Immune cell-related prognostic risk model and tumor immune environment modulation in esophageal carcinoma based on single-cell and bulk RNA sequencing.

BACKGROUND: Immune cells play a pivotal role in the tumor microenvironment, exerting significant influence on tumor progression and patient outcomes, but the current biomarkers are insufficient to fully capture the complex and diverse tumor immune microenvironment and the impact of immunotherapy. METHODS: The advent of single-cell sequencing allows us to explore the tumor microenvironment at an unprecedented resolution, enabling the identification and characterization of distinct subsets of immune cells, thereby paving the way for the development of prognostic models using immune cells. Leveraging single-cell data, our study deeply investigated the intricacies of immune microenvironment heterogeneity in esophageal carcinoma. RESULTS: We elucidated the composition, functionality, evolution, and intercellular communication patterns of immune cells, culminating in the construction of an independent prognostic model at the single-cell level. Furthermore, we conducted a comprehensive analysis of disparities in immune infiltration and immune checkpoint expression between patients categorized into high- and low-risk groups, which may impact patient prognosis. CONCLUSION: In summary, our study harnessed multiomics data to delineate the immune profile of esophageal carcinoma patients, provide a method for leveraging molecular signatures of immune cells to identify potential biomarkers, while concurrently providing evidence for the potential benefits of immunotherapy.

A pair of transporters controls mitochondrial Zn2+ levels to maintain mitochondrial homeostasis

Zn2+ is required for the activity of many mitochondrial proteins, which regulate mitochondrial dynamics, apoptosis and mitophagy. However, it is not understood how the proper mitochondrial Zn2+ level is achieved to maintain mitochondrial homeostasis. Using Caenorhabditis elegans, we reveal here that a pair of mitochondrion-localized transporters controls the mitochondrial level of Zn2+. We demonstrate that SLC-30A9/ZnT9 is a mitochondrial Zn2+ exporter. Loss of SLC-30A9 leads to mitochondrial Zn2+ accumulation, which damages mitochondria, impairs animal development and shortens the life span. We further identify SLC-25A25/SCaMC-2 as an important regulator of mitochondrial Zn2+ import. Loss of SLC-25A25 suppresses the abnormal mitochondrial Zn2+ accumulation and defective mitochondrial structure and functions caused by loss of SLC-30A9. Moreover, we reveal that the endoplasmic reticulum contains the Zn2+ pool from which mitochondrial Zn2+ is imported. These findings establish the molecular basis for controlling the correct mitochondrial Zn2+ levels for normal mitochondrial structure and functions.

The Role of Disease Severity and Demographics in the Clinical Course of COVID-19 Patients Treated with Convalescent Plasma

Treatment of patients with COVID-19 using convalescent plasma from recently recovered patients has been shown to be safe, but the time course of change in clinical status following plasma transfusion in relation to baseline disease severity has not yet been described. We analyzed short, descriptive daily reports of patient status in 7,180 hospitalized recipients of COVID-19 convalescent plasma in the Mayo Clinic Expanded Access Program. We assessed, from the day following transfusion, whether the patient was categorized by his or her physician as better, worse or unchanged compared to the day before, and whether, on the reporting day, the patient received mechanical ventilation, was in the ICU, had died or had been discharged. Most patients improved following transfusion, but clinical improvement was most notable in mild to moderately ill patients. Patients classified as severely ill upon enrollment improved, but not as rapidly, while patients classified as critically ill/end-stage and patients on ventilators showed worsening of disease status even after treatment with convalescent plasma. Patients age 80 and over showed little or no clinical improvement following transfusion. Clinical status at enrollment and age appear to be the primary factors in determining the therapeutic effectiveness of COVID-19 convalescent plasma among hospitalized patients.

Effects of ultrasonic vibration on the microstructure and mechanical properties of high alloying TiAl.

To modify the microstructure and enhance performances, the ultrasonic vibration is applied in the mould casting of TiAl alloy. The effects and mechanism of ultrasonic vibration on the solidifying microstructure and mechanical properties are investigated and the model for predicting lamellar colony size is established. After ultrasonic vibration, the coarse microstructure is well modified and lamellar colony is refined from 534 µm to 56 µm. Most of precipitated phases are dissolved into the lamellar colony leading to a homogenous element distribution. The phase ratio of α2-Ti3Al and γ-TiAl is increased, and the chemical composition is promoted to more close to equilibrium level by weakening the influence of ß-alloying elements. The microhardness and yield strength are gradually improved by 23.72% and 181.88% due to the fine grain strengthening, while the compressive strength is enhanced by 24.47% through solution strengthening. The critical ultrasonic intensity (Ib) for TiAl alloy is estimated at 220 W cm-2 and the model for average lamellar colony size is established as . The ultrasonic refinement efficiency exponentially increases as the ultrasonic vibration time with a theoretic limit maximum value of Elim = 88% and the dominating refinement mechanism by ultrasonic vibration is the cavitation-enhanced nucleation rather than cavitation-induced dendrite fragmentation.

Comparison of landiolol and esmolol for treatment of intraoperative arrhythmia in dogs / 中华麻醉学杂志

Objective To compare landiolol and esmolol for treatment of intraoperative arrhythmia in dogs.Methods Experiment Ⅰ Eighty-eight KM mice (44 males, 44 females) , aged 4-6 weeks, were studied.The median lethal dose (LD50) and median effective dose (ED50) of landiolol and esmolol were determined using the sequential method.Treatment index (TI) was calculated.Experiment Ⅱ Eighteen dogs (9 males, 9 females), aged 8-12 months, weighing 7-10 kg, were equally and randomly divided into 3 groups: model group (group M) , landiolol group (group L) and esmolol group (group E).Intraoperative arrhythmia model was established by using gastrointestinal surgery combined with epinephrine.When sustained ventricular arrhythmias occurred, normal saline 0.5 ml/kg, landiolol 8.3 mg/kg and esmolol 10.0 mg/kg were given intravenously in C, L and E groups, respectively.The duration of arrhythmias was recorded.If bradycardia occurred (decrease in heart rate [HR] ≥ 25％ of the baseline value) , isoprenaline 0.05 mg/kg and atropine 0.03 mg/kg were injected intravenously.The occurrence of bradycardia after the initial administration of landiolol and esmolol, and the accumulated dose of landiolol and esmolol consumed when bradycardia occurred were recorded.Isoprenaline and atropine-induced improvement in bradycardia was recorded.Results Compared with esmolol, the LD50 and TI of landiolol were significantly increased (P＜0.01), and no significant change was found in ED50 of landiolol (P＞0.05).The duration of arrhythmias was significantly shorter in L and E groups than in group C, and in group L than in group E (P＜0.01).After the initial administration of landiolol and esmolol, the incidence of bradycardia was 0 and 100％, respectively, and the accumulated dose of landiolol and esmolol consumed when bradycardia occurred was (30± 13) mg/kg.Atropine could not effectively treat bradycardia, while isoprenaline could treat bradycardia.Compared with group L, the time for HR to rise and the duration for HR returning to the baseline value were significantly prolonged in group E (P＜0.05).Conclusion Compared with esmolol, landiolol provides faster improvement in intraoperative arrhythmia, weaker negative chronotropic effect, and higher safety;isoproterenol produces better efficacy in treating landiololinduced bradycardia in dogs.

Protective effects of penehyclidine hydrochloride on transient forebrain ischemia reperfusion injury in gerbils / 中国临床药理学与治疗学

AIM:To study the protective effects of penehyclidine hydrochloride(PHC) on transient forebrain ischemia reperfusion injury in gerbils.METHODS:The model of transient forebrain ischemia reperfusion was established in gerbils by bilateral carotid artery clamping.The effects of PHC on neurological function scores and the morphous of hippocampal pyramidal neuron of gerbils were observed after receiving transient forebrain ischemia reperfusion.SOD activities and contents of MDA in the hippocampus and cortex of gerbils were measured.RESULTS:In the groups of PHC(0.08),(0.24)(mg?kg~(-1)) and atropine,the stroke index was decreased,compared with the ischemia-reperfusion group after the gerbils received transient forebrain ischemia reperfusion for six hours.PHC could reduce the degree of injury in hippocampal pyramidal neuron after ischemia reperfusion for three days.CONCLUSION: PHC has protective effects on transient forebrain ischemia reperfusion injury in gerbils.