Organophosphate esters (OPEs) pollution characteristics, bioaccumulation and human consumption implication in wild marine organisms from the Yellow River Estuary, China.

As the substitutes of polybrominated diphenyl ethers, organophosphate esters (OPEs) with high concentrations have accumulated in the estuaries, bays, and harbors. However, limited information is available about the OPEs in the estuary organism categories, especially under the multiple industrial pressure. This study investigated the occurrence, bioaccumulation and human consumption implication in wild marine organisms from the Yellow River Estuary, where located many petroleum and chemical manufacturing industries. This study found that concentrations of Σ13OPEs ranged from 547 ng/L to 1164 ng/L in seawater (median: 802 ng/L), from 384 to 1366 ng/g dw in the sediment (median: 601 ng/g dw), and from 419 to 959 ng/g dw (median: 560 ng/g dw) in the marine organisms. The congener compositions in the organisms were dominated by alkyl-OPEs (80.7 %), followed by halogenated-OPEs (18.8 %) and aryl-OPEs (0.5 %). Based on the principal component analysis, petrochemical pollution, and industrial wastewater discharge were distinguished as the main plausible sources of OPEs to the YRE ecosystem. Most OPEs had potential or strong bioaccumulation capacity on the organisms, with a positive correlation between log BAF (Bioaccumulation Factor) and log Kow of OPEs. The highest estimated daily intake value of OPEs was tri-n-propyl phosphate, exceeding 300 ng/kg·bw/day via consuming fish. The highest hazard quotients from OPEs ranged from 0.001 to 0.1, indicating a low risk to human health by consuming marine organisms in the YRE. As the consumption of OPEs increases year by year, the risks of OPEs still cannot be ignored.

Measurement error in hydrostatic leveling system due to temperature effect and their reduction method.

Temperature is a crucial factor influencing the accuracy of the hydrostatic leveling system (HLS), necessitating a temperature compensation test for HLS. This paper investigates HLS temperature compensation through theoretical correction and experimental verification. The influence of temperature on the accuracy of hydrostatic level products is determined through temperature tests on 34 hydrostatic level products. The optimal temperature compensation formula is derived using the non-linear curve fitting method. The HLS is enhanced with a temperature compensation algorithm and temperature sensor, resulting in a new, high-precision, and high-stability hydrostatic leveling product with temperature compensation. Experimental findings reveal that the stability of the improved hydrostatic leveling product exceeds 30% compared to products on the market and surpasses 70% compared to the original products.

A cellular senescence-related signature for predicting prognosis, immunotherapy response, and candidate drugs in patients treated with transarterial chemoembolization (TACE).

BACKGROUND: Cellular senescence is essential to TME development, progression, and remodeling. Few studies have examined cellular senescence in HCC after TACE. Investigating the relationship between cellular senescence, post-TACE prognosis, the TME, and immune treatment responses is crucial. METHODS: We analyzed the GSE104580 dataset to identify DEGs. A cellular senescence-related signature was developed using LASSO Cox regression in the GSE14520 dataset and validated in the ICGC dataset. High- and low-risk subgroups were compared using GSVA and GSEA. Correlation studies were conducted to explore the relationship between the prognostic model, immune infiltration, immunotherapy response, and drug sensitivity. RESULTS: A cellular senescence-related signature comprising FOXM1, CDK1, CHEK1, and SERPINE1 was created and validated. High-risk patients showed significantly lower OS than low-risk patients. High-risk patients had carcinogenetic pathways activated, immunosuppressive cells infiltrated, and immunomodulatory genes overexpressed. They also showed higher sensitivity to EPZ004777_1237 and MK-2206_1053 and potential benefits from GSK-3 inhibitor IX, nortriptyline, lestaurtinib, and JNK-9L. CONCLUSIONS: This study constructed a cellular senescence-related signature that could be used to predict HCC patients' responses to and prognosis after TACE treatment, aiding in the development of personalized treatment plans.

Antireflective Superhydrophobic and Robust Coating Based on Chitin Nanofibers and Methylsilanized Silica for Outdoor Applications.

Antireflective coatings with superhydrophobicity have many outdoor applications, such as solar photovoltaic panels and windshields. In this study, we fabricated an omnidirectional antireflective and superhydrophobic coating with good mechanical robustness and environmental durability via the spin coating technique. The coating consisted of a layer of phytic acid (PA)/polyacrylamide (PAM)/calcium ions (Ca2+) (referred to as Binder), an antireflective layer composed of chitin nanofibers (ChNFs), and a hydrophobic layer composed of methylsilanized silica (referred to as Mosil). The transmittance of a glass slide with the Binder/ChNFs/Mosil coating had a 5.2% gain at a wavelength of 550 nm, and the antireflective coating showed a water contact angle as high as 160° and a water sliding angle of 8°. The mechanical robustness and environmental durability of the coating, including resistance to peeling, dynamic impact, chemical erosion, ultraviolet (UV) irradiation, and high temperature, were evaluated. The coating retained excellent antireflective capacity and self-cleaning performance in the harsh conditions. The increase in voltage per unit area of a solar panel with a Binder/ChNFs/Mosil coating reached 0.4 mV/cm2 compared to the solar panel exposed to sunlight with an intensity of 54.3 × 103 lx. This work not only demonstrates that ChNFs can be used as raw materials to fabricate antireflective superhydrophobic coatings for outdoor applications but also provides a feasible and efficient approach to do so.

Clinical efficacy of Gamma Knife® combined with transarterial chemoembolization and immunotherapy in the treatment of primary liver cancer.

BACKGROUND: This study was designed to investigate the clinical efficacy and safety of Gamma Knife® combined with transarterial chemoembolization (TACE) and immunotherapy in the treatment of primary liver cancer. AIM: To investigate the clinical efficacy and safety of Gamma Knife® combined with TACE and immune-targeted therapy in the treatment of primary liver cancer. METHODS: Clinical data from 51 patients with primary liver cancer admitted to our hospital between May 2018 and October 2022 were retrospectively collected. All patients underwent Gamma Knife® treatment combined with TACE and immunotherapy. The clinical efficacy, changes in liver function, overall survival (OS), and progression-free survival (PFS) of patients with different treatment responses were evaluated, and adverse reactions were recorded. RESULTS: The last follow-up for this study was conducted on October 31, 2023. Clinical evaluation of the 51 patients with primary liver cancer revealed a partial response (PR) in 27 patients, accounting for 52.94% (27/51); stable disease (SD) in 16 patients, accounting for 31.37% (16/51); and progressive disease (PD) in 8 patients, accounting for 15.69% (8/51). The objective response rate was 52.94%, and the disease control rate was 84.31%. Alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and alpha-fetoprotein isoform levels decreased after treatment compared with pretreatment (all P = 0.000). The median OS was 26 months [95% confidence interval (95%CI): 19.946-32.054] in the PR group and 19 months (95%CI: 14.156-23.125) in the SD + PD group, with a statistically significant difference (P = 0.015). The median PFS was 20 months (95%CI: 18.441-34.559) in the PR group and 12 months (95%CI: 8.745-13.425) in the SD + PD group, with a statistically significant difference (P = 0.002). Common adverse reactions during treatment included nausea and vomiting (39.22%), thrombocytopenia (27.45%), and leukopenia (25.49%), with no treatment-related deaths reported. CONCLUSION: Gamma Knife® combined with TACE and immune-targeted therapy is safe and effective in the treatment of primary liver cancer and has a good effect on improving the clinical benefit rate and liver function of patients.

Performance improvement of reflective phosphor film via adjusting the thickness realizing bright and efficient laser lighting.

Phosphor-in-glass-film (PiG-F) has been extensively investigated, showing great potential for use in laser lighting technique. Thickness is apparently a key parameter for PiG-F, affecting the heat dissipation, absorption, and reabsorption, thus determining the luminous efficacy and luminescence saturation threshold (LST). Conventional studies suggest that thinner films often have lower thermal load than that of the thicker ones. Unexpectedly, we found that the Lu3Al5O12:Ce (LuAG:Ce)-based PiG-F with a moderate thickness (78 µm) yielded the optimal LST of 31.9 W (14.2 W·mm-2, rather than 28.0 W (12.3 W·mm-2) for the thinnest one (56 µm). This unexpected result was further verified by thermal simulations. With the high saturation threshold together with a high luminous efficacy (∼296 lm·W-1), an ultrahigh luminous flux of 7178 lm with a luminous exitance of 2930 lm·mm-2 was thus attained. We believe the new, to the best of our knowledge, findings in this study will substantially impact the design principles of phosphors for laser lighting.

Study on the Occurrence Characteristics of the Remaining Oil in Sandstone Reservoirs with Different Permeability after Polymer Flooding.

After polymer flooding, the heterogeneity between different layers intensifies, forming intricate seepage channels and fluid diversions, which results in decreased circulation efficiency and lower recovery rates, leaving a significant amount of residual oil trapped within the reservoir. Understanding the characteristics of residual oil occurrence is crucial for enhancing oil recovery post-polymer flooding. This study focused on sandstone reservoirs with varying permeability in the Saertu block of the Daqing oilfield. Using cryosectioning and laser scanning confocal microscopy, the occurrence characteristics of the residual oil in these sandstone reservoirs post-polymer flooding were investigated. Additionally, micro-CT and scanning electron microscopy were employed to analyze the impact of the pore structure on the distribution characteristics of the residual oil. The results indicate that laser scanning confocal images reveal that post-polymer flooding, the residual oil in high- and low-permeability sandstone reservoirs predominantly exists in a bound state (average > 47%), mostly as particle-adsorbed oil. In contrast, the residual oil in medium-permeability reservoirs is primarily in a free state (average > 49%), mostly as intergranular-adsorbed oil. In high-permeability sandstone reservoirs, heavy oil components are mainly in a particle-adsorbed form; in medium-permeability sandstone reservoirs, residual oil predominantly consists of heavy components, with most light components occurring in a clustered form; in low-permeability sandstone reservoirs, clustered residual oil exists in a balanced coexistence of light and heavy components, while the heavy components primarily exist in a particle-adsorbed form. Post-polymer flooding, the large pore-throat structure in high-permeability sandstone reservoirs results in effective displacement and less free residual oil; medium-permeability sandstone reservoirs, with medium-large pores and throats, have preferential channels and fine particles blocking the throats, leading to some unswept pores and more free residual oil; low-permeability sandstone reservoirs, with small pores and throats, exhibit weak displacement forces and poor mobility, resulting in more bound residual oil. The distribution and content of clay particles and clay minerals, along with the complex microscopic pore structure, are the main factors causing the differences in the residual oil occurrence states in sandstones with varying permeability.

The GE296_RS03820 and GE296_RS03830 genes are involved in capsular polysaccharide biosynthesis in Riemerella anatipestifer.

Riemerella anatipestifer is a pathogenic bacterium that causes duck serositis and meningitis, leading to significant harm to the duck industry. To escape from the host immune system, the meningitis-causing bacteria must survive and multiply in the bloodstream, relying on specific virulence factors such as capsules. Therefore, it is essential to study the genes involved in capsule biosynthesis in R. anatipestifer. In this study, we successfully constructed gene deletion mutants Δ3820 and Δ3830, targeting the GE296_RS03820 and GE296_RS03830 genes, respectively, using the RA-LZ01 strain as the parental strain. The growth kinetics analysis revealed that these two genes contribute to bacterial growth. Transmission and scanning electron microscopy (TEM and SEM) and silver staining showed that Δ3820 and Δ3830 produced the altered capsules and compounds of capsular polysaccharides (CPSs). Serum resistance test showed the mutants also exhibited reduced C3b deposition and decreased resistance serum killing. In vivo, Δ3820 and Δ3830 exhibited markedly declining capacity to cross the blood-brain barrier, compared to RA-LZ01. These findings indicate that the GE296_RS03820 and GE296_RS03830 genes are involved in CPSs biosynthesis and play a key role in the pathogenicity of R. anatipestifer. Furthermore, Δ3820 and Δ3830 mutants presented a tendency toward higher survival rates from RA-LZ01 challenge in vivo. Additionally, sera from ducklings immunized with the mutants showed cross-immunoreactivity with different serotypes of R. anatipestifer, including 1, 2, 7 and 10. Western blot and SDS-PAGE assays revealed that the altered CPSs of Δ3820 and Δ3830 resulted in the exposure of some conserved proteins playing the key role in the cross-immunoreactivity. Our study clearly demonstrated that the GE296_RS03820 and GE296_RS03830 genes are involved in CPS biosynthesis in R. anatipestifer and the capsule is a target for attenuation in vaccine development.

High-sensitivity C-reactive protein predicts microalbuminuria progression in essential hypertensive patients: a 3-year follow-up study.

OBJECTIVES: To determine the independent effect of high-sensitivity C-reactive protein (hs-CRP) and the combined effects of hs-CRP and other traditional risk factors on microalbuminuria in hypertensive patients during the 3-year follow-up period. METHODS AND RESULTS: Baseline hs-CRP levels and other risk factors were measured in 280 adults in 2007. In the third year of examination, 199 patients (mean age 62.5 ±â€…9.5, men 59.3%) were approached for the measurement of microalbuminuria. The subjects were classified into two groups by the median of baseline hs-CRP. Compared to the patients with baseline hs-CRP below the median group (n = 99, 50%), the group with baseline hs-CRP above the median (n = 100, 50%) had higher urinary albumin-to-creatinine ratio (ACR) (P = 0.007) at the end of follow-up period. ACR at the end of follow-up period was significantly correlated with baseline diabetes (ß = 0.342; P < 0.001), baseline SBP (ß = 0.148; P = 0.02), and baseline log-transformed hs-CRP (ß = 0.169; P = 0.01), while adversely correlated with baseline estimated glomerular filtration rate (eGFR) (ß = -0.163; P = 0.02) in multivariate stepwise linear analysis. In addition, ACR change during follow-up period was significantly correlated with baseline diabetes (ß = 0.359; P < 0.001) and baseline log-transformed hs-CRP (ß = 0.190; P = 0.004) in multivariate stepwise linear analysis. The combined effects of baseline hs-CRP and conventional risk factors, such as male sex, diabetes, smoking status, hyperlipidemia, hyperuricemia, and mildly reduced eGFR had a greater risk for microalbuminuria progression. There was no difference in eGFR changes during the follow-up period between two groups. CONCLUSION: Our findings offer a new piece of evidence on the predictive value of baseline hs-CRP for microalbuminuria progression in essential hypertensive patients, and highlight those who combined with traditional cardiovascular risk factors had a greater risk for developing microalbuminuria.

Longitudinal associations of social jetlag with obesity indicators among adolescents - Shanghai adolescent cohort.

OBJECTIVE: To explore the longitudinal association between social-jetlag (SJL) and obesity development among adolescents, sex-difference and related modifying factors in the association. METHODS: Based on Shanghai-Adolescent-Cohort during 2017-2021, a total of 609 students were investigated. In grade 6, 7 and 9, the information on SJL was collected using questionnaires, and anthropometric measures were conducted. The fingernail cortisol and progesterone levels in grade 6 (using LC-MS/MS) and body composition in grade 9 (using Inbody-S10) were measured. By the latent-class-mixture-modeling, two trajectories for SJL (high-level vs. low-level) throughout 4 years were developed. The prospective associations of SJL trajectories and weight/fat gains were analyzed by sex and under different (high/moderate/low) cortisol/progesterone stratifications. RESULTS: In grades 6-9, 39.00%-44.50 % of adolescents experienced at least 1 h of SJL. Compared with the low-level SJL trajectory, the high-level SJL trajectory was associated with greater differences in body-mass-index Z-scores and waist-to-height ratios across 4 years, higher levels of body-fat-percentage and fat-mass-index in grade 9 (P-values<0.05), and such associations were stronger among girls and under moderate-to-high (vs. low) baseline cortisol and progesterone levels. However, no significant associations among boys were observed. CONCLUSIONS: High-level SJL in adolescents may be associated with the development of obesity, especially among adolescent girls and under relatively high baseline cortisol and progesterone levels.

Phenotypic subgroup in serologically active clinically quiescent systemic lupus erythematosus: A cluster analysis based on CSTAR cohort.

BACKGROUND: Serologically active clinically quiescent (SACQ) is a state within systemic lupus erythematosus (SLE) characterized by elevated serologic markers without clinical activity. The heterogeneity in SACQ patients poses challenges in disease management. This multicenter prospective study aimed to identify distinct SACQ subgroups and assess their utility in predicting organ damage. METHODS: SACQ was defined as a sustained period of at least 6 months with persistent serologic activity, marked by positive anti-double-stranded DNA (dsDNA) antibodies and/or hypocomplementemia, and without clinical activity. Cluster analysis was employed, utilizing 16 independent components to delineate phenotypes. FINDINGS: Among the 4,107 patients with SLE, 990 (24.1%) achieved SACQ within 2.0 ± 2.3 years on average. Over a total follow-up of 7,105.1 patient years, 340 (34.3%) experienced flares, and 134 (13.5%) developed organ damage. Three distinct SACQ subgroups were identified. Cluster 1 (n = 219, 22.1%) consisted predominantly of elderly males with a history of major organ involvement at SLE diagnosis, showing the highest risk of severe flares (16.4%) and organ damage (27.9%). Cluster 2 (n = 279, 28.2%) was characterized by milder disease and a lower risk of damage accrual (5.7%). Notably, 86 patients (30.8%) in cluster 2 successfully discontinued low-dose glucocorticoids, with 49 of them doing so without experiencing flares. Cluster 3 (n = 492, 49.7%) featured the highest proportion of lupus nephritis and a moderate risk of organ damage (11.8%), with male patients showing significantly higher risk of damage (hazard ratio [HR] = 4.51, 95% confidence interval [CI], 1.82-11.79). CONCLUSION: This study identified three distinct SACQ clusters, each with specific prognostic implications. This classification could enhance personalized management for SACQ patients. FUNDING: This work was funded by the National Key R&D Program (2021YFC2501300), the Beijing Municipal Science & Technology Commission (Z201100005520023), the CAMS Innovation Fund (2021-I2M-1-005), and National High-Level Hospital Clinical Research Funding (2022-PUMCH-D-009).

A semantic segmentation model for road cracks combining channel-space convolution and frequency feature aggregation.

In transportation, roads sometimes have cracks due to overloading and other reasons, which seriously affect driving safety, and it is crucial to identify and fill road cracks in time. Aiming at the defects of existing semantic segmentation models that have degraded the segmentation performance of road crack images and the standard convolution makes it challenging to capture the spatial and channel coupling relationship between pixels. It is difficult to differentiate crack pixels from background pixels in complex backgrounds; this paper proposes a semantic segmentation model for road cracks that combines channel-spatial convolution with the aggregation of frequency features. A new convolutional block is proposed to accurately identify cracked pixels by grouping spatial displacements and convolutional kernel weight dynamization while modeling pixel spatial relationships linked to channel features. To enhance the contrast of crack edges, a frequency domain feature aggregation module is proposed, which uses a simple windowing strategy to solve the problem of mismatch of frequency domain inputs and, at the same time, takes into account the effect of the frequency imaginary part on the features to model the deep frequency features effectively. Finally, a feature refinement module is designed to refine the semantic features to improve the segmentation accuracy. Many experiments have proved that the model proposed in this paper has better performance and more application potential than the current popular general model.

Land use and river-lake connectivity: Biodiversity determinants of lake ecosystems.

Lake ecosystems confront escalating challenges to their stability and resilience, most intuitively leading to biodiversity loss, necessitating effective preservation strategies to safeguard aquatic environments. However, the complexity of ecological processes governing lake biodiversity under multi-stressor interactions remains an ongoing concern, primarily due to insufficient long-term bioindicator data, particularly concerning macroinvertebrate biodiversity. Here we utilize a unique, continuous, and in situ biomonitoring dataset spanning from 2011 to 2019 to investigate the spatio-temporal variation of macroinvertebrate communities. We assess the impact of four crucial environmental parameters on Lake Dongting and Lake Taihu, i.e., water quality, hydrology, climate change, and land use. These two systems are representative of lakes with Yangtze-connected and disconnected subtropical floodplains in China. We find an alarming trend of declining taxonomic and functional diversities among macroinvertebrate communities despite improvements in water quality. Primary contributing factors to this decline include persistent anthropogenic pressures, particularly alterations in human land use around the lakes, including intensified nutrient loads and reduced habitat heterogeneity. Notably, river-lake connectivity is pivotal in shaping differential responses to multiple stressors. Our results highlight a strong correlation between biodiversity alterations and land use within a 2-5 km radius and 0.05-2.5 km from the shorelines of Lakes Dongting and Taihu, respectively. These findings highlight the importance of implementing land buffer zones with specific spatial scales to enhance taxonomic and functional diversity, securing essential ecosystem services and enhancing the resilience of crucial lake ecosystems.

Origami-Enhanced Mechanical Properties for Worm-Like Robot.

In recent years, the exploration of worm-like robots has garnered much attention for their adaptability in confined environments. However, current designs face challenges in fully utilizing the mechanical properties of structures/materials to replicate the superior performance of real worms. In this article, we propose an approach to address this limitation based on the stacked Miura origami structure, achieving the seamless integration of structural design, mechanical properties, and robotic functionalities, that is, the mechanical properties originate from the geometric design of the origami structure and at the same time serve the locomotion capability of the robot. Three major advantages of our design are: the implementation of origami technology facilitates a more accessible and convenient fabrication process for segmented robotic skin with periodicity and flexibility, as well as robotic bristles with anchoring effect; the utilization of the Poisson's ratio effect for deformation amplification; and the incorporation of localized folding motion for continuous peristaltic locomotion. Utilizing the high geometric designability inherent in origami, our robot demonstrates customizable morphing and quantifiable mechanical properties. Based on the origami worm-like robot prototype, we experimentally verified the effectiveness of the proposed design in realizing the deformation amplification effect and localized folding motion. By comparing this to a conventional worm-like robot with discontinuous deformation, we highlight the merits of these mechanical properties in enhancing the robot's mobility. To sum up, this article showcases a bottom-up approach to robot development, including geometric design, mechanical characterization, and functionality realization, presenting a unique perspective for advancing the development of bioinspired soft robots.

Effect of delayed diagnosis on neuroendocrine function in individuals with suprasellar germ cell tumors.

Purpose: The impact of delayed diagnosis on tumor-related prognosis appears to be minimal in individuals with intracranial germ cell tumors (iGCTs). However, its effect on neuroendocrine functions remains unclear. We aimed to assess the effects of delayed diagnosis on neuroendocrine function in individuals with suprasellar GCTs. Methods: We conducted a retrospective cohort study of 459 individuals with suprasellar GCTs and categorized them into two groups based on disease duration: delayed diagnosis (> 6 months) and non-delayed diagnosis (≤ 6 months). We compared endocrinological symptoms, neuroendocrine dysfunction and its grading (categorized into 0-3 grades based on severity), and recovery from neuroendocrine dysfunction in both groups. Results: Patients with delayed diagnosis exhibited higher incidences of amenorrhea, slow growth, fatigue, and polyuria/polydipsia. Neuroendocrine dysfunction, including central adrenal insufficiency (CAI), central hypothyroidism (CHT), arginine vasopressin deficiency (AVP-D), growth hormone deficiency, hypogonadism, and hyperprolactinemia, was more pronounced in the delayed diagnosis group at diagnosis, the end of treatment, and the last follow-up. Furthermore, individuals with delayed diagnosis showed higher grades of neuroendocrine dysfunction at diagnosis (OR=3.005, 95% CI 1.929-4.845, p<0.001), end of oncologic treatment (OR=4.802, 95% CI 2.878-8.004, p<0.001), and last follow-up(OR=2.335, 95% CI 1.307-4.170, p=0.005) after adjusting for confounders. Finally, less recovery, particularly in CAI, CHT, and AVP-D, was seen among the group with delayed diagnosis after treatment. Conclusion: Among individuals with suprasellar GCTs, delayed diagnosis is associated with increased, more severe, and less recovered neuroendocrine dysfunction, emphasizing the importance of early diagnosis and treatment to reduce neuroendocrine dysfunction.

Prior to ABOi liver transplant with PD-1 inhibitor in patients with hepatocellular carcinoma: A case report.

BACKGROUND: Liver transplantation (LT) is a unique and effective method for treating end-stage liver diseases and acute liver failure, bringing hope to many patients with liver cancer. LT is currently widely used in the treatment of liver diseases. However, there have been no patients with liver cancer who have undergone ABO-incompatible (ABOi) LT after treatment with the programmed cell death protein 1 (PD-1) inhibitor reported in the literature. CASE PRESENTATION: A patient with liver cancer who received sintilimab injection, an anti-PD1 therapy, before LT was admitted in the transplantation centre. This patient underwent ABOi LT. The perioperative treatment strategy of this patient was reported. A desensitisation protocol was conducted urgently for the patient before operation, and the immunosuppression programme of LT was adjusted. After operation, isoagglutinin titer and liver function indicators were strictly monitored. The patient recovered well after operation, and no sign of rejection reaction was observed. CONCLUSION: We reported a patient with hepatocellular carcinoma (HCC) who received PD-1 inhibitor treatment before operation and successfully underwent ABOi LT. The present case report provides novel insights into the perioperative management of utilizing PD-1 inhibitors prior to ABOi LT in patients diagnosed with hepatocellular carcinoma (HCC).

Development and validation of a clinical risk score nomogram for predicting voriconazole trough concentration above 5 mg/L: a retrospective cohort study.

The therapeutic range of voriconazole (VRC) is narrow, this study aimed to explore factors influencing VRC plasma concentrations > 5 mg/L and to construct a clinical risk score nomogram prediction model. Clinical data from 221 patients with VRC prophylaxis and treatment were retrospectively analyzed. The patients were randomly divided into a training cohort and a validation cohort at a 7:3 ratio. Univariate and binary logistic regression analysis was used to select independent risk factors for VRC plasma concentration above the high limit (5 mg/L). Four indicators including age, weight, CYP2C19 genotype, and albumin were selected to construct the nomogram prediction model. The area under the curve values of the training cohort and the validation cohort were 0.841 and 0.802, respectively. The decision curve analysis suggests that the nomogram model had good clinical applicability. In conclusion, the nomogram provides a reference for early screening and intervention in a high-risk population.

Silylene-Stabilized Neutral Dibora-Aromatics with a B═B Bond.

The unprecedented silylene-supported dibenzodiboraoxepin 2 and 9,10-diboraphenanthrene complexes 6 and 8 were synthesized. The (NHSi)2B2(xanthene) [NHSi = PhC(NtBu)2(Me2N)Si:] 2 results from debromination of the bis(NHSi)-stabilized bis(dibromoboryl)xanthene 1 with potassium graphite (KC8); 2 is capable of activating white phosphorus and ammonia to form the B2P4 cage compound 3 and H2N-B-B-H diborane species 4, respectively. The thermal rearrangement of 2 affords the 9,10-dihydro-9,10-diboraphenanthrene 5 through a bis(NHSi)-assisted intramolecular reductive C-O-C deoxygenation process. Notably, the 9,10-diboraphenanthrene derivatives 6 and 8 could be generated by deoxygenation of 2 with KC8 and 1,3,4,5-tetramethylimidazol-2-ylidene, respectively. The aromaticity of 6 and 8 was confirmed by computational studies. Strikingly, the NHSi ligand in 8 engenders the monodeoxygenation of carbon dioxide in toluene at room temperature to form the CO-stabilized 9,10-diboraphenanthrene derivative 9 via the silaoxadiborinanone intermediate 10.

Kaempferol from Alpinia officinarum hance induces G2/M cell cycle arrest in hepatocellular carcinoma cells by regulating the ATM/CHEK2/KNL1 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Alpinia officinarum Hance (A. officinarum), a perennial herb known for its medicinal properties, has been used to treat various ailments, such as stomach pain, abdominal pain, emesis, and digestive system cancers. A. officinarum is extensively cultivated in the Qiongzhong and Baisha regions of Hainan, and it holds substantial therapeutic value for the local Li people of Hainan. Kaempferol, a flavonoid derived from A. officinarum, has demonstrated anticancer properties in various experimental and biological studies. Nevertheless, the precise mechanisms through which it exerts its anti-hepatocellular carcinoma (HCC) effects remain to be comprehensively delineated. AIM OF THE STUDY: This investigation aims to elucidate the anti-HCC effects of kaempferol derived from A. officinarum and to delve into its underlying mechanistic pathways. MATERIALS AND METHODS: Using ultra-high performance liquid chromatography-mass spectrometry/mass spectrometry (UPLC-MS/MS) to identify active compounds in A. officinarum. HCCLM3 and Huh7 cells were used to study the anti-HCC effect of kaempferol from A. officinarum. The cytotoxicity and proliferation of kaempferol and A. officinarum were measured using CCK-8 and EDU staining. Wound-healing assays and three-dimensional tumor spheroid models were further used to evaluate migration and the anti-HCC activity of kaempferol. The cell cycle and apoptosis were evaluated by flow cytometry. Western blot and qRT-PCR were used to detect the expression of proteins and genes associated with the cell cycle checkpoints. Finally, bioinformatics was used to analyze the relationship between the differential expression of core targets in the ATM/CHEK2/KNL1 pathway and a poor prognosis in clinical HCC samples. RESULTS: UPLC-MS/MS was employed to detect five active compounds in A. officinarum, such as kaempferol. The CCK-8 and EDU assays showed that kaempferol and A. officinarum significantly inhibited the proliferation of HCC cells. A wound-healing assay revealed that kaempferol remarkably inhibited the migration of HCC cells. Kaempferol significantly suppressed the growth of tumor spheroids. In addition, kaempferol markedly induced G2/M arrest and promoted apoptosis of HCC cells. Mechanically, kaempferol significantly reduced the protein and mRNA expression levels of ATM, CHEK2, CDC25C, CDK1, CCNB1, MPS1, KNL1, and Bub1. Additionally, the combination of kaempferol and the ATM inhibitor KU55933 had a more significant anti-HCC effect. The results of bioinformatics showed that ATM, CHEK2, CDC25C, CDK1, and KNL1 were highly expressed in patients with HCC and cancer tissues, indicating that these genes have certain value in the clinical diagnosis of HCC. CONCLUSIONS: Collectively, our results revealed that kaempferol from A. officinarum inhibits the cell cycle by regulating the ATM/CHEK2/KNL1 pathway in HCC cells. In summary, our research presents an innovative supplementary strategy for HCC treatment.