Examining attentional control deficits in adolescents with test anxiety: An evidential synthesis using self-report, behavioral, and resting-state EEG measures.

Attentional control theory suggests that test anxiety hinders individuals' attentional control, aiding our understanding of how test anxiety may impair cognitive function. However, various methods used to assess attentional control have yielded inconsistent findings. Moreover, past studies, especially on adolescents, that examine the distinct impacts of worry and the emotional components of test anxiety on individuals' attentional control capacity are scarce. This study, using self-report, behavioral, and resting-state EEG measures, explores how worry and emotionality, impact attentional control in adolescents. It enhances our understanding of the link between test anxiety and cognitive function. Referring to the effect size from prior studies, a total of 42 adolescents took part in the study. We used the Test Anxiety Inventory, due to it can assess worry and emotionality components. We employed three widely-utilized measures of attentional control: the Attentional Control Scale (ACS), the Go/Nogo task, and resting-state electroencephalography measures (alpha oscillation and the theta/beta power ratio). Both worry and emotionality components were significantly and negatively correlated with the ACS scores. Unlike worry, emotionality demonstrated a significant positive correlation with response times for the Go trials and alpha power in the parietal cortex. These results suggest that, emotionality, but not worry, is highly correlated with attentional control deficits in adolescents. This study underscores the significance of distinguishing between the components of test anxiety, which aids in comprehending the negative impacts of test anxiety on adolescents' academic performance.

Decreased serum tryptophan levels in patients with MOGAD:a cross-sectional survey.

BACKGROUND: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an inflammatory demyelinating disorder of central nervous system (CNS). Tryptophan indole catabolites have been reported to associate with the inflammatory diseases of the CNS. However, the roles of tryptophan indole catabolites have been rarely elucidated in MOGAD. METHODS: This cross-sectional study enrolled forty MOGAD patients, twenty patients with other non-inflammatory neurological diseases (OND) and thirty-five healthy participants. Serum and cerebrospinal fluid (CSF) samples of MOGAD and OND subjects during clinical attacks, serum samples of healthy participants were obtained. The concentrations of tryptophan, indoleacetic acid (IAA), indoleacrylic acid (IA) and indole-3-carboxylic acid (I-3-CA) were measured using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The correlations between tryptophan indole catabolites and maintenance immunotherapy, disease duration, overall numbers of attacks, short-term outcome in MOGAD patients were investigated. RESULTS: Levels of serum tryptophan, IAA, IA and CSF tryptophan in MOGAD patients were significantly decreased, while levels of serum I-3-CA and CSF IA were markedly increased compared with OND patients and healthy controls. Levels of serum tryptophan, CSF tryptophan and IA were significantly decreased in MOGAD patients who had received maintenance immunotherapy within 6 months before the attack. In MOGAD patients, serum and CSF tryptophan conversely correlated with disease duration and overall numbers of attacks, and serum IA negatively correlated with disease duration. Furthermore, serum tryptophan in MOGAD patients negatively correlated with the modified Rankin Scale (mRS) scores at 3 months. CONCLUSION: This study manifested decreased serum tryptophan levels and serum tryptophan may be the potential marker to predict the short-term outcome in MOGAD patients.

Time-series analysis of the association between air pollution exposure and outpatient visits for dry eye disease: a case study in Zhengzhou, China.

Background: Dry eye disease (DED) is a prevalent ocular surface disease that significantly impacts patients' quality of life. The association between air pollution and the risk of dry eye disease remains uncertain. Methods: Data on outdoor air pollutants, meteorological information, and outpatient visits for DED were collected from July 1, 2014, to December 31, 2019. The relationship between ambient air pollutants and DED outpatient visits was analyzed using a generalized additive model with a Poisson distribution. Results: Among the 5,204 DED patients included in the study, 63.76% were female and 36.24% were male. The single-pollutant model revealed a significant association between a 10 µg/m3 increase in concentrations of fine-particulate matter with a median aerometric diameter of less than 10 µm (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), and carbon monoxide (CO) and outpatient visits for DED. Fine-particulate matter with a median aerometric diameter of less than 2.5 µm (PM2.5) showed a significant association with DED outpatient visits in males and the 19-59 years age group. The strongest associations between air pollutants and outpatient visits were observed in male patients and during the cold season. Conclusion: The noteworthy correlation between air pollutants and DED outpatient visits can offer evidence for policy makers and underscore the significance of reinforcing environmental protection.

The landscape of PBMCs in AQP4-IgG seropositive NMOSD and MOGAD, assessed by high dimensional mass cytometry.

OBJECTIVES: Data on peripheral blood mononuclear cells (PBMCs) characteristics of aquaporin-4 (AQP4)-IgG seropositive neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are lacking. In this study, we describe the whole PBMCs landscape of the above diseases using cytometry by time-of-flight mass spectrometry (CyTOF). METHODS: The immune cell populations were phenotyped and clustered using CyTOF isolated from 27 AQP4-IgG seropositive NMOSD, 11 MOGAD patients, and 15 healthy individuals. RNA sequencing was employed to identify critical genes. Fluorescence cytometry and qPCR analysis were applied to further validate the algorithm-based results that were obtained. RESULTS: We identified an increased population of CD11b+ mononuclear phagocytes (MNPs) in patients with high expression of CCR2, whose abundance may correlate with brain inflammatory infiltration. Using fluorescence cytometry, we confirmed the CCR2+ monocyte subsets in a second cohort of patients. Moreover, there was a wavering of B, CD4+ T, and NKT cells between AQP4-IgG seropositive NMOSD and MOGAD. CONCLUSIONS: Our findings describe the whole landscape of PBMCs in two similar demyelinated diseases and suggest that, besides MNPs, T, NK and B, cells were all involved in the pathogenesis. The identified cell population may be used as a predictor for monitoring disease development or treatment responses.

Antibiotic susceptibility and genomic analysis of ciprofloxacin-resistant and ESBLs-producing Escherichia coli in vegetables and their irrigation water and growing soil.

The rise of antibiotic resistance in Escherichia coli has become a major global public health concern. While there is extensive research on antibiotic-resistant E. coli from human and animal sources, studies on vegetables and their environments are limited. This study investigated the prevalence and characteristics of ciprofloxacin-resistant (CIPR) E. coli in 13 types of edible raw vegetables, along with their irrigation water and soil in Shaanxi, China. Of 349 samples collected (157 vegetables, 59 water, and 133 soil), a total of 48 positive samples were detected, with one CIPRE. coli strain isolated from each sample being selected for further analyses. A striking observation was its high prevalence in irrigation water at 44.1 %, markedly exceeding that in vegetables (12.0 %) and soil (4.5 %). The susceptibility of Forty-eight CIPRE. coli isolates was evaluated using the disc diffusion method for 18 different antibiotics, all these isolates were not only resistant to the tested fluoroquinolones antibiotics (levofloxacin, nalidixic acid), but also displayed a multi-drug resistance (MDR) pattern. Twenty-eight (58.3 %) of 48 CIPRE. coli isolates exhibited extended spectrum ß-lactamases (ESBLs) (CIPR-ESBLs) producing phenotype. Subsequently, whole-genome sequencing was performed on these 28 isolates. We identified 12 serotypes and STs each, with O101: H9 (35.7 %, 10/28) and ST10 (21.4 %, 6/28) being the most common. Further classification placed these isolates into five phylogenetic groups: A (57.1 %, 16/28), B1 (32.1 %, 9/28), D (3.6 %, 1/28), B2 (3.6 %,1/28), and F (3.6 %,1/28). Notelly, Identical ST types, serotypes and phylogroups were found in certain CIPR-ESBLs-producing E. coli from both vegetables and adjacent irrigation water. Genomic analysis of the 28 CIPR-ESBLs-producing E. coli isolates unveiled 73 resistance genes, associated with 13 amino acid mutations in resistance-determining regions (QRDRs) and resistance to 12 types of antibiotics. Each isolate was confirmed to carry both ESBLs and fluoroquinolone resistance genes, with the Ser83Ala mutation in GyrA (96.4 %, 27/28) being the most prevalent. A detailed analysis of Mobile Genetic Elements (MGEs) revealed that IncFIB and IncFII plasmid subtypes were most prevalent in 60.7 % and 67.9 % of isolates, respectively, with 75 % containing over 10 insertion sequences (IS) each. Furthermore, we observed that certain ESBL and PMQR genes were located on plasmids or in proximity to insertion sequences. In conclusion, our research highlights the widespread presence of CIPRE. coli in irrigation water and thoroughly examines the genetic characteristics of CIPR-ESBLs-producing E. coli strains, underlining the need for ongoing monitoring and management to reduce multidrug-resistant bacteria in vegetables and their environment.

Radiation-Activated Resiquimod Prodrug Nanomaterials for Enhancing Immune Checkpoint Inhibitor Therapy.

Immune checkpoint inhibitor (ICI) therapy is effectively employed in treating various malignancies. However, the response rate is constrained to 5-30%, which is attributed to differences in immune responses across different tumors. Overcoming all obstacles of multistep immune activation with monotherapy is difficult. Here, maleimide-modified resiquimod (R848) prodrug nanoparticles (MAL-NPs) are reported and combined with radiotherapy (RT) and anti-PD1 to enhance ICI therapy. MAL-NPs can promote antigen endocytosis by dendritic cells and are radio-reduced to produce R848. When combined with RT, MAL-NPs can augment the concentration of nanoparticles at tumor sites and be selectively radio-reduced within the tumor, thereby triggering a potent antitumor immune response. The systemic immune response and long-term memory efficacy induced by MAL-NPs + RT + anti-PD1 significantly inhibit the abscopal tumor growth and prevent tumor recurrence. This strategy can achieve systemic therapy through selective training of the tumor immune microenvironment, offering a new approach to overcome the obstacles of ICI therapy.

Acupoint transplantation versus non-acupoint transplantation using autologous peripheral blood mononuclear cells in treating peripheral arterial disease.

Numerous studies have discussed the therapeutic outcomes of using cell therapy or acupuncture to treat peripheral artery disease (PAD). However, there are no long-term studies on the safety and efficacy of transplanting peripheral blood mononuclear cells (PBMNCs) via acupoints to treat PAD. We first reviewed the short-term and long-term clinical results of PAD patients treated with PBMNCs through intramuscular non-acupoint transplantation (control group; n = 45) or intramuscular acupoint transplantation (acupoint group; n = 45) at a single university hospital general medical center between December 2002 and September 2022. Pain intensity (assessed with the verbal rating scale [VRS] score) in the acupoint group was considerably lower than that in the control group at month 1 (mean ± standard deviation [SD]: 1.29 ± 0.96 vs 1.76 ± 0.82; P = 0.016) and month 3 (mean ± SD: 1.27 ± 0.90 vs 1.61 ± 0.86; P = 0.042). We observed significant improvement of VRS score (P < .001 for all) and ankle-brachial index (ABI; P < .001 for all) from baseline in both groups at months 1, 3, 6, 12, 36, and 60. The 10-year cumulative rate of major amputation-free survival (MAFS) was higher in the acupoint group as compared to the control group (81.9%, 95% confidence interval [CI]: 71.3%-94.1% vs 78.5%, 95% CI: 66.7%-92.3%; P = 0.768). Compared with the routine injection method, intramuscular transplantation of PBMNCs via selected acupoints could significantly decrease the short-term pain intensity in patients with PAD, which remains an option for consideration.

Additive value of single intralesional bleomycin injection to propranolol in the management of proliferative infantile hemangioma.

BACKGROUND: /Objective: We aimed to evaluate whether additional intralesional bleomycin injections benefit children with proliferative infantile hemangiomas (IHs). METHODS: In this retrospective case-control study, we examined the medical records of 216 infants who were followed up for proliferative IH. Patients in group 1 were treated with propranolol orally at 2 mg/kg/day. Group 2 was treated with oral propranolol combined with intralesional bleomycin injections. RESULTS: We retrospectively reviewed 95 and 121 patients in groups 1 and 2, respectively. No significant differences were observed between both groups regarding visiting age, sex, lesion thickness, or risk site. The overall cure rates in groups 1 and 2 were 77.89% (74/95) and 84.30% (102/121), respectively. The overall distribution of the length of cure significantly differed between both groups (P = 0.035). From the survival analysis (P = 0.026), the median survival time was 198 days (95% confidence interval (CI) 174.46-221.54) for group 1 and 139 days (95% CI 114.58-163.42) for group 2. The effect of treatment modality (hazard ratio (HR) = 1.41, P = 0.031) and risk site on survival time (HR = .54, P < 0.001) was significant. CONCLUSION: No significant differences were observed in the resolution of proliferative IH; however, intralesional bleomycin injection with systemic propranolol for proliferative IH treatment may provide a more rapid resolution.

Hypoxia-activated glutamine antagonist prodrug combined with combretastatin A4 nanoparticles for tumor-selective metabolic blockade.

6-Diazo-5-oxo-L-norleucine (DON) is a potent glutamine antagonist with toxic side effects; in order to reduce these effects, multiple prodrugs have been designed. However, there are currently no reports of a DON prodrug with a defined mechanism to achieve high tumor selectivity. To improve the selective toxicity of DON to tumor cells while reducing systemic toxicity, a hypoxia-activated prodrug, termed HDON, was designed. HDON achieved remarkable tumor suppression of 76.4 ± 5.2% without leading to weight loss in an H22 murine liver cancer model with high hypoxia. Moreover, to augment the therapeutic efficacy of HDON, combretastatin A4 nanoparticles were used to aggravate tumor hypoxia of MC38 murine colon cancer and 4T1 murine breast cancer, activate HDON to DON, and stimulate a robust anti-tumor immune response while selectively killing in tumor cells in vivo, achieving significantly elevated tumor suppression rates of 98.3 ± 3.4% and 98.1 ± 3.1%, with cure rates of 80.0% and 20.0%, respectively.

The risk of muscle involvement in focal venous malformations in children.

BACKGROUND: Venous malformations (VMs) are the most common vascular malformations, which can be classified as focal, multifocal, or diffuse types. But the risk of focal venous malformations with muscle involvement is not well defined. METHODS: This is a single-center, retrospective review of patients treated for focal VMs between February 2021 and February 2022. RESULTS: We assessed 26 patients focal VMs with 47 lesions; 18 (69%) were unifocal, 3 (12%) were dual-focal, and 5 (19%) were multifocal type VMs, and 29 (62%) were intramuscular VMs. The lower limbs intramuscular VMs had a significantly elevated risk of focal VMs (relative risk [RR],1.7; 95% confidence interval [CI], 1.148-2.394). CONCLUSION: Intramuscular involvement of the body should be considered in focal VMs. The lower limbs intramuscular VMs had a significantly elevated risk of focal VMs.

Sequence and directivity in cardiac muscle injury of COVID-19 patients: an observational study.

Objective: To compare cardiac function indicators between mild and moderate to severe COVID-19 patients and to try to identify the sequence and directivity in cardiac muscle injury of COVID-19 patients. Methods: From December 2022 to January 2023, all patients with laboratory-confirmed SARS-CoV-2 infection in Shanghai General Hospital Jiading Branch were enrolled. The clinical classification was stratified into mild, moderate, or severe groups. We collected the clinical and laboratory information, transthoracic echocardiographic and speckle-tracking echocardiographic parameters of patients and compared the differences among different groups. Results: The values of echocardiographic parameters in mild group were lower than that in moderate or severe group (P < 0.05) except LVEF. The values of LVEF of mild and moderate group were higher than severe group (P < 0.05). There were no significant differences between moderate and severe group. Positive correlations were observed between left ventricular global longitudinal strain (LVGLS) and myoglobin (r = 0.72), E/e' and age (r = 0.79), E/e' and BNP (r = 0.67). The multivariate analysis shows that SpO2 (OR = 0.360, P = 0.02), LVGLS (OR = 3.196, P = 0.003) and E/e' (OR = 1.307, P = 0.036) were the independent risk factors for mild cases progressing to moderate or severe. According to the receiver operating characteristic (ROC) curves, when all the COVID-19 patients was taken as the sample size, the area under the curve (AUC) of the LVGLS was the highest (AUC = 0.861). The AUC of the LVGLS was higher than LVGCS (AUC = 0.565, P < 0.001). Conclusion: When mild COVID-19 progresses to moderate or severe, both systolic and diastolic functions of the heart are impaired. LVGLS was the independent risk factor for mild cases progressing to moderate or severe cases. Longitudinal changes may manifest earlier than circumferential changes as myocardial disease progresses in COVID-19.

Multimodal MRI study of the relationship between plaque characteristics and hypoperfusion in patients with transient ischemic attack.

Objective: Transient ischemic attack is a significant risk factor for acute cerebral infarction. Previous studies have demonstrated that hypoperfusion in patients with transient ischemic attack was associated with the recurrence of transient ischemic attack, stroke, and persistent worsening of neurological symptoms. Moreover, transient ischemic attack patients classified as high-risk group according to the ABCD2 score have a higher incidence of stroke. Therefore, the objective of this study was to investigate the plaque characteristics of transient ischemic attack patients with concomitant cerebral hypoperfusion using multimodal MRI, as well as hemodynamic changes in the high-risk group with transient ischemic attack patients. Materials and methods: A total of 151 patients with transient ischemic attack were prospectively recruited for this study. All enrolled patients underwent multimodal MRI, including DWI, TOF-MRA, HR-VWI, and DSC-PWI. Finally, 56 patients met the inclusion criteria. Based on DSC-PWI images, patients were divided into two groups: hypoperfusion (n = 41) and non-hypoperfusion (n = 15). Clinical baseline characteristics and plaque characteristics were analyzed between the two groups. Furthermore, within the hypoperfusion group, patients were further classified into low-risk (n = 11) and high-risk (n = 30) subgroups based on the ABCD2 score. Hemodynamic differences between these subgroups were also analyzed. Results: Compared with the non-hypoperfusion group, the hypoperfusion group had a significantly higher prevalence of hypertension (68.3% vs. 33.3%, p = 0.019) and hyperhomocysteinemia (65.9% vs. 33.3%, p = 0.029). Moreover, the hypoperfusion group exhibited more significant luminal stenosis degree [41.79 ±31.36 vs. 17.62±13.62, p = 0.006] and greater NWI (57.1%±20.47% vs. 40.21%± 21.56%, p = 0.009) compared to the non-hypoperfusion group. In addition, the high-risk group identified by the ABCD2 score had a higher rMTT [117.6(109.31-128.14) vs. 108.36(100.67-119.92), p = 0.037]. Conclusion: Transient ischemic attack patients with hypoperfusion exhibited a higher prevalence of hypertension and hyperhomocysteinemia, as well as higher luminal stenosis degree, and greater NWI. Furthermore, Transient ischemic attack patients in the high-risk group demonstrated higher MTT.

Predicting acute ischemic stroke using the revised Framingham stroke risk profile and multimodal magnetic resonance imaging.

Background and purpose: Patients with transient ischemic attacks (TIA) have a significant risk of developing acute ischemic strokes (AIS), emphasizing the critical need for hierarchical management. This study aims to develop a clinical-imaging model utilizing multimodal magnetic resonance imaging (mMRI) and the revised Framingham Stroke Risk Profile (FSRP) to predict AIS and achieve early secondary prevention. Methods: mMRI scans were conducted on patients with symptomatic intracranial atherosclerotic disease (ICAD) to assess vascular wall features and cerebral perfusion parameters. Based on diffusion-weighted imaging (DWI), patients were divided into two groups: TIA and AIS. Clinical data were evaluated to calculate the FSRP score. Differences in clinical and imaging characteristics between the groups were analyzed, and a predictive model for AIS probability in patients with ICAD was established. Results: A total of 112 TIA and AIS patients were included in the study. The results showed that the AIS group had higher proportions of FSRP-high risk, hyperhomocysteinemia, and higher value of low-density lipoprotein (LDL), standardized plaque index (SQI), and enhancement rate (ER) compared to the TIA group (p < 0.05). Mean transit time (MTT) and time to peak (TTP) in the lesion area were significantly longer in the AIS group (p < 0.05). Multivariate analysis identified FSRP-high risk (p = 0.027) and high ER (p = 0.046) as independent risk factors for AIS. The combined clinical and mMRI model produced an area under the curve (AUC) of 0.791 in receiver operating characteristic (ROC) analysis. The constructed nomogram model combining clinical and mMRI features demonstrated favorable clinical net benefits. Conclusion: FSRP-high risk and high ER were confirmed as independent risk factors for AIS. The combined prediction model utilizing clinical and imaging markers effectively predicts stroke risk in symptomatic ICAD patients.

Uncoupling of the center-to-periphery arterial stiffness gradient and pulse pressure amplification in viral pneumonia infection.

OBJECTIVES: Arterial stiffness is a common manifestation of viral pneumonia infections, including COVID-19. Nevertheless, the relationship between the center-to-periphery arterial stiffness gradient and pulse pressure amplification (PPA) in infectious diseases remains unclear. This study aimed to investigate this relationship utilizing arterial pressure volume index (API) and arterial velocity pulse index (AVI) ratio. METHODS: API/AVI and PPA were measured in 219 participants with COVID-19 and 374 normal participants. Multiple linear regression was used to assess the association of API/AVI and PPA, and restricted cubic spline was used to investigate the non-linear relationship between API/AVI and PPA. Receiver operating characteristic curve (ROC) analysis was used to evaluate the effects of API/AVI in identifying COVID-19 infection and severe stage. RESULTS: There was a significant J-shaped relationship between API/AVI and PPA in COVID-19 group, while a M-shaped relationship was observed in normal group. API/AVI decreased rapidly as PPA decreased until API/AVI decreased slowly at PPA of 1.07, and then API/AVI decreased slowly again at PPA of 0.78. ROC results showed that API/AVI demonstrated excellent accuracy in identifying COVID-19 infection (AUC = 0.781) and a high specificity (84.88%) in identifying severe stage. CONCLUSIONS: There was a J-shaped association between the API/AVI and PPA in viral infected patients, while a M-shaped relationship in the normal participants. API/AVI is better for identifying infected and uninfected patients, with a high specificity in identifying those in severe stages of the disease. The attenuation or reversal of API/AVI may be associated with the loss of PPA coupling.

Temporomandibular joint disc repositioning and occlusal splint for adolescents with skeletal class II malocclusion: a single-center, randomized, open-label trial.

BACKGROUND: Temporomandibular joint (TMJ) disc repositioning through open suturing (OSu) is a new disc repositioning method. Its result for adolescents with condylar resorption and dentofacial deformities combined with and without postoperative occlusal splints (POS) has not been well studied. OBJECTIVE: This study was to evaluate and compare the effects of OSu with and without POS in the treatment of TMJ anterior disc displacement without reduction (ADDwoR) in adolescent skeletal Class II malocclusion. METHODS: A total of 60 adolescents with bilateral ADDwoR were enrolled in this study. They were randomly allocated into two groups: OSu with and without POS. Magnetic resonance imaging (MRI) and lateral cephalometric radiographs were used to measure changes in condylar height and the degree of skeletal Class II malocclusion from before operation and at 12 months postoperatively. Changes in these indicators were compared within and between the two groups. RESULTS: After OSu, both groups exhibited significant improvements in condylar height and occlusion at the end of 12 months follow-up (P < 0.05). The group of OSu with POS had significantly more new bone formation (2.83 ± 0.75 mm vs. 1.42 ± 0.81 mm, P < 0.001) and improvement in dentofacial deformity than the group of OSu only (P < 0.05). The new bone height was significantly correlated with POS (P < 0.001), the changes of SNB (P = 0.018), overjet (P = 0.012), and Wits appraisal (P < 0.001). CONCLUSION: These findings indicated that OSu can effectively stimulate condylar regeneration and improve skeletal Class II malocclusion in adolescents with bilateral ADDwoR. The results are better when combined with POS. TRIAL REGISTRATION: This trial was prospectively registered on the chictr.org.cn registry with ID: ChiCTR1900021821 on 11/03/2019.

Preparation of an Ultrahigh-DAR PDL1 monoclonal antibody-polymeric-SN38 conjugate for precise colon cancer therapy.

Antibody-drug conjugates (ADCs) are the most potent active tumor-targeting agents used clinically. However, the preparation of ADCs with high drug-to-antibody ratios (DARs) remains a major challenge. Herein, a Fab-nondestructive SN38-loaded antibody-polymeric-drug conjugate (APDC), aPDL1-NPLG-SN38, was prepared that had a DAR as high as 72 for the first time, by increased numbers of payload binding sites via the carboxyl groups of poly (l-glutamic acid) (PLG). The bonding of Fc-III-4C peptide with PLG-graft-mPEG/SN38 (Fc-NPLG-SN38) was achieved using a click reaction between azide and DBCO groups. The aPDL1-NPLG-SN38 conjugate was then synthesized by the high-affinity interaction between the Fc-III-4C peptide in Fc-NPLG-SN38 and the crystallizable fragment (Fc) of PDL1 monoclonal antibody (aPDL1). This approach avoided the potential deleterious effects on the Fab structure of the monoclonal antibody. The aqueous environment used in its preparation helped maintain monoclonal antibody recognition capability. Through the specific recognition by aPDL1 of PDL1 that is highly expressed on MC38 tumors, the accumulation of aPDL1-NPLG-SN38 in the tumors was 2.8-fold greater than achieved with IgG-NPLG-SN38 that had no active tumor-targeting capability. aPDL1-NPLG-SN38 exhibited excellent therapeutic properties in both medium-sized and large MC38 tumor animal models. The present study provides the details of a novel preparation strategy for SN38-loaded ADCs having a high DAR.

ClpP protease modulates bacterial growth, stress response, and bacterial virulence in Brucella abortus.

The process of intracellular proteolysis through ATP-dependent proteases is a biologically conserved phenomenon. The stress responses and bacterial virulence of various pathogenic bacteria are associated with the ATP-dependent Clp protease. In this study, a Brucella abortus 2308 strain, ΔclpP, was constructed to characterize the function of ClpP peptidase. The growth of the ΔclpP mutant strain was significantly impaired in the TSB medium. The results showed that the ΔclpP mutant was sensitive to acidic pH stress, oxidative stress, high temperature, detergents, high osmotic environment, and iron deficient environment. Additionally, the deletion of clpP significantly affected Brucella virulence in macrophage and mouse infection models. Integrated transcriptomic and proteomic analyses of the ΔclpP strain showed that 1965 genes were significantly affected at the mRNA and/or protein levels. The RNA-seq analysis indicated that the ΔclpP strain exhibited distinct gene expression patterns related to energy production and conversion, cell wall/membrane/envelope biogenesis, carbohydrate transport, and metabolism. The iTRAQ analysis revealed that the differentially expressed proteins primarily participated in amino acid transport and metabolism, energy production and conversion, and secondary metabolites biosynthesis, transport and catabolism. This study provided insights into the preliminary molecular mechanism between Clp protease to bacterial growth, stress response, and bacterial virulence in Brucella strains.

Transcriptome and the gut microbiome analysis of the impacts of Brucella abortus oral infection in BALB/c mice.

Brucellosis is a zoonotic infectious disease caused by Brucella spp, which could cause serious economic losses to animal husbandry and threaten human public health. Ingestion of contaminated animal products is a common way to acquire Brucella infection in humans, while research on effect of oral Brucella infection on host gut microbiota and the gene expression in intestinal tissues is limited. In the present study, 16S rRNA sequencing and RNA sequencing were conducted to explore gut microbiota and expression profiles of mRNAs in the colon of BALB/c mice, which were infected by Brucella abortus 2308. The fecal samples were collected at 7 and 28 days post infection to observe changes in the gut microbiota during Brucella infection. In the alpha diversity analysis, significantly increased Chao 1 index was observed at 28 days after Brucella infection. The Bray-Curtis distancebased principal coordinate analysis indicated that the WT group showed a separation from the Brucella infection groups. In addition, analysis of composition of microbes revealed that Prevotellaceae_NK3B31_group were more abundant in 1 week and 4 week infection groups, while Turicibacter was only more abundant in 4 week infection group. Based on the RNA-seq assay, a total of 45 differentially expressed genes were detected between Brucella abortus infection group and control group. Furthermore, KEGG pathway enrichment analysis showed that protein processing in endoplasmic reticulum, Legionellosis, Spliceosome, Hippo signaling pathway and Influenza A were significantly enriched in response to Brucella abortus infection. Our finding will help to improve the knowledge of the mechanisms underlying Brucella infection and may provide novel targets for future treatment of this pathogen infection.