Atomic Ruthenium-Promoted Cadmium Sulfide for Photocatalytic Production of Amino Acids from Biomass Derivatives.

Amino acids are the building blocks of proteins and are widely used as important ingredients for other nitrogen-containing molecules. Here, we report the sustainable production of amino acids from biomass-derived hydroxy acids with high activity under visible-light irradiation and mild conditions, using atomic ruthenium-promoted cadmium sulfide (Ru1/CdS). On a metal basis, the optimized Ru1/CdS exhibits a maximal alanine formation rate of 26.0 molAla·gRu­1·h­1, which is 1.7 times and more than two orders of magnitude higher than that of its nanoparticle counterpart and the conventional thermocatalytic process, respectively. Integrated spectroscopic analysis and density functional theory calculations attribute the high performance of Ru1/CdS to the facilitated charge separation and O-H bond dissociation of the a-hydroxy group, here of lactic acid. The operando nuclear magnetic resonance further infers a unique "double activation" mechanism of both the CH-OH and CH3-CH-OH structures in lactic acid, which significantly accelerates its photocatalytic amination toward alanine.

[Postoperative effect analysis of different surgical techniques used in facial nerve reconstruction].

Objective:To investigate the factors and efficacy of different surgical techniques used in facial nerve（FN） reconstruction. Methods:A retrospective analysis was conducted on 24 patients who underwent facial nerve reconstruction surgery in our department from January 2016 to January 2021. The duration of total facial nerve paralysis was less than 18 months. The study included 5 surgical techniques, including 6 cases of FN anastomosis（Group A）, 5 cases of FN grafting（sural nerve or great auricular nerve）（Group B）, 5 cases of side-to-end facial-hypoglossal nerve anastomosis（Group C）, 4 cases of side-to-end FN grafting（sural nerve or great auricular nerve） hypoglossal nerve anastomosis（Group D）, and 4 cases of dual nerve reanimation（Group E）. The postoperative follow-up period was ≥1 year. Results:The HB-Ⅲ level of FN function at 1 year after surgery was 83.3%（5/6） in group A, 60.0%（3/5） in group B, 40.0%（2/5） in group C, 25.0%（1/4） in group D, and 50.0%（2/4） in group E. In patients without multiple FN repair, the incidence of synkinesis was 15.0%（3/20）, while no cases of synkinesis were observed in patients with dual nerve reanimation. The patients who underwent hypoglossal-facial side-to-end anastomosis showed no hypoglossal nerve dysfunction. Conclusion:Different FN repair techniques result in varying postoperative FN function recovery, as personalized repair should be managed. Among the various techniques, FN end-to-end anastomosis after FN transposition is recommended as to reduce the number of anastomotic stoma, while hypoglossal-facial side-to-end anastomosis is advocated as to prevent postoperative hypoglossal nerve dysfunction. Additionally, dual nerve repair can effectively improve smile symmetry and reduce synkinesis, which enhances patients' quality.

Spinal gout with intervertebral foramen infiltration: A rare case perfectly mimicking degenerative lumbar disc disease.

Spinal gout is a relatively rare disease characterized by significant clinical symptoms. In the current study, the first case of spinal gout with tophus in the intervertebral foramen, which perfectly mimicked degenerative lumbar disc disorders, was presented. The patient was a 57-year-old man with a medical history of gout who had suffered from progressive neurological deterioration for the last 12 months. Imaging examination revealed bilateral stenosis in the L5/S1 intervertebral foramen, mimicking degenerative lumbar disc disease. Nerve root radiculography and blocking were performed and the neurological symptoms were completely relieved. Open surgery was further performed and unexpectedly, the intra-operative findings were amorphous chalky white lesions. Histopathology confirmed the diagnosis of spinal gout. After surgery, the patient was prescribed a medication and achieved complete remission of clinical symptoms. No deterioration was found at the 1-year follow-up. To the best of our knowledge, this is the first report of spinal gout tophus in intervertebral foramen in the literature. It was concluded that, although intraspinal tophaceous gout is relatively rare, orthopedic surgeons should take it into consideration as a differential diagnosis, particularly if the patient has a medical history of gout. Early diagnosis and timely medical management may possibly be able to avoid neurological compromise and the need for surgery.

Long-term follow-up of comparative study of open and endoscopic lymphadenectomy in patients with penile carcinoma.

BACKGROUND: Penile carcinoma is an uncommon cancer that develops in the penis tissue. The standard surgical method to manage regional lymph nodes after local excision is radical inguinal lymphadenectomy, but it has a high rate of complications. The objective of this retrospective study was to compare the long-term outcomes of endoscopic inguinal lymphadenectomy and open inguinal lymphadenectomy in patients with penile carcinoma. METHODS: The study included patients diagnosed with penile carcinoma who underwent open inguinal lymphadenectomy (n = 23) or endoscopic inguinal lymphadenectomy (n = 27) at a single hospital between January 2013 and January 2021. Operation time, blood loss, drainage, hospital stay, postoperative complications, and survival rates were assessed and compared between the two groups. RESULTS: The two groups were comparable in terms of age, tumor size and stage, inguinal lymph nodes, and follow-up. The endoscopic group had significantly lower blood loss (27.1 ± 1.5 ml vs 55.0 ± 2.7 ml, P < 0.05), shorter drainage time and hospital stay (4.7 ± 1.1 days vs 8.1 ± 2.2 days, and 13.4 ± 1.0 days vs 19 ± 2.0 days, respectively, P < 0.05), and longer operation time compared to the open group (82.2 ± 4.3 min in endoscopic group vs 53.1 ± 2.2 min in open group, P < 0.05). There were significant differences in the incidence of incisional infection, necrosis, and lymphorrhagia in both groups (4 vs 0, 4 vs 0, and 2 vs 0, respectively, P < 0.05). The inguinal lymph node harvested was comparable between the two groups. The mean follow-up time was similar for both groups (60.4 ± 7.7 m vs 59.8 ± 7.3 m), and the recurrence mortality rates were not significantly different. CONCLUSIONS: The study shows that both open and endoscopic methods work well for controlling penile carcinoma in the long term. But the endoscopic approach is better because it has fewer severe complications. So, the choice of surgery method might depend on factors like the surgeon's experience, what they like, and what resources are available.

Fatty Acid Metabolism-Related lncRNAs are Potential Biomarkers for Predicting Prognoses and Immune Responses in Patients with Skin Cutaneous Melanoma.

Introduction: Skin cutaneous melanoma is becoming more dangerous since it has a poor prognosis and is resistant to treatment. Previous research has shown that lncRNAs and fatty acid metabolism are essential for numerous biological activities. There are no studies on the relationship between fatty acid metabolism-Related lncRNAs and skin cutaneous melanoma. Methods and Results: In order to better understand the prognosis and survival of SKCM patients, we investigated the significance of lncRNAs related to fatty acid metabolism. In this work, we looked at the fatty acid metabolism genes and lncRNAs expression patterns. On the basis of lncRNAs associated with fatty acid metabolism, a nomogram and a prognosis prediction model were created. Based on the profile of lncRNAs associated with fatty acid metabolism, functional and pharmacological sensitivity investigations were also carried out. We also looked at the connection between immunotherapy and the immune response. The findings demonstrated that a risk score model based on 11 essential lncRNAs for fatty acid metabolism may discriminate between the clinical condition of SKCM and more accurately predict prognosis and survival. We conducted quantitative reverse transcription polymerase-chain reaction (RT-PCR) to verify the model. Conclusion: These important lncRNAs further showed a strong association with the tumor immune system, and these important lncRNAs also showed a connection between SKCM and chemotherapeutic treatment sensitivity. Our research strives to provide fresh viewpoints and innovative approaches to the treatment and administration of SKCM.

Mitophagy-dependent cardioprotection of resistance training on heart failure.

Resistance exercise is an indispensable mode of exercise rehabilitation for heart failure. Here we elucidate the cardiac effects of resistance training alone or combined with different aerobic trainings on heart failure and explore the critical regulation of mitophagy. The chronic heart failure model was constructed by transverse aortic constriction surgery, followed by 8 wk of resistance training (RT), moderate-intensity continuous training combined with resistance training (MRT), and high-intensity interval training combined with resistance training (HRT), and subsequently analyzed the changes of maximum load, cardiac structure and function, and myocardial mitophagic activity. The role and signaling of mitophagy in exercise protection of heart failure were investigated by knockdown of Hif1α and Parkin genes in primary neonatal cardiomyocytes. RT and especially MRT improved maximum load (P < 0.0001), myocardial morphology and fibrosis (P < 0.0001), reduced left ventricular diameter and enhanced left ventricular systolic function (P < 0.01), and enhanced myocardial mitophagic activity and HIF1α expression (P < 0.05) in heart failure mice. However, HRT had no obvious protective effect on ventricular diameter and function or mitophagy. The abilities of exercise stimulation to regulate reactive oxygen species, adenosine triphosphate, and brain natriuretic peptide were impaired after knockdown of Hif1α and Parkin genes inhibited mitophagy in failing cardiomyocytes (P < 0.05). Different exercise modalities provide discrepant cardiovascular effects on heart failure, and MRT exhibits optimal protection. The HIF1α-Parkin-mitophagy pathway is involved in the protection and regulation of exercise on heart failure.NEW & NOTEWORTHY Impaired myocardial mitophagy is implicated in the pathogenesis of heart failure. Resistance training alone or combined with different aerobic trainings provide discrepant cardiovascular effects on heart failure, and the cardioprotective function depends on HIF1α-Parkin-mitophagy pathway.

PP121, a dual inhibitor of tyrosine and phosphoinositide kinases, relieves airway hyperresponsiveness, mucus hypersecretion and inflammation in a murine asthma model.

BACKGROUND: Tyrosine kinase and phosphoinositide kinase pathways play important roles in asthma formation. As a dual tyrosine and phosphoinositide kinase inhibitor, PP121 has shown anticancer efficacy in multiple tumors. However, the study of PP121 in pulmonary diseases is still limited. Herein, we investigated the therapeutic activities of PP121 in asthma treatment. METHODS: Tension measurements and patch clamp recordings were made to investigate the anticontractile characteristics of PP121 in vitro. Then, an asthma mouse model was established to further explore the therapeutic characteristics of PP121 via measurement of respiratory system resistance, histological analysis and western blotting. RESULTS: We discovered that PP121 could relax precontracted mouse tracheal rings (mTRs) by blocking certain ion channels, including L-type voltage-dependent Ca2+ channels (L-VDCCs), nonselective cation channels (NSCCs), transient receptor potential channels (TRPCs), Na+/Ca2+ exchangers (NCXs) and K+ channels, and accelerating calcium mobilization. Furthermore, PP121 relieved asthmatic pathological features, including airway hyperresponsiveness, systematic inflammation and mucus secretion, via downregulation of inflammatory factors, mucins and the mitogen-activated protein kinase (MAPK)/Akt signaling pathway in asthmatic mice. CONCLUSION: In summary, PP121 exerts dual anti-contractile and anti-inflammatory effects in asthma treatment, which suggests that PP121 might be a promising therapeutic compound and shed new light on asthma therapy.

Duloxetine HCl Alleviates Asthma Symptoms by Regulating PI3K/AKT/mTOR and Nrf2/HO-1 Signaling Pathways.

Asthma is an inflammatory disease characterized by airway hyperresponsiveness, airway remodeling, and airway inflammation. In recent years, the prevalence of asthma has been increasing steadily and the pathogenesis of asthma varies from person to person. Due to poor compliance or resistance, existing drugs cannot achieve the desired therapeutic effect. Therefore, developing or screening asthma therapeutic drugs with high curative effects, low toxicity, and strong specificity is very urgent. Duloxetine HCl (DUX) is a selective serotonin and norepinephrine reuptake inhibitor, and it was mainly used to treat depression, osteoarthritis, and neuropathic pain. It was also reported that DUX has potential anti-infection, anti-inflammation, analgesic, antioxidative, and other pharmacological effects. However, whether DUX has some effects on asthma remains unknown. In order to investigate it, a series of ex vivo and in vivo experiments, including biological tension tests, patch clamp, histopathological analysis, lung function detection, oxidative stress enzyme activity detection, and molecular biology experiments, were designed in this study. We found that DUX can not only relax high potassium or ACh precontracted tracheal smooth muscle by regulating L-type voltage-dependent Ca2+ channel (L-VDCC) and nonselective cation channel (NSCC) ion channels but also alleviate asthma symptoms through anti-inflammatory and antioxidative response regulated by PI3K/AKT/mTOR and Nrf2/HO-1 signaling pathways. Our data suggests that DUX is expected to become a potential new drug for relieving or treating asthma.

Epstein-Barr virus: To be a trigger of autoimmune glial fibrillary acidic protein astrocytopathy?

BACKGROUND: Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is a novel autoimmune disease of central nervous system (CNS). It is unclear whether Epstein-Barr virus (EBV) is related to autoimmune GFAP astrocytopathy. OBJECTIVE: To describe the clinical, laboratory, and imaging characteristics of patients with autoimmune GFAP astrocytopathy. METHODS: The clinical, laboratory, and imaging findings of patients are presented. The levels of GFAP in CSF were detected by ELISA. T and B cell subsets in CSF were detected by flow cytometry. GFAP-IgG in serum and cerebrospinal fluid (CSF) were tested by cell-based assay (CBA) and tissue-based assay (TBA). RESULTS: All three patients had fever, cognitive dysfunction, limb weakness, and positive GFAP-IgG with EBV infection in CSF. Enteric glia cells may involve in this disease. Typical imaging findings include the gadolinium enhancement of linear perivascular radial perpendicular to the ventricle, meningeal enhancement (especially in midbrain interpeduncal fossa), longitudinally extensive lesions involving spindle cords, and more T2/Flair-hyperintense lesions in the periventricular white matter at late stage. The patients had poor response to antiviral treatment and strong response to steroid pulse therapy. CONCLUSION: EBV could induce CNS autoimmune response in autoimmune GFAP astrocytopathy. The detection of GFAP-IgG and EBV may facilitate the early diagnosis in these patients.

Differentiation of geniculate ganglion venous malformation from schwannoma: dynamic T1-weighted imaging provides unique diagnostic value.

OBJECTIVE: To distinguish geniculate ganglion venous malformation (GGVM) from schwannoma (GGS) by using high-resolution CT (HRCT), routine MRI, and dynamic T1-weighted imaging (T1WI) characteristics. METHODS: Surgically confirmed GGVMs and GGSs between 2016 and 2021 were retrospectively included. Preoperative HRCT, routine MR, and dynamic T1WI were performed on all patients. Clinical data, imaging characteristics including lesion size, involvement of facial nerve (FN), signal intensity, enhancement pattern on dynamic T1WI, and bone destruction on HRCT were evaluated. Logistic regression model was developed to identify independent factors for GGVMs, and the diagnostic performance was accessed by receiving operative curve (ROC) analysis. Histological characteristics were explored for both GGVMs and GGSs. RESULTS: Twenty GGVMs and 23 GGSs with mean age of 31 were included. On dynamic T1WI, 18 GGVMs (18/20) showed "pattern A" enhancement (a progressive filling enhancement), while all 23 GGSs showed "pattern B" enhancement (a gradual whole-lesion enhancement) (p < 0.001). Thirteen GGVMs (13/20) showed the "honeycomb" sign whereas all GGS (23/23) showed extensive bone changes on HRCT (p < 0.001). Lesion size, involvement of FN segment, signal intensity on non-contrast T1WI and T2-weighted imaging (T2WI), and homogeneity on enhanced T1WI were obviously differed between two lesions (p < 0.001, p = 0.002, p < 0.001, p = 0.01, p = 0.02, respectively). Regression model showed the "honeycomb" sign and "pattern A" enhancement were independent risk factors. Histologically, GGVM was characterized by interwoven dilated and tortuous veins, while GGS was characterized by abundant spindle cells with dense arterioles or capillaries. CONCLUSIONS: The "honeycomb" sign on HRCT and "pattern A" enhancement on dynamic T1WI are the most promising imaging characteristics for differentiating GGVM from GGS. CLINICAL RELEVANCE STATEMENT: The characteristic sign and enhancement pattern on HRCT and dynamic T1-weighted imaging allow preoperative differentiation of geniculate ganglion venous malformation and schwannoma feasible, which will improve clinical management and benefit patient prognosis. KEY POINTS: • The "honeycomb" sign on HRCT is a reliable finding to differentiate GGVM from GGS. • GGVM typically shows "pattern A" enhancement (focal enhancement of the tumor on early dynamic T1WI, followed by progressive contrast filling of the tumor in the delayed phase), while "pattern B" enhancement (gradual heterogeneous or homogeneous enhancement of the whole lesion) is observed in GGS on dynamic T1WI.

Indications of and Efficacy of Facial Nerve Decompression Through Endoscopic Transcanal Approach for Patients with Traumatic Facial Paralysis.

BACKGROUND: The aim of this study is to evaluate the indications and efficacy of facial nerve decompression through an endoscopic transcanal approach for patients with traumatic facial paralysis. METHODS: This single-center retrospective study included 11 patients with traumatic facial paralysis from February 2018 to April 2019. We compared the facial nerve and auditory function before and after operation so as to reveal the feasibility and effect of the surgical approach. RESULTS: All 11 patients have successfully received facial nerve decompression through endoscopic transcanal approach. Facial nerve function was objectively evaluated by electroneurography test and House-Brackmann facial nerve grading system. All patients were graded HB-VI with electroneurography ≥ 95% before surgery. The recovery of facial nerve function was good (HB-I or II) (90.9%) a year after surgery with only one case (9.1%) for HB-III. Preoperative high-resolution computed tomography showed that 1 patient had ossicular chain interruption, which was confirmed during operation. Meanwhile, 2 patients with air-bone gap >35 dBHL and whose computed tomography failed to diagnose were found with ossicular chain interruption during operation. The air-bone gap of patients with normal ossicular chain connection was all <30 dBHL. The average air-bone gap was reduced from 27.5 ± 10.1 dBHL to 7.8 ± 3.3 dBHL after operation. CONCLUSION: Preoperative high-resolution computed tomography combined with localization test can accurately estimate the location of facial nerve injury. Facial nerve decompression through endoscopic transcanal approach can decompress the geniculate ganglion to pyramidal segment of facial nerve, which is suitable for patients with traumatic facial paralysis of this segment. In addition, air-bone gap >35 dBHL may indicate the ossicular chain interruption when it is difficult to be completely judged by high-resolution computed tomography.

Facile and selective separation of anthraquinones by alizarin-modified iron oxide magnetic nanoparticles.

Anthraquinones are widely distributed in higher plants and possess broad biological activities. The conventional separation procedures for isolating anthraquinones from the plant crude extracts require multiple extraction, concentration, and column chromatography steps. In this study, we synthesized three alizarin (AZ)-modified Fe3O4 nanoparticles (Fe3O4@AZ, Fe3O4@SiO2-AZ, and Fe3O4@SiO2-PEI-AZ) by thermal solubilization method. Fe3O4@SiO2-PEI-AZ showed strong magnetic responsiveness, high methanol/water dispersion, good recyclability, and high loading capacity for anthraquinones. To evaluate the feasibility of using Fe3O4@SiO2-PEI-AZ for separating various aromatic compounds, we employed molecular dynamics simulations to predict the adsorption/desorption effects of PEI-AZ for various aromatic compounds in different methanol concentrations. The results showed that the anthraquinones could be efficiently separated from the monocyclic and bicyclic aromatic compounds by adjusting the methanol/water ratio. The Fe3O4@SiO2-PEI-AZ nanoparticles were then used to separate the anthraquinones from the rhubarb extract. At 5% methanol, all the anthraquinones were adsorbed by the nanoparticles, thus allowing their separation from other components in the crude extract. Compared with the conventional separation methods, this adsorption method has the advantages of high adsorption specificity, simple operation, and solvent saving. This method sheds light on the future application of functionalized Fe3O4 magnetic nanoparticles to selectively separate desired components from complex plant and microbial crude extracts.

Safety and Efficacy of Concurrent or Sequential Radiotherapy Plus (PD-1) Inhibitors in Oligometastatic Esophageal Cancer.

Purpose: We assess real-world outcomes, including safety and efficacy, of concurrent or sequential treatment with radiotherapy plus programmed cell death protein 1 (PD-1) inhibitors in patients with oligometastatic esophageal cancer (OMEC). Methods: This cohort study retrospectively collected clinical data of patients with synchronous or metachronous OMEC. All patients underwent concurrent or sequential treatment with radiotherapy plus PD-1 inhibitors. Each patient had up to five measurable metastatic lesions and up to three organs involved. Study endpoints were progression-free survival (PFS), treatment-related toxicities, locoregional progression-free survival (LRPFS), objective response rate (ORR), and disease control rate (DCR). Description statistics and Kaplan-Meier models were used for statistical analysis. Results: A total of 86 patients were included, most of whom were diagnosed with squamous cell carcinoma histology (98%) and presented with synchronous OMEC (64%). The median follow-up period was 17 months (range: 6-32 months), the median PFS was 15.2 months (95% confidence interval: 12.1-18.2 months); and the 1- and 2-year PFS rates were 61.4% and 26.7%, respectively. The 1- and 2-year LRPFS were 91.3% and 57.3%, respectively. The ORR and DCR were 46.5% and 91.8%, respectively. Forty-two patients (48.8%) experienced grade 3 or higher treatment-related adverse events (TRAEs); a grade 5 treatment-related adverse event was observed in one patient (1.2%) who died of immune-related pneumonitis. Conclusion: Combining radiotherapy with PD-1 inhibitors is a safe and effective treatment option for patients with OMEC. No new safety concerns were identified in this study. However, due to the potential risk of cumulative toxicity, an individual risk-benefit assessment for each patient is required prior to treatment initiation.

Fabrication and characterization of l-ascorbyl palmitate and phospholipid-based hybrid liposomes and their impacts on the stability of loaded hydrophobic polyphenols.

The aim of this study was to evaluate the influence of l-ascorbyl palmitate (LAP) as an additive to liposome formulations by self-assembling with soy lecithin to form hybrid liposomes, in order to enhance the physical stability and bioactivator-loaded retention ratio of the LAP incorporated liposomes (LAP-LP). The addition of LAP significantly increased its surface negative charge and strong hydrophobic interactions occurred between the hydrophobic tails of LAP and phospholipids resulting in more compactly ordered, rigid and hydrophobic phospholipid bilayers as indicated by surface tension, fluorescence probes and DSC. These changes enhanced the stability of hydrophobic polyphenol loaded LAP-LP during storage. Particularly, after four weeks storage at 37 °C for naringenin loaded liposomes, the retention ratio of pure liposome decreased dramatically to 12.5 %, while the LAP-LP remained above 74.5 %. This study opens up the potential for the LAP-LP to be developed as a food-grade multifunctional formulation for encapsulating and delivering bioactivators.

Reduced Expression of Voltage-Gated Sodium Channel Beta 2 Restores Neuronal Injury and Improves Cognitive Dysfunction Induced by Aß1-42.

Voltage-gated sodium channel beta 2 (Nav2.2 or Navß2, coded by SCN2B mRNA), a gene involved in maintaining normal physiological functions of the prefrontal cortex and hippocampus, might be associated with prefrontal cortex aging and memory decline. This study investigated the effects of Navß2 in amyloid-ß 1-42- (Aß1-42-) induced neural injury model and the potential underlying molecular mechanism. The results showed that Navß2 knockdown restored neuronal viability of Aß1-42-induced injury in neurons; increased the contents of brain-derived neurotrophic factor (BDNF), enzyme neprilysin (NEP) protein, and NEP enzyme activity; and effectively altered the proportions of the amyloid precursor protein (APP) metabolites including Aß42, sAPPα, and sAPPß, thus ameliorating cognitive dysfunction. This may be achieved through regulating NEP transcription and APP metabolism, accelerating Aß degradation, alleviating neuronal impairment, and regulating BDNF-related signal pathways to repair neuronal synaptic efficiency. This study provides novel evidence indicating that Navß2 plays crucial roles in the repair of neuronal injury induced by Aß1-42 both in vivo and in vitro.

Oral arsenic and retinoic acid for high-risk acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL) has become curable over 95% patients under a complete chemo-free treatment with all-trans retinoic acid (ATRA) and arsenic trioxide in low-risk patients. Minimizing chemotherapy has proven feasible in high-risk patients. We evaluated oral arsenic and ATRA without chemotherapy as an outpatient consolidation therapy and no maintenance for high-risk APL. We conducted a multicenter, single-arm, phase 2 study with consolidation phases. The consolidation therapy included Realgar-Indigo naturalis formula (60 mg/kg daily in an oral divided dose) in a 4-week-on and 4-week-off regimen for 4 cycles and ATRA (25 mg/m2 daily in an oral divided dose) in a 2-week-on and 2-week-off regimen for 7 cycles. The primary end point was the disease-free survival (DFS). Secondary end points included measurable resident disease, overall survival (OS), and safety. A total of 54 participants were enrolled at seven centers from May 2019. The median age was 40 years. At the median follow-up of 13.8 months (through April 2022), estimated 2-year DFS and OS were 94% and 100% in an intention-to-treat analysis. All the patients achieved complete molecular remission at the end of consolidation phase. Two patients relapsed after consolidation with a cumulative incidence of relapse of 6.2%. The majority of adverse events were grade 1-2, and only three grade 3 adverse events were observed. Oral arsenic plus ATRA without chemotherapy was active as a first-line consolidation therapy for high-risk APL.Trial registration: chictr.org.cn number, ChiCTR1900023309.

The neuroprotective effects of Lutongkeli in traumatic brain injury rats by anti-apoptosis mechanism.

PURPOSE: To explore the neuroprotective effects of Lutongkeli (LTKL) in traumatic brain injury (TBI) and detect the related mechanism. METHODS: TBI model was established with LTKL administration (2 and 4 g/kg/d, p.o.). Motor function of rats was examined by Rotarod test. Nissl staining was used to show neuron morphology. Furthermore, the disease-medicine common targets were obtained with the network pharmacology and analyzed with Kyoto Encyclopedia of Genes and Genomes. Lastly, the predicted targets were validated by real-time polymerase chain reaction. RESULTS: After LTKL administration, neural behavior was significantly improved, and the number of spared neurons in brain was largely increased. Moreover, 68 bioactive compounds were identified, corresponding to 148 LTKL targets; 2,855 genes were closely associated with TBI, of which 87 overlapped with the LTKL targets and were considered to be therapeutically relevant. Functional enrichment analysis suggested LTKL exerted its pharmacological effects in TBI by modulating multiple pathways including apoptosis, inflammation, etc. Lastly, we found LTKL administration could increase the mRNA level of Bcl-2 and decrease the expression of Bax and caspase-3. CONCLUSIONS: This study reported the neuroprotective effect of LTKL against TBI is accompanied with anti-apoptosis mechanism, which provides a scientific explanation for the clinical application of LTKL in the treatment of TBI.

Construction of five cuproptosis-related lncRNA signature for predicting prognosis and immune activity in skin cutaneous melanoma.

Cuproptosis is a newly discovered new mechanism of programmed cell death, and its unique pathway to regulate cell death is thought to have a unique role in understanding cancer progression and guiding cancer therapy. However, this regulation has not been studied in SKCM at present. In this study, data on Skin Cutaneous Melanoma (SKCM) patients were downloaded from the TCGA database. We screened the genes related to cuproptosis from the published papers and confirmed the lncRNAs related to them. We applied Univariate/multivariate and LASSO Cox regression algorithms, and finally identified 5 cuproptosis-related lncRNAs for constructing prognosis prediction models (VIM-AS1, AC012443.2, MALINC1, AL354696.2, HSD11B1-AS1). The reliability and validity test of the model indicated that the model could well distinguish the prognosis and survival of SKCM patients. Next, immune microenvironment, immunotherapy analysis, and functional enrichment analysis were also performed. In conclusion, this study is the first analysis based on cuproptosis-related lncRNAs in SKCM and aims to open up new directions for SKCM therapy.

Alfalfa's response to atrazine stress and its secreted atrazine metabolites.

Although listed as endocrine disruptor compounds, atrazine (ATZ) is still used in large quantities in agricultural production. Here, alfalfa seedling was cultivated in hydroponic media to investigate the toxic effects of ATZ on alfalfa and accumulation of ATZ in tissues of different plant parts. Alfalfa had a strong upward translocation ability to ATZ. The stress response of alfalfa under ATZ stress was studied using metabolomic and transcriptomic techniques. S-adenosylmethionine, glutathione, 3-mercaptopyruvic acid, ornithine, and aminopropylcadaverine were significantly increased by ATZ in pathways mtr00270 and mtr00480. Several genes of cysteine synthase and spermidine synthase were significantly up-regulated by ATZ induction. They may be markers and genes with potential physiological functions of alfalfa in response to ATZ stress. In addition, using high resolution mass spectrometry, a total of five ATZ metabolites secreted from alfalfa roots were detected. Among them, acetylated deisopropylated ATZ was discovered for the first time. Hydroxylated ATZ and acetylated deethylated ATZ were more readily excreted by the root system. This study not only provides potential genes for the construction of engineering plants to remediate ATZ-contaminated soil, but also provides monitoring objects for the ecological research of ATZ metabolites.