Plasma Inflammation Markers Linked to Complications and Outcomes after Spontaneous Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) could trigger inflammatory responses. However, the specific role of inflammatory proteins in the pathological mechanism, complications, and prognosis of ICH remains unclear. In this study, we investigated the expression of 92 plasma inflammation-related proteins in patients with ICH (n = 55) and healthy controls (n = 20) using an Olink inflammation panel and discussed the relation to the severity of stroke, clinical complications, 30-day mortality, and 90-day outcomes. Our result showed that six proteins were upregulated in ICH patients compared with healthy controls, while seventy-four proteins were downregulated. In patients with ICH, seven proteins were increased in the severe stroke group compared with the moderate stroke group. In terms of complications, two proteins were downregulated in patients with pneumonia, while nine proteins were upregulated in patients with sepsis. Compared with the survival group, three proteins were upregulated, and one protein was downregulated in the death group. Compared with the good outcome group, eight proteins were upregulated, and four proteins were downregulated in the poor outcome group. In summary, an in-depth exploration of the differential inflammatory factors in the early stages of ICH could deepen our understanding of the pathogenesis of ICH, predict patient prognosis, and explore new treatment strategies.

A novel cancer-associated fibroblasts risk score model predict survival and immunotherapy in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is the leading cause of cancer-related death worldwide. Cancer-associated fibroblasts (CAFs) are a special type of fibroblasts, which play an important role in the development and immune escape of tumors. Weighted gene co-expression network analysis (WGCNA) was used to construct the co-expression module. In combination with univariate Cox regression and analysis of least absolute shrinkage operator (LASSO), characteristics associated with CAFs were developed for a prognostic model. The migration and proliferation of lung cancer cells were evaluated in vitro. Finally, the expression levels of proteins were analyzed by Western blot. LASSO Cox regression algorithm was then performed to select hub genes. Finally, a total of 2 Genes (COL5A2, COL6A2) were obtained. We then divided LUAD patients into high- and low-risk groups based on CAFs risk scores. Survival analysis, CAFs score correlation analysis and tumor mutation load analysis showed that COL5A2 and COL6A2 were high-risk genes for LUAD. Human Protein Atlas (HPA), western blot and PCR results showed that COL5A2 and COL6A2 were up-regulated in LUAD tissues. When COL5A2 and COL6A2 were knocked down, the proliferation, invasion and migration of lung cancer cells were significantly decreased. Finally, COL5A2 can affect LUAD progression through the Wnt/ß-Catenin and TGF-ß signaling pathways. Our CAFs risk score model offers a new approach for predicting the prognosis of LUAD patients. Furthermore, the identification of high-risk genes COL5A2 and COL6A2 and drug sensitivity analysis can provide valuable candidate clues for clinical treatment of LUAD.

Lateral habenula IL-10 controls GABAA receptor trafficking and modulates depression susceptibility after maternal separation.

Maternal separation (MS), a form of early life adversity, increases the risk of psychiatric disorders in adulthood by intricately linking cytokines and mood-regulating brain circuits. The Lateral Habenula (LHb) encodes aversive experiences, contributes to negative moods, and is pivotal in depression development. However, the precise impact of MS on LHb cytokine signaling and synaptic plasticity remains unclear. We reported that adolescent MS offspring mice displayed susceptibility to depression behavioral phylotypes, with neuronal hyperactivity and an imbalance in pro-inflammatory and anti-inflammatory cytokines in the LHb. Moreover, the decreased IL-10 level negatively correlated with depressive-like behaviors in susceptible mice. Functionally, LHb IL-10 overexpression restored decreased levels of PI3K, phosphorylated AKT (pAKT), gephyrin, and membrane GABAA receptor proteins while reducing abnormally elevated GSK3ß and Fos expression, rescuing the MS-induced depression. Conversely, LHb neuronal IL-10 receptor knockdown in naive mice increased Fos expression and elicited depression-like symptoms, potentially through impaired membrane GABAA receptor trafficking by suppressing the PI3K/pAKT/gephyrin cascades. Hence, this work establishes a mechanism by which MS promotes susceptibility to adolescent depression by impeding the critical role of IL-10 signaling on neuronal GABAA receptor function.

Muscle synergy and kinematic synergy analyses during sit-to-stand motions in hallux valgus patients before and after treatment with Kinesio taping.

OBJECTIVES: To explore the impact of hallux valgus (HV) on lower limb neuromuscular control strategies during the sit-to-stand (STS) movement, and to evaluate the effects of Kinesio taping (KT) intervention on these control strategies in HV patients. METHODS: We included 14 young healthy controls (HY), 13 patients in the HV group (HV), and 11 patients in the HV group (HVI) who underwent a Kinesio taping (KT) intervention during sit-to-stand (STS) motions. We extracted muscle and kinematic synergies from EMG and motion capture data using non-negative matrix factorization (NNMF). In addition, we calculated the center of pressure (COP) and ground reaction forces (GRF) to assess balance performance. RESULTS: There were no significant differences in the numbers of muscle and kinematic synergies between groups. In the HV group, knee flexors and ankle plantar flexors were abnormally activated, and muscle synergy D was differentiated. Muscle synergy D was not differentiated in the HVI group. CONCLUSION: Abnormal activation of knee flexors and plantar flexors led to the differentiation of module D in HV patients, which can be used as an indicator of the progress of HV rehabilitation. KT intervention improved motor control mechanisms in HV patients.

Enhancement of hydrogenotrophic methanogenesis for methane production by nano zero-valent iron in soils.

Nanoscale zero-valent iron (nZVI) is attracting increasing attention as the most commonly used environmental remediation material. However, given the high surface area and strong reducing capabilities of nZVI, there is a lack of understanding regarding its effects on the complex anaerobic methane production process in flooded soils. To elucidate the mechanism of CH4 production in soil exposed to nZVI, paddy soil was collected and subjected to anaerobic culture under continuous flooding conditions, with various dosages of nZVI applied. The results showed that the introduction of nZVI into anaerobic flooded rice paddy systems promoted microbial utilization of acetate and carbon dioxide as carbon sources for methane production, ultimately leading to increased methane production. Following the introduction of nZVI into the soil, there was a rapid increase in hydrogen levels in the headspace, surpassing that of the control group. The hydrogen levels in both the experimental and control groups were depleted by the 29th day of culture. These findings suggest that nZVI exposure facilitates the enrichment of hydrogenotrophic methanogens, providing them with a favorable environment for growth. Additionally, it affected soil physicochemical properties by increasing pH and electrical conductivity. The metagenomic analysis further indicates that under exposure to nZVI, hydrogenotrophic methanogens, particularly Methanobacteriaceae and Methanocellaceae, were enriched. The relative abundance of genes such as mcrA and mcrB associated with methane production was increased. This study provides important theoretical insights into the response of key microbes, functional genes, and methane production pathways to nZVI during anaerobic methane production in rice paddy soils, offering fundamental insights into the long-term fate and risks associated with the introduction of nZVI into soils.

Suppressed Renin Status is a Risk Factor for Cardiocerebrovascular Events in Bilateral Primary Aldosteronism Treated with Mineralocorticoid Receptor Antagonists.

BACKGROUND: Mineralocorticoid receptor antagonists (MRAs) are the recommended medical therapy for bilateral primary aldosteronism (BPA). Compared with essential hypertension (EH), patients with BPA have higher cardiocerebrovascular disease (CCVD). There is no consensus on the criteria to assess the effectiveness of medical therapy for BPA. OBJECTIVE: To investigate the incidence and the risk factors for CCVD after medical therapy of BPA. METHODS: We conducted a retrospective cohort study including 240 BPA patients treated with MRA. The post-treatment plasma renin activity (PRA) was defined as unsuppressed (PRA≥1ng/ml/h) otherwise, it was defined as suppressed. We analyzed the association of post-treatment PRA status with CCVD outcomes. RESULTS: 7.1% (17/240) of patients with BPA developed CCVD at a median follow-up of 5.0 (2.96,7.66) years. 57.1% of patients had PRA ≥ 1ng/ml/h after treatment. Patients with PRA <1ng/ml/h have a higher incidence of CCVD (12.6% vs. 2.9%, P < 0.05) and they are at greater risk than those with PRA ≥1ng/ml/h (HR=4.50, 95% CI: 1.47-13.83, P<0.05; adjusted HR=3.98, 95% CI: 1.22-13.02, P<0.05). CONCLUSION: Patients with BPA treated with pharmacological have a high incidence of CCVD. PRA may be an indicator that mineralocorticoids are being adequately antagonized.

Anatomical variations of the brachial plexus in adult cadavers: A descriptive study and clinical significance.

BACKGROUND: Brachial plexus injury is recognized as one of the most severe clinical challenges due to the complex anatomical configuration of the brachial plexus and its propensity for variation, which complicates safe clinical interventions. This study aimed to ascertain the prevalence and characterize the types of brachial plexus variations, and to elucidate their clinical implications. MATERIALS AND METHODS: We conducted meticulous dissections of 60 formalin-fixed cadavers' upper arm, axilla and lower neck to reveal and assess the roots, trunks, divisions, cords, and branches of the brachial plexus. The pattern of branching was noted by groups of dissecting medical students and confirmed by the senior anatomists. The variations discovered were record and photographed using a digital camera for further analysis. RESULTS: Variations in the brachial plexus were identified in 40 of the 60 cadavers, yielding a prevalence rate of 66.7%. These variations were classified into root anomalies (2.1%), trunk anomalies (8.5%), division anomalies (2.1%), and cord anomalies (4.3%). Notably, anomalies in communicating branches were observed in 39 cadavers (83.0%): 14 with bilateral anomalies, 14 with anomalies on the left side, and 11 on the right side. These communicating branches formed connections between the roots and other segments, including trunks, cords, and terminal nerves, and involved the median, musculocutaneous, and ulnar nerves. CONCLUSION: The frequency and diversity of brachial plexus variations, particularly in communicating branches, are significant in cadavers. It is imperative that these variations are carefully considered during the diagnostic process, treatment planning, and prior to procedures such as supraclavicular brachial plexus blocks and nerve transfers, to mitigate the risk of iatrogenic complications.

The Value of Visfatin in the Prediction of Metabolic Syndrome: A Systematic Review and Meta-Analysis.

Various studies have shown that visfatin may be connected to metabolic syndrome (MS). However, epidemiological studies yielded conflicting outcomes. The purpose of this article was to highlight the relationship between the plasma visfatin level and MS risk by conducting a meta-analysis of available literature. A comprehensive literature search of eligible studies was done up to January 2023. Data were presented as standard mean difference (SMD). Observational methodological meta-analysis was conducted to assess the relationships between visfatin levels and MS. The visfatin levels between patients with MS or not were calculated by SMD and 95% confidence interval (CI) using the random-effects model. Funnel plot (visually inspect publication bias), Egger's linear regression test and Begger's linear regression test were applied to describe the risk of publication bias. A sensitivity analysis was performed via sequentially omitting each of the study one by one. In total, 16 eligible studies comprising 1016 cases and 1414 healthy controls finally enrolled in the current meta-analysis for pooling meta-analysis. Overall, the meta-analysis results revealed that visfatin levels in MS patients were significantly greater than that of controls group (SMD: 0.60, 95% CI=0.18-1.03, I2=95%, p<0.001). The results of the subgroup analysis showed that gender did not affect the results of meta-analysis. This meta-analysis shed light on the fact that circulating visfatin levels were significantly higher in patients with MS than in the controls group. Visfatin may a chance to predict the occurrence of MS.

A data-driven approach for understanding the structure dependence of redox activity in humic substances.

Humic substances (HS) can facilitate electron transfer during biogeochemical processes due to their redox properties, but the structure-redox activity relationships are still difficult to describe and poorly understood. Herein, the linear (Partial Least Squares regressions; PLS) and nonlinear (artificial neural network; ANN) models were applied to monitor the structure dependence of HS redox activities in terms of electron accepting (EAC), electron donating (EDC) and overall electron transfer capacities (ETC) using its physicochemical features as input variables. The PLS model exhibited a moderate ability with R2 values of 0.60, 0.53 and 0.65 to evaluate EAC, EDC and ETC, respectively. The variable influence in the projection (VIP) scores of the PLS identified that the phenols, quinones and aromatic systems were particularly important for describing the redox activities of HS. Compared with the PLS model, the back-propagation ANN model achieved higher performance with R2 values of 0.81, 0.65 and 0.78 for monitoring the EAC, EDC and ETC, respectively. Sensitivity analysis of the ANN separately identified that the EAC highly depended on quinones, aromatics and protein-like fluorophores, while the EDC depended on phenols, aromatics and humic-like fluorophores (or stable free radicals). Additionally, carboxylic groups were the best indicator for evaluating both the EAC and EDC. Good model performances were obtained from the selected features via the PLS and sensitivity analysis, further confirming the accuracy of describing the structure-redox activity relationships with these analyses. This study provides a potential approach for identifying the structure-activity relationships of HS and an efficient machine-learning model for predicting HS redox activities.

Herbaceous ornamental plants with conspicuous aesthetic traits contribute to plant invasion risk in subtropical urban parks.

Global ornamental horticulture is a major pathway for plant invasions, while urban parks are key areas for introducing non-native ornamental plants. To react appropriately to the challenges (e.g., biological invasion issues) and opportunities (e.g., urban ecosystem services) of herbaceous ornamentals in urban parks, we conducted a comprehensive invasive risk assessment in 363 urban parks in Chongqing, a subtropical city in China. The results found more than 1/3 of the 119 non-native species recorded in urban parks had a high invasion risk, and more than five species had potential invasion risk in 96.29% of the study area, indicating herbaceous ornamentals in urban parks are potentially a pool of invasive species that deserves attention. Moreover, humans have chosen herbaceous ornamentals with more aesthetic characteristics in urban parks, where exotic species were more prominent than native species in floral traits, such as more conspicuous flowers and longer flowering periods. The findings can inform urban plant management, provide an integrated approach to assessing herbaceous ornamentals' invasion risk, and offer insights into understanding the filtering effects of human aesthetic preferences.

Novel Ag-bridged dual Z-scheme g-C3N4/BiOI/AgI plasmonic heterojunction: Exceptional photocatalytic activity towards tetracycline and the mechanism insight.

Rational design and synthesis of highly efficient and robust photocatalysts with positive exciton splitting and interfacial charge transfer for environmental applications is critical. Herein, aiming at overcoming the common shortcomings of traditional photocatalysts such as weak photoresponsivity, rapid combination of photo-generated carriers and unstable structure, a novel Ag-bridged dual Z-scheme g-C3N4/BiOI/AgI plasmonic heterojunction was successfully synthesized using a facile method. Results showed that Ag-AgI nanoparticles and three-dimensional (3D) BiOI microspheres were decorated highly uniformly on the 3D porous g-C3N4 nanosheet, resulting in a higher specific surface area and abundant active sites. The optimized 3D porous dual Z-scheme g-C3N4/BiOI/Ag-AgI manifested exceptional photocatalytic degradation efficiency of tetracycline (TC) in water with approximately 91.8% degradation efficiency within 165 min, outperforming majority of the reported g-C3N4-based photocatalysts. Moreover, g-C3N4/BiOI/Ag-AgI exhibited good stability in terms of activity and structure. In-depth radical scavenging and electron paramagnetic resonance (EPR) analyses confirmed the relative contributions of various scavengers. Mechanism analysis indicated that the improved photocatalytic performance and stability were ascribed to the highly ordered 3D porous framework, fast electron transfer of dual Z-scheme heterojunction, desirable photocatalytic performance of BiOI/AgI and synergistic effect of Ag plasmas. Therefore, the 3D porous Z-scheme g-C3N4/BiOI/Ag-AgI heterojunction had a good prospect for applications in water remediation. The current work provides new insight and useful guidance for designing novel structural photocatalysts for environment-related applications.

Rational Design, Synthesis of Fluorescence Probes for Quantitative Detection of Amyloid-ß in Alzheimer's Disease Based on Rhodamine-Metal Complex.

The efficient detection and monitoring of amyloid-ß plaques (Aß42) can greatly promote the diagnosis and therapy of Alzheimer's disease (AD). Fluorescence imaging is a promising method for this, but the accurate determination of Aß42 still remains a challenge. The development of a reliable fluorescent probe to detect Aß42 is essential. Herein, we report a rational design strategy for Aß42 fluorescence probes based on rhodamine-copper complexes, Rho1-Cu-Rho4-Cu, among them Rho4-Cu exhibits the best performance including high sensitivity (detection limit = 24 nM), high affinity (Kd = 23.4 nM), and high selectivity; hence, Rho4-Cu is selected for imaging Aß42 in AD mice, and the results showed that this probe can differentiate normal mice and AD mice effectively.

Motor neuron survival is associated with reduced neuroinflammation and increased autophagy after brachial plexus avulsion injury in aldose reductase-deficient mice.

Brachial plexus root avulsion (BPRA) is frequently caused by high-energy trauma including traffic accident and birth trauma, which will induces massive motoneurons (MNs) death as well as loss of motor and sensory function in the upper limb. The death of MNs is attributed to energy deficiency, neuroinflammation and oxidative stress at the injured ventral horn of spinal cord triggered by BPRA injury. It has been reported which aldose reductase (AR), an endogenous enzyme that catalyzes fructose synthesis, positively correlates with the poor prognosis following cerebral ischemic injury, diabetic retinopathy and diabetic peripheral neuropathy. However, the role of AR in BPRA remains unknown. Herein, we used a mouse model and found that in the spinal cord of BPRA mice, the upregulation of AR correlated significantly with (1) an inactivated SIRT1-AMPK-mTOR pathway and disrupted autophagy; (2) increased byproducts accumulation of lipid peroxidation metabolism and neuroinflammation; and (3) increased MNs death. Furthermore, our results demonstrated the role of AR in BPRA injury whereby the absence of AR (AR knockout mice, AR-/-) prevented the hyper-neuroinflammation and disrupted autophagy as well as motor neuron death caused by BPRA injury. Finally, we further demonstrate that AR inhibitor epalrestat is neuroprotective against BPRA injury by increasing autophagy level, alleviating neuroinflammation and rescuing MNs death in mice. Collectively, our data demonstrate that the AR upregulation in the spinal cord is an important factor contributing to autophagy disruption, neuroinflammation and MNs death following brachial plexus roots avulsion in mice. Our study also provides a promising therapy drug to assist re-implantation surgery for the treatment of BPRA.

An easily available endoplasmic reticulum targeting near-infrared fluorescent probe for esterase imaging in vitro and in vivo.

Here, we report an easily available endoplasmic reticulum-targeting near-infrared fluorescent probe (ER-CE), which can detect esterase in the endoplasmic reticulum and monitor the changes in the esterase amount in tumors in mice in real time. These results indicate that ER-CE is expected to become a powerful analysis tool for the research of endoplasmic reticulum esterase-related diseases.

Actively implementing an evidence-based feeding guideline for critically ill patients (NEED): a multicenter, cluster-randomized, controlled trial.

BACKGROUND: Previous cluster-randomized controlled trials evaluating the impact of implementing evidence-based guidelines for nutrition therapy in critical illness do not consistently demonstrate patient benefits. A large-scale, sufficiently powered study is therefore warranted to ascertain the effects of guideline implementation on patient-centered outcomes. METHODS: We conducted a multicenter, cluster-randomized, parallel-controlled trial in intensive care units (ICUs) across China. We developed an evidence-based feeding guideline. ICUs randomly allocated to the guideline group formed a local "intervention team", which actively implemented the guideline using standardized educational materials, a graphical feeding protocol, and live online education outreach meetings conducted by members of the study management committee. ICUs assigned to the control group remained unaware of the guideline content. All ICUs enrolled patients who were expected to stay in the ICU longer than seven days. The primary outcome was all-cause mortality within 28 days of enrollment. RESULTS: Forty-eight ICUs were randomized to the guideline group and 49 to the control group. From March 2018 to July 2019, the guideline ICUs enrolled 1399 patients, and the control ICUs enrolled 1373 patients. Implementation of the guideline resulted in significantly earlier EN initiation (1.20 vs. 1.55 mean days to initiation of EN; difference - 0.40 [95% CI - 0.71 to - 0.09]; P = 0.01) and delayed PN initiation (1.29 vs. 0.80 mean days to start of PN; difference 1.06 [95% CI 0.44 to 1.67]; P = 0.001). There was no significant difference in 28-day mortality (14.2% vs. 15.2%; difference - 1.6% [95% CI - 4.3% to 1.2%]; P = 0.42) between groups. CONCLUSIONS: In this large-scale, multicenter trial, active implementation of an evidence-based feeding guideline reduced the time to commencement of EN and overall PN use but did not translate to a reduction in mortality from critical illness. TRIAL REGISTRATION: ISRCTN, ISRCTN12233792 . Registered November 20th, 2017.

Re-expression of circ_0043610 contributes to trophoblast dysfunction through the miR-558/RYBP pathway in preeclampsia.

An increasing number of data have shown the pathogenesis of preeclampsia (PE) involves circular RNA (circRNA). The study aims to investigate the function and the potential mechanism of circ_0043610 in PE. The study was performed on two human placental trophoblastic cell lines (JEG-3 and HTR-8/SVneo). The expression of circ_0043610, microRNA-558 (miR-558), and RING1 and YY1 binding protein (RYBP) was detected by quantitative real-time polymerase chain reaction. The protein levels of N-cadherin, E-cadherin, and RYBP were assessed by Western blotting. Cell viability, proliferation, apoptosis, invasion, and migration were evaluated by cell counting kit-8, 5-Ethynyl-29-deoxyuridine, flow cytometry analysis, transwell invasion assay, and wound-healing assay, respectively. Dual-luciferase reporter assay, RNA immunoprecipitation assay, and RNA pull-down assay were performed to identify the associations among circ_0043610, miR-558, and RYBP. Compared with normal placental controls, the increased expression of circ_0043610 and RYBP and the decreased miR-558 expression were detected in PE placental tissues. The overexpression of circ_0043610 led to decreased trophoblast cell proliferation, invasion, and migration but increased cell apoptosis. Mechanistically, circ_0043610 acted as a miR-558 sponge, and miR-558 bound to RYBP. Besides, miR-558 introduction remitted circ_0043610-mediated effects in JEG-3 and HTR-8/SVneo cells. Moreover, RYBP participated in the regulation of miR-558 on trophoblast cell behaviors. Further, the ectopic expression of circ_0043610 led to RYBP upregulation through miR-558. Circ_0043610 induced RYBP production to promote trophoblast dysfunction by binding to miR-558 in PE.

Frailty and risks of all-cause and cause-specific death in community-dwelling adults: a systematic review and meta-analysis.

BACKGROUND: The associations of frailty with all-cause and cause-specific mortality remain unclear. Therefore, we performed this meta-analysis to fill this gap. METHODS: We searched the PubMed and Embase databases through June 2022. Prospective cohort studies or clinical trials examining frailty were evaluated, and the multiple adjusted risk estimates of all-cause and cause-specific mortality, such as death from cardiovascular disease (CVD), cancer, respiratory illness, dementia, infection, and coronavirus disease 2019 (COVID-19), were included. A random effects model was used to calculate the summary hazard ratio (HR). RESULTS: Fifty-eight studies were included for the qualitative systematic review, of which fifty-six studies were eligible for the quantitative meta-analysis, and the studies included a total of 1,852,951 individuals and more than 145,276 deaths. Compared with healthy adults, frail adults had a significantly higher risk of mortality from all causes (HR 2.40; 95% CI 2.17-2.65), CVD (HR 2.64; 95% CI 2.20-3.17), respiratory illness (HR 4.91; 95% CI 2.97-8.12), and cancer (HR 1.97; 95% CI 1.50-2.57). Similar results were found for the association between prefrail adults and mortality risk. In addition, based on the studies that have reported the HRs of the mortality risk per 0.1 and per 0.01 increase in the frailty index, we obtained consistent results. CONCLUSIONS: The present study demonstrated that frailty was not only significantly related to an increased risk of all-cause mortality but was also a strong predictor of cause-specific mortality from CVD, cancer, and respiratory illness in community-dwelling adults. More studies are warranted to clarify the relationship between frailty and cause-specific mortality from dementia, infection, and COVID-19. TRIAL REGISTRATION: PROSPERO (CRD42021276021).

Paper mill sludge-based carbon quantum dots as a specifically ratiometric fluorescent probe for the sensitive and selective detection of coptisine.

Coptisine (COP), one of the bioactive components in Rhizoma Coptidis, has many pharmacological effects. Meanwhile, the determination of COP is essential in pharmacological and clinical applications. Herein, we prepared carbon quantum dots (CQDs) by one-step oil-thermal method using paper mill sludge (PMS) as precursor, and developed a ratiometric fluorescence method for the determination of COP. The structural and optical properties of PMS-CQDs were evaluated through high-resolution transmission electron microscopy (HRTEM), Fourier-transform infrared (FTIR) spectroscopy, X-ray photoelectron spectroscopy (XPS), X-ray powder diffraction (XRD), ultraviolet-visible (UV-vis), fluorescence, zeta potential and fluorescence lifetime experiments. Fluorescence intensity ratio at 550 nm and 425 nm (I550 /I425 ) was recorded as an index for quantitative detection of COP. The detection concentration of COP ranges from 0.1 to 50 µM in good linear correlation (R2  = 0.9974) with a limit of detection of 0.028 µM (3σ/k). The quenching mechanism was deduced to be inner filter effect and static quenching. The ratiometric fluorescent probe showed impressive selectivity and sensitivity towards COP, and was successfully applied to the detection of COP in human urine with expected recoveries (95.22-111.00%) and relative standard deviations (0.46-2.95%), indicating that our developed method has a great application prospect in actual sample detection.

The use of a surgical boot camp combining anatomical education and surgical simulation for internship preparedness among senior medical students.

BACKGROUND: Senior medical students feel unprepared for surgical procedures and care for surgery patients when they begin their internship. This study sought to introduce and evaluate a surgical boot camp training for senior medical students. METHODS: A 44-h surgical boot camp program of lectures on clinical practice simulation, anatomical dissections, and simulated operation on cadavers was designed, implemented, and evaluated during the 2018 to 2019 academic year. A self-administered questionnaire was used to assess students' perceptions of the content, delivery, and self-confidence. The mini-Clinical Evaluation Exercise (mini-CEX) and the Operative Performance Rating System were used to assess skills essential to good clinical care and to facilitate feedback. RESULTS: Over 93% of the students were satisfied with the surgical boot camp, training equipment, and learning materials provided. After six sessions of training, 85.3% reported gaining self-confidence and performed better in some surgical procedures such as major gastrectomy. The mini-CEX scores suggested significant improvement in the students' clinical skills, attitudes, and behaviors (P < 0.01). Ninety-eight percent of students felt that the anatomical knowledge taught met their needs. The scores of the Operative Performance Rating System suggested that the students' surgical skills such as instruments handling, incising, treatment of surrounding tissues (blood vessels, nerves), and smoothness of the whole operation had increased significantly following the surgical boot camp (All P < 0.01). CONCLUSION: The surgical boot camp curriculum improved students' satisfaction and confidence in core clinical practice competencies. Therefore, medical schools the world over should continue to seek ways to bridge the gaps between pre-clinical, clinical, and internship training.

Combination RSL3 Treatment Sensitizes Ferroptosis- and EGFR-Inhibition-Resistant HNSCCs to Cetuximab.

Head and neck squamous cell carcinomas (HNSCCs) are a type of cancer originating in the mucosal epithelium of the mouth, pharynx, and larynx, the sixth most common cancer in the world. However, there is no effective treatment for HNSCCs. More than 90% of HNSCCs overexpress epidermal growth factor receptors (EGFRs). Although small molecule inhibitors and monoclonal antibodies have been developed to target EGFRs, few EGFR-targeted therapeutics are approved for clinical use. Ferroptosis is a new kind of programmed death induced by the iron catalyzed excessive peroxidation of polyunsaturated fatty acids. A growing body of evidence suggests that ferroptosis plays a pivotal role in inhibiting the tumor process. However, whether and how ferroptosis-inducers (FINs) play roles in hindering HNSCCs are unclear. In this study, we analyzed the sensitivity of different HNSCCs to ferroptosis-inducers. We found that only tongue squamous cell carcinoma cells and laryngeal squamous cell carcinoma cells, but not nasopharyngeal carcinoma cells, actively respond to ferroptosis-inducers. The different sensitivities of HNSCC cells to ferroptosis induction may be attributed to the expression of KRAS and ferritin heavy chain (FTH1) since a high level of FTH1 is associated with the poor prognostic survival of HNSCCs, but knocked down FTH1 can promote HNSCC cell death. Excitingly, the ferroptosis-inducer RSL3 plays a synthetic role with EGFR monoclonal antibody Cetuximab to inhibit the survival of nasopharyngeal carcinoma cells (CNE-2), which are insensitive to both ferroptosis induction and EGFR inhibition due to a high level of FTH1 and a low level of EGFR, respectively. Our findings prove that FTH1 plays a vital role in ferroptosis resistance in HNSCCs and also provide clues to target HNSCCs resistant to ferroptosis induction and/or EGFR inhibition.