells that play an inhibitory role-immune checkpoints-and kill tumors in the form of an immune response by activating a variety of immune cells in the immune system. The sensitivity of patients with different types of colorectal cancer to ICI treatment varies greatly. The phenotype and function of TAMs in the colorectal cancer microenvironment are closely related to the efficacy of ICIs. ICIs can regulate the phenotypic function of TAMs, and TAMs can also affect the tolerance of colorectal cancer to ICI therapy. TAMs play an important role in ICI resistance, and making full use of this target as a therapeutic strategy is expected to improve the immunotherapy efficacy and prognosis of patients with colorectal cancer., 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.)

Background: In recent years, studies have confirmed the predictive capability of spectral computer tomography (CT) in determining microvascular invasion (MVI) in patients with hepatocellular carcinoma (HCC). Discrepancies in the predicted MVI values between conventional CT imaging features and spectral CT parameters necessitate additional validation., Methods: In this retrospective study, 105 cases of small HCC were reviewed, and participants were divided into MVI-negative (n=53, Male:48 (90.57%); mean age, 59.40 ± 11.79 years) and MVI-positive (n=52, Male:50(96.15%); mean age, 58.74 ± 9.21 years) groups using pathological results. Imaging features and iodine density (ID) obtained from three-phase enhancement spectral CT scans were gathered from all participants. The study evaluated differences in imaging features and ID values of HCC between two groups, assessing their diagnostic accuracy in predicting MVI occurrence in HCC patients. Furthermore, the diagnostic efficacy of imaging features and ID in predicting MVI was compared., Results: Significant differences were noted in the presence of mosaic architecture, nodule-in-nodule architecture, and corona enhancement between the groups, all with p-values < 0.001. There were also notable disparities in IDs between the two groups across the arterial phase, portal phase, and delayed phases, all with p-values < 0.001. The imaging features of nodule-in-nodule architecture, corona enhancement, and nonsmooth tumor margin demonstrate significant diagnostic efficacy, with area under the curve (AUC) of 0.761, 0.742, and 0.752, respectively. In spectral CT analysis, the arterial, portal, and delayed phase IDs exhibit remarkable diagnostic accuracy in detecting MVI, with AUCs of 0.821, 0.832, and 0.802, respectively. Furthermore, the combined models of imaging features, ID, and imaging features with ID reveal substantial predictive capabilities, with AUCs of 0.846, 0.872, and 0.904, respectively. DeLong test results indicated no statistically significant differences between imaging features and IDs., Conclusions: Substantial differences were noted in imaging features and ID between the MVI-negative and MVI-positive groups in this study. The ID and imaging features exhibited a robust diagnostic precision in predicting MVI. Additionally, our results suggest that both imaging features and ID showed similar predictive efficacy for MVI., Competing Interests: Authors XML and ZS are employed by Philips China Investment Co. 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 Lv, Li, Mu, Zheng, Yang, Huang, Liu, Liu, Song, Qin and Zhu.)

Two new polycyclic polyprenylated acylphloroglucinols, along with four previously known compounds, were isolated and identified from the fruits of Garcinia oblongifolia. The structures of these compounds were elucidated through a combination of spectroscopic techniques, including MS, UV, IR, and 1D/2D NMR, as well as their chemical properties. Additionally, the cytotoxic activities of compounds 1‒6 against the H134B cell line were evaluated using the MTT assay, revealing that compounds 1 and 2 exhibit promising antitumor activity., (© 2024 Wiley‐VCH GmbH.)

Purpose: To compare the clinical efficacy of 3D-printed artificial discs with that of ACDF for treating cervical spondylosis., Methods: This was a retrospective analysis of 73 patients with single-level cervical spondylosis who met the inclusion criteria between January 2020 and December 2022 at XX Hospital. The patients were divided: 38 patients in the ACDF group and 35 patients in the CADR group. Patient general information, including operation time and intraoperative blood loss, was collected. The clinical effect of the combination therapy was evaluated by the VAS, JOA, and NDI. The radiological effect was evaluated using the ROM test. Ethics No. 201,606,009., Results: The average follow-up times in the ACDF and CADR groups were 28.24 ± 4.65 and 29.11 ± 5.06 months, respectively (P = 0.443). Clinical symptoms (evaluated by VAS, NDI, and JOA) are significantly improved in both the ACDF and CADR groups with similar efficacy. The preoperative ROM of the ACDF group was 40.03 ± 8.79, while that of the CADR group was 42.11 ± 7.98 (P = 0.293). However, the postoperative ROM in the ACDF group was 35.29 ± 7.23, which was lower than that in the CADR group (40.43 ± 6.98) (P = 0.003). Furthermore, only one patient in the ACDF group experienced mild dysphagia after surgery, and the patient recovered within three days. ASD occurred in nine patients in the ACDF group and in two patients in the CADR group (Χ²=4.597, P = 0.032)., Conclusions: Compared with ACDF, 3D-printed artificial discs for treating single-level cervical spondylosis have proven to be clinically effective; it associated with less blood loss and a lower incidence of ASD, and maintain a better cervical ROM., (© 2024. The Author(s) under exclusive licence to SICOT aisbl.)

Biochar is a porous carbon material generated by the thermal treatment of biomass under anaerobic or anoxic conditions with wealthy Oxygen-containing functional groups (OCFGs). To date, OCFGs of biochar have been extensively studied for their significant utility in pollutant removal, catalysis, capacitive applications, etc. This review adopted a whole system philosophy and systematically summarizes up-to-date knowledge of formation, detection methods, engineering, and application for OCFGs. The formation mechanisms and detection methods of OCFGs, as well as the relationships between OCFGs and pyrolysis conditions (such as feedstocks, temperature, atmosphere, and heating rate), were discussed in detail. The review also summarized strategies and mechanisms for the oxidation of biochar to afford OCFGs, with the performances and mechanisms of OCFGs in the various application fields (environmental remediation, catalytic biorefinery, and electrode material) being highlighted. In the end, the future research direction of biochar OCFGs was put forward., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Rare diseases affect one in ten people but only a small fraction of these diseases have an FDA-approved treatment. Haploinsufficiency, caused by a dominant loss-of-function mutation, is a unique rare disease group because patients have one normal allele of the affected gene. This makes rare haploinsufficiency diseases promising candidates for drug development by increasing expression of the normal gene allele, decreasing the target protein degradation and enhancing the target protein function. This review summarizes recent progresses and approaches used in the translational research of therapeutics to treat haploinsufficiency diseases including gene therapy, nucleotide-based therapeutics and small-molecule drug development. We hope that these drug development strategies will accelerate therapeutic development to treat haploinsufficiency diseases., (Published by Elsevier Ltd.)

Background: Chronic hepatitis B virus (HBV) infection remains a serious health issue, and determining the optimal time for antiviral therapy is challenging. We aimed to assess liver histological changes in patients with HBeAg-positive chronic hepatitis B (CHB) and those with HBeAg-negative CHB who had persistently normal alanine aminotransferase and to determine the association between significant liver injury and various clinical parameters., Methods: We retrospectively included, in this study, 339 treatment-naïve patients with chronic HBV infections who had persistently normal alanine aminotransferase and underwent liver biopsy from 2013 to 2023. Histologic assessment was based on the Metavir scoring system to evaluate the association between clinical characteristics and the severity of liver inflammation and fibrosis., Results: Among the included participants, 138 were HBeAg-positive and 201 were HBeAg-negative. Lower hepatitis B surface antigen (HBsAg) (P = 0.003) and higher aspartate aminotransferase (AST) (P = 0.002) levels were associated with significant necroinflammation, whereas increasing age (P = 0.004) and lower HBV DNA (P < 0.001) levels were associated with significant fibrosis in HBeAg-positive patients with normal ALT levels. Higher HBV-DNA (P = 0.001) and AST levels(P < 0.001) were associated with significant necroinflammation, and higher AST(P < 0.001) levels were associated with significant fibrosis in HBeAg-negative patients., Conclusions: A substantial proportion of patients with HBV infection who had normal ALT presented significant liver injury. HBsAg and AST were independent predictive factors for evaluating inflammation, while HBV DNA load and age were independent predictive factors for evaluating fibrosis in the HBeAg-positive group. HBV DNA load and AST were independent predictive factors for evaluating inflammation, while AST were independent predictive factors for evaluating fibrosis in the HBeAg-negative group., (© 2024. The Author(s).)

Traumatic brain injury (TBI) frequently results in cardiac dysfunction and impacts the quality of survivors' life. It has been reported that carbon monoxide-releasing molecule-3 (CORM-3) administration immediately after hemorrhagic shock and resuscitation (HSR) ameliorated the HSR‑induced cardiac dysfunctions. The purpose of this study was to determine whether the application of CORM-3 on TBI exerted therapeutic effects against TBI-induced cardiac dysfunctions. Rats were randomly divided into four groups (n = 12) including Sham, TBI, TBI/CORM-3 and TBI/inactive CORM-3 (iCORM-3) groups. TBI was established by a weight-drop model. The rats in the TBI/CORM-3 group and TBI/iCORM-3 group were intravenously injected with CORM-3 and iCORM-3 (4 mg/kg) following TBI, respectively. The time of death in the rats that did not survive within 24 h was recorded. 24 h post-trauma, the cardiac function, pathological change, serum troponin T and creatine kinase-MB (CK-MB) levels, pyroptosis, apoptosis and expressions of TUNEL staining, Gasdermin D (GSDMD), IL-1β, IL-18, ratio Bax/Bcl-2 were assessed by echocardiography, hematoxylin-eosin staining, chemiluminescence, immunofluorescence, and western blot assays, respectively. TBI-treated rats exhibited dramatically decreased ejection fraction and aggravated myocardial injury, increased mortality rate, elevated levels of serum troponin T and CK-MB, promoted cardiac pyroptosis and apoptosis, and upregulated expressions of cleaved caspase-3, GSDMD N-terminal fragments, IL-1β, IL-18, and ratio of Bax/Bcl-2, whereas CORM-3 partially reversed these changes. CORM-3 ameliorated TBI-induced cardiac injury and dysfunction. This mechanism may be responsible for the inhibition of pyroptosis and apoptosis in cardiomyocyte., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The synthesis of novel water-soluble polymers with biodegradability is an effective way to mitigate their negative environmental impacts. In this study, semi-aromatic copolyester poly(butylene succinate-co-butylene terephthalate) (PBST) with exceptional biodegradability is used as the resin matrix. Anionic sodium 1-3-isophthalate-5-sulfonate (SIPA) is introduced as a fourth monomer to prepare random poly(butylene succinate-co-butylene terephthalate-co-butylene 5-sodiosulfoisophthalate) (PBSTS) copolyesters by melt copolymerization. The incorporation of ionic groups enhances the hydrophilicity and water absorption of the copolyesters, resulting in water-soluble materials that exhibit ionic and temperature responsivity. Furthermore, the ionized biodegradable copolyesters demonstrate distinct pH-dependent degradation, which is accelerated at pH = 5.5 and 8.5 but inhibited at pH = 7.2. Degradation assessments in simulated body fluids reveal that the PBSTS copolyesters exhibit significant degradation in gastric fluids at pH = 1.5 with minimal degradation in intestinal fluids at pH = 6.8 and in body fluids at pH = 7.0. This unique degradation performance highlights the potential of these materials for addressing the challenges associated with selective drug delivery and localized controlled release in the human body., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Objectives: To evaluate changes in the age at menarche in Asian populations., Study Design: Retrospective cohort study., Methods: We included 548,830 women from six countries in Asia. The data were sourced from 20 cohorts participating in the Asia Cohort Consortium (ACC) and two additional cohort studies: Japan Multi-institutional Collaborative Cohorts (J-MICC), and Japan Nurse Health Study (JNHS) with data on age at menarche. Joinpoint regression was used to evaluate changes in age at menarche by birth year and by country., Results: The study includes data from cohorts in six Asian countries namely, China, Iran, Japan, Korea, Malaysia and Singapore. Birth cohorts ranged from 1873 to 1995. The mean age of menarche was 14.0 years with a standard deviation (SD) of 1.4 years, ranged from 12.6 to 15.5 years. Over 100 years age at menarche showed an overall decrease in all six countries. China showed a mixed pattern of decrease, increase, and subsequent decrease from 1926 to 1960. Iran and Malaysia experienced a sharp decline between about 1985 and 1990, with APC values of -4.48 and -1.24, respectively, while Japan, South Korea, and Singapore exhibited a nearly linear decline since the 1980s, notably with an APC of -3.41 in Singapore from 1993 to 1995., Conclusions: Overall, we observed a declining age at menarche, while the pace of the change differed by country. Additional long-term observation is needed to examine the contributing factors of differences in trend across Asian countries. The study could serve as a tool to strengthen global health campaigns., (Copyright © 2024 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Background: We aimed to explore the association of socioeconomic status (SES) and life's essential 8 (LE8) with cardiovascular disease (CVD) and all-cause mortality in north China., Methods: A total of 91,365 adults from the Kailuan study were included in this study. Comprehensive individual SES, mainly including monthly household income, education, Occupation position, and community environment, was confirmed by latent class analysis. Furthermore, the mediation and combination effects of SES and LE8 on CVD and all-cause mortality were further assessed. The Cox regression model was conducted to estimate HRs and 95% CI., Results: During about 13 years of follow-up, 7,646 cardiovascular events and 11,749 deaths were recorded. Relative to the high SES, there were decreased risks of CVD [HR (95% CI): 1.57(1.43-1.72)] and high all-cause death [HR (95% CI): 1.43(1.31-1.53)] in the low SES. The associations between SES and CVD [Mediation % (95% CI): 22.3 (16.4-30.4)] and mortality [Mediation % (95% CI): 10.1 (7.1-14.0)] were partially mediated by LE8 when comparing medium SES to high SES. Meanwhile, relative to high LE8, the elevated risk of death [HR (95% CI): 1.72(1.56-1.89)], and incident CVD [HR (95% CI): 3.34(2.91-3.83)] were detected in low LE8. Compared to participants who had the high SES and LE8, participants who had both the low SES and LE8 further increased the risk of CVD [HR (95% CI): 7.76(5.21-11.55)] and all-cause mortality [HR (95% CI): 2.80(2.19-3.58)]., Conclusion: Low SES was related to a higher risk of CVD and mortality in low- and middle-income countries, which was partially mediated by LE8., (© 2024. The Author(s).)

Photoelectron spectroscopy and theoretical calculations have identified the global minimum structure of the 16-valence electron Si 3 Cu 3 - cluster, which features a planar tetracoordinate silicon (ptSi) in a rhombic arrangement. The Si 3 and Cu 3 triangles are interconnected by a Si 2 /Cu 2 edge, forming an ordered chain-like structure. Besides the conventional 2c-2e σ-bond connecting Si 3 and Cu 3 , the stability of this cluster is reinforced by a delocalized 3c-2e σ-bond in Cu 3 and a π-bond in Si 3 . Our study provides experimental confirmation of a planar hypercoordinate heavier Group 14 element, opening possibilities for exploring similar structures in two-dimensional materials., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Family history of lung cancer (FHLC) has been widely studied but most prospective cohort studies have primarily been conducted in non-Asian countries. We assessed the association between FHLC with risk of lung cancer (LC) incidence and mortality in a population of East Asian individuals. A total of 478,354 participants from 11 population-based cohorts in the Asia Cohort Consortium were included. A Cox proportional hazards regression model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 7,785 LC incident cases were identified. FHLC (any LC subtype) was associated with an increased risk of LC incidence (HR = 1.45, 95% CI = 1.30-1.63). The positive association was observed in men and women (HR = 1.44, 95% CI = 1.26-1.66 in men; HR = 1.47, 95% CI = 1.22-1.79 in women), and in both never-smokers and ever-smokers (HR = 1.43, 95% CI = 1.18-1.73 in never-smokers; HR = 1.46, 95% CI =1.27-1.67 in ever-smokers). FHLC was associated with an increased risk of lung adenocarcinoma (HR = 1.63, 95% CI: 1.36-1. 94), squamous cell carcinoma (HR = 1.88, 95% CI: 1.46-2.44), and other non-small cell LC (HR = 1.94, 95% CI: 1.02-3.68). However, we found no evidence of significant effect modification by sex, smoking status, and ethnic groups. In conclusion, FHLC was associated with increased risk of LC incidence and mortality, and the associations remained consistent regardless of sex, smoking status and ethnic groups among the East Asian population., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Background: To enhance the accuracy of hepatocellular carcinoma (HCC) diagnosis using contrast-enhanced (CE) US, the American College of Radiology developed the CEUS Liver Imaging Reporting and Data System (LI-RADS). However, the system still exhibits limitations in distinguishing between HCC and non-HCC lesions., Purpose: To investigate the viability of employing machine learning methods based on quantitative parameters of contrast-enhanced ultrasound for distinguishing HCC within LR-M nodules., Materials and Methods: This retrospective analysis was conducted on pre-treatment CEUS data from liver nodule patients across multiple centers between January 2013 and June 2022. Quantitative analysis was performed using CEUS images, and the machine learning diagnostic models based on quantitative parameters were utilized for the classification diagnosis of LR-M nodules. The performance of the model was assessed using the area under the receiver operating characteristic curve (AUC) and compared with the performance of four radiologists., Results: The training and internal testing datasets comprised 168 patients (median age, 53 years [IQR, 18 years]), while the external testing datasets from two other centers included 110 patients (median age, 54 years [IQR, 16 years]). In the internal independent test set, the top-performing Random Forest model achieved an AUC of 0.796 (95%CI: 0.729-0.853) for diagnosing HCC. This model exhibited a sensitivity of 0.752 (95%CI: 0.750-0.755) and a specificity of 0.761 (95%CI: 0.758-0.764), outperforming junior radiologists who achieved an AUC of 0.619 (95%CI: 0.543-0.691, p  < .01) with sensitivity and specificity of 0.716 (95%CI: 0.713-0.718) and 0.522 (95%CI: 0.519-0.526), respectively., Conclusion: Significant differences in contrast-enhanced ultrasound quantitative parameters are observed between HCC and non-HCC lesions. Machine learning models leveraging these parameters effectively distinguish HCC categorized as LR-M, offering a valuable adjunct for the accurate classification of liver nodules within the CEUS LI-RADS framework., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Background: The role of environmental factors in Alzheimer's disease (AD) pathogenesis remains elusive. Mounting evidence suggests that acute and past exposure to the environmental toxicant lead (Pb) is associated with longitudinal decline in cognitive function, brain atrophy, and greater brain β -amyloid ( A β ) deposition. However, the nature of Pb-induced amyloid deposition and how it contributes to AD development remain unclear., Objectives: This study investigates the role of Pb in the pathogenesis of cerebral amyloid angiopathy (CAA) and whether plasminogen activator inhibitor-1 (PAI-1) contributes to this process in the APP/PS1 mouse model., Methods: Female APP/PS1 mice at 8 wk of age were administered either 50 mg / kg Pb-acetate (PbAc) (i.e., 27 mg   Pb / kg ) or an equivalent molar concentration of sodium acetate (NaAc) via oral gavage once daily for 8 wk. Amyloid deposition and vascular amyloid were determined by immunostaining. In addition, A β perivascular drainage, vascular binding assay, and microglial endocytosis were examined to determine underlying mechanisms. Furthermore, magnetic resonance imaging demyelination imaging was performed in vivo measure the level of demyelination. Finally, Y-maze and Morris water maze tests were assessed to evaluate the cognitive function of mice., Results: APP/PS1 mice (an AD mice model) exposed to PbAc demonstrated more vascular amyloid deposition less neocortical myelination, and lower cognitive function, as well as greater vascular binding to A β 40 , higher A β 40 / A β 42 ratios, strikingly lower A β 40 levels in the perivascular drainage, and microglial endocytosis. Importantly, exposure to a specific PAI-1 inhibitor, tiplaxtinin, which previously was reported to lower CAA pathology in mice, resulted in less CAA-related outcomes following PbAc exposure., Discussion: Our findings suggest that PbAc induced CAA/AD pathogenesis via the PAI-1 signaling in the APP/PS1 mouse model, and the inhibition of PAI-1 could be a potential therapeutic target for PbAc-mediated CAA/AD disorders. https://doi.org/10.1289/EHP14384.

Competing Interests: Declaration of Competing Interest The authors declare no competing interests.