An optimal combination of four active components in Huangqin decoction for the synergistic sensitization of irinotecan against colorectal cancer.

BACKGROUND: Irinotecan (CPT-11) is a first-line treatment for advanced colorectal cancer (CRC). Four components (baicalin, baicalein, wogonin, and glycyrrhizic acid) derived from Huangqin Decoction (HQD) have been proven to enhance the anticancer activity of CPT-11 in our previous study. OBJECTIVE: This study aimed to determine the optimal combination of the four components for sensitizing CPT-11 as well as to explore the underlying mechanism. METHODS: The orthogonal design method was applied to obtain candidate combinations (Cmb1-9) of the four components. The influence of different combinations on the anticancer effect of CPT-11 was first evaluated in vitro by cell viability, wound healing ability, cloning formation, apoptosis, and cell cycle arrest. Then, a CRC xenograft mice model was constructed to evaluate the anticancer effect of the optimal combination in vivo. Potential mechanisms of the optimal combination exerting a sensitization effect combined with CPT-11 against CRC were analyzed by targeted metabolomics. RESULTS: In vitro experiments determined that Cmb8 comprised of baicalin, baicalein, wogonin, and glycyrrhizic acid at the concentrations of 17 µM, 47 µM, 46.5 µM and 9.8 µM respectively was the most effective combination. Importantly, the cell viability assay showed that Cmb8 exhibited synergistic anticancer activity in combination with CPT-11. In in vivo experiments, this combination (15 mg/kg of baicalin, 24 mg/kg of baicalein, 24 mg/kg of wogonin, and 15 mg/kg of glycyrrhizic acid) also showed a synergistic anticancer effect. Meanwhile, inflammatory factors and pathological examination of the colon showed that Cmb8 could alleviate the gastrointestinal damage induced by CPT-11. Metabolic profiling of the tumors suggested that the synergistic anticancer effect of Cmb8 might be related to the regulation of fatty acid metabolism. CONCLUSION: The optimal combination of four components derived from HQD for the synergistic sensitization of CPT-11 against CRC was identified.

Asian = machine, Black = animal? The racial asymmetry of dehumanization.

How different racial minorities experience racism differently remains underexplored in existing research. Here, we show that Asian and Black people are often dehumanized differently. Twelve studies spotlight a racial asymmetry in dehumanization using a wide array of methods (experimental, archival, and computational) and data sources (online samples, word embeddings, and U.S. Bureau of Labor Statistics data): Whereas Black people are more often subjected to animalistic dehumanization, Asian people are predominantly subjected to mechanistic dehumanization. We demonstrate this asymmetry from the vantage point of victims (Studies 1a and 1b) and perpetrators (Studies 2a-2d). We further document the prevalence of this asymmetry across diverse domains, from everyday language (Study 3) to perceptions in the realms of romantic relationships (Study 4a), crime rates (Study 4b), and business skills (Study 4c). Finally, we demonstrate the asymmetry's real-world consequences in labor market segregation (Studies 5 and 6). Our findings shed light on the distinct experiences of racism encountered by different racial groups and, more critically, introduce a framework that unifies and integrates scattered empirical observations on perceptions of Asian people. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Analysis of Lipid GPCR Molecular Interactions by Proximity Labeling.

G-protein-coupled receptors (GPCRs) are hepta-helical transmembrane proteins that mediate various intracellular signaling events in response to their specific ligands including many lipid mediators. Although analyses of GPCR molecular interactions are pivotal to understanding diverse intracellular signaling events, affinity purification of interacting proteins by a conventional co-immunoprecipitation method is challenging due to the hydrophobic nature of GPCRs and their dynamic molecular interactions. Proximity labeling catalyzed by a TurboID system is a powerful technique for defining the molecular interactions of target proteins in living cells. TurboID and miniTurbo (a modified version of TurboID) are engineered biotin ligases that biotinylate neighboring proteins in a promiscuous manner. When fused with a target protein and expressed in living cells, TurboID or miniTurbo mediates the biotin labeling of the proteins with close proximity to the target protein, allowing efficient purification of the biotinylated proteins followed by a shot-gun proteomic analysis. In this chapter, we describe a step-by-step protocol for the labeling of GPCR neighboring proteins by TurboID or miniTurbo, purification of the biotin-labeled proteins, and subsequent sample preparation for proteomic analysis. We utilized S1PR1 as a model GPCR, a receptor for a bioactive lipid molecule sphingosine 1-phosphate (S1P) that plays various roles in physiological and pathological conditions. This analysis pipeline enables the mapping of interacting proteins of lipid GPCRs in living cells.

Analysis of human papillomavirus type 16 E4, E5 and L2 gene variations among women with cervical infection in Xinjiang, China.

BACKGROUND: There is a high incidence of cervical cancer in Xinjiang. Genetic variation in human papillomavirus may increase its ability to invade, spread, and escape host immune response. METHODS: HPV16 genome was sequenced for 90 positive samples of HPV16 infection. Sequences of the E4, E5 and L2 genes were analysed to reveal sequence variation of HPV16 in Xinjiang and the distribution of variation among the positive samples of HPV16 infection. RESULTS: Eighty-one of the 90 samples of HPV16 infection showed variation in HPV16 E4 gene with 18 nucleotide variation sites, of which 8 sites were synonymous variations and 11 missense variations. 90 samples of HPV16 infection showed variation in HPV16 E5 and L2 genes with 16 nucleotide variation sites (6 synonymous, 11 missense variations) in the E5 gene and 100 nucleotide variation sites in L2 gene (37 synonymous, 67 missense variations). The frequency of HPV16 L2 gene missense variations G3377A, G3599A, G3703A, and G3757A was higher in the case groups than in the control groups. CONCLUSIONS: Phylogenetic tree analysis showed that 87 samples were European strains, 3 cases were Asian strains, there were no other variations, and G4181A was related to Asian strains. HPV16 L2 gene missense variations G3377A, G3599A, G3703A, and G3757A were significantly more frequent in the case groups than in the control groups.

Effect of electroacupuncture pre-conditioning on the expression rhythm of core clock gene Bmal1 in uterine tissue of controlled hyperstimulation rats. / ç”µé’ˆé¢„å¤„ç†å¯¹ä¿ƒæŽ’åµå¤§é¼ å­å®«ç»„ç»‡æ ¸å¿ƒæ—¶é’ŸåŸºå› Bmal1表达节律的影响.

OBJECTIVES: To observe the effect of electroacupuncture (EA) pre-conditioning on the expression rhythm of clock gene Bmal1 in the uterine tissue of rats with controlled ovarian hyperstimulation(COH), so as to explore its mechanisms underlying improvement of the endometrial receptivity of ovarian superovulation during implantation. METHODS: Seventy-two female SD rats with typical estrous cycles were randomly divided into normal control, model and EA pre-conditioning (pre-EA) groups, with 24 rats in each group. The COH model was established by giving the rats with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (HCG) by intraperitoneal injection. The rats of the pre-EA group received EA stimulation (1 Hz/5 Hz, a tolerable strength) of "Guanyuan"(CV4) and "Sanyinjiao"(SP6) for 15 min each time, once daily (at 21：00 every day). After successive EA intervention during the first two estrous cycles, the modeling began in the third estrus cycle and the EA intervention was continued till the end of modeling, followed by raising the rats with superovulation induction and male rats undergoing vasoligation in one cage (1∶1). The rats during the estrum in the normal control group or those of the model group at the end of modeling were raised together with the male rats undergoing vasoligation in one cage. On the 5th day (04：00 AM) after raising in one cage, the rats in the three groups were sacrificed in six batches every 4 hours, with 4 rats in each group in each batch. The H.E. staining was used for revealing alterations of the endometrial thickness, number of glands and blood vessels and tissue histology, and ELISA employed to ascertain the contents of estradiol (E2) and progesterone (Pg) in serum. The expression rhythm of core clock gene Bmal1 ［In the present study, Zeitgeber time (ZT) is an artificially set laboratory time, i.e., ZT7 (07：00) is light on and ZT19 (19：00) is light off.］ and the expression of endometrial HoxA10 and leukemia inhibitory factor (LIF) mRNAs were detected by quantitative real-time PCR. The Western blot was employed to detect the expression levels of HoxA10 and LIF proteins. RESULTS: Findings of the clock gene Bmal1 level showed that the expression peak was at ZT12 and the valley value at ZT20 in the normal control group, and that of the peak value was at ZT20 and valley value at ZT12 in the model group, while in the pre-EA group, the peak value was at ZT8, and the valley value at ZT4. The difference of Bmal1 levels among the three groups was most significant at ZT12 (12：00), therefore, the tissue samples were taken at ZT12 in this study for comparison of the levels of different indexes among the 3 groups. Compared with the control group, the endometrial thickness, number of glands and blood vessels, HoxA10 and LIF mRNAs and proteins were significantly down-regulated (P<0.01, P<0.05), and contents of serum E2 and Pg were considerably up-regulated in the model group (P<0.01, P<0.05). Relevant to the model group, the pre-EA group had an apparent increase in the endometrial thickness, number of glands and blood vessels, and expression levels of HoxA10 and LIF mRNAs and proteins (P<0.05, P<0.01), and a marked decrease in the serum Pg (P<0.05). At the ZT12 (12：00 noon), compared with the normal control group, the mRNA level of Bmal1 was significantly decreased in the model group (P<0.01)；and compared with the model group, the level of Bmal1 mRNA was significantly increased in the pre-EA group (P<0.05). In addition, at the node of ZT16, the mRNA level of Bmal1 was significantly decreased in the model group in comparison with the normal control group (P<0.01). CONCLUSIONS: EA preconditioning can improve the endometrial receptivity during the implantation window period in rats with COH, which may be related to its functions in regulating the expression of clock gene Bmal1 in the uterine tissue and in correcting the disturbance of clock gene rhythm.

CT-guided radiofrequency ablation of facial and mandibular nerves in the treatment of compound Meige's syndrome.

This retrospective study examined the clinical outcomes and complications in 6 cases of compound Meige's syndrome, presenting with blepharospasm and masticatory muscle spasm, following treatment with CT-guided radiofrequency ablation targeting bilateral facial nerves and mandibular branches of the trigeminal nerve. After the operation, the symptoms of eyelid spasm and masticatory muscle spasm resolved, but mild facial paralysis and numbness of mandibular nerve innervation persisted. Follow-up for 4-28 months showed that the symptoms of facial paralysis resolved within 2-5 (3.17 ± 0.94) months after the operation, whereas the numbness in the mandibular region persisted, accompanied by a decrease in masticatory function. During the follow-up period, none of the 6 patients experienced a recurrence of Meige's syndrome. These findings suggest that CT-guided radiofrequency ablation of the bilateral facial nerve and mandibular branches of the trigeminal nerve may offer a promising approach to treating compound Meige's syndrome.

Clinical efficacy of intradermal type I collagen injections in treating skin photoaging in patients from high-altitude areas.

BACKGROUND: Photoaging, a result of chronic sun exposure, leads to skin damage and pigmentation changes. Traditional treatments may have limitations in high-altitude areas like Yunnan Province. Intradermal Col Ι injections stimulate collagen production, potentially improving skin quality. This study aims to assess the efficacy and safety of this treatment for photoaging. AIM: To evaluate the efficacy and safety of intradermal type Ι collagen (Col Ι) injection for treating photoaging. METHODS: This prospective, self-controlled study investigated the impact of intradermal injections of Col Ι on skin photodamage in 20 patients from the Yunnan Province. Total six treatment sessions were conducted every 4 wk ± 3 d. Before and after each treatment, facial skin characteristics were quantified using a VISIA skin detector. Skin thickness data were assessed using the ultrasound probes of the Dermalab skin detector. The Face-Q scale was used for subjective evaluation of the treatment effect by the patients. RESULTS: The skin thickness of the right cheek consistently increased after each treatment session compared with baseline. The skin thickness of the left cheek significantly increased after the third through sixth treatment sessions compared with baseline. The skin thickness of the right zygomatic region increased after the second to sixth treatment sessions, whereas that of the left zygomatic region showed a significant increase after the fourth through sixth treatment sessions. The skin thickness of both temporal regions significantly increased after the fifth and sixth treatment sessions compared with baseline (P < 0.05). These findings were also supported by skin ultrasound images. The feature count for the red areas and wrinkle feature count decreased following the treatment (P < 0.05). VISIA assessments also revealed a decrease in the red areas after treatment. The Face-Q-Satisfaction with Facial Appearance Overall and Face-Q-Satisfaction with Skin scores significantly increased after each treatment session. The overall appearance of the patients improved after treatment. CONCLUSION: Intradermal Col Ι injection improves photoaging, with higher patient satisfaction and fewer adverse reactions, and could be an effective treatment method for populations residing in high-altitude areas.

Intraplatelet miRNA-126 regulates thrombosis and its reduction contributes to platelet inhibition.

AIMS: MicroRNA-126 (miR-126), one of the most abundant microRNAs in platelets, is involved in the regulation of platelet activity and the circulating miR-126 is reduced during antiplatelet therapy. However, whether intraplatelet miR-126 plays a role in thrombosis and platelet inhibition remains unclear. METHODS AND RESULTS: Here, using tissue-specific knockout mice, we reported that the deficiency of miR-126 in platelets and vascular endothelial cells significantly prevented thrombosis and prolonged bleeding time. Using chimeric mice, we identified that the lack of intraplatelet miR-126 significantly prevented thrombosis. Ex vivo experiments further demonstrated that miR-126-deficient platelets displayed impaired platelet aggregation, spreading and secretory functions. Next, miR-126 was confirmed to target phosphoinositol-3 kinase regulatory subunit 2 (PIK3R2) in platelet, which encodes a negative regulator of the PI3 K/AKT pathway, enhancing platelet activation through activating the integrin αIIbß3-mediated outside-in signaling. After undergoing myocardial infarction (MI), chimeric mice lacking intraplatelet miR-126 displayed reduced microvascular obstruction and prevented MI expansion in vivo. In contrast, overexpression of miR-126 by the administration of miR-126 agonist (agomiR-126) in wild-type mice aggravated microvascular obstruction and promoted MI expansion, which can be almost abolished by aspirin administration. In patients with cardiovascular diseases, antiplatelet therapies, either aspirin alone or combined with clopidogrel, decreased the level of intraplatelet miR-126. The reduction of intraplatelet miR-126 level was associated with the decrease of platelet activity. CONCLUSIONS: Our murine and human data reveal that (i) intraplatelet miR-126 contributes to platelet activity and promotes thrombus formation, and (ii) the reduction of intraplatelet miR-126 contributes to platelet inhibition during antiplatelet therapy.

The therapeutic role of γδT cells in TNBC.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that presents significant therapeutic challenges due to the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. As a result, conventional hormonal and targeted therapies are largely ineffective, underscoring the urgent need for novel treatment strategies. γδT cells, known for their robust anti-tumor properties, show considerable potential in TNBC treatment as they can identify and eliminate tumor cells without reliance on MHC restrictions. These cells demonstrate extensive proliferation both in vitro and in vivo, and can directly target tumors through cytotoxic effects or indirectly by promoting other immune responses. Studies suggest that expansion and adoptive transfer strategies targeting Vδ2 and Vδ1 γδT cell subtypes have shown promise in preclinical TNBC models. This review compiles and discusses the existing literature on the primary subgroups of γδT cells, their roles in cancer therapy, their contributions to tumor cell cytotoxicity and immune modulation, and proposes potential strategies for future γδT cell-based immunotherapies in TNBC.

Oxford Nanopore Technologies (ONT) Full-length Transcriptomics Shows Electroacupuncture ameliorates Lipid Metabolic Disorder through Suppressing Hepatic Pdia3/Perk/Qrich1 Expression in Rats.

BACKGROUND: The incidence of dyslipidemia increases after menopause. Electroacupuncture (EA) has been recommended for menopause-related disease. However, the positive effect on lipid metabolism disorders is still unclear. OBJECTIVES: To investigate the underlying mechanism of EA treatment on lipid metabolism disorders through ONT full-length transcriptome sequencing Methods: Adult female SD rats were randomly divided into Ctrl, sham operation+high-fat feed(Sham+HFD), Ovariectomized+high-fat feed (OVX+HFD), Ovariectomized+high-fat feed + Atorvastatin (OVX+HFD+ATO) and OVX+HFD+EA groups. Periovarian adipose tissue around the bilateral ovaries of rats in the Sham+HFD group was resected. Rats in the OVX+HFD, OVX+HFD+ATO and OVX+HFD+EA groups were subjected to bilateral oophorectomy to prepare the ovariectomized rat model. Treatment was applied to rats in the OVX+HFD+EA group. ST36, PC6, SP6, BL18 and ST40 were the selected acupoints. Daily food intake and body weights of rats were recorded. The samples were collected 30 days after treatment. The serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein (HDL-C) were detected to assess the improvement of lipid metabolism disorders. HE and oil red O staining were used to stain the liver tissues. Total RNA was extracted from liver tissues, and its transcriptional changes were determined by high-throughput sequencing. Additionally, RTÁqPCR and immunofluorescence staining were used to verify the crucial signal pathway screened by the ONT fullÁlength transcriptome sequencing. RESULTS: EA treatment resulted in a lowered weight of perirenal fat and liver and a significant improvement in the color of the liver. In addition, EA could improve the lipid profile and hepatic steatosis in OVX+HFD rats. According to fullÁlength transcriptome sequencing, 2292 genes showed differential expression in the OVX+HFD group; of these, 1121 were upregulated and 1171 down-regulated. 609 DEGs were found in the OVX+HFD+EA group compared to the OVX+HFD group; 235 up-regulated and 374 down-regulated. We also found that 77 genes are significantly upregulated after EA intervention through Venn map analysis (including Agtr1a, Pdia3, etc.), which may be the targeted genes for EA treatment of lipid metabolism disorders. Finally, we verified the expression of Pdia3, Perk and Qrich1 levels in liver tissues. HFD feeding could increase the expression of Pdia3 and its downstream signal pathways molecular Perk and Qrich1. But these effects were reversed by EA treatment, the results demonstrated that the expression of pdia3, Perk, as well as Qrich1 of OVX+HFD rats had a decreasing trend after EA treatment. CONCLUSIONS: EA could ameliorate lipid metabolic disorder in OVX+HFD rats. The Pdia3/Perk/Qrich1 signal pathway may play crucial roles in the improvement of lipid metabolism disorder of OVX+HFD rats after EA treatment.

High-efficiency single-frequency DBR fiber laser at 1091 nm utilizing a Yb:YAG crystal-derived silica fiber.

A single-frequency distributed Bragg Reflector (DBR) fiber laser operating at 1091 nm was demonstrated by using a Yb:YAG crystal-derived silica fiber (YDSF). The YDSF was prepared via the molten core (MC) method, with a Yb2O3 doping concentration of 5.60 wt.% in the core, resulting in a gain coefficient of 1.45 dB/cm at 1091 nm. Employing 0.8 cm of the YDSF, we attained a single-frequency laser with a maximum output power of 145 mW and a slope efficiency of 31.8%. The laser exhibited an optical signal-to-noise ratio (OSNR) exceeding 71 dB, a linewidth of ∼34 kHz, and a stabilized relative intensity noise (RIN) at -132 dB/Hz for frequencies over 4.5 MHz. The fiber laser could serve as an outstanding seed source for high-power, narrow-linewidth fiber amplifiers operating at 1091 nm.

Stem cell-derived extracellular vesicles in the therapeutic intervention of Alzheimer's Disease, Parkinson's Disease, and stroke.

With the increase in the aging population, the occurrence of neurological disorders is rising. Recently, stem cell therapy has garnered attention due to its convenient sourcing, minimal invasiveness, and capacity for directed differentiation. However, there are some disadvantages, such as poor quality control, safety assessments, and ethical and logistical issues. Consequently, scientists have started to shift their attention from stem cells to extracellular vesicles due to their similar structures and properties. Beyond these parallels, extracellular vesicles can enhance biocompatibility, facilitate easy traversal of barriers, and minimize side effects. Furthermore, stem cell-derived extracellular vesicles can be engineered to load drugs and modify surfaces to enhance treatment outcomes. In this review, we summarize the functions of native stem cell-derived extracellular vesicles, subsequently review the strategies for the engineering of stem cell-derived extracellular vesicles and their applications in Alzheimer's disease, Parkinson's disease, and stroke, and discuss the challenges and solutions associated with the clinical translation of stem cell-derived extracellular vesicles.

Quantum dot-enabled infrared hyperspectral imaging with single-pixel detection.

Near-infrared (NIR) hyperspectral imaging is a powerful technique that enables the capture of three-dimensional (3D) spectra-spatial information within the NIR spectral range, offering a wide array of applications. However, the high cost associated with InGaAs focal plane array (FPA) has impeded the widespread adoption of NIR hyperspectral imaging. Addressing this challenge, in this study, we adopt an alternative approach-single-pixel detection for NIR hyperspectral imaging. Our investigation reveals that single-pixel detection outperforms conventional FPA, delivering a superior signal-to-noise ratio (SNR) for both spectral and imaging reconstruction. To implement this strategy, we leverage self-assembled colloidal quantum dots (CQDs) and a digital micromirror device (DMD) for NIR spectral and spatial information multiplexing, complemented by single-pixel detection for simultaneous spectral and image reconstruction. Our experimental results demonstrate successful NIR hyperspectral imaging with a detection window about 600 nm and an average spectral resolution of 8.6 nm with a pixel resolution of 128 × 128. The resulting spectral and spatial data align well with reference instruments, which validates the effectiveness of our approach. By circumventing the need for expensive and bulky FPA and wavelength selection components, our solution shows promise in advancing affordable and accessible NIR hyperspectral imaging technologies, thereby expanding the range of potential applications.

Realization of fractional quantum Hall state with interacting photons.

Fractional quantum Hall (FQH) states are known for their robust topological order and possess properties that are appealing for applications in fault-tolerant quantum computing. An engineered quantum platform would provide opportunities to operate FQH states without an external magnetic field and enhance local and coherent manipulation of these exotic states. We demonstrate a lattice version of photon FQH states using a programmable on-chip platform based on photon blockade and engineering gauge fields on a two-dimensional circuit quantum electrodynamics system. We observe the effective photon Lorentz force and butterfly spectrum in the artificial gauge field, a prerequisite for FQH states. After adiabatic assembly of Laughlin FQH wave function of 1/2 filling factor from localized photons, we observe strong density correlation and chiral topological flow among the FQH photons. We then verify the unique features of FQH states in response to external fields, including the incompressibility of generating quasiparticles and the smoking-gun signature of fractional quantum Hall conductivity. Our work illustrates a route to the creation and manipulation of novel strongly correlated topological quantum matter composed of photons and opens up possibilities for fault-tolerant quantum information devices.

Optimization of a Ge2Sb2Te5-Based Electrically Tunable Phase-Change Thermal Emitter for Dynamic Thermal Camouflage.

Controlling infrared thermal radiations can significantly improve the environmental adaptability of targets and has attracted increasing attention in the field of thermal camouflage. Thermal emitters based on Ge2Sb2Te5 (GST) can flexibly change their radiation energy by controlling the reversible phase transition of GST, which possesses fast switching speed and low power consumption. However, the feasibility of the dynamic regulation of GST emitters lacks experimental and simulation verification. In this paper, we propose an electrically tunable thermal emitter consisting of a metal-insulator-metal plasmonic metasurface based on GST. Both optical and thermal simulations are conducted to optimize the structural parameters of the GST emitter. The results indicate that this emitter possesses large emissivity tunability, wide incident angle, polarization insensitivity, phase-transition feasibility, and dynamic thermal camouflage capability. Therefore, this work proposes a reliable optimization method to design viable GST-based thermal emitters. Moreover, it provides theoretical support for the practical application of phase-change materials in dynamic infrared thermal camouflage technology.

Prediction of risk factors for linezolid-induced thrombocytopenia based on neural network model.

Background: Based on real-world medical data, the artificial neural network model was used to predict the risk factors of linezolid-induced thrombocytopenia to provide a reference for better clinical use of this drug and achieve the timely prevention of adverse reactions. Methods: The artificial neural network algorithm was used to construct the prediction model of the risk factors of linezolid-induced thrombocytopenia and further evaluate the effectiveness of the artificial neural network model compared with the traditional Logistic regression model. Results: A total of 1,837 patients receiving linezolid treatment in a hospital in Xi 'an, Shaanxi Province from 1 January 2011 to 1 January 2021 were recruited. According to the exclusion criteria, 1,273 cases that did not meet the requirements of the study were excluded. A total of 564 valid cases were included in the study, with 89 (15.78%) having thrombocytopenia. The prediction accuracy of the artificial neural network model was 96.32%, and the AUROC was 0.944, which was significantly higher than that of the Logistic regression model, which was 86.14%, and the AUROC was 0.796. In the artificial neural network model, urea, platelet baseline value and serum albumin were among the top three important risk factors. Conclusion: The predictive performance of the artificial neural network model is better than that of the traditional Logistic regression model, and it can well predict the risk factors of linezolid-induced thrombocytopenia.

Development and evaluation of a novel knowledge assessment tool for pediatric emergency medicine clerkships.

Objectives: This study seeks to determine validity evidence for a newly developed multiple-choice examination (MCE) tool to assess retention and application of medical knowledge of students enrolled in a pediatric emergency medicine (PEM) clerkship. Methods: A team of PEM physicians created a 110-item MCE covering the range of clinical topics in PEM relevant for medical students. The researchers determined examination content using the report of Clerkship Directors in Emergency Medicine and PEM Interest Group of the Society for Academic Emergency Medicine (SAEM). The authors administered the MCE to fourth-year medical students at the end of their PEM rotation from May 2020 to April 2023 at four institutions and then analyzed the examination using four of Messick's five sources of validity evidence: content, response process, internal structure, and relation to other variables. Results: A total of 158 students took the test. In academic year (AY)20-21, 47 students took the test and scored, on average, 81%. After revision of poor and indeterminate questions, the 111 medical students who took the revised version of the test in AY21-AY23 scored on average 77.3% with a standard deviation of 5.7% with a normal distribution in scores. The revised questions were rated as excellent (10.0%), good (26.4%), fair (34.5%), poor (24.5%), or indeterminate (4.5%) based on test item discrimination. There was a positive correlation between MCE scores and students' clinical evaluations but no correlation between MCE scores and scores that students received on their clinical notes or patient presentations during case conference. Conclusions: This novel PEM clerkship examination is a reliable test of medical knowledge. Future directions involve evaluating consequences of the MCE and offering the test to medical students in a dedicated PEM rotation at the national level.

Phosphorylation of AGO2 by TBK1 Promotes the Formation of Oncogenic miRISC in NSCLC.

Non-small-cell lung cancer (NSCLC) is a highly lethal tumor that often develops resistance to targeted therapy. It is shown that Tank-binding kinase 1 (TBK1) phosphorylates AGO2 at S417 (pS417-AGO2), which promotes NSCLC progression by increasing the formation of microRNA-induced silencing complex (miRISC). High levels of pS417-AGO2 in clinical NSCLC specimens are positively associated with poor prognosis. Interestingly, the treatment with EGFR inhibitor Gefitinib can significantly induce pS417-AGO2, thereby increasing the formation and activity of oncogenic miRISC, which may contribute to NSCLC resistance to Gefitinib. Based on these, two therapeutic strategies is developed. One is jointly to antagonize multiple oncogenic miRNAs highly expressed in NSCLC and use TBK1 inhibitor Amlexanox reducing the formation of oncogenic miRISC. Another approach is to combine Gefitinib with Amlexanox to inhibit the progression of Gefitinib-resistant NSCLC. This findings reveal a novel mechanism of oncogenic miRISC regulation by TBK1-mediated pS417-AGO2 and suggest potential therapeutic approaches for NSCLC.

Role of INPP4B in the proliferation, migration, invasion, and survival of human endometrial cancer cells.

BACKGROUND: Inositol polyphosphate 4-phosphatase type II (INPP4B) has been identified as a tumor repressor in several human cancers while its role in endometrial cancer has not been investigated yet. Therefore, the current study was designed to determine whether INPP4B participates in the progression of endometrial cancer by utilizing clinical data and experimental determination. MATERIALS AND METHODS: We first include six chemotherapy-treated patients with recurrent and metastatic endometrioid carcinoma to determine the relationship between INPP4B mutation and relative tumor burden. By using siRNA-mediated gene silencing and vector-mediated gene overexpression, we further determined the effect of manipulating INPP4B expression on the proliferation, invasion, and survival of endometrial cancer cells. Furthermore, the repressing effect of INPP4B together with its role in chemotherapy was further validated by xenograft tumor-bearing mice models. Western blot analysis was used to explore further downstream signaling modulated by INPP4B expression manipulation. RESULTS: Two of the patients were found to have INPP4B mutations and the mutation frequency of INPP4B increased during the progression of chemotherapy resistance. Endometrial cancer cells with silenced INPP4B expression were found to have promoted tumor cell proliferation, invasion, and survival. Endometrial cancer cells overexpressing INPP4B were found to have decreased tumor cell proliferation, invasion, and survival. An in vivo study using six xenograft tumor-bearing mice in each group revealed that INPP4B overexpression could suppress tumor progression and enhance chemosensitivity. Furthermore, INPP4B overexpression was found to modulate the activation of Wnt3a signaling. CONCLUSION: The current study suggested that INPP4B could be a suppressor in endometrial cancer progression and might be a target for endometrial cancer treatment. Also, INPP4B might serve as a predictor of chemosensitivity determination.