Co-delivery of PROTAC and siRNA via novel liposomes for the treatment of malignant tumors.

Targeted elimination of damaged or overexpressed proteins within the tumor serves a pivotal role in regulating cellular function and restraining tumor cell growth. Researchers have been striving to identify safer and more effective methods for protein removal. Here, we propose the synergistic employment of a small molecule degrading agent (PROTAC) and siRNA to attain enhanced protein clearance efficiency and tumor therapeutic effects. Co-delivery liposomes were prepared to facilitate the efficient encapsulation of PROTAC and siRNA. Specifically, the cationic liposome significantly improved the solubility of the insoluble PROTAC (DT2216). The cationic polymer (F-PEI) achieved efficient encapsulation of the nucleic acid drug, thereby promoting endocytosis and enhancing the therapeutic impact of the drug. Both in vivo and in vitro experiments demonstrated remarkable degradation of target proteins and inhibition of tumor cells by the co-delivery system. In conclusion, the co-delivery liposomes furnished a nano-delivery system proficient in effectively encapsulating both hydrophilic and hydrophobic drugs, thereby presenting a novel strategy for targeted combination therapy in treating tumors.

Construction of porous Cu/CeO2 catalyst with abundant interfacial sites for effective methanol steam reforming.

Methanol is a promising hydrogen carrier for fuel cell vehicles (FCVs) via methanol steam reforming (MSR) reaction. Ceria supported copper catalyst has attracted extensive attentions due to the extraordinary oxygen storage capacity and abundant oxygen vacancies. Herein, we developed a colloidal solution combustion (CSC) method to synthesize a porous Cu/CeO2(CSC) catalyst. Compared with Cu/CeO2 catalysts prepared by other methods, the Cu/CeO2(CSC) catalyst possesses highly dispersed copper species and abundant Cu+-Ov-Ce3+ sites at the copper-ceria interface, contributing to methanol conversion of 66.3 %, CO2 selectivity of 99.2 %, and outstanding hydrogen production rate of 490 mmol gcat-1 h-1 under 250 °C. The linear correlation between TOF values and Cu+-Ov-Ce3+ sites amount indicates the vital role of Cu+-Ov-Ce3+ sites in MSR reaction, presenting efficient ability in activation of water. Subsequently, a deep understanding of CSC method is further presented. In addition to serving as a hard template, the colloidal silica also acts as disperser between nanoparticles, enhancing the copper-ceria interactions and facilitating the generation of Cu+-Ov-Ce3+ sites. This study offers an alternative approach to synthesize highly dispersed supported copper catalysts.

Long-Time Coherent Integration Method for Passive Bistatic Radar Using Frequency Hopping Signals.

Long-time coherent integration using frequency hopping signals is a challenging problem for passive bistatic radar due to its frequency hopping characteristics. Apart from range walk, range curve, and Doppler frequency migration, Doppler diffusion caused by frequency hopping characteristics occurs within the observation time, which also lowers the detection performance. To deal with this problem, a novel coherent integration method for frequency hopping signals based on passive bistatic radar is proposed in this paper. In this novel method, range curve and range walk are eliminated by applying generalized Keystone transform. Then, Doppler frequency migration caused by the target's acceleration is compensated for by a parameter search with a designed search scope. Finally, Doppler frequency migration caused by frequency hopping characteristics is compensated for by designing a new acceleration compensation function and a revised rotation factor for Fourier transform. Since migration effects caused by frequency hopping characteristics are considered and compensated for when using frequency hopping signals, the weak target echo can be better integrated in the observation time compared to when using the existing methods. The simulation results and performance analysis illustrate the effectiveness of the proposed method.

Extensive pedunculated fibrolipoma of the buttocks that had accompanied the patient for 50 years: a rare case report.

Lipomas are the most prevalent benign soft-tissue tumours, however, pedunculated fibrolipoma in the buttock is rare. Here, the case of a Chinese male patient in his early 70s with a 50-year history of a growing pedunculated fibrolipoma on his right buttock is presented. The attending physician and the registered nurse collaborated on a treatment plan, leading to a successful resection with rhomboid flap transfer. The operation went smoothly, and with continued home care and follow-ups, the patient recovered well, without complications. At 4 months post-surgery, the incision had healed perfectly, boosting the patient's psychological state and allowing him to resume his daily activities unhindered.

The intervention mechanism of Tanshinone IIA in alleviating neuronal injury induced by HMGB1 or TNF-α-mediated microglial activation.

Tanshinone IIA (Tan IIA), a neuroprotective natural compound extracted from Salvia miltiorrhiza, is used in stroke treatment. However, elucidating Tan IIA's neuroprotective mechanisms remains challenging due to limitations in assessing drug efficacy and biochemical parameters in clinical studies. This study investigated Tan IIA's impact on neuroinflammatory responses and its neuroprotective mechanisms using HMGB1- or TNF-α-stimulated BV2 microglia in a co-culture system with primary neuron cells. The results indicated that Tan IIA significantly reduced microglial activation induced by TNF-α or HMGB1. Concurrently, Tan IIA disrupted the interactions between HMGB1 and toll-like receptor 4 (TLR4), and between TNF-α and TNF receptor 1 (TNFR1), modulating the HMGB1/TLR4/nuclear factor-kappa B (NF-κB) and TNF-α/TNFR1/NF-κB signaling pathways and related protein expressions. Moreover, co-culture experiments showed that neuronal apoptosis induced by microglial activation was reversed by Tan IIA. In conclusion, Tan IIA provides neuroprotection by modulating signaling pathways in microglia, thus preventing neuronal apoptosis. This study offers new insights into therapeutic targets for ischemic stroke.

Understanding wrist skin temperature changes to hormone variations across the menstrual cycle.

Consumer devices are increasingly used to monitor peripheral body temperature (PBT) for menstrual cycle tracking, but the link between PBT and hormone variations remains underexplored. This study examines the relationship between these variables with a focus on nightly wrist skin temperature (WST). Fifty participants provided physiological and self-reported data, including WST, daily step counts, glucose levels, hormone levels (E3G, LH), and diary entries. Results show a negative correlation between WST and hormone levels when E3G and LH are below average, and this trend was robust to demographics and self-reported stress. Increased variance between mid-cycle hormonal peaks and WST fluctuations may stem from differences between basal body temperature (BBT) and WST. This research suggests that algorithms reliant on body temperature for tracking hormonal changes or other aspects of the menstrual cycle may need to account for increased variance in WST trends if they are meant to be deployed on wearable devices.

Biological characteristics of a new long-chain fatty acid transport protein 1 from Trichinella spiralis and its participation in lipid metabolism, larval moulting, and development.

Long-chain fatty acid transport protein 1 (FATP1) is a member of the fatty acid transporter family. It facilitates transmembrane transport of fatty acids and participates in lipid metabolism. Lipids are essential components of the cell and organelle membranes of Trichinella spiralis. The nematode has lost the capacity to synthesise the necessary lipids de novo and has instead evolved to obtain fatty acids and their derivatives from its host. This study aims to ascertain the primary biological characteristics and roles of T. spiralis FATP1 (TsFATP1) in lipid metabolism, larval moulting, and the development of this nematode. The results show that TsFATP1 is highly expressed at enteral T. spiralis stages, mainly localised at the cuticle, the stichosome and the intrauterine embryos of the parasite. The silencing of the TsFATP1 gene by TsFATP1-specific dsRNA significantly decreases the expression levels of TsFATP1 in the worm. It reduces the contents of ATP, triglycerides, total cholesterol, and phospholipids both in vitro and in vivo. RNAi inhibits lipid metabolism, moulting, and the growth of this nematode. The results demonstrate that TsFATP1 plays an essential role in lipid metabolism, moulting, and the development of T. spiralis. It could also be a target candidate for the anti-Trichinella vaccine and drugs.

Osteogenic mechanism of deciduous teeth periodontal ligament stem cells in inflammatory environment.

This study aimed to illustrate the biological behavior and changes in cell function during the progression of apical periodontitis in deciduous teeth and to explore the underlying molecular mechanism. Deciduous teeth periodontal ligament stem cells (DePDLSCs) were derived and their identity was confirmed. The viability, inflammation, and osteogenic ability of cells were tested by exposing them to various concentrations of lipopolysaccharide (LPS) (0-100 µg/mL) using the cell counting kit-8 (CCK-8) assay, reverse transcription polymerase chain reaction (real-time PCR), alkaline phosphatase (ALP) staining, and ALP activity assay. In addition, osteogenic-induced cells with and without 10 µg/mL LPS were harvested for high-throughput sequencing. Based on sequencing data, proinflammatory factors and ALP expression were measured after interference with the PI3K-AKT signaling pathway activator, 740Y-P. LPS biphasically affected the proliferation and osteogenesis of DePDLSCs. Low concentrations of LPS showed stimulatory effects, whereas inhibitory effects were observed at high concentrations. Sequencing analysis showed that the PI3K-AKT signaling pathway was significantly downregulated when DePDLSCs were treated with 10 µg/mL LPS. The LPS-induced inflammation and osteogenesis inhibition of DePDLSCs were partially rescued by 740Y-P treatment. In conclusion, LPS affected DePDLSCs proliferation and osteogenesis in a biphasic manner. Moderate activation of PI3K-AKT signaling pathway was beneficial for osteogenic differentiation and anti-inflammatory effect in DePDLSCs. This research may provide etiological probes for apical periodontitis and its treatment.

Puerarin: a hepatoprotective drug from bench to bedside.

Pueraria is a time-honored food and medicinal plant, which is widely used in China. Puerarin, the main component extracted from pueraria, has a variety of pharmacological characteristics. In recent years, puerarin has received increasing attention for its significant hepatoprotective effects, such as metabolic dysfunction-associated steatotic liver disease, alcohol-related liver disease, and hepatic carcinoma. This paper explores the pharmacological effects of puerarin on various liver diseases through multiple mechanisms, including inflammation factors, oxidative stress, lipid metabolism, apoptosis, and autophagy. Due to its restricted solubility, pharmacokinetic studies revealed that puerarin has a low bioavailability. However, combining puerarin with novel drug delivery systems can improve its bioavailability. Meanwhile, puerarin has very low toxicity and high safety, providing a solid foundation for its further. In addition, this paper discusses puerarin's clinical trials, highlighting its unique advantages. Given its excellent pharmacological effects, puerarin is expected to be a potential drug for the treatment of various liver diseases.

Regulation of the NF-κB/NLRP3 signalling pathway by Shenghui Yizhi decoction reduces neuroinflammation in mice with Alzheimer's disease.

BACKGROUND: Shenghui Yizhi Decoction (SHYZD) has exhibited the capacity to enhance cognitive function and learning abilities in individuals diagnosed with Alzheimer's disease (AD) while ameliorating pre-existing neuroinflammation. Nevertheless, the precise mechanism underlying its therapeutic effects on AD remains to be elucidated. METHODS: Twenty-four male SAMP8 mice were randomly divided into three groups, and eight male SAMR1 mice were used as a blank control, to examine their learning and spatial memory abilities. The expression of amyloid ß1-42 (Aß1-42) was detected by immunohistochemical staining of hippocampal tissue. ELISA was used to detect the interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) expressions. Real time PCR was used to detect NOD-like receptor thermal protein domain associated protein 3 (NLRP3), cysteine protease-1 (Caspase-1), and IL-1ß mRNA expression. Western blot was used to detect nuclear factor kappa-B (NF-κB), inhibitor of NF-κB α (IκBα), IκB kinase α (IKKα), NLRP3, Caspase-1, and IL-1ß protein expression. RESULTS: In this study, SAMP8 mice, employed as an AD model, displayed markedly diminished abilities in terms of spatial localization, navigation, and spatial exploration when compared to the blank control group. Additionally, there was a substantial upregulation of Aß1-42 expression in the hippocampus of these mice, along with a significant increase in the levels of inflammation-associated factors, including IL-1ß, IL-6, TNF-α, NLRP3, Caspase-1, as well as the NF-κB pathway-related proteins, namely, NF-κB, IκBα, and IKKα. Moreover, after treatment with positive drugs (donepezil hydrochloride) and SHYZD, the learning abilities of the mice exhibited significant improvements. Furthermore, the hallmark AD protein Aß1-42, inflammatory factors, and NF-κB/NLRP3 signalling pathway proteins were significantly reduced. These findings collectively suggest that SHYZD exerts a therapeutic effect on AD. CONCLUSION: In summary, the specific molecular mechanisms through which SHYZD alleviates AD and the potential role for SHYZD in the NF-κB/NLRP3 signalling pathway are identified in this study.

Precipitation, solar radiation, and their interaction modify leaf hydraulic efficiency-safety trade-off across angiosperms at the global scale.

In theory, there is a trade-off between hydraulic efficiency and safety. However, the strength and direction of this trade-off at the leaf level are not consistent across studies, and habitat climate may impact this trade-off. We compiled a leaf hydraulic efficiency and safety dataset for 362 species from 81 sites world-wide, with 280 paired observations of both traits, and tested whether climate was associated with departure from the proposed trade-off. The leaf hydraulic efficiency-safety trade-off was weak (R2 = 0.144) at the global scale. Mean annual precipitation and solar radiation (SR) modified the trade-off. Species from dry and high SR habitats (e.g. desert and tropical savanna) were generally located above the trade-off line, indicating that these species tended to have higher leaf hydraulic safety and efficiency than species from wet habitats with low SR (e.g. subtropical monsoon forest and montane rainforest), which were located below the trade-off line. Leaves with high vein density, dry leaf mass per area, and osmotic regulation enhanced safety without compromising hydraulic efficiency. Variation in the hydraulic efficiency-safety trade-off at the leaf level likely facilitates plant survival in specific habitats and allows for a more nuanced view of leaf hydraulic adaption strategies at the global scale.

Effects of Wab-WPPEP on post-intensive care syndrome-family in family caregivers of heart valve replacement patients: A randomized controlled trial.

OBJECTIVES: To evaluate the effects of a WeChat applet-based whole process psychological empowerment program (Wab-WPPEP) on post-intensive care syndrome-family in family caregivers of heart valve replacement patients. DESIGN: Two-arm, parallel, randomized controlled clinical trial. SETTINGS: A tertiary general hospital in Fuzhou, China. METHODS: Participants were randomly assigned to two groups. The intervention group received Wab-WPPEP, while the control group received routine care. The intervention was implemented from ICU admission to one month post-discharge. The primary outcome was anxiety, while secondary outcomes included depression, post-traumatic stress disorder (PTSD), and quality of life. Outcomes were assessed at baseline (T0), before ICU transfer (T1), pre-discharge (T2), and one month post-discharge (T3) using standardized questionnaires. Generalized estimating equations were used to analyze the repeated-measures data. RESULTS: The intervention group exhibited greater improvements in anxiety (T1: ß = -1.92, 95 % CI: -2.35 to -1.49, P < 0.001; T2: ß = -1.66, 95 % CI: -2.03 to -1.29, P < 0.001; T3: ß = -3.98, 95 % CI: -4.34 to -3.62, P < 0.001), depression (T1: ß = -1.32, 95 % CI: -1.79 to -0.85, P < 0.001; T2: ß = -1.70, 95 % CI: -2.08 to -1.32, P < 0.001), and quality of life (T2: ß = 31.16, 95 % CI: 21.35 to 40.98, P < 0.001) compared to the routine-care group. PTSD scores were also significantly lower in the intervention group (t = -6.454, P < 0.001). CONCLUSIONS: Wab-WPPEP significantly reduced anxiety and depression, improved quality of life, and alleviated PTSD symptoms in family caregivers of heart valve replacement patients. IMPLICATIONS FOR CLINICAL PRACTICE: Comprehensive psychological interventions should be implemented throughout the ICU stay and recovery period to improve family caregiver well-being.

Fine-Tuning the d-Band Center Position of Zinc to Increase the Anti-Tumor Activity of Single-Atom Nanozymes.

The exceptional biocompatibility of Zn-based single-atom nanozymes (SAzymes) has led to extensive research in their application for disease diagnosis and treatment. However, the fully occupied 3d10 electron configuration has seriously hampered the enzymatic-like activity of Zn-based SAzymes. Herein, a B-doped Zn-based SAzymes is fabricated by carbonizing zeolite-like Zn-based boron imidazolate framework at different temperatures (Zn-SAs@BNCx, x = 800, 900, 1000, and 1100 °C). The formed B─N bond yielded a local electric field, which changes the position of the d-band center and improved the oxidation state of Zn by facilitating the electron transfer from Zn to N to B. These changes enhanced the adsorption and activation of H2O2 and O2 by Zn-SAs@BNC1000, increasing the nanozymes' multi-enzyme catalytic activity. B doping led to 24.81-, 32.37-, and 13.98-fold increase in the peroxidase-, oxidase- and catalase-like, respectively, catalytic efficiency (Kcat/Km) of Zn-SAs@BNC1000 when compared with no B doping. In addition, Zn-SAs@BNC1000 showed excellent ability to kill tumor cells both in vitro and in vivo. This study demonstrates that the modulation of the electron configuration of Zn is an effective strategy to develop efficient anti-tumor approaches by boosting the enzymatic activity of Zn-based SAzymes.

Nesfatin-1 enhances vascular smooth muscle calcification through facilitating BMP-2 osteogenic signaling.

Vascular calcification (VC) arises from the accumulation of calcium salts in the intimal or tunica media layer of the aorta, contributing to higher risk of cardiovascular events and mortality. Despite this, the mechanisms driving VC remain incompletely understood. We previously described that nesfatin-1 functioned as a switch for vascular smooth muscle cells (VSMCs) plasticity in hypertension and neointimal hyperplasia. In this study, we sought to investigate the role and mechanism of nesfatin-1 in VC. The expression of nesfatin-1 was measured in calcified VSMCs and aortas, as well as in patients. Loss- and gain-of-function experiments were evaluated the roles of nesfatin-1 in VC pathogenesis. The transcription activation of nesfatin-1 was detected using a mass spectrometry. We found higher levels of nesfatin-1 in both calcified VSMCs and aortas, as well as in patients with coronary calcification. Loss-of-function and gain-of-function experiments revealed that nesfatin-1 was a key regulator of VC by facilitating the osteogenic transformation of VSMCs. Mechanistically, nesfatin-1 promoted the de-ubiquitination and stability of BMP-2 via inhibiting the E3 ligase SYTL4, and the interaction of nesfatin-1 with BMP-2 potentiated BMP-2 signaling and induced phosphorylation of Smad, followed by HDAC4 phosphorylation and nuclear exclusion. The dissociation of HDAC4 from RUNX2 elicited RUNX2 acetylation and subsequent nuclear translocation, leading to the transcription upregulation of OPN, a critical player in VC. From a small library of natural compounds, we identified that Curculigoside and Chebulagic acid reduced VC development via binding to and inhibiting nesfatin-1. Eventually, we designed a mass spectrometry-based DNA-protein interaction screening to identify that STAT3 mediated the transcription activation of nesfatin-1 in the context of VC. Overall, our study demonstrates that nesfatin-1 enhances BMP-2 signaling by inhibiting the E3 ligase SYTL4, thereby stabilizing BMP-2 and facilitating the downstream phosphorylation of SMAD1/5/9 and HDAC4. This signaling cascade leads to RUNX2 activation and the transcriptional upregulation of MSX2, driving VC. These insights position nesfatin-1 as a potential therapeutic target for preventing or treating VC, advancing our understanding of the molecular mechanisms underlying this critical cardiovascular condition.

Gut microbiome and metabolites mediate the benefits of caloric restriction in mice after acute kidney injury.

The role of gut microbiome in acute kidney injury (AKI) is increasing recognized. Caloric restriction (CR) has been shown to enhance the resistance to ischemia/reperfusion injury to the kidneys in rodents. Nonetheless, it is unknown whether intestinal microbiota mediated CR protection against ischemic/reperfusion-induced injury (IRI) in the kidneys. Herein, we showed that CR ameliorated IRI-elicited renal dysfunction, oxidative stress, apoptosis, and inflammation, along with enhanced intestinal barrier function. In addition, gut microbiota depletion blocked the favorable effects of CR in AKI mice. 16S rRNA and metabolomics analysis showed that CR enriched the gut commensal Parabacteroides goldsteinii (P. goldsteinii) and upregulated the level of serum metabolite dodecafluorpentan. Intestinal colonization of P. goldsteinii and oral administration of dodecafluorpentan showed the similar beneficial effects as CR in AKI mice. RNA sequencing and experimental data revealed that dodecafluorpentan protected against AKI-induced renal injury by antagonizing oxidative burst and NFκB-induced NLRP3 inflammasome activation. In addition, we screened and found that Hamaudol improved renal insufficiency by boosting the growth of P. goldsteinii. Our results shed light on the role of intestinal microbiota P. goldsteinii and serum metabolites dodecafluorpentan in CR benefits to AKI.

Clinical characteristics and prognostic factors of pulmonary and extrapulmonary cryptococcosis.

BACKGROUND: Cryptococcosis is progressively acknowledged among people, irrespective of the human with or without immunodeficiency virus (HIV). This change in epidemiology has been recorded in recent years, prompting closer examination and a broader understanding of the disease manifestations and risk factors. METHODS: The data of cryptococcal infections in China during 11 years were retrospectively analyzed. According to the position of infection, the patients were categorized into the pulmonary infection group and extrapulmonary infection group. The composition of the two groups was compared, and the potential risk factors of disseminated infection were analyzed. Logistic regression was used to analyze the prognostic risk factors of the disease. RESULTS: A total of 165 patients were enrolled. 113 (68.5%) were male, and the age was 47.49 (18-82) years. 101 cases (61.2%) had a normal immune function and 64 cases (38.8%) had impaired immune function. 45 patients had extrapulmonary infection, involving the central nervous system, bone and joint, skin and bloodstream, and 120 patients had simple pulmonary infection. The mortality of the extrapulmonary infection group (48.9%) was significantly higher than that of the pulmonary infection group (0.8%). According to univariate logistic regression analysis, immune status (hazard ratio [HR], 4.476; 95% confidence interval [CI], 1.725-11.618; P = 0.002), infection position ([HR], 113.826; [CI], 14.607-886.967; P < 0.001), white blood cell count, ([HR],1.209;[CI], 1.054-1.386; P = 0.007), hemoglobin ([HR], 0.970; [CI], 0.955-0.986; P < 0.001), platelet count ([HR], 0.993; [CI], 0.987-0.999; P = 0.026), neutrophil percentage ([HR], 1.115; [CI], 1.065-1.168; P < 0.001), lymphocyte percentage ([HR], 0.875; [CI], 0.827-0.927; P < 0.001), neutrophil-to-lymphocyte Ratio (NLR) ([HR], 1.144; [CI], 1.072-1.221; P < 0.001), monocyte percentage ([HR], 0.752; [CI], 0.618-0.915; P = 0.004) were related to the prognosis. Multivariate logistic regression analysis showed that the infection position was remained related to the prognosis with statistical significance ([HR], 0.018; [CI], 0.001-0.384; P = 0.001). CONCLUSION: Extrapulmonary infection of Cryptococcosis is an important risk factor for prognosis. High levels of neutrophils and NLR, and low levels of lymphocytes and monocytes may lead to disseminated infection of Cryptococcosis. Further studies are needed to reduce the occurrence rate of extrapulmonary infection and mortality.

Metagenomic next-generation sequencing promotes pathogen detection over culture in joint infections with previous antibiotic exposure.

Objective: To investigate the diagnostic value of metagenomic next-generation sequencing (mNGS) in detecting pathogens from joint infection (JI) synovial fluid (SF) samples with previous antibiotic exposure. Methods: From January 2019 to January 2022, 59 cases with suspected JI were enrolled. All cases had antibiotic exposure within 2 weeks before sample collection. mNGS and conventional culture were performed on SF samples. JI was diagnosed based on history and clinical symptoms in conjunction with MSIS criteria. The diagnostic values, including sensitivity, specificity, positive/negative predictive values (PPV/NPV), and accuracy, were in comparison with mNGS and culture. Results: There were 47 of the 59 cases diagnosed with JI, while the remaining 12 were diagnosed with non-infectious diseases. The sensitivity of mNGS was 68.1%, which was significantly higher than that of culture (25.5%, p<0.01). The accuracy of mNGS was significantly higher at 71.2% compared to the culture at 39.0% (p <0.01). Eleven pathogenic strains were detected by mNGS but not by microbiological culture, which included Staphylococcus lugdunensis, Staphylococcus cohnii, Finegoldia magna, Enterococcus faecalis, Staphylococcus saprophytics, Escherichia coli, Salmonella enterica, Pseudomonas aeruginosa, Acinetobacter pittii, Brucella ovis, andCoxiella burnetii. Antibiotic therapy was adjusted based on the mNGS results in 32 (68.1%) patients, including 12 (25.5%) and 20 (42.6%) patients, in whom treatment was upgraded and changed, respectively. All JI patients underwent surgery and received subsequent antibiotic therapy. They were followed up for an average of 23 months (20-27 months), and the success rate of treatment was 89.4%. Out of the 33 patients who had positive results for pathogens, reoperation was performed in 1 case (3.03%), while out of the 14 cases with negative results for both mNGS and cultures, reoperation was performed in 4 cases (28.6%). Conclusions: mNGS has advantages over conventional culture in detecting pathogens in SF samples from JI patients previously treated with antibiotics, potentially improving clinical outcomes.

Impact of lung adenocarcinoma subtypes on survival and timing of brain metastases.

Purpose: Lung cancer is a devastating disease, with brain metastasis being one of the most common distant metastases of lung adenocarcinoma. This study aimed to investigate the prognostic characteristics of individuals with brain metastases originating from invasive lung adenocarcinoma of distinct pathological subtypes, providing a reference for the management of these patients. Methods: Clinical data from 156 patients with lung adenocarcinoma-derived brain metastases were collected, including age, sex, smoking status, Karnofsky Performance Status scores, pathological subtype, lymph node metastasis, tumor site, treatment mode, T stage, and N stage. Patients were classified into two groups (highly differentiated and poorly differentiated) based on their pathological subtypes. Propensity score matching was used to control for confounding factors. The prognostic value of pathological subtypes was assessed using Kaplan-Meier analysis and Cox proportional hazards regression modeling. Results: Kaplan-Meier analysis indicated that patients in the moderately to highly differentiated group had better prognoses. Multivariate analysis revealed that being in the poorly differentiated group was a risk factor for poorer prognosis. Thoracic tumor radiation therapy, chemotherapy, and surgery positively influenced the time interval between lung cancer diagnosis and brain metastasis. Conclusions: The pathological subtypes of lung adenocarcinoma-derived brain metastases are associated with patient prognosis. Patients in the poorly differentiated group have worse prognoses compared to those in the moderately to highly differentiated group. Therefore, patients in the poorly differentiated group may require more frequent follow-ups and aggressive treatment.

Current status and hotspots of in vitro oocyte maturation: a bibliometric study of the past two decades.

PURPOSE: In vitro maturation (IVM) of oocytes is a promising technique among assisted reproductive technologies. Although IVM has been used for many years, its efficiency is still relatively low compared to that of traditional in vitro fertilization (IVF) procedures. Therefore, we aimed to explore the hotspots and frontiers of IVM research over the past two decades and provide direction for IVM advancement. METHODS: The articles and reviews related to IVM in the Web of Science Core Collection (WoSCC) were retrieved on June 03, 2024. Three bibliometric tools, VOSviewer 1.6.18 (2010), CiteSpace 6.1. R6 (2006), and Bibliometrix R package 4.1.0 (2017), were used to generate network maps and explore knowledge frontiers and trends. To uncover the latest research advancements and frontiers in the IVM field, we conducted an analysis of the entire IVM field, including all species. Given our focus on human IVM developments, we identified the leading countries, institutions, authors, and journals driving progress in human IVM. RESULTS: A total of 5150 publications about IVM and 1534 publications in the specific context of human IVM were retrieved from the WoSCC. The number of publications on both overall IVM and human IVM fields has increased steadily. In human IVM, the United States (USA) and McGill University were the most prolific country and institution, respectively. Human Reproduction was both the most published in and the most cited journal in human IVM. Seang Lin, Tan was the most productive author, and Ri-Cheng, Chian's papers were the most cited in human IVM. Furthermore, five hotspot topics were summarized, namely, culture system, supplementation, cooperation in the ovarian follicle, gene expression, and oocyte cryopreservation. CONCLUSIONS: Further studies could concentrate on the following topics: (1) the mechanisms involved in oocyte maturation in vivo and in vitro, especially in energy metabolism and intercellular communications; (2) the establishment of IVM culture systems, including standardization of the biphasic IVM culture system and supplementation; (3) the genetic differences between oocytes matured in vivo and in vitro; and (4) the mechanism of cryopreservation-inflicted damage and solutions to this challenge. For human IVM, it is necessary to precisely assess the developmental stages of oocytes and adjust the IVM process accordingly to develop tailored culture media. Concurrently, clinical trials are essential for evaluating the effectiveness and safety of IVM.

Lipid droplets sequester palmitic acid to disrupt endothelial ciliation and exacerbate atherosclerosis in male mice.

Disruption of ciliary homeostasis in vascular endothelial cells has been implicated in the development of atherosclerosis. However, the molecular basis for the regulation of endothelial cilia during atherosclerosis remains poorly understood. Herein, we provide evidence in male mice that the accumulation of lipid droplets in vascular endothelial cells induces ciliary loss and contributes to atherosclerosis. Triglyceride accumulation in vascular endothelial cells differentially affects the abundance of free fatty acid species in the cytosol, leading to stimulated lipid droplet formation and suppressed protein S-palmitoylation. Reduced S-palmitoylation of ciliary proteins, including ADP ribosylation factor like GTPase 13B, results in the loss of cilia. Restoring palmitic acid availability, either through pharmacological inhibition of stearoyl-CoA desaturase 1 or a palmitic acid-enriched diet, significantly restores endothelial cilia and mitigates the progression of atherosclerosis. These findings thus uncover a previously unrecognized role of lipid droplets in regulating ciliary homeostasis and provide a feasible intervention strategy for preventing and treating atherosclerosis.