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Cylindrical tubes in cross-flow, like the ones found in heat exchangers, are excellent acoustic dampers and as such have the potential to mitigate thermoacoustic instabilities. Flow separation and vortex shedding downstream of the tube row are key to significantly enhancing sound attenuation. However, constructing an analytical solution for the aeroacoustic response of tube rows in cross-flow is very challenging owing to the complex flow structure, vortex shedding and coupling with acoustics. To overcome this, we propose the adaptation of a slit model for tube row acoustic scattering (aeroacoustic response) predictions at low Strouhal numbers. The slit model was modified such that the loss coefficients across the slit and the tube row matches. The model is then validated against numerical predictions using Linearised Navier Stokes Equations and experimental measurements. The predictions for both magnitude and phase for transmission and reflection coefficients agree well with the simulations and experiments.

A slug length is widely used to describe additional mass inertia at low frequencies in duct acoustics. It is often used in acoustic energy analysis, e.g. as one of the inputs for semi-analytical or empirical models to obtain the acoustic reflection and transmission coefficients. However, the calculation of slug length is usually empirical and limited to many conditions, such as simple geometric configurations, low frequencies, no mean flow, etc. In this paper, the slug length at a contraction with mean flow between two half cylinders is calculated by different methods: solving the Laplace's equation both analytically and numerically, solving the Helmholtz equation, and using the Cummings - Fant equation based on the numerical results of frequency-domain linearized Navier-Stokes equations. Both the frequency-dependence and the mean flow effect are discussed. The calculated slug lengths are then used in the semi-analytical model to predict the acoustic scattering at tube rows in the presence of a cross mean flow.

This is the first example of the construction of harmaline-based spiropolycyclic scaffolds using harmaline-based N–C synthons and evaluation of 3cb as an anticancer agent.

Combinational therapy such as taking tranexamic acid while using laser treatment has been proved potential efficacy by many experiments. However, there is few research which contains large samples and consistent observations.We evaluated clinical efficacy and safety of a new systemic treatment of drug-laser-photon therapy.Retrospective and randomized investigator-blinded study of 75 patients with mixed type melasma was analyzed. At each visit, standardized photographs were taken using VISIA. Modified melasma area and severity index (mMASI) scores were marked using photographs by two dermatologists.The mMASI score decreased significantly from 6.92 to 3.84 after the treatment. The VISIA analyze right cheek data shows: Spots (from 49.67 ± 3.43 to 56.09 ± 3.31), UV spots (from 41.39 ± 24.45 to 44.56 ± 25.86), and Brown spots (from 23.97 ± 17.89 to 28.16 ± 21.28) are statistically increased (p = 0.035, p = 0.018, p = 0.07). All patients feel varying degrees of improvement, about 10.17% felt very much improved, 30.51% felt much improved (51%-75%), 45.76% felt moderately improved (26%-50%), and 13.56% felt little improved (1%-25%).This study was no control group.The efficacy and safety profile of the combination of drug-laser-photon therapy systemic treatment in melasma patients has been proved. It has potential possibility to become a new, reliable, widely suitable therapy strategy.

Nicotinamide mononucleotide (NMN), a key intermediate of nicotinamide adenine dinucleotide, plays an important in anti-aging and disease. Lactococcus lactis, an important probiotic lactic acid bacteria (LAB), has shown great potential for the biosynthesis of NMN, which will significantly affect the probiotic effects of the dairy products.We used the CRISPR/nCas9 technique to knockout nadR gene of L. lactis NZ9000 to enhance the accumulation of NMN by 61%. The nadE* gene from Francisella tularensis with codon optimization was heterologous in L. lactis NZ9000ΔnadR and has a positive effect on NMN production. Combined with optimization of the concentration of substrate nicotinamide, a final intracellular NMN titer was 2289 μmol LOur study provides a better understanding of the NMN biosynthesis pathway in L. lactis, and can facilitate NMN production in LAB via synthetic biology approaches. © 2022 Society of Chemical Industry.

Immunosuppression commonly occurs after a stroke, which is believed to be associated with the increased risk of infectious comorbidities of stroke patients, while the mechanisms underlying post-stroke immunosuppression is yet to be elucidated. In the brains of intracerebral hemorrhage (ICH) patients and murine ICH models, we identified that neuron-derived programmed death-ligand 1 (PD-L1) is reduced in the perihematomal area, associating increased soluble PD-L1 level in the peripheral blood. ICH induced a significant decrease of T and natural killer (NK) cell numbers in the periphery with an upregulation of programed death-1 (PD-1) in these cells. Blocking PD-1 pathway with an anti-PD1 monoclonal antibody prevented the T and NK cell compartment contraction and spleen atrophy post-ICH, with reduced pulmonary bacterial burden and improved neurological outcome. Thus, we here identified that brain-derived PD-L1 as a new mechanism driving post-stroke immunosuppression, and anti-PD1 treatment could be potentially developed to reducing the risk of post-stroke infections.

Circular RNAs (circRNAs) have been accepted to play key roles in the development and progression of mutiple cancers including colorectal cancer (CRC). Here, we identified circ-METTL9, derived from 2-4 exons of METTL9 gene, may promote CRC progression by accelerating cell cycle progression. However, the role and mechanism of circ-METTL9 in CRC remains unclear. Based on our data, the expression of circ-METTL9 was significantly upregulated in CRC tissues and markedly increased in advanced tumors in CRC patients. Functional experiments demonstrated that circ-METTL9 overexpression promoted CRC cells proliferation and migration in vitro, and simultaneously enhanced CRC tumor growth and metastasis in vivo. Mechanistically, RNA immunoprecipitation (RIP) assays proved that circ-METTL9 might be a miRNA sponge, and RNA pulldown assays showed the interaction between circ-METTL9 and miR-551b-5p. Notably, cyclin-dependent kinase 6 (CDK6), a key regulator in cell cycle, is a conserved downstream target of miR-551b-5p. Taken together, our findings highlight a novel oncogenic function of circ-METTL9 in CRC progression via circ-METTL9/miR-551b-5p/CDK6 axis, which may serve as a prognostic biomarker and therapeutic target for CRC patients.

BackgroundMutations in the dynein cytoplasmic 1 heavy chain 1 (DYNC1H1) gene are linked to malformations of cortical development (MCD), which may be accompanied by central nervous system (CNS) manifestations. Here, we present the case of a patient with MCD harboring a variant of DYNC1H1 and review the relevant literature to explore genotype-phenotype relationships.Case presentationA girl having infantile spasms, was unsuccessfully administered multiple antiseizure medications and developed drug-resistant epilepsy. Brain magnetic resonance imaging (MRI) at 14 months-of-age revealed pachygyria. At 4 years-of-age, the patient exhibited severe developmental delay and mental retardation. A de novo heterozygous mutation (p.Arg292Trp) in the DYNC1H1 gene was identified. A search of multiple databases, including PubMed and Embase, using the search strategy DYNC1H1 AND [malformations of cortical development OR seizure OR intellectual OR clinical symptoms] up to June 2022, identified 129 patients from 43 studies (including the case presented herein). A review of these cases showed that patients with DYNC1H1-related MCD had higher risks of epilepsy (odds ratio [OR] = 33.67, 95% confidence interval [CI] = 11.59, 97.84) and intellectual disability/developmental delay (OR = 52.64, 95% CI = 16.27, 170.38). Patients with the variants in the regions encoding the protein stalk or microtubule-binding domain had the most prevalence of MCD (95%).ConclusionMCD, particularly pachygyria, is a common neurodevelopmental disorder in patients with DYNC1H1 mutations. Literature searches reveales that most (95%) patients who carried mutations in the protein stalk or microtubule binding domains exhibited DYNC1H1-related MCD, whereas almost two-thirds of patients (63%) who carried mutations in the tail domain did not display MCD. Patients with DYNC1H1 mutations may experience central nervous system (CNS) manifestations due to MCD.

The subduction model of the Neo-Tethys during the Early Cretaceous has always been a controversial topic, and the scarcity of Early Cretaceous magmatic rocks in the southern part of the Gangdese batholith is the main cause of this debate. To address this issue, this article presents new zircon U–Pb chronology, zircon Hf isotope, whole-rock geochemistry and Sr–Nd isotope data for the Early Cretaceous quartz diorite dykes with adakite affinity in Liuqiong, Gongga. Zircon U–Pb dating of three samples yielded ages of c. 141–137 Ma, indicating that the Liuqiong quartz diorite was emplaced in the Early Cretaceous. The whole-rock geochemical analysis shows that the Liuqiong quartz diorite is enriched in large-ion lithophile elements (LILEs) and light rare-earth elements (LREEs) and is depleted in high-field-strength elements (HFSEs), which are related to slab subduction. Additionally, the Liuqiong quartz diorite has high SiO2, Al2O3 and Sr contents, high Sr/Y ratios and low heavy rare-earth element (HREE) and Y contents, which are compatible with typical adakite signatures. The initial 87Sr/86Sr values of the Liuqiong adakite range from 0.705617 to 0.705853, and the whole-rock ϵNd(t) values vary between +5.78 and +6.24. The zircon ϵHf(t) values vary from +11.5 to +16.4. Our results show that the Liuqiong adakite magma was derived from partial melting of the Neo-Tethyan oceanic plate (mid-ocean ridge basalt (MORB) + sediment + fluid), with some degree of subsequent peridotite interaction within the overlying mantle wedge. Combining regional data, we favour the interpretation that the Neo-Tethyan oceanic crust was subducted at a low angle beneath the Gangdese during the Early Cretaceous.

Background: Dendrobium nobile Lindl. (DNL) is effective for the treatment of alcohol liver disease (ALD), but the underly mechanism is still unclear. Objectives: This research aimed to investigate the effects and mechanism of aqueous extract of Dendrobium nobile Lindl (AEDNL) in ALD rats based on a metabolomics approach. Materials and Methods: In this study, 18 Sprague-Dawley male rats were randomly divided into control, model, and AEDNL groups (n=six). Rats in the AEDNL group were given AEDNL (152 mg/kg) intragastric administration from the first day for 30 consecutive days. From day 15 to day 30, model and AEDNL groups were given 30% ethanol (10 ml/kg) after 4 h of daily administration. Then, serum and liver samples were collected for biochemical analysis, histopathological examination, and Ultra Performance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry (UPLC-Q-TOF/MS) determination for metabolomic analysis. Results: Compared with the model group, the liver/body weight index and serum levels of TC, LDL-C, and TBIL in the AEDNL group were significantly decreased. Hepatocyte cord arrangement, hepatocyte balloon, and fat vacuolization were significantly improved in the AEDNL group. Metabolism profiles were changed in the model and AEDNL groups. Seven and two common differential metabolites (Guanosine3',5'-cyclic monophosphate, and Glutaric acid) were found in serum and liver, respectively. In addition, the hepatoprotective effect of AEDNL on ALD was related to steroid hormone biosynthesis, riboflavin metabolism, and glycerophospholipid metabolism. Conclusion: The research could provide novel evidence of the protective effects of AEDNL on ALD.

Objectives: To investigate the difference of application of core needle biopsy histology and fine needle aspiration cytology in cervical lymphadenopathy. Methods: A retrospective analysis was made on 80 patients with cervical lymphadenopathy admitted to Baoding No.1 Central Hospital from to October 2018 to February 2020, and they were randomly divided into two groups: core needle group and fine needle group. Patients in the core needle group were given core needle biopsy histology, while those in the fine needle group were given fine needle aspiration cytology, and the puncture results and surgical complications were compared between the two groups. Results: The accuracy rates of the core needle group and the fine needle group in the diagnosis of malignant cervical lymph nodes were 95.83% and 72.22% respectively, with a statistically significant difference (χ²=4.683, p=0.030). The sensitivity, specificity, positive predictive value and negative predictive value of the core needle group were 100.00%, 93.75%, 95.83% and 100.00% respectively, while those of the fine needle group were 86.67%, 90.00%, 86.67% and 90.00% respectively, with no statistically significant differences between the two groups (p>0.05). The complication rate in the core needle group was 22.50%, which was higher than the 5.00% in the fine needle group (χ²=5.165, p=0.023). Conclusions: No significant difference was observed between core needle biopsy histology and fine needle aspiration cytology in diagnosing cervical lymphadenopathy, but the former has a high complication rate. doi: https://doi.org/10.12669/pjms.39.3.6630 How to cite this: Mu W, Li J, Liu Y, Wen Y, Liu X. Clinical application of ultrasound-guided Core Needle Biopsy Histology and Fine Needle Aspiration Cytology in Cervical Lymph Nodes. Pak J Med Sci. 2023;39(3):752-756. doi: https://doi.org/10.12669/pjms.39.3.6630 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Given the inconsistency between the information value and the weight value in the weighted information value model, a weight model based on the Apriori algorithm is established in this paper to analyze the correlation between the second-level intervals of disaster factors and the susceptibility of geological disasters. The objective weight of the second-level intervals of each index factor is calculated through the mining of association rules by the Apriori algorithm. The subjective uncertainty of the existing second-level factor weighting method is eliminated. Taking the geological disaster data of Xiangtan urban area as an example, 10 evaluation indexes were selected to establish the entropy weight method-information value (EWM-IV) model and the entropy weight method-Apriori algorithm-information value (EWM-Apriori-IV) model to evaluate the geological disaster susceptibility, and the disaster area ratio and the receiver operating characteristic curve (ROC) verification method were used to test and analyze the evaluation results. The results showed that compared with the EWM-IV model, the EWM-Apriori-IV model is used to evaluate the disaster area ratio of high-prone area increased by 58.3%, and the disaster area ratio of low-prone area decreased by 43.1%, the area under the curve (AUC) increased by 7.4%, and the evaluation accuracy was relatively improved compared with the former. This paper proves the rationality and practicability of the weighting method of the geological hazard susceptibility evaluation index based on the Apriori algorithm.

In order to find out the contamination of mycotoxins in Triticeae crops of Qinghai-Tibet Plateau, a total of 153 Triticeae crop fruits were collected as target samples, and 22 mycotoxins were tested. High detection rate was found in the Alternaria mycotoxins, including tentoxin (TEN), tenuazonic acid (TEA) and alternariol (AOH) toxins. To further clarify the production rules of Alternaria mycotoxins. A number of 9 high yield toxic strains were selected from 65 bacterial strains and the gene sequences of each were determined. The nine selected Alternaria alternate were cultured under specific pH of the culture medium, temperature and ultraviolet (UV) irradiation, and their growth and toxicity were analyzed. The results showed that the toxic capacity of most A. alternate increased with the increase of culture environment temperature and decreased with the increase of UV irradiation. However, the production of some toxins did not meet this principle, or even met the principle of relativity. In the culture experiments, a total of five Alternaria toxins were detected as positive, which were TEN, AOH, alternariol monomethyl ether (AME), TEA, and Alternaria (ALT). The altenusin (ALS) toxin was not detected in the metabolites of the nine Alternaria strains. It indicated that the TEN, AOH, AME, TEA, and ALT toxins should be particularly valued in the future risk assessments. This finding provided comprehensive information of mycotoxins contamination in the Tibetan Plateau Triticeae crops, it pointed out a direction to the Tibetan Plateau food crops’ quality control.

Background: Shenxiong Glucose Injection (SGI) is a traditional Chinese medicine formula composed of ligustrazine hydrochloride and Danshen (Radix et rhizoma Salviae miltiorrhizae; Salvia miltiorrhiza Bunge, Lamiaceae). Our previous studies and others have shown that SGI has excellent therapeutic effects on myocardial ischemia (MI). However, the potential mechanisms of action have yet to be elucidated. This study aimed to explore the molecular mechanism of SGI in MI treatment.Methods: Sprague-Dawley rats were treated with isoproterenol (ISO) to establish the MI model. Electrocardiograms, hemodynamic parameters, echocardiograms, reactive oxygen species (ROS) levels, and serum concentrations of cardiac troponin I (cTnI) and cardiac troponin T (cTnT) were analyzed to explore the protective effect of SGI on MI. In addition, a model of oxidative damage and apoptosis in human umbilical vein endothelial cells (HUVECs) was established using CoCl2. Cell viability, Ca2+ concentration, mitochondrial membrane potential (MMP), apoptosis, intracellular ROS, and cell cycle parameters were detected in the HUVEC model. The expression of apoptosis-related proteins (Bcl-2, Caspase-3, PARP, cytoplasmic and mitochondrial Cyt-c and Bax, and p-ERK1/2) was determined by western blotting, and the expression of cleaved caspase-3 was analyzed by immunofluorescence.Results: SGI significantly reduced ROS production and serum concentrations of cTnI and cTnT, reversed ST-segment elevation, and attenuated the deterioration of left ventricular function in ISO-induced MI rats. In vitro, SGI treatment significantly inhibited intracellular ROS overexpression, Ca2+ influx, MMP disruption, and G2/M arrest in the cell cycle. Additionally, SGI treatment markedly upregulated the expression of anti-apoptotic protein Bcl-2 and downregulated the expression of pro-apoptotic proteins p-ERK1/2, mitochondrial Bax, cytoplasmic Cyt-c, cleaved caspase-3, and PARP.Conclusion: SGI could improve MI by inhibiting the oxidative stress and apoptosis signaling pathways. These findings provide evidence to explain the pharmacological action and underlying molecular mechanisms of SGI in the treatment of MI.

In this study, we reported a coumarin-pyrazole-based probe for the fluorescence detection of phosgene. Probe 1 responded rapidly to phosgene with good selectivity and high sensitivity, especially for phosgene gas-phase detection.

This study was to elucidate the effects of dietary pantothenic acid (PA) on growth, lipid metabolism, and antioxidant status in juvenile blunt snout bream Megalobrama amblycephala. Fish were fed with four experimental diets containing two lipid levels (5% and 11%) and two PA supplementation levels (24 mg kg-1 and 240 mg kg-1) for eight weeks. The results showed that diets containing 11% lipid significantly increased condition factor, mesenteric fat index, triacylglycerol (TG), and cholesterol (TCH) in the liver as well as total lipid content and TCH in the muscle ( P < 0.05 ), but significantly decreased specific growth rate and whole-body protein ( P < 0.05 ). As the dietary lipid level increased, hepatic antioxidant enzyme activities were significantly increased ( P < 0.05 ) as well as malondialdehyde content ( P < 0.05 ). Besides, cytosolic cytochrome c concentration was also significantly ( P < 0.05 ) increased, while mitochondrial protein, cytochrome c, and Na+-K+-ATPase activities were significantly decreased ( P < 0.05 ). There were no significant changes on growth performance and body composition of PA supplementation. Then, significantly negative ( P < 0.05 ) interactions were observed between dietary lipid and PA supplementation on EPA, DHA, and EPA + DHA content of the muscle. Saturated fatty acid (SFA) and polyunsaturated fatty acid (PUFA) contents in the liver were significantly increased ( P < 0.05 ) with dietary lipid level increased, while liver monounsaturated fatty acid (MUFA) was significantly decreased ( P < 0.05 ). Muscle SFA, DHA, and EPA + DHA contents were significantly decreased ( P < 0.05 ) when dietary fat level increased. Meanwhile, EPA, DHA, and EPA + DHA content was significantly decreased ( P < 0.05 ) with dietary high PA supplementation. On the whole, a high PA supplementation level of 240 mg kg-1 could alleviate lipid content accumulated and oxidative damage induced by a high-fat diet.

Objective. To investigate the clinical efficacy and safety of bevacizumab, apatinib, and recombinant human endothelial inhibitor in the treatment of advanced gastric cancer. Methods. The medical data of 204 patients with a medium to advanced gastric cancer assessed for eligibility treated in our hospital from February 2019 to April 2020 were retrospectively analyzed. The eligible patients were assigned at a ratio of 1 : 1:1 : 1 to either the control group (chemotherapy), study group I (bevacizumab combined with chemotherapy), study group II (apatinib combined with chemotherapy), or study group III (recombinant human endothelial inhibitor combined with chemotherapy) according to different treatment methods. The treatment efficacy, drug toxicity, quality of life, and serum tumor marker levels before and after treatment were compared among the four groups. Results. Regarding the treatment effects, the effective rate of study group II (68.63%) was significantly higher than that of the control group (33.33%), study group I (58.82%), and study group III (49.02%) ( P < 0.05 ). The four groups showed similar safety and tolerability profiles ( P > 0.05 ). The treatment in study group II led to a significantly higher physiological function score vs. the other three groups, but the scores of other items were not significantly different. Significant reduction was observed in the serum tumor markers after treatment in the four groups ( P < 0.05 ), but treatment in study group II led to a significantly greater reduction than the other three groups ( P < 0.05 ). Conclusion. The addition of apatinib, bevacizumab, and recombinant human endothelial inhibitor injection to chemotherapy for the treatment of medium to advanced gastric cancer can significantly improve the clinical treatment efficacy, among which the use of apatinib combined with chemotherapy achieves the best results, which is worthy of clinical promotion.

Foamy viruses belong to the Spumaretrovirinae subfamily member of the Retroviridae family and produce nonpathogenic infection to hosts in the natural conditions. However, infections of foamy viruses can dramatically cause severe cytopathic effects in vitro. To date, the exact molecular mechanism has remained unclear which implied the tremendous importance of virus-host cell immune reactions. In this study, we found that the transactivator Tas in two foamy viruses isolated from Old World Monkey (OWM) induced obvious inhibition of cell proliferation via the upregulation of Foxo3a expression. It was mediated by the generation of ROS and the initiation of ER stress, and ultimately, the mitochondrial apoptosis pathway was triggered. Notably, PFV Tas contributed to the accumulation of G0/G1 phase cycle arrest induced by the activation of the p53 signaling pathway and the nuclear transportation of HDAC4 via upregulating PPM1E expression. Together, these results demonstrated the different survival strategies by which foamy virus can hijack host cell cytokines and regulate virus-host cell interactions.

Stroke accounts for a large proportion of morbidity and mortality burden in China. Moreover, there is a high prevalence of the leading risk factors for stroke, including hypertension and smoking. Understanding the underlying mechanisms and developing effective therapeutic interventions for patients with stroke is a key imperative. The pathophysiology of stroke involves a complex interplay between the immune and inflammatory mechanisms. Focal brain inflammation triggered by neuronal cell death and the release of factors such as damage-associated molecular patterns can further exacerbate neuronal injury; in addition, impairment of the blood-brain barrier, oxidative stress, microvascular dysfunction, and brain edema cause secondary brain injury. Immune cells, including microglia and other infiltrating inflammatory cells, play a key role in triggering focal and global brain inflammation. Anti-inflammatory therapies targeting the aforementioned mechanisms can alleviate primary and secondary brain injury in the aftermath of a stroke. Further experimental and clinical studies are required to explore the beneficial effects of anti-inflammatory drugs in stroke.

The first example of 3-vinyl oxindole-chromones in the ring opening and recyclization reaction.

Herein is reported the first example of ring opening and skeletal reconstruction of 3-vinyl benzofuranone-chromones 1 as versatile synthons, which can react with ammonia or primary aliphatic amines as binucleophiles, for the eco-friendly and atom-economical synthesis of diverse and functionalized 2-pyridones 3 with potential biological activity in good to excellent yields (77-93%). When using optically active 1,2-diphenylethylenediamine 2 as the binucleophile, the

目的：透過異常通報資料庫分析，探討96小時對照72小時重置周邊靜脈導管，對於靜脈炎發生率之影響。 方法：方便取樣臺灣南部某醫學中心之異常通報資料庫，分析2011年9月1日至2014年8月31日之72小時重置組，與2014年9月1日至2017年8月31日之96小時重置組，2個時期之住院個案的靜脈炎發生率。 結果：96小時對照72小時重置周邊靜脈導管，並未增加靜脈炎發生率。靜脈炎總發生率（勝算比[odds ratio,OR] = 0.70, p=.0290）與細菌性靜脈炎發生率(OR= 0.11, p=.0097)顯著減少，化學性與機械性靜脈炎發生率則無顯著差異。 結論：本土性資料庫分析結果為在臺灣熱帶海島型潮濕氣候，三班評估無靜脈炎症狀下，96小時重置周邊靜脈導管並不會顯著增加靜脈炎風險，建議醫療機構可據此調整臨床作業規範，落實實證知識轉譯。 "Purpose: To compare the effect of replacement of peripheral venous catheters at 96-hour intervals on the incidence of phlebitis with that at 72-hour intervals through analysis of an incident-reporting database. Methods: Convenience sampling of records from the incident-reporting database of a medical center in southern Taiwan was used to analyze the incidence of phlebitis among hospitalized patients with replacement of peripheral venous catheters at 72-hour intervals (from September 1, 2011, to August 31, 2014) or 96-hour intervals (from September 1, 2014, to August 31, 2017). Result: The analysis revealed that replacing peripheral venous catheters every 96 hours rather than every 72 hours did not increase the incidence of phlebitis. The total incidence of phlebitis (odds ratio [OR]=0.70, p=.0290) and the incidence of bacterial phlebitis (OR=0.11, p=.0097) decreased significantly, and no significant differences in the incidence rates of chemical or mechanical phlebitis were identified. Conclusion: According to the analysis results of a local database, under the humid tropical insular climate of Taiwan, replacement of peripheral venous catheters at 96-hour intervals did not significantly increase the risk of phlebitis in patients who exhibited no symptoms of phlebitis as assessed in three shifts. Medical institutions can adjust their clinical operation standards and implement knowledge translation accordingly. &nbsp

The SARS-CoV-2 is constantly mutating, and the new coronavirus such as Omicron has spread to many countries around the world. Anexelekto (AXL) is a transmembrane protein with biological functions such as promoting cell growth, migration, aggregation, metastasis and adhesion, and plays an important role in cancers and coronavirus disease 2019 (COVID-19). Unlike angiotensin-converting enzyme 2 (ACE2), AXL was highly expressed in respiratory system cells. In this study, we verified the AXL expression in cancer and normal tissues and found AXL expression was strongly correlated with cancer prognosis, tumor mutation burden (TMB), the microsatellite instability (MSI) in most tumor types. Immune infiltration analysis also demonstrated that there was an inextricable link between AXL expression and immune scores in cancer patients, especially in BLCA, BRCA and CESC. The NK-cells, plasmacytoid dendritic cells, myeloid dendritic cells, as one of the important components of the tumor microenvironment, were highly expressed AXL. In addition, AXL-related tumor neoantigens were identified and might provide the novel potential targets for tumor vaccines or SARS-Cov-2 vaccines research in cancer patients.

C17H17N5, monoclinic, P21/c (no. 14), a = 9.4347(9) Å, b = 15.6392(15) Å, c = 11.0939(11) Å, β = 100.215 ( 2 ) ° $100.215(2){}^{\circ}$ , V = 1611.0(3) Å3, Z = 4, R gt (F) = 0.0392, wR ref (F 2) = 0.1105, T = 296 K.

Background Abnormal alternative splicing is frequently associated with carcinogenesis. In B-cell acute lymphoblastic leukemia (B-ALL), double homeobox 4 fused with immunoglobulin heavy chain (DUX4/IGH) can lead to the aberrant production of E-26 transformation-specific family related gene abnormal transcript (ERGalt ) and other splicing variants. However, the molecular mechanism underpinning this process remains elusive. Here, we aimed to know how DUX4/IGH triggers abnormal splicing in leukemia. Methods The differential intron retention analysis was conducted to identify novel DUX4/IGH-driven splicing in B-ALL patients. X-ray crystallography, small angle X-ray scattering (SAXS), and analytical ultracentrifugation were used to investigate how DUX4/IGH recognize double DUX4 responsive element (DRE)-DRE sites. The ERGalt biogenesis and B-cell differentiation assays were performed to characterize the DUX4/IGH crosslinking activity. To check whether recombination-activating gene 1/2 (RAG1/2) was required for DUX4/IGH-driven splicing, the proximity ligation assay, co-immunoprecipitation, mammalian two hybrid characterizations, in vitro RAG1/2 cleavage, and shRNA knock-down assays were performed. Results We reported previously unrecognized intron retention events in C-type lectin domain family 12, member A abnormal transcript (CLEC12Aalt ) and chromosome 6 open reading frame 89 abnormal transcript (C6orf89alt ), where also harbored repetitive DRE-DRE sites. Supportively, X-ray crystallography and SAXS characterization revealed that DUX4 homeobox domain (HD)1-HD2 might dimerize into a dumbbell-shape trans configuration to crosslink two adjacent DRE sites. Impaired DUX4/IGH-mediated crosslinking abolishes ERGalt , CLEC12Aalt , and C6orf89alt biogenesis, resulting in marked alleviation of its inhibitory effect on B-cell differentiation. Furthermore, we also observed a rare RAG1/2-mediated recombination signal sequence-like DNA edition in DUX4/IGH target genes. Supportively, shRNA knock-down of RAG1/2 in leukemic Reh cells consistently impaired the biogenesis of ERGalt , CLEC12Aalt , and C6orf89alt . Conclusions All these results suggest that DUX4/IGH-driven DNA crosslinking is required for RAG1/2 recruitment onto the double tandem DRE-DRE sites, catalyzing V(D)J-like recombination and oncogenic splicing in acute lymphoblastic leukemia.

More than 2,000 yeast strains isolated from 1200 samples mostly collected from Tibet and Yunnan provinces were identified as 466 species according to the internal transcribed spacer including the 5.8S rDNA (ITS) and the D1/D2 domains of the large subunit rDNA (LSU) sequence analyses. Among them, 78 new basidiomycetous yeast species were proposed based on the multi-locus phylogenetic analyses including the D1/D2 domains, the ITS, the small subunit rDNA (SSU), the largest subunit of RNA polymerase II (RPB1), the second largest subunit of RNA polymerase II (RPB2) and translation elongation factor 1-α (TEF1), as well as the phenotypic comparisons. Fifty-three new species belong to 17 genera in the Agaricomycotina, 19 new species occur in 12 genera in the Pucciniomycotina and six new species distribute in four genera in the Ustilaginomycotina, and eleven new species were classified in nine newly established genera. Two new families and one new order were also proposed based on two of these new genera. The genus Guomyces and the species Guomyces nicotianae were validated.

Background The recruitment of a sufficient number of immune cells to induce an inflamed tumor microenvironment (TME) is a prerequisite for effective response to cancer immunotherapy. The immunological phenotypes in the TME of EGFR–mutated lung cancer were characterized as non-inflamed, for which immunotherapy is largely ineffective. Methods Global proteomic and phosphoproteomic data from lung cancer tissues were analyzed aiming to map proteins related to non-inflamed TME. The ex vivo and in vivo studies were carried out to evaluate the anti-tumor effect. Proteomics was applied to identify the potential target and signaling pathways. CRISPR-Cas9 was used to knock out target genes. The changes of immune cells were monitored by flow cytometry. The correlation between PKCδ and PD-L1 was verified by clinical samples. Results We proposed that PKCδ, a gatekeeper of immune homeostasis with kinase activity, is responsible for the un-inflamed phenotype in EGFR-mutated lung tumors. It promotes tumor progression by stimulating extracellular matrix (ECM) and PD-L1 expression which leads to immune exclusion and assists cancer cell escape from T cell surveillance. Ablation of PKCδ enhances the intratumoral penetration of T cells and suppresses the growth of tumors. Furthermore, blocking PKCδ significantly sensitizes the tumor to immune checkpoint blockade (ICB) therapy (αPD-1) in vitro and in vivo model. Conclusions These findings revealed that PKCδ is a critical switch to induce inflamed tumors and consequently enhances the efficacy of ICB therapy in EGFR-mutated lung cancer. This opens a new avenue for applying immunotherapy against recalcitrant tumors. Graphical Abstract