Quantitative Analysis of Primary Compressive Trabeculae Distribution in the Proximal Femur of the Elderly.

OBJECTIVE: As osteoporosis progresses, the primary compressive trabeculae (PCT) in the proximal femur remains preserved and is deemed the principal load-bearing structure that links the femoral head with the femoral neck. This study aims to elucidate the distribution patterns of PCT within the proximal femur in the elderly population, and to assess its implications for the development and optimization of internal fixation devices used in hip fracture surgeries. METHODS: This is a retrospective cohort study conducted from March 2022 to April 2023. A total of 125 patients who underwent bilateral hip joint CT scans in our hospital were enrolled. CT data of the unaffected side of the hip were analyzed. Key parameters regarding the PCT distribution in the proximal femur were measured, including the femoral head's radius (R), the neck-shaft angle (NSA), the angle between the PCT-axis and the head-neck axis (α), the distance from the femoral head center to the PCT-axis (δ), and the lengths of the PCT's bottom and top boundaries (L-bottom and L-top respectively). The impact of gender differences on PCT distribution patterns was also investigated. Student's t-test or Mann-Whitney U test were used to compare continuous variables between genders. The relationship between various variables was investigated through Pearson's correlation analysis. RESULTS: PCT was the most prominent bone structure within the femoral head. The average NSA, α, and δ were 126.85 ± 5.85°, 37.33 ± 4.23°, and 0.39 ± 1.22 mm, respectively, showing no significant gender differences (p > 0.05). Pearson's correlation analysis revealed strong correlations between α and NSA (r = -0.689, p < 0.001), and R and L-top (r = 0.623, p < 0.001), with mild correlations observed between δ and NSA (r = -0.487, p < 0.001), and R and L-bottom (r = 0.427, p < 0.001). Importantly, our study establishes a method to accurately localize PCT distribution in true anteroposterior (AP) radiographs of the hip joint, facilitating precise screw placement in proximal femur fixation procedures. CONCLUSION: Our study provided unprecedented insights into the distribution patterns of PCT in the proximal femur of the elderly population. The distribution of PCT in the proximal femur is predominantly influenced by anatomical and geometric factors, such as NSA and femoral head size, rather than demographic factors like gender. These insights have crucial implications for the design of internal fixation devices and surgical planning, offering objective guidance for the placement of screws in hip fracture treatments.

CCL11/CCR3-dependent eosinophilia alleviates malignant pleural effusions and improves prognosis.

Malignant pleural effusion (MPE) is a common occurrence in advanced cancer and is often linked with a poor prognosis. Eosinophils were reported to involve in the development of MPE. However, the role of eosinophils in MPE remains unclear. To investigate this, we conducted studies using both human samples and mouse models. Increased eosinophil counts were observed in patients with MPE, indicating that the higher the number of eosinophils is, the lower the LENT score is. In our animal models, eosinophils were found to migrate to pleural cavity actively upon exposure to tumor cells. Intriguingly, we discovered that a deficiency in eosinophils exacerbated MPE, possibly due to their anti-tumor effects generated by modifying the microenvironment of MPE. Furthermore, our experiments explored the role of the C-C motif chemokine ligand 11 (CCL11) and its receptor C-C motif chemokine receptor 3 (CCR3) in MPE pathology. As a conclusion, our study underscores the protective potential of eosinophils against the development of MPE, and that an increase in eosinophils through adoptive transfer of eosinophils or increasing their numbers improved MPE.

Application of amphiregulin in IVM culture of immature human oocytes and pre-insemination culture for COCs in IVF cycles.

Background: Amphiregulin (AR) is a growth factor that resembles the epidermal growth factor (EGF) and serves various functions in different cells. However, no systematic studies or reports on the role of AR in human oocytes have currently been performed or reported. This study aimed to explore the role of AR in human immature oocytes during in vitro maturation (IVM) and in vitro fertilization (IVF) in achieving better embryonic development and to provide a basis for the development of a pre-insemination culture medium specific for cumulus oocyte complexes (COCs). Methods: First, we examined the concentration of AR in the follicular fluid (FF) of patients who underwent routine IVF and explored the correlation between AR levels and oocyte maturation and subsequent embryonic development. Second, AR was added to the IVM medium to culture immature oocytes and investigate whether AR could improve the effects of IVM. Finally, we pioneered the use of a fertilization medium supplemented with AR for the pre-insemination culture of COCs to explore whether the involvement of AR can promote the maturation and fertilization of IVF oocytes, as well as subsequent embryonic development. Results: A total of 609 FF samples were examined, and a positive correlation between AR levels and blastocyst formation was observed. In our IVM study, the development potential and IVM rate of immature oocytes, as well as the fertilization rate of IVM oocytes in the AR-added groups, were ameliorated significantly compared to the control group (All P < 0.05). Only the IVM-50 group had a significantly higher blastocyst formation rate than the control group (P < 0.05). In the final IVF study, the maturation, fertilization, high-quality embryo, blastocyst formation, and high-quality blastocyst rates of the AR-added group were significantly higher than those of the control group (All P < 0.05). Conclusion: AR levels in the FF positively correlated with blastocyst formation, and AR involvement in pre-insemination cultures of COCs can effectively improve laboratory outcomes in IVF. Furthermore, AR can directly promote the in vitro maturation and developmental potential of human immature oocytes at an optimal concentration of 50 ng/ml.

Cholinergic modulation in the vertebrate auditory pathway.

Acetylcholine (ACh) is a prevalent neurotransmitter throughout the nervous system. In the brain, ACh is widely regarded as a potent neuromodulator. In neurons, ACh signals are conferred through a variety of receptors that influence a broad range of neurophysiological phenomena such as transmitter release or membrane excitability. In sensory circuitry, ACh modifies neural responses to stimuli and coordinates the activity of neurons across multiple levels of processing. These factors enable individual neurons or entire circuits to rapidly adapt to the dynamics of complex sensory stimuli, underscoring an essential role for ACh in sensory processing. In the auditory system, histological evidence shows that acetylcholine receptors (AChRs) are expressed at virtually every level of the ascending auditory pathway. Despite its apparent ubiquity in auditory circuitry, investigation of the roles of this cholinergic network has been mainly focused on the inner ear or forebrain structures, while less attention has been directed at regions between the cochlear nuclei and midbrain. In this review, we highlight what is known about cholinergic function throughout the auditory system from the ear to the cortex, but with a particular emphasis on brainstem and midbrain auditory centers. We will focus on receptor expression, mechanisms of modulation, and the functional implications of ACh for sound processing, with the broad goal of providing an overview of a newly emerging view of impactful cholinergic modulation throughout the auditory pathway.

Highly Efficient Organic Solar Cells with the Highly Crystalline Third Component as a Morphology Regulator.

The morphology of the active layer is crucial for highly efficient organic solar cells (OSCs), which can be regulated by selecting a rational third component. In this work, the highly crystalline nonfullerene acceptor BTP-eC9 is selected as the morphology regulator in OSCs with PM6:BTP-BO-4Cl as the main system. The addition of BTP-eC9 can prolong the nucleation and crystallization progress of acceptor and donor molecules, thereby enhancing the order of molecular arrangement. Meanwhile, the nucleation and crystallization time of the donor is earlier than that of the acceptors after introducing BTP-eC9, which is beneficial for obtaining a better vertical structural phase separation. The exciton dissociation, charge transport, and charge collection are promoted effectively by the optimized morphology of the active layer, which improves the short-circuit current density and filling factor. After introducing BTP-eC9, the power conversion efficiencies (PCEs) of the ternary OSCs are improved from 17.31% to 18.15%. The PCE is further improved to 18.39% by introducing gold nanopyramid (Au NBPs) into the hole transport layer to improve photon utilization efficiency. This work indicates that the morphology can be optimized by selecting a highly crystalline third component to regulate the nucleation and crystallization progress of the acceptor and donor molecules.

RNA modification gene WDR4 facilitates tumor progression and immunotherapy resistance in breast cancer.

INTRODUCTION: Growing interest toward RNA modification in cancer has inspired the exploration of gene sets related to multiple RNA modifications. However, a comprehensive elucidation of the clinical value of various RNA modifications in breast cancer is still lacking. OBJECTIVES: This study aimed to provide a strategy based on RNA modification-related genes for predicting therapy response and survival outcomes in breast cancer patients. METHODS: Genes related to thirteen RNA modification patterns were integrated for establishing a nine-gene-containing signature-RMscore. Alterations of tumor immune microenvironment and therapy response featured by different RMscore levels were assessed by bulk transcriptome, single-cell transcriptome and genomics analyses. The biological function of key RMscore-related molecules was investigated by cellular experiments in vitro and in vivo, using flow cytometry, immunohistochemistry and immunofluorescence staining. RESULTS: This study has raised an effective therapy strategy for breast cancer patients after a well-rounded investigation of RNA modification-related genes. With a great performance of predicting patient prognosis, high levels of the RMscore proposed in this study represented suppressive immune microenvironment and therapy resistance, including adjuvant chemotherapy and PD-L1 blockade treatment. As the key contributor of the RMscore, inhibition of WDR4 impaired breast cancer progression significantly in vitro and in vivo, as well as participated in regulating cell cycle and mTORC1 signaling pathway via m7G modification. CONCLUSION: Briefly, this study has developed promising and effective tactics to achieve the prediction of survival probabilities and treatment response in breast cancer patients.

Highly efficient and stable adsorption of lithium from brine with microcapsules containing 1-phenylazo-2-naphthol and trioctylphosphine oxide.

Lithium extraction from salt lake brine is still challenging due to the existence of similar elements, e.g. sodium. In the present work, polysulfone (PSF) microcapsules containing 1-phenylazo-2-naphthol (HS) and trioctylphosphine oxide (TOPO) as extractants were successfully prepared by microfluidic technology for the separation of Li+ from brine with Li+ and Na+. The morphology, composition, and structure of HS-TOPO-based microcapsules were characterized systematically. The results showed that microcapsules consisting of 20 wt% (m m-1) polysulfone and 80 wt% (m m-1) 1-phenylazo-2-naphthol-trioctylphosphine oxide as the extractant, which was labeled as PSF/HS-TOPO-2/8, exhibited the best performance for Li+ adsorption. The separation factor (SF) of Li+ over Na+ is up to 653 and the adsorption capacity for Li+ in the simulated brine could reach 3.67 mg g-1 for microcapsules PSF/HS-TOPO-2/8, which demonstrated that Li+ can be separated with high selectivity. Besides, the kinetic results demonstrated that the adsorption followed quasi-secondary adsorption kinetic models, indicating that the adsorption mechanism of lithium by microcapsules involved chemisorption. After ten cycles of adsorption-elution, the maximum equilibrium adsorption capacity still remained at 87%. All these results demonstrate that PSF/HS-TOPO-2/8 microcapsules can be used as an efficient adsorber for the adsorption of Li+ from brine with high selectivity and stability.

Impact and migration behavior of triclosan on waste-activated sludge anaerobic digestion.

Triclosan (TCS), a hydrophobic antibacterial agent, is extensive application in daily life. Despite a low biodegradability rate, its hydrophobicity results in its accumulation in waste-activated sludge (WAS) during domestic and industrial wastewater treatment. While anaerobic digestion is the foremost strategy for WAS treatment, limited research has explored the interphase migration behavior and impacts of TCS on WAS degradation during anaerobic digestion. This study revealed TCS migration between solid- and liquid-phase in WAS digestion. The solid-liquid distribution coefficients of TCS were negative for proteins and polysaccharides and positive for ammonium. High TCS levels promoted volatile-fatty-acid accumulation and reduced methane production. Enzyme activity tests and functional prediction indicated that TCS increased enzyme activity associated with acid production, in contrast to the inhibition of key methanogenic enzymes. The findings of the TCS migration behavior and its impacts on WAS anaerobic digestion provide an in-depth understanding of the evolution of enhanced TCS-removing technology.

A novel rapid visual nucleic acid detection technique for tick-borne encephalitis virus by combining RT-recombinase-aided amplification and CRISPR/Cas13a coupled with a lateral flow dipstick.

Tick-borne encephalitis virus (TBEV), a zoonotic pathogen, can cause severe neurological complications and fatal outcomes in humans. Early diagnosis of TBEV infection is crucial for clinical practice. Although serological assays are frequently employed for detection, the lack of antibodies in the early stages of infection and the cross-reactivity of antibodies limit their efficacy. Conventional molecular diagnostic methods such as RT-qPCR can achieve early and accurate identification but require specialized instrumentation and professionals, hindering their application in resource-limited areas. Our study developed a rapid and visual TBEV molecular detection method by combining RT-recombinase-aided amplification, the CRISPR/Cas13a system, and lateral flow dipsticks. The diagnostic sensitivity of this method is 50 CFU/ml, with no cross-reactivity with a variety of viruses. The detection can be carried out within 1 h at a temperature between 37 and 42 °C, and the results can be visually determined without the need for complex instruments and professionals. Subsequently, this assay was used to analyze clinical samples from 15 patients suspected of TBEV infection and 10 healthy volunteers, and its sensitivity and specificity reached 100 %, which was consistent with the results of RT-qPCR. These results indicate that this new method can be a promising point-of-care test for the diagnosis of tick-borne encephalitis.

Integrated Transcriptomic Landscape and Deep Learning Based Survival Prediction in Uterine Sarcomas.

Purpose: The genomic characteristics of uterine sarcomas have not been fully elucidated. This study aimed to explore the genomic landscape of the USs. Materials and Methods: Comprehensive genomic analysis through RNA-sequencing was conducted. Gene fusion, differentially expressed genes (DEGs), signaling pathway enrichment, immune cell infiltration, and prognosis were analyzed. A deep learning model was constructed to predict the survival of US patients. Results: A total of 71 US samples were examined, including 47 endometrial stromal sarcomas (ESS), 18 uterine leiomyosarcomas (uLMS), 3 adenosarcomas, 2 carcinosarcomas, and 1 uterine tumor resembling an ovarian sex-cord tumor (UTROSCT). ESS (including high-grade ESS and low-grade ESS) and uLMS showed distinct gene fusion signatures; a novel gene fusion site, MRPS18A - PDC-AS1 could be a potential diagnostic marker for the pathology differential diagnosis of uLMS and ESS; 797 and 477 uDEGs were identified in the ESS vs. uLMS and HGESS vs. LGESS groups, respectively. The uDEGs were enriched in multiple pathways. Fifteen genes including LAMB4 were confirmed with prognostic value in USs; immune infiltration analysis revealed the prognositic value of myeloid dendritic cells, plasmacytoid dendritic cells, natural killer cells, macrophage M1, monocytes and hematopoietic stem cells in USs; the deep learning model named MMN-MIL showed satisfactory performance in predicting the survival of US patients, with the area under the receiver operating curve curve reached 0.909 and accuracy achieved 0.804. Conclusion: USs harbored distinct gene fusion characteristics and gene expression features between HGESS, LGESS, and uLMS. The MMN-MIL model could effectively predict the survival of US patients.

Pro-inflammatory diets promote the formation of hyperuricemia.

Background: Hyperuricemia, as a very prevalent chronic metabolic disease with increasing prevalence year by year, poses a significant burden on individual patients as well as on the global health care and disease burden, and there is growing evidence that it is associated with other underlying diseases such as hypertension and cardiovascular disease. The association between hyperuricemia and dietary inflammatory index (DII) scores was investigated in this study. Methods: This study enrolled 13, 040 adult subjects (aged ≥ 20 years) from the US National Health and Nutrition Survey from 2003 to 2018. The inflammatory potential of the diet was assessed by the DII score, and logistic regression was performed to evaluate the relationship between the DII score and the development of hyperuricemia; subgroup analyses were used to discuss the influence of other factors on the relationship. Results: Participants in the other quartiles had an increased risk of hyperuricemia compared to those in the lowest quartile of DII scores. Stratification analyses stratified by body mass index (BMI), sex, hypertension, drinking, diabetes, education level and albumin-creatinine-ratio (ACR) revealed that the DII score was also associated with the risk of hyperuricemia (P<0.05). There was an interaction in subgroup analysis stratified by sex, age, and hypertension (P for interaction <0.05). The results showed a linear-like relationship between DII and hyperuricemia, with a relatively low risk of developing hyperuricemia at lower DII scores and an increased risk of developing hyperuricemia as DII scores increased. Conclusions: This study showed that the risk of hyperuricemia increased at slightly higher DII scores (i.e., with pro-inflammatory diets), but not significantly at lower levels (i.e., with anti-inflammatory diets). The contribution of the DII score to the development of hyperuricemia increased with higher scores. The relationship between inflammatory diets and hyperuricemia requires more research on inflammation, and this study alerts the public that pro-inflammatory diets may increase the risk of developing hyperuricemia.

Expanding the targeting scope of CRISPR/Cas9-mediated genome editing by Cas9 variants in Brassica.

CRISPR/Cas9, presently the most widely used genome editing technology, has provided great potential for functional studies and plant breeding. However, the strict requirement for a protospacer adjacent motif (PAM) has hindered the application of the CRISPR/Cas9 system because the number of targetable genomic sites is limited. Recently, the engineered variants Cas9-NG, SpG, and SpRY, which recognize non-canonical PAMs, have been successfully tested in plants (mainly in rice, a monocot). In this study, we evaluated the targeted mutagenesis capabilities of these Cas9 variants in two important Brassica vegetables, Chinese cabbage (Brassica rapa spp. pekinensis) and cabbage (Brassica oleracea var. capitata). Both Cas9-NG and SpG induced efficient mutagenesis at NGN PAMs, while SpG outperformed Cas9-NG at NGC and NGT PAMs. SpRY achieved efficient editing at almost all PAMs (NRN > NYN), albeit with some self-targeting activity at transfer (T)-DNA sequences. And SpRY-induced mutants were detected in cabbage plants in a PAM-less fashion. Moreover, an adenine base editor was developed using SpRY and TadA8e deaminase that induced A-to-G conversions within target sites using non-canonical PAMs. Together, the toolboxes developed here induced successful genome editing in Chinese cabbage and cabbage. Our work further expands the targeting scope of genome editing and paves the way for future basic research and genetic improvement in Brassica. Supplementary Information: The online version contains supplementary material available at 10.1007/s42994-024-00155-7.

LINC01138 expresses two novel isoforms and functions as a repressive factor in glioma cells.

Objective: The objective of this study is to investigate the aggressive infiltration of glioblastoma into adjacent brain tissue, considering its challenging prognosis. Initially classified as an intergenic non-coding RNA, we aim to elucidate the functional implications of LINC01138 in glioblastoma. Method: Glioma grading was performed utilizing H&E staining, which unveiled distinct nuclear morphology in high-grade gliomas. The downregulation of LINC01138 in glioma tissues was corroborated through qRT-PCR and gel electrophoresis, concurrently identifying two previously unrecognized LINC01138 isoforms. Expression profiling of all four LINC01138 isoforms was executed in glioma cell lines (A172, SHG-44, U251, U87-MG). The impact of LINC01138 overexpression in U87-MG and U251 cells was evaluated for cell proliferation, migration, and invasion through cell counting, CCK-8 analysis, and Transwell assays. Furthermore, the suppression of LINC01138 in SHG-44 cells substantiated its involvement in fostering tumor malignancy. Transcriptome sequencing revealed the inhibitory influence of LINC01138 on IGF1 expression. These findings contribute to an enriched comprehension of glioma biology by exploring the engagement of LINC01138 through diverse methodologies, thereby elucidating its potential therapeutic significance. Results: Our investigation elucidates the intricate involvement of LINC01138 in gliomas. High-grade gliomas are characterized by elevated cell density and distinctive nuclear features. LINC01138 demonstrates a substantial downregulation in glioma tissues, with the identification of two novel isoforms. The expression of all four LINC01138 isoforms is notably diminished in both glioma tissues and cell lines. Elevated expression of LINC01138 demonstrates inhibitory effects on tumor cell proliferation, migration, and invasion, while its downregulation exacerbates malignancy. The regulatory function of LINC01138 as a repressor of IGF1 expression was elucidated through transcriptome sequencing. Conclusion: The LINC01138 isoforms display notable tumor-suppressive effects, suggesting a promising potential for impeding glioma progression.

Association between Branched-Chain amino acids and Epilepsy: A Mendelian randomized study.

BACKGROUND: Branched-chain amino acids (BCAAs) have been affected epilepsy, yet conclusions remain inconclusive, lacking causal evidence regarding whether BCAAs affect epilepsy. Systematic exploration of the causal relationship between BCAAs and epilepsy could hand out new ideas for the treatment of epilepsy. METHODS: Utilizing bidirectional Mendelian randomization (MR) study, we investigated the causal relationship between BCAA levels and epilepsy. BCAA levels from genome-wide association studies (GWAS), including total BCAAs, leucine levels, isoleucine levels, and valine levels, were employed. Causal relationships were explored applying the method of inverse variance-weighted (IVW) and MR-Egger, followed by sensitivity analyses of the results to evaluate heterogeneity and pleiotropy. RESULTS: Through strict genetic variant selection, we find some related SNPs, total BCAA levels (9), leucine levels (11), isoleucine levels (7), and valine levels (6) as instrumental variables for our MR analysis. Following IVW and sensitivity analysis, total BCAAs levels (OR = 1.14, 95 % CI = 1.019 âˆ¼ 1.285, P = 0.022) and leucine levels (OR = 1.15, 95 % CI = 1.018 âˆ¼ 1.304, P = 0.025) had significant correlation with epilepsy. CONCLUSIONS: There exists a causal relationship between the levels of total BCAAs and leucine with epilepsy, offering the new ideas into epilepsy potential mechanisms, holding significant implications for its prevention and treatment.

Role of mitophagy in pulmonary hypertension: Targeting the mechanism and pharmacological intervention.

Mitophagy, a crucial pathway in eukaryotic cells, selectively eliminates dysfunctional mitochondria, thereby maintaining cellular homeostasis via mitochondrial quality control. Pulmonary hypertension (PH) refers to a pathological condition where pulmonary arterial pressure is abnormally elevated due to various reasons, and the underlying pathogenesis remains elusive. This article examines the molecular mechanisms underlying mitophagy, emphasizing its role in PH and the progress in elucidating related molecular signaling pathways. Additionally, it highlights current drug regulatory pathways, aiming to provide novel insights into the prevention and treatment of pulmonary hypertension.

Effect of Stroke Etiology on Endovascular Treatment for Acute Basilar-Artery Occlusion: A Post Hoc Analysis of the ATTENTION Randomized Trial.

BACKGROUND: Stroke etiology could influence the outcomes in patients with basilar-artery occlusion (BAO). This study aimed to evaluate the differences in efficacy and safety of best medical treatment (BMT) plus endovascular treatment (EVT) versus BMT alone in acute BAO across different stroke etiologies. METHODS: The study was a post hoc analysis of the ATTENTION trial (Trial of Endovascular Treatment of Acute Basilar-Artery Occlusion), which was a multicenter, randomized trial at 36 centers in China from February 2021 to September 2022. Patients with acute BAO were classified into 3 groups according to stroke etiology (large-artery atherosclerosis [LAA], cardioembolism, and undetermined cause/other determined cause [UC/ODC]). The primary outcome was a favorable outcome (modified Rankin Scale score of 0-3) at 90 days. Safety outcomes included symptomatic intracranial hemorrhage and 90-day mortality. RESULTS: A total of 340 patients with BAO were included, 150 (44.1%) had LAA, 72 (21.2%) had cardioembolism, and 118 (34.7%) had UC/ODC. For patients treated with BMT plus EVT and BMT alone, respectively, the rate of favorable outcome at 90 days was 49.1% and 23.8% in the LAA group (odds ratio, 3.08 [95% CI, 1.38-6.89]); 52.2% and 30.8% in the cardioembolism group (odds ratio, 2.45 [95% CI, 0.89-6.77]); and 37.5% and 17.4% in the UC/ODC group (odds ratio, 2.85 [95% CI, 1.16-7.01]), with P=0.89 for the stroke etiology×treatment interaction. The rate of symptomatic intracranial hemorrhage in EVT-treated patients with LAA, cardioembolism, and UC/ODC was 8.3%, 2.2%, and 3.2%, respectively, and none of the BMT-treated patients. Lower 90-day mortality was observed in patients with EVT compared with BMT alone across 3 etiology groups. CONCLUSIONS: Among patients with acute BAO, EVT compared with BMT alone might be associated with favorable outcomes and lower 90-day mortality, regardless of cardioembolism, LAA, or UC/ODC etiologies. The influence of stroke etiology on the benefit of EVT should be explored by further trials. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04751708.