Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

The xylitol dehydrogenase(XDH)is a crucial enzyme involved in the xylose utilization in pentose-catabolizing yeasts and fungi.In addition to producing xylulose,XDH can also be employed to develop a biosensor for monitoring xylitol concentration.In this study,the gene encoding the thermophilic fungus Talaromyces emersonii XDH(TeXDH)was heterologously expressed in Escherichia coli BL21(DE3)at 16 ℃ in the soluble form.Recombinant TeXDH with high purity was purified by using a Ni-NTA affinity column.Size-exclusion chromatography and SDS-PAGE analysis demonstrated that the puri-fied recombinant TeXDH exists as a native trimer with a molecular mass of approximately 116 kD,and is composed of three identical subunits,each with a molecular weight of around 39 kD.The TeXDH strictly preferred NAD+as a coenzyme to NADP+.The optimal temperature and pH of the TeXDH were 40 ℃and 10.0,respectively.After EDTA treatment,the enzyme activity of TeXDH decreased to 43.26％of the initial enzyme activity,while the divalent metal ions Mg2+or Ca2+could recover the enzyme activity of TeXDH,reaching 103.32％and 110.69％of the initial enzyme activity,respectively,making them the optimal divalent metal ion cofactors for TeXDH enzyme.However,the divalent metal ions of Mn2+,Ni2+,Cu2+,Zn2+,Co2+,and Cd2+significantly inhibited the activity of TeXDH.ICP-MS and molecular doc-king studies revealed that 1 mol/L of TeXDH bound 2 mol/L Zn2+ions and 1 mol/L Mg2+ion.Further-more,TeXDH exhibited a high specificity for xylitol,laying the foundation for the development of future xylitol biosensors.

Non-functioning pituitary adenomas(NFPAs)are relatively common.Apart from hyperprolactinemia caused by pituitary compression,they typically lack overt hormonal hypersecretion and usually present with clinical symptoms due to mass effects.Previously considered a uniform entity,NFPAs are actually a highly heterogeneous group of tumors,including aggressive subtypes like silent corticotroph adenomas(SCA)and null cell adenomas.The 2022 WHO new classification of pituitary tumors employs transcription factors[e.g.,pituitary-specific transcription factor 1(PIT-1),T-box transcription factor 19(TBX19,also known as TPIT),steroidogenic factor 1(SF-1)]for detailed categorization,allowing precise subclassification of NFPAs into multiple subtypes derived from distinct cell lineages,including silent gonadotroph adenomas,SCA,and plurihormonal PIT-1-positive adenomas.This helps identify highly invasive subtypes with high recurrence risk,guiding clinical diagnosis and treatment,prognostic assessment,and individualized management.The new classification also provides a theoretical basis for targeted therapies of NFPAs(e.g.,somatostatin analogs and temozolomide).This review comprehensively discusses the latest pathological classification of NFPAs and its clinical implications,aiming to enhance understanding of this disease and offer valuable insights for precise diagnosis,treatment,and prognostic assessment.

The xylitol dehydrogenase(XDH)is a crucial enzyme involved in the xylose utilization in pentose-catabolizing yeasts and fungi.In addition to producing xylulose,XDH can also be employed to develop a biosensor for monitoring xylitol concentration.In this study,the gene encoding the thermophilic fungus Talaromyces emersonii XDH(TeXDH)was heterologously expressed in Escherichia coli BL21(DE3)at 16 ℃ in the soluble form.Recombinant TeXDH with high purity was purified by using a Ni-NTA affinity column.Size-exclusion chromatography and SDS-PAGE analysis demonstrated that the puri-fied recombinant TeXDH exists as a native trimer with a molecular mass of approximately 116 kD,and is composed of three identical subunits,each with a molecular weight of around 39 kD.The TeXDH strictly preferred NAD+as a coenzyme to NADP+.The optimal temperature and pH of the TeXDH were 40 ℃and 10.0,respectively.After EDTA treatment,the enzyme activity of TeXDH decreased to 43.26％of the initial enzyme activity,while the divalent metal ions Mg2+or Ca2+could recover the enzyme activity of TeXDH,reaching 103.32％and 110.69％of the initial enzyme activity,respectively,making them the optimal divalent metal ion cofactors for TeXDH enzyme.However,the divalent metal ions of Mn2+,Ni2+,Cu2+,Zn2+,Co2+,and Cd2+significantly inhibited the activity of TeXDH.ICP-MS and molecular doc-king studies revealed that 1 mol/L of TeXDH bound 2 mol/L Zn2+ions and 1 mol/L Mg2+ion.Further-more,TeXDH exhibited a high specificity for xylitol,laying the foundation for the development of future xylitol biosensors.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective:To investigate the influencing factors of pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (NCRT) in patients with locally advanced esophageal squamous cell carcinoma (ESCC), and to compare the clinical prognosis of ESCC patients with and without pCR after NCRT (40 Gy/ 20F).Methods:Among patients enrolled in a prospective clinical study, 87 ESCC patients treated with NCRT followed by surgery in Tianjin Medical University Cancer Institute & Hospital between June 2015 and October 2019 were selected. They were divided into the pCR ( n=35) and non-pCR groups ( n=52). Clinicopathological characteristics were retrospectively analyzed and subsequent follow-up was performed. Clinical prognosis and influencing factors were compared between two groups by using Kaplan-Meier and Cox regression analyses. Results:After NCRT, 40% of the ESCC patients could achieve pCR. Univariate analysis showed that patients in the pCR group had a disease-free survival (DFS) of 39.3 months and an overall survival (OS) of 64.0 months. In comparison, patients in the non-pCR group had a DFS of only 14.1 months and an OS of only 25.2 months. The differences were statistically significant (DFS: P<0.01, OS: P<0.05). Multivariate analysis revealed that whether pCR or not after NCRT, age, number of primary lesions, evaluation results after NCRT and postoperative pathological outcomes were important prognostic factors. The differences were statistically significant between two groups (all P<0.05). Conclusion:pCR after NCRT is significantly correlated with long-time survival of patients with ESCC, and pCR after NCRT has an important value in predicting clinical prognosis for long-term survival of ESCC patients.

Objective:To analyse the core genes and mechanisms of brain injury induced by isoflurane using the bioinformatics analysis.Methods:The GSE358 and GSE359 isoflurane anesthesia data set were downloaded from the GEO database. Debatch processing, screening of differentially expressed genes (DEGs), construction and analysis of protein-protein interaction network, and functional enrichment analysis were performed. The gene expression heat map was plotted, and the diseases most related to the core genes were found by Comparative Toxicogenomics Database analysis.Results:A total of 500 DEGs were identified. According to the results of Gene Ontology analysis, they were mainly enriched in the response to foreign stimuli, the response to hypoxia, the apoptotic process, and the inflammatory response in the Biological Process analysis. In Cellular Component analysis, they were mainly enriched in the cytoplasm, extracellular space, and neuronal projections. In Molecular Function analysis, they focused on protein binding and sequence specific DNA binding in transcriptional regulatory regions. In Kyoto Encyclopedia of Genes and Genomes analysis, they were mainly enriched in phosphatidylinositol 3-kinase/protein kinase B signaling pathway, neuroactive ligand-receptor interaction, Toll-like receptor (TLR) signaling pathway, apoptosis and cAMP signaling pathway. Six core genes (interferon gamma [IFN-γ], TLR4, nuclear factor kappa B inhibitor alpha [NFKBIA], interleukins-1α [IL-1α], proto-oncogene fos[Fos]), CCAAT enhancer binding protein β [CEBPB]) were obtained by protein-protein interaction network. Comparative Toxicogenomics Database analysis revealed that core genes (IFN-γ, IL-1α, Fos) were associated with neurological disorders, brain injury, hyperalgesia, drug-related side effects and adverse reactions, neurodegeneration, etc. The inference score could reflect the degree of association between the gene and the disease, among which IFN-γ, IL-1α and Fos had higher inference scores in brain damage.Conclusions:IFN-γ, IL-1α, Fos, TLR4, NFKBIA and CEBPB are six core genes associated with isoflurane-induced brain injury, and these genes may play important roles in immune and inflammatory responses.

OBJECTIVE: To investigate whether Omicron BA.1 breakthrough infection after receiving the SARS-CoV-2 vaccine could create a strong immunity barrier. METHODS: Blood samples were collected at two different time points from 124 Omicron BA.1 breakthrough infected patients and 124 controls matched for age, gender, and vaccination profile. Live virus-neutralizing antibodies against five SARS-CoV-2 variants, including WT, Gamma, Beta, Delta, and Omicron BA.1, and T-lymphocyte lymphocyte counts in both groups were measured and statistically analyzed. RESULTS: The neutralizing antibody titers against five different variants of SARS-CoV-2 were significantly increased in the vaccinated population infected with the Omicron BA.1 variant at 3 months after infection, but mainly increased the antibody level against the WT strain, and the antibody against the Omicron strain was the lowest. The neutralizing antibody level decreased rapidly 6 months after infection. The T-lymphocyte cell counts of patients with mild and moderate disease recovered at 3 months and completely returned to the normal state at 6 months. CONCLUSION Omicron BA.1 breakthrough infection mainly evoked humoral immune memory in the original strain after vaccination and hardly produced neutralizing antibodies specific to Omicron BA.1. Neutralizing antibodies against the different strains declined rapidly and showed features similar to those of influenza. Thus, T-lymphocytes may play an important role in recovery.
Humans ; Antibodies, Neutralizing ; Prospective Studies ; SARS-CoV-2 ; Breakthrough Infections ; COVID-19 Vaccines ; COVID-19 ; T-Lymphocytes ; China/epidemiology* ; Antibodies, Viral

Objective: To investigate the early effect and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with a 10-day decitabine-containing conditioning regimen in the treatment of acute myeloid leukemia (AML) /myelodysplastic syndrome (MDS) . Methods: From April 2021 to May 2022, 31 AML/MDS patients who received allo-HSCT with a 10-day decitabine-containing conditioning regimen were analyzed. Results: AML (n=10), MDS-AML (n=6), CMML-AML (n=1), and MDS (n=14) were identified in 31 patients, 16 males, and 15 females, with a median age of 41 (20-55) yr. Neutrophils and platelets were successfully implanted in 31 patients (100%), with a median implantation duration of 12 (9-30) and 14 (9-42) days, respectively. During the preconditioning period, 16 patients (51.6%) developed oral mucositis, with 15 cases of Ⅰ/Ⅱ grade (48.4%) and one case of Ⅲ grade (3.2%). After transplantation, 13 patients (41.9%) developed CMV viremia, six patients (19.4%) developed hemorrhagic cystitis, and four patients (12.9%) developed a local infection. The median time of acute graft versus host disease (aGVHD) following transplantation was 33 (12-111) days. The cumulative incidence of aGVHD and Ⅲ/Ⅳ grade aGVHD was 41.9% (95% CI 26.9%-61.0%) and 22.9% (95% CI 13.5%-47.5%), respectively. There was no severe cGVHD, and mild and moderate chronic GVHD (cGVHD) incidence was 23.5% (95% CI 12.1%-43.6%). As of November 30, 2022, only one of the 31 patients had relapsed, with a 1-yr cumulative relapse rate (CIR) of 3.2% (95% CI 0.5%-20.7%). There was only one relapse patient death and no non-relapse deaths. The 1-yr overall survival (OS) and disease-free survival (DFS) rates were 92.9% (95% CI 80.3%-100%) and 96.8% (95% CI 90.8%-100%), respectively. Conclusions: A 10-day decitabine-containing conditioning regimen for allo-HSCT reduced relapse and was safe and feasible in treating AML/MDS.
Male ; Female ; Humans ; Decitabine ; Myelodysplastic Syndromes/therapy* ; Leukemia, Myeloid, Acute/complications* ; Disease-Free Survival ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Recurrence ; Chronic Disease ; Graft vs Host Disease/etiology* ; Transplantation Conditioning/adverse effects* ; Bronchiolitis Obliterans Syndrome ; Retrospective Studies