Early differential diagnosis of pancytopenia related diseases based on serum surface-enhanced Raman spectroscopy.

Pancytopenia is a common blood disorder defined as the decrease of red blood cells, white blood cells and platelets in the peripheral blood. Its genesis mechanism is typically complex and a variety of diseases have been found to be capable of causing pancytopenia, some of which are featured by their high mortality rates. Early judgement on the cause of pancytopenia can benefit timely and appropriate treatment to improve patient survival significantly. In this study, a serum surface-enhanced Raman spectroscopy (SERS) method was explored for the early differential diagnosis of three pancytopenia related diseases, i.e., aplastic anemia (AA), myelodysplastic syndrome (MDS) and spontaneous remission of pancytopenia (SRP), in which the patients with those pancytopenia related diseases at initial stage exhibited same pancytopenia symptom but cannot be conclusively diagnosed through conventional clinical examinations. The SERS spectral analysis results suggested that certain amino acids, protein substances and nucleic acids are expected to be potential biomarkers for their early differential diagnosis. In addition, a diagnostic model was established based on the joint use of partial least squares analysis and linear discriminant analysis (PLS-LDA), and an overall accuracy of 86.67 % was achieved to differentiate those pancytopenia related diseases, even at the time that confirmed diagnosis cannot be made by routine clinical examinations. Therefore, the proposed method has demonstrated great potential for the early differential diagnosis of pancytopenia related diseases, thus it has significant clinical importance for the timely and rational guidance on subsequent treatment to improve patient survival.

Study on the High-Efficiency Preparation of Superhydrophobic Polymer Thin Films by Continuous Micro/Nano Imprinting.

In order to improve the preparation efficiency, quality stability, and large-area preparation of superhydrophobic thin films, a roll-to-roll continuous micro-nano imprinting method for the efficient preparation of superhydrophobic polymer films is proposed. A wear-resistant mold roller with hierarchical microstructure is prepared by wire electrical discharge machining (WEDM). The rheological filling model is constructed for revealing the forming mechanism of superhydrophobic polymer films during continuous micro/nano imprinting. The effects of imprinting temperature, rolling speed and the surface texture size of the template on the surface texture formation rate of polymer films are analyzed. The experimental results show that, compared with other process methods, the template processed by WEDM shows excellent wear resistance. Moreover, the optimal micro/nano imprinting parameters are the mold temperature of 190 °C (corresponding film temperature of 85 ± 5 °C), rolling speed of 3 rpm and roller gap of 0.1 mm. The maximum contact angle of the polymer film is 154°. In addition, the superhydrophobic polymer thin film has been proven to have good self-cleaning and anti-icing performance.

Reductive prodrug and AIE copolymer nanoparticle for monitoring and chemotherapy.

Polymeric micelle systems for drug delivery, monitor and chemotherapy have gained significant attention, and reductive polymeric micelle systems have become particularly attractive due to their controlled release behavior without additional assistance. However, there are challenges in accurately controlling drug and probe release from the nanoparticles and determining the loading content of drug and probe. To address these issues, we have developed a reduction-responsive Pt(IV) prodrug-based polymeric delivery system that can be dynamically monitored using aggregation-induced emission luminogens (AIE) based bioprobes. These polymeric micelle can self-assemble into nanoparticles and release both bio-active Pt(II) drug and bio-probe upon reduction activation. TPE molecules released in the inner endo/lysosomal microenvironment aggregate and fluoresce upon irradiation, thus allowing real-time tracking of drug biodistribution without additional contrast agents. Advantages of this system include position-specific chemical bond cleavage, control of platinum content, and monitoring of drug reduction and biodistribution.

Human mutations in SLITRK3 implicated in GABAergic synapse development in mice.

This study reports on biallelic homozygous and monoallelic de novo variants in SLITRK3 in three unrelated families presenting with epileptic encephalopathy associated with a broad neurological involvement characterized by microcephaly, intellectual disability, seizures, and global developmental delay. SLITRK3 encodes for a transmembrane protein that is involved in controlling neurite outgrowth and inhibitory synapse development and that has an important role in brain function and neurological diseases. Using primary cultures of hippocampal neurons carrying patients' SLITRK3 variants and in combination with electrophysiology, we demonstrate that recessive variants are loss-of-function alleles. Immunostaining experiments in HEK-293 cells showed that human variants C566R and E606X change SLITRK3 protein expression patterns on the cell surface, resulting in highly accumulating defective proteins in the Golgi apparatus. By analyzing the development and phenotype of SLITRK3 KO (SLITRK3-/-) mice, the study shows evidence of enhanced susceptibility to pentylenetetrazole-induced seizure with the appearance of spontaneous epileptiform EEG as well as developmental deficits such as higher motor activities and reduced parvalbumin interneurons. Taken together, the results exhibit impaired development of the peripheral and central nervous system and support a conserved role of this transmembrane protein in neurological function. The study delineates an emerging spectrum of human core synaptopathies caused by variants in genes that encode SLITRK proteins and essential regulatory components of the synaptic machinery. The hallmark of these disorders is impaired postsynaptic neurotransmission at nerve terminals; an impaired neurotransmission resulting in a wide array of (often overlapping) clinical features, including neurodevelopmental impairment, weakness, seizures, and abnormal movements. The genetic synaptopathy caused by SLITRK3 mutations highlights the key roles of this gene in human brain development and function.

Emerging Drug Delivery Vectors: Engineering of Plant-Derived Nanovesicles and Their Applications in Biomedicine.

Extracellular vesicles can transmit intercellular information and transport biomolecules to recipient cells during various pathophysiological processes in the organism. Animal cell exosomes have been identified as potential nanodrugs delivery vehicles, yet they have some shortcomings such as high immunogenicity, high cytotoxicity, and complicated preparation procedures. In addition to exosomes, plant-derived extracellular vesicles (PDVs), which carry a variety of active substances, are another promising nano-transport vehicles emerging in recent years due to their stable physicochemical properties, wide source, and low cost. This work briefly introduces the collection and characterization of PDVs, then focuses on the application of PDVs as natural or engineered drug carriers in biomedicine, and finally discusses the development and challenges of PDVs in future applications.

Identification of potential biomarkers for neuromyelitis optica by quantitative proteomics.

OBJECTIVE: Neuromyelitis optica (NMO) was a serious autoimmune inflammatory condition affecting the central nervous system. Currently, there was a lack of diagnostic biomarkers for AQP4-IgG-negative NMO patients. METHODS: A comparative proteomic analysis was conducted on the CSF of 10 patients with NMO and 10 patients with non-inflammatory neurological disorders (NND) using tandem mass tagging technology. Differentially expressed proteins (DEPs) were analyzed using bioinformatic methods. The candidate proteins were then validated through ELISAs in a subsequent cohort of 160 samples, consisting of paired CSF and plasma samples from 50 NMO patients, CSF samples from 30 NND patients, and plasma samples from 30 healthy individuals. RESULTS: We identified 389 proteins via proteomics, screening 79 DEPs. NCAM1, SST and AHSG were selected as candidate molecules for further validation. Compared to NND patients, there were decreased levels of AHSG in CSF and increased levels of NCAM1 and SST in NMO patients. The ELISA results revealed significantly higher levels of AHSG, SST and NCAM1 in the CSF of the NMO group compared to the NND group. Similarly, the serum levels of these three proteins were also higher in the NMO group compared to the healthy control group. It was found that serum NCAM1 levels significantly decreased in patients with non-relapsed NMO compared to patients with relapsed NMO and CSF NCAM1 level increased in patients with bilateral NMO compared to patients with unilateral NMO. Furthermore, CSF SST levels increased in AQP4 antibody-positive NMO patients compared to AQP4 antibody-negative patients. INTERPRETATION: CSF NCAM1, serum NCAM1 and serum SST may serve as potential biomarkers for NMO patients and aid in the diagnosis of AQP4 antibody-negative NMO patients.

Pt,P-codoped carbon nitride nanoenzymes for fluorescence and colorimetric dual-mode detection of cholesterol.

Cholesterol is an important lipid compound found in a variety of foods, and its level in human blood is closely related to human health. Therefore, development of rapid and accurate POCT (point-of-care testing) methods for cholesterol detection is crucial for assessing food quality and early diagnosis of diseases, in particular, in a resource-limited environment. In this study, a smartphone-assisted colorimetric biosensor is constructed based on platinum,phosphorus-codoped carbon nitride (PtCNP2) for the rapid detection of cholesterol. Phosphorus-doped carbon nitride is prepared by thermal annealing of urea and NH4PF6, into which platinum is atomically dispersed by thermal refluxing. The obtained PtCNP2 exhibits an excellent peroxidase-like activity under physiological pH, whereby colorless o-phenylenediamine (OPD) is oxidized to colored 2,3-diaminophenazine (DAP) in the presence of hydrogen peroxide (H2O2), which can be produced during the oxidation of cholesterol by cholesterol oxidase. A smartphone-assisted visual sensing system is then constructed based on the color recognition software, and rapid on-site detection of cholesterol is achieved by reading the RGB values. Meanwhile, the generated DAP shows an apparent fluorescence signal and can realize highly sensitive detection of cholesterol by the change of the fluorescence signal intensity. Such a cholesterol sensor exhibits a wide linear detection range of 0.5-600 µg mL-1 and a low detection limit of 59 ng mL-1. The practicality of the sensor is successfully demonstrated in the rapid detection of cholesterol in serum and food.

First-line penpulimab combined with paclitaxel and carboplatin for metastatic squamous non-small-cell lung cancer in China (AK105-302): a multicentre, randomised, double-blind, placebo-controlled phase 3 clinical trial.

BACKGROUND: Penpulimab is a novel programmed death (PD)-1 inhibitor. This study aimed to establish the efficacy and safety of first line penpulimab plus chemotherapy for advanced squamous non-small-cell lung cancer. METHODS: This multicentre, randomised, double-blind, placebo-controlled, phase 3 clinical trial enrolled patients with locally advanced or metastatic squamous non-small-cell lung cancer from 74 hospitals in China. Eligible participants were aged 18-75 years, had histologically or cytologically confirmed locally advanced (stage IIIb or IIIc) or metastatic (stage IV) squamous non-small-cell lung cancer, were ineligible to complete surgical resection and concurrent or sequential chemoradiotherapy, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, did not have previous systemic chemotherapy for locally advanced or metastatic non-small-cell lung cancer, and had one or more measurable lesions according to RECIST (version 1.1). Participants were randomly assigned (1:1) to receive intravenous penpulimab 200 mg or placebo (excipient of penpulimab injection), plus paclitaxel 175 mg/m2 and carboplatin AUC of 5 intravenously on day 1 every 3 weeks for four cycles, followed by penpulimab or placebo as maintenance therapy. Stratification was done according to the PD-L1 tumour proportion score (<1% vs 1-49% vs ≥50%) and sex (male vs female). The participants, investigators, and other research staff were masked to group assignment. The primary outcome was progression-free survival assessed by the masked Independent Radiology Review Committee in the intention-to-treat population and patients with a PD-L1 tumour proportion score of 1% or more (PD-L1-positive subgroup). The primary analysis was based on the intention-to-treat analysis set (ie, all randomly assigned participants) and the PD-L1-positive subgroup. The safety analysis included all participants who received at least one dose of study drug after enrolment. This trial was registered with ClinicalTrials.gov (NCT03866993). FINDINGS: Between Dec 20, 2018, and Oct 10, 2020, 485 patients were screened, and 350 participants were randomly assigned (175 in the penpulimab group and 175 in the placebo group). Of 350 participants, 324 (93%) were male and 26 (7%) were female, and 347 (99%) were of Han ethnicity. In the final analysis (June 1, 2022; median follow-up, 24·7 months [IQR 0-41·4]), the penpulimab group showed an improved progression-free survival compared with the placebo group, both in the intention-to-treat population (median 7·6 months, 95% CI 6·8--9·6 vs 4·2 months, 95% CI 4·2-4·3; HR 0·43, 95% CI 0·33-0·56; p<0·0001) and in the PD-L1-positive subgroup (8·1 months, 5·7-9·7 vs 4·2 months, 4·1-4·3; HR 0·37, 0·27-0·52, p<0·0001). Grade 3 or worse treatment-emergent adverse events occurred in 120 (69%) 173 patients in the penpulimab group and 119 (68%) of 175 in the placebo group. INTERPRETATION: Penpulimab plus chemotherapy significantly improved progression-free survival in patients with advanced squamous non-small-cell lung cancer compared with chemotherapy alone. The treatment was safe and tolerable. Penpulimab combined with paclitaxel and carboplatin is a new option for first-line treatment in patients with this advanced disease. FUNDING: The National Natural Science Foundation of China, Shanghai Municipal Health Commission, Chia Tai Tianqing Pharmaceutical, Akeso.

Downregulating DNA methyltransferase 3B by suppressing the PI3K/Akt signaling pathway enhances the chemosensitivity of glioblastoma to temozolomide.

Glioblastoma (GBM) is the most common malignant brain tumor and has the poorest prognosis attributed to its chemoresistance to temozolomide (TMZ), the first-line drug for treating GBM. TMZ resistance represents a significant obstacle to successful GBM treatment, necessitating the development of new strategies to overcome this resistance and augment the chemosensitivity of GBM cells to TMZ. This study established a TMZ-resistant U251 (U251-TMZ) cell line by exposing it to increasing doses of TMZ in vitro. We focused on the DNA methyltransferase 3B (DNMT3B) gene, phosphorylated Akt (p-Akt), total Akt (t-Akt), phosphorylated PI3K (p-PI3K), and total PI3K (t-PI3K) protein expression. Results showed that the DNMT3B gene was significantly upregulated in the U251-TMZ cell line. The p-Akt and p-PI3K protein expression in U251-TMZ cells was also significantly elevated. Moreover, we found that DNMT3B downregulation was correlated with the increased chemosensitivity of GBM cells to TMZ. LY294002 suppressed the PI3K/Akt signaling pathway, leading to a notable inhibition of PI3K phosphorylation and a significant decrease in DNMT3B expression in U251-TMZ cells. Given that DNMT3B expression is mediated by the PI3K/Akt signaling pathway, its downregulation further increased the chemosensitivity of GBM cells to TMZ and therefore is a promising therapeutic for GBM treatment. Our results suggested that DNMT3B downregulation can inhibit the proliferation of GBM cells and induce GBM cell apoptosis in vitro. In addition, the PI3K/Akt signaling pathway plays an important role in the chemosensitivity of GBM cells to TMZ by regulating DNMT3B expression.

Effects of transcutaneous auricular vagus nerve stimulation and exploration of brain network mechanisms in children with high-functioning autism spectrum disorder: study protocol for a randomized controlled trial.

Background: Autism Spectrum Disorders (ASD) are a collection of neurodevelopmental diseases characterized by poor social interaction and communication, a limited range of interests, and stereotyped behavior. High-functioning autism (HFA) indicates a subgroup of individuals with autism who possess cognitive and/or language skills that are within the average to above-normal range for their age. Transcutaneous auricular vagus nerve stimulation (taVNS) holds promise in children with HFA. However, few studies have used randomized controlled trials to validate the effectiveness of taVNS. Therefore, in this study, we intend to provide a study protocol to examine the therapeutic effects of taVNS in individuals diagnosed with HFA and to investigate the process of brain network remodeling in individuals with ASD using functional imaging techniques to observe alterations in large-scale neural networks. Methods and design: We planned to employ a randomized, double-blind experimental design, including 40 children receiving sham stimulation and 40 children receiving real stimulation. We will assess clinical scales and perform functional imaging examinations before and after the stimulation. Additionally, we will include age- and gender-matched healthy children as controls and conduct functional imaging examinations. We plan first to observe the therapeutic effects of taVNS. Furthermore, we will observe the impact of taVNS stimulation on the brain network. Discussion: taVNS was a low-risk, easy-to-administer, low-cost, and portable option to modulate the vagus system. taVNS may improve the social performance of HFA. Changes in the network properties of the large-scale brain network may be related to the efficacy of taVNS. Clinical trial registration: http://www.chictr.org.cn, identifier ChiCTR2300074035.

Profiles of Cough and Associated Risk Factors in Nonhospitalized Individuals With SARS-CoV-2 Omicron Variant Infection: Cross-Sectional Online Survey in China.

BACKGROUND: Cough is a common symptom during and after COVID-19 infection; however, few studies have described the cough profiles of COVID-19. OBJECTIVE: The aim of this study was to investigate the prevalence, severity, and associated risk factors of severe and persistent cough in individuals with COVID-19 during the latest wave of the Omicron variant in China. METHODS: In this nationwide cross-sectional study, we collected information of the characteristics of cough from individuals with infection of the SARS-CoV-2 Omicron variant using an online questionnaire sent between December 31, 2022, and January 11, 2023. RESULTS: There were 11,718 (n=7978, 68.1% female) nonhospitalized responders, with a median age of 37 (IQR 30-47) years who responded at a median of 16 (IQR 12-20) days from infection onset to the time of the survey. Cough was the most common symptom, occurring in 91.7% of participants, followed by fever, fatigue, and nasal congestion (68.8%-87.4%). The median cough visual analog scale (VAS) score was 70 (IQR 50-80) mm. Being female (odds ratio [OR] 1.31, 95% CI 1.20-1.43), having a COVID-19 vaccination history (OR 1.71, 95% CI 1.37-2.12), current smoking (OR 0.48, 95% CI 0.41-0.58), chronic cough (OR 2.04, 95% CI 1.69-2.45), coronary heart disease (OR 1.71, 95% CI 1.17-2.52), asthma (OR 1.22, 95% CI 1.02-1.46), and gastroesophageal reflux disease (GERD) (OR 1.21, 95% CI 1.01-1.45) were independent factors for severe cough (VAS>70, 37.4%). Among all respondents, 35.0% indicated having a productive cough, which was associated with risk factors of being female (OR 1.44, 95% CI 1.31-1.57), having asthma (OR 1.84, 95% CI 1.52-2.22), chronic cough (OR 1.44, 95% CI 1.19-1.74), and GERD (OR 1.22, 95% CI 1.01-1.47). Persistent cough (>3 weeks) occurred in 13.0% of individuals, which was associated with the risk factors of having diabetes (OR 2.24, 95% CI 1.30-3.85), asthma (OR 1.70, 95% CI 1.11-2.62), and chronic cough (OR 1.97, 95% CI 1.32-2.94). CONCLUSIONS: Cough is the most common symptom in nonhospitalized individuals with Omicron SARS-CoV-2 variant infection. Being female, having asthma, chronic cough, GERD, coronary heart disease, diabetes, and a COVID-19 vaccination history emerged as independent factors associated with severe cough, productive cough, and persistent cough.

Effects of landscape pattern on water quality at multi-spatial scales in Wuding River Basin, China.

Urbanization and agricultural land use have led to water quality deterioration. Studies have been conducted on the relationship between landscape patterns and river water quality; however, the Wuding River Basin (WDRB), which is a complex ecosystem structure, is facing resource problems in river basins. Thus, the multi-scale effects of landscape patterns on river water quality in the WDRB must be quantified. This study explored the spatial and seasonal effects of land use distribution on river water quality. Using the data of 22 samples and land use images from the WDRB for 2022, we quantitatively described the correlation between river water quality and land use at spatial and seasonal scales. Stepwise multiple linear regression (SMLR) and redundancy analyses (RDA) were used to quantitatively screen and compare the relationships between land use structure, landscape patterns, and water quality at different spatial scales. The results showed that the sub-watershed scale is the best spatial scale model that explains the relationship between land use and water quality. With the gradual narrowing of the spatial scale range, cultivated land, grassland, and construction land had strong water quality interpretation abilities. The influence of land use type on water quality parameter variables was more distinct in rainy season than in the dry season. Therefore, in the layout of watershed management, reasonably adjusting the proportion relationship of vegetation and artificial building land in the sub-basin scale and basin scope can realize the effective control of water quality optimization.

Recent advances in the precision control strategy of artificial pancreas.

The scientific diagnosis and treatment of patients with diabetes require frequent blood glucose testing and insulin delivery to normoglycemia. Therefore, an artificial pancreas with a continuous blood glucose (BG) monitoring function is an urgent research target in the medical industry. The problem of closed-loop algorithmic control of the BG with a time delay is a key and difficult issue that needs to be overcome in the development of an artificial pancreas. Firstly, the composition, structure, and control characteristics of the artificial pancreas are introduced. Subsequently, the research progress of artificial pancreas control algorithms is reviewed, and the characteristics, advantages, and disadvantages of proportional-integral-differential control, model predictive control, and artificial intelligence control are compared and analyzed to determine whether they are suitable for the practical application of the artificial pancreas. Additionally, key advancements in areas such as blood glucose data monitoring, adaptive models, wearable devices, and fully automated artificial pancreas systems are also reviewed. Finally, this review highlights that meal prediction, control safety, integration, streamlining the optimization of control algorithms, constant temperature preservation of insulin, and dual-hormone artificial pancreas are issues that require further attention in the future.

A High-Resolution 3D Ultrasound Imaging System Oriented towards a Specific Application in Breast Cancer Detection Based on a 1 × 256 Ring Array.

This paper presents the design and development of a high-resolution 3D ultrasound imaging system based on a 1 × 256 piezoelectric ring array, achieving an accuracy of 0.1 mm in both ascending and descending modes. The system achieves an imaging spatial resolution of approximately 0.78 mm. A 256 × 32 cylindrical sensor array and a digital phantom of breast tissue were constructed using the k-Wave toolbox. The signal is acquired layer by layer using 3D acoustic time-domain simulation, resulting in the collection of data from each of the 32 layers. The 1 × 256 ring array moves on a vertical trajectory from the chest wall to the nipple at a constant speed. A data set was collected at intervals of 1.5 mm, resulting in a total of 32 data sets. Surface rendering and volume rendering algorithms were used to reconstruct 3D ultrasound images from the volume data obtained via simulation so that the smallest simulated reconstructed lesion had a diameter of 0.3 mm. The reconstructed three-dimensional image derived from the experimental data exhibits the contour of the breast model along with its internal mass. Reconstructable dimensions can be achieved up to approximately 0.78 mm. The feasibility of applying the system to 3D breast ultrasound imaging has been demonstrated, demonstrating its attributes of resolution, precision, and exceptional efficiency.

A Drug Molecule-Modified Graphene Field-Effect Transistor Nanosensor for Rapid, Label-Free, and Ultrasensitive Detection of Estrogen Receptor α Protein.

Estrogen receptor α (ERα) is an important biomarker in breast cancer diagnosis and treatment. Sensitive and accurate detection of ERα protein expression is crucial in guiding selection of an appropriate therapeutic strategy to improve the effectiveness and prognosis of breast cancer treatment. Herein, we report a liquid-gated graphene field-effect transistor (FET) biosensor that enables rapid, sensitive, and label-free detection of the ERα protein by employing a novel drug molecule as a capture probe. The drug molecule was synthesized and subsequently immobilized onto the sensing surface of the fabricated graphene FET, which was able to distinguish the ERα-positive from the ERα-negative protein. The developed sensor not only demonstrated a low detection limit (LOD: 2.62 fM) but also achieved a fast response to ERα protein samples within 30 min. Moreover, depending on the relationship between the change of dirac point and the ERα protein concentrations, the dissociation constant (Kd) was estimated to be 7.35 ± 0.06 pM, indicating that the drug probe-modified graphene FET had a good affinity with ERα protein. The nanosensor was able to analyze ERα proteins from 36 cell samples lysates. These results show that the graphene FET sensor was able to differentiate between ERα-positive and ERα-negative cells, indicating a promising biosensor for the ultrasensitive and rapid detection of ERα protein without antibody labeling.

Plug-and-play smart transistor bio-chips implementing point-of-care diagnosis of AMI with modified CRISPR/Cas12a system.

The point-of-care diagnosis of acute myocardial infarction (AMI), an extremely lethal disease with only a few hours of golden rescue time, is significant and urgently required. Here, we describe a plug-and-play carbon nanotube field effect transistor (CNT-FET) bio-chip supported with a smart portable readout for ultrasensitive and on-site testing of cardiac troponin I (cTnI), which is one of the most specific and valuable biomarkers of AMI. A modified clustered regularly interspaced short palindromic repeats (CRISPR)/Cas12a system, featuring the G-triplex structured reporter, was first combined with the CNT-FET to realize non-nucleic acid detection. Such a unique CNT-FET biosensor achieved the high sensitivity (LOD: 0.33 fg/mL), which is expected to give timely warning in the early stage of myocardial injury. In addition, a bilayer gate dielectric consisting of Y2O3/HfO2, employed into the passivation process, enabled the high environmental stability and repeatability of CNT-FET. More importantly, the homemade compact chip readout forged a field-deployable cTnI analytical tool, realizing "plasma-to-answer" performance for AMI patients in point-of-care testing scenarios. The developed technology holds promise to help doctors make clinical decisions faster, especially in remote areas.

Characterization of three glutathione S-transferases potentially associated with adaptation of the wheat blossom midge Sitodiplosis mosellana to host plant defense.

BACKGROUND: Insect glutathione S-transferases (GSTs), a multifunctional protein family, play a crucial role in detoxification of plant defensive compounds. However, they have been rarely investigated in Sitodiplosis mosellana, a destructive pest of wheat worldwide. In this study, we characterized for the first time a delta (SmGSTd1) and two epsilon GST genes (SmGSTe1 and SmGSTe2) and analyzed their expression patterns and functions associated with adaptation to host plant defense in this species. RESULTS: Expression of these SmGST genes greatly increased in S. mosellana larvae feeding on resistant wheat varieties Kenong1006, Shanmai139 and Jinmai47 which contain higher tannin and ferulic acid, the major defensive compounds of wheat against this pest, compared with those feeding on susceptible varieties Xinong822, Xinong88 and Xiaoyan22. Their expression was also tissue-specific, most predominant in larval midgut. Recombinant SmGSTs expressed in Escherichia coli could catalyze the conjugation of 1-chloro-2,4-dinitrobenzene, with activity peak at pH around 7.0 and temperature between 30 and 40 °C. Notably, they could metabolize tannin and ferulic acid, with the strongest metabolic ability by SmGSTe2 against two compounds, followed by SmGSTd1 on tannin, and SmGSTe1 on ferulic acid. CONCLUSION: The results suggest that these SmGSTs are important in metabolizing wheat defensive chemicals during feeding, which may be related to host plant adaptation of S. mosellana. Our study has provided information for future investigation and development of strategies such as host-induced gene silencing of insect-detoxifying genes for managing pest adaptation. © 2023 Society of Chemical Industry.

Serum apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) is a novel stroke biomarker.

BACKGROUND: Apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) is a promising stroke biomarker. However, a large study of human serum ASC has not yet to be reported; additionally, the diagnostic value of prehospital concentration and practicality of ASC remains unknown. METHODS: We recruited 774 Chinese stroke patients, including 523 with ischemic stroke (IS) and 251 with hemorrhagic stroke (HS) within 14 days following symptom onset in the emergency department, alongside 481 healthy individuals and 64 cognitive impairment patients as controls. Serum ASC concentrations were determined using automated chemiluminescence immunoassay, exploring the relationship between serum ASC concentration and subtypes, severity, and sampling timepoints of stroke. RESULTS: ASC concentrations were significantly higher in stroke patients compared with all controls (P < 0.001). HS patients had greater ASC concentrations than IS patients (P < 0.05). With increasing ASC concentration, the proportion of severe cases increased. The area under the receiver operating characteristic curve (AUC) for differentiating between healthy individuals and stroke patients in the hyperacute phase was 0.78; this markedly improved (0.90) when considering samples from healthy individuals and patients with subarachnoid hemorrhage (SAH) ≤ 3  h from last-known-well (LKW). CONCLUSIONS: Serum ASC is a valuable biomarker for stroke differentiation and aids in the clinical diagnosis of stroke severity and subtypes.

Diagnostic and Monitoring Value of ß-2 Transferrin and Transferrin for Intracranial Infection After Neurosurgery.

BACKGROUND AND OBJECTIVES: After neurosurgery, intracranial infection is a common complication with high rates of clinical impairment and death. Traditional diagnostic approaches are time-consuming. Early and correct diagnosis improves infection control, treatment success, and survival. Novel markers are used to diagnose and classify post-neurosurgical meningitis (PNM) to overcome the difficulties of diagnosing postoperative intracranial infections and avoid the drawbacks of existing diagnostic measures. The objective was to investigate the diagnostic value of ß-2 transferrin (ß-2TF) and transferrin (TF) in the cerebrospinal fluid (CSF) for the identification of intracranial infection after neurosurgery. METHODS: Owing to their symptoms and laboratory results, 168 patients with suspected intracranial infection after neurosurgery were divided into 3 groups: post-neurosurgical bacterial meningitis (PNBM; n = 61), post-neurosurgical aseptic meningitis (PNAM; n = 45), and non-PNM (n = 62). We measured lactate (LA), ß-2TF, and TF levels in the CSF. RESULTS: CSF LA levels were significantly higher in the PNM, PNBM, and PNAM groups compared with the non-PNM group (P < .05). The CSF ß-2TF level in PNM, PNBM, and PNAM were statistically higher than those in non-PNMs (P < .05). CSF TF levels in the PNBM group were statistically higher than those in the PNAM and non-PNM groups (P < .05). The PNBM and non-PNM receiver operating curve (ROC) analysis indicates that the cutoff values for the combination (LA, ß-2TF, TF) was 0.347, and the area under the curve (AUC) was 0.945 (P < .0001), with 92.86% sensitivity and 92.98% specificity. The PNAM and non-PNM ROC analysis indicates that the cutoff values for the combination (LA, ß-2TF, TF) was 0.346, and the AUC was 0.942 (P < .0001), with 89.29% sensitivity and 90.24% specificity. The PNM and non-PNM ROC analysis indicates that the cutoff values for the combination (LA, ß-2TF, TF) was 0.609, and the AUC was 0.941 (P < .0001), with 96.36% sensitivity and 82.83% specificity. A Glasgow Coma Scale score ≤8, LA, ß-2TF/TF ratio, length of hospital stay, intensive care unit admission, poor surgical wound, and craniotomy were associated with poor outcomes (P < .05). LA and ß-2TF were independent risk factors for intracranial infection. CONCLUSION: Postoperative cerebral infections can be identified using CSF ß-2TF as a particular marker protein. CSF TF helps distinguish PNBM from PNAM. Combining CSF LA with them improves diagnostic speed, sensitivity, and accuracy. LA and ß-2TF were independent risk factors for cerebral infection.