Conversion of Propargylic Amines with CO2 Catalyzed by a Highly Stable Copper(I) Iodide Thorium-Based Heterometal-Organic Framework.

The conversion of CO2 to generate high-value-added chemicals has become one of the hot research topics in green synthesis. Thereinto, the cyclization reaction of propargylic amines with CO2 is highly attractive because the resultant oxazolidinones are widely found in pharmaceutical chemistry. Cu(I)-based metal-organic frameworks (MOFs) as catalysts exhibit promising application prospects for CO2 conversion. However, their practical application was greatly limited due to Cu(I) being liable to disproportionation or oxidization. Herein, the solid copper(I) iodide thorium-based porous framework {[Cu5I6Th6(µ3-O)4(µ3-OH)4(H2O)10(L)10]·OH·4DMF·H2O}n (1) (HL = 2-methylpyridine-4-carboxylic acid) constructed by [Th6] clusters and [CuxIy] subunits was successfully prepared and structurally characterized. To our knowledge, this is the first copper(I) iodide-based actinide organic framework. Catalytic investigations indicate that 1 can effectively catalyze the cyclization of propargylic amines with CO2 under ambient conditions, which can be reused at least five times without a remarkable decline of catalytic activity. Importantly, 1 exhibits excellent chemical stability and the oxidation state of Cu(I) in it can remain stable under various conditions. This work can provide a valuable strategy for the synthesis of stable Cu(I)-MOF materials.

The prognostic value of pretreatment 18F-FDG PET-CT parameters with peripheral blood markers in patients with de novo metastatic nasopharyngeal carcinoma.

BACKGROUND AND PURPOSE: To develop and validate a prognostic nomogram based on pretreatment 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET-CT)radiomics parameters and peripheral blood markers for risk stratification in patients with de novo metastatic nasopharyngeal carcinoma (dmNPC). MATERIALS AND METHODS: A total of 558 patients with dmNPC were retrospectively enrolled between 2011 and 2019. Eligible patients were randomly divided into training and validation cohorts (7:3 ratio). A Cox regression model was used to identify prognostic factors for overall survival (OS). The predictive accuracy and discriminative ability of the prognostic nomogram were determined using the concordance index (C-index) and calibration curve. RESULTS: Independent factors derived from multivariable analysis of the training cohort to predict death were lactate dehydrogenase levels, pretreatment Epstein-Barr virus DNA, total lesion glycolysis of locoregional lesions, number of metastatic lesions, and age, all of which were assembled into a nomogram with (nomogram B) or without PET-CT parameters (nomogram A). The C-index of nomogram B for predicting death was 0.70, which was significantly higher than the C-index values for nomogram A. Patients were then stratified into low- and high-risk groups based on the scores calculated using nomogram B for OS. The median OS was significantly higher in the low-risk group than in the high-risk group (69.60 months [95 % CI: 58.50-108.66] vs. 21.40 months [95 % CI: 19.20-23.90]; p＜0.01). All the results were confirmed in the validation cohort. CONCLUSION: The proposed nomogram including PET-CT parameters yielded accurate prognostic predictions for patients with dmNPC, enabling effective risk stratification for these patients.

Prognostic significance of hemoglobin, albumin, lymphocyte, and platelet (HALP) score in breast cancer: a propensity score-matching study.

BACKGROUND: The hemoglobin-albumin-lymphocyte-platelet (HALP) score functions as a comprehensive index that assesses the systemic inflammatory response, nutritional, and immune status. This study aimed to explore the relationship between preoperative HALP score and the prognosis of BC patients and to develop predictive nomograms. METHODS: Clinicopathological data were collected for BC patients who underwent mastectomy between December 2010 and April 2014 from Sun Yat-sen University Cancer Center. The optimal cutoff value for HALP was determined by maximally selected rank statistics for overall survival data. Propensity score matching (PSM) was applied to develop comparable cohorts of high-HALP group and low-HALP group. Kaplan-Meier curves and Cox regression analyses were performed to determine the impact of HALP on BC patients. Prognostic nomograms were developed based on the multivariate Cox regression method. Then, the concordance index (C-index), calibration plots, and decision curves analysis (DCA) were applied to evaluate the prognostic performance of the nomograms. RESULTS: A total of 1,856 patients were included as the primary cohort, and 1,470 patients were matched and considered as the PSM cohort. In the primary cohort, the 5-year overall survival (OS) and progression-free survival (PFS) rates for high-HALP group (≥ 47.89) and low-HALP group (< 47.89) were 94.4% vs. 91.0% (P = 0.005) and 87.8% vs. 82.1% (P = 0.005), respectively. Similar results were observed in PSM cohort (5-year OS, 94.3% vs. 90.8%, P = 0.015; 5-year PFS, 87.5% vs. 83.2%, P = 0.036). Notably, multivariate Cox regression analysis in the PSM cohort showed that HALP could independently predict BC patient prognosis in both OS (HR: 0.596, 95%CI [0.405-0.875], P = 0.008) and PFS (HR: 0.707, 95%CI [0.538-0.930], P = 0.013). OS and PFS nomograms showed excellent predictive performance with the C-indexes of 0.783 and 0.720, respectively. The calibration plots and DCA also indicated the good predictability of the nomograms. Finally, subgroup analysis further demonstrated a favorable impact of HALP on both OS and PFS. CONCLUSION: Preoperative HALP score can be used as a reliable independent predictor of OS and PFS in BC patients, and the nomograms may provide a personalized treatment strategy.

Quercetin Protects Blood-Brain Barrier Integrity via the PI3K/Akt/Erk Signaling Pathway in a Mouse Model of Meningitis Induced by Glaesserella parasuis.

Glaesserella parasuis (G. parasuis) causes serious inflammation and meningitis in piglets. Quercetin has anti-inflammatory and anti-bacterial activities; however, whether quercetin can alleviate brain inflammation and provide protective effects during G. parasuis infection has not been studied. Here, we established a mouse model of G. parasuis infection in vivo and in vitro to investigate transcriptome changes in the mouse cerebrum and determine the protective effects of quercetin on brain inflammation and blood-brain barrier (BBB) integrity during G. parasuis infection. The results showed that G. parasuis induced brain inflammation, destroyed BBB integrity, and suppressed PI3K/Akt/Erk signaling-pathway activation in mice. Quercetin decreased the expression of inflammatory cytokines (Il-18, Il-6, Il-8, and Tnf-α) and BBB-permeability marker genes (Mmp9, Vegf, Ang-2, and Et-1), increased the expression of angiogenetic genes (Sema4D and PlexinB1), reduced G. parasuis-induced tight junction disruption, and reactivated G. parasuis-induced suppression of the PI3K/Akt/Erk signaling pathway in vitro. Thus, we concluded that quercetin may protect BBB integrity via the PI3K/Akt/Erk signaling pathway during G. parasuis infection. This was the first attempt to explore the protective effects of quercetin on brain inflammation and BBB integrity in a G. parasuis-infected mouse model. Our findings indicated that quercetin is a promising natural agent for the prevention and treatment of G. parasuis infection.

Single-cell transcriptomics of blood identified IFIT1+ neutrophil subcluster expansion in NTM-PD patients.

OBJECTIVE: Non-tuberculous mycobacterial pulmonary disease (NTM-PD) is caused by an imbalance between pathogens and impaired host immune responses. Mycobacterium avium complex (MAC) and Mycobacterium abscessus (MAB) are the two major pathogens that cause NTM-PD. In this study, we sought to dissect the transcriptomes of peripheral blood immune cells at the single-cell resolution in NTM-PD patients and explore potential clinical markers for NTM-PD diagnosis and treatment. METHODS: Peripheral blood samples were collected from six NTM-PD patients, including three MAB-PD patients, three MAC-PD patients, and two healthy controls. We employed single-cell RNA sequencing (scRNA-seq) to define the transcriptomic landscape at a single-cell resolution. A comprehensive scRNA-seq analysis was performed, and flow cytometry was conducted to validate the results of scRNA-seq. RESULTS: A total of 27,898 cells were analyzed. Nine T-cells, six mononuclear phagocytes (MPs), and four neutrophil subclusters were defined. During NTM infection, naïve T-cells were reduced, and effector T-cells increased. High cytotoxic activities were shown in T-cells of NTM-PD patients. The proportion of inflammatory and activated MPs subclusters was enriched in NTM-PD patients. Among neutrophil subclusters, an IFIT1+ neutrophil subcluster was expanded in NTM-PD compared to healthy controls. This suggests that IFIT1+ neutrophil subcluster might play an important role in host defense against NTM. Functional enrichment analysis of this subcluster suggested that it is related to interferon response. Cell-cell interaction analysis revealed enhanced CXCL8-CXCR1/2 interactions between the IFIT1+ neutrophil subcluster and NK cells, NKT cells, classical mononuclear phagocytes subcluster 1 (classical Mo1), classical mononuclear phagocytes subcluster 2 (classical Mo2) in NTM-PD patients compared to healthy controls. CONCLUSIONS: Our data revealed disease-specific immune cell subclusters and provided potential new targets of NTM-PD. Specific expansion of IFIT1+ neutrophil subclusters and the CXCL8-CXCR1/2 axis may be involved in the pathogenesis of NTM-PD. These insights may have implications for the diagnosis and treatment of NTM-PD.

Group A Streptococcal meningitis in children: a short case series and systematic review.

BACKGROUND: Group A streptococcal(GAS) meningitis is a severe disease with a high case fatality rate. In the era of increasing GAS meningitis, our understanding about this disease is limited. PURPOSE: To gain a better understanding about GAS meningitis. METHODS: Five new cases with GAS meningitis were reported. GAS meningitis related literatures were searched for systematic review in PUBMED and EMBASE. Case reports and case series on paediatric cases were included. Information on demographics, risk factors, symptoms, treatments, outcomes, and emm types of GAS was summarized. RESULTS: Totally 263 cases were included. Among 100 individuals, 9.9% (8/81) had prior varicella, 11.1% (9/81) had anatomical factors, and 53.2% (42/79) had extracranial infections. Soft tissue infections were common among infants (10/29, 34.5%), while ear/sinus infections were more prevalent in children ≥ 3 years (21/42, 50.0%). The overall case fatality rate (CFR) was 16.2% (12/74). High risk of death was found in patients with shock or systemic complications, young children(< 3 years) and cases related to hematogenic spread. The predominate cause of death was shock(6/8). Among the 163 patients included in case series studies, ear/sinus infections ranged from 21.4 to 62.5%, while STSS/shock ranged from 12.5 to 35.7%, and the CFR ranged from 5.9 to 42.9%. CONCLUSIONS: A history of varicella, soft tissue infections, parameningeal infections and CSF leaks are important clinical clues to GAS in children with meningitis. Young children and hematogenic spread related cases need to be closely monitored for shock due to the high risk of death.

Progress in the study of antibody-drug conjugates for the treatment of cervical cancer.

Cervical cancer is the second most prevalent malignancy affecting women's health globally, and the number of morbidity and mortality from cervical cancer continues to rise worldwide. The 5-year survival rate of patients with recurrent or metastatic cervical cancer is significantly reduced, and existing treatment modalities have low efficacy and high adverse effects, so there is a strong need for new, effective, and well-tolerated therapies. Antibody-drug conjugates (ADCs) are a new targeted therapeutic modality that can efficiently kill tumor cells. This review aims to summarize the composition, research, and development history and mechanism of action of ADCs, to review the research progress of ADCs in the treatment of cervical cancer, and to summarize and prospect the application of ADCs.

Glomerulus-Targeted ROS-Responsive Polymeric Nanoparticles for Effective Membranous Nephropathy Therapy.

Membranous nephropathy (MN) is a common immune-mediated glomerular disease that requires the development of safe and highly effective therapies. Celastrol (CLT) has shown promise as a therapeutic molecule candidate, but its clinical use is currently limited due to off-target toxicity. Given that excess levels of reactive oxygen species (ROS) contributing to podocyte damage is a key driver of MN progression to end-stage renal disease, we rationally designed ROS-responsive cationic polymeric nanoparticles (PPS-CPNs) with a well-defined particle size and surface charge by employing poly(propylene sulfide)-polyethylene glycol (PPS-PEG) and poly(propylene sulfide)-polyethylenimine (PPS-PEI) to selectively deliver CLT to the damaged glomerulus for MN therapy. Experimental results show that PPS-CPNs successfully crossed the fenestrated endothelium, accumulated in the glomerular basement membrane (GBM), and were internalized by podocytes where rapid drug release was triggered by the overproduction of ROS, thereby outperforming nonresponsive CLT nanotherapy to alleviate subepithelial immune deposits, podocyte foot process effacement, and GBM expansion in a rat MN model. Moreover, the ROS-responsive CLT nanotherapy was associated with significantly lower toxicity to major organs than free CLT. These results suggest that encapsulating CLT into PPS-CPNs can improve efficacy and reduce toxicity as a promising treatment option for MN.

Screening potential antileukemia agents from duckweed: Integration of chemical profiling, network pharmacology, and experimental validation.

INTRODUCTION: The identification of active dietary flavonoids in food is promising for novel drug discovery. The active ingredients of duckweed (a widely recognized food and herb with abundant flavonoids) that are associated with acute myeloid leukemia (AML) have yet to be identified, and their underlying mechanisms have not been elucidated. OBJECTIVES: The objective of this study was to identify novel constituents exhibiting antileukemia activity in duckweed through the integration of chemical profiling, network pharmacology, and experimental validation. METHODS: First, high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was used to characterize the primary constituents of duckweed. Subsequently, AML cell-xenograft tumor models were used to validate the anticancer effect of duckweed extract. Furthermore, network pharmacology analysis was conducted to predict the potential active compounds and drug targets against AML. Lastly, based on these findings, two monomers (apiin and luteoloside) were selected for experimental validation. RESULTS: A total of 17 compounds, all of which are apigenin and luteolin derivatives, were identified in duckweed. The duckweed extract significantly inhibited AML cell growth in vivo. Furthermore, a total of 88 targets for duckweed against AML were predicted, with key targets including PTGS2, MYC, MDM2, VEGFA, CTNNB1, CASP3, EGFR, TP53, HSP90AA1, CCND1, MMP9, TNF, and MAPK1. GO and KEGG pathway enrichment analyses indicated that these targets were primarily involved in the apoptotic signaling pathway. Lastly, both apiin and luteoloside effectively induced apoptosis through CASP3 activation, and this effect could be partially reversed by a caspase inhibitor (Z-VAD). CONCLUSION: Duckweed extract has an antileukemic effect, and apiin derived from duckweed shows potential as a treatment for AML.

Postoperative lenvatinib + PD-1 blockade reduces early tumor recurrence in hepatocellular carcinoma with microvascular invasion (Barcelona Clinic Liver Cancer stage 0 or A): a propensity score matching analysis.

BACKGROUND: This study aimed to determine the effectiveness of postoperative adjuvant lenvatinib + PD-1 blockade for patients with early-stage hepatocellular carcinoma (HCC) with microvascular invasion (MVI). METHODS: A total of 393 patients with HCC (Barcelona Clinic Liver Cancer stage 0 or A) who underwent curative hepatectomy with histopathologically proven MVI were enrolled according to the inclusion and exclusion criteria and assigned to 2 groups: surgery alone (surgery-alone group) and surgery with lenvatinib and PD-1 blockade (surgery + lenvatinib + PD-1 group) to compare recurrence-free survival (RFS), overall survival (OS), recurrence type, and annual recurrence rate after the application of propensity score matching (PSM). The Cox proportional hazards model was used for univariate and multivariate analyses. RESULTS: Overall, 99 matched pairs were selected using PSM. Patients in the surgery + lenvatinib + PD-1 group had significantly higher 3-year RFS rates (76.8%, 65.7%, and 53.5%) than patients in the surgery-alone group (60.6%, 45.5%, and 37.4%) (P = .012). The 2 groups showed no significant difference in recurrence types and OS. Surgery alone, MVI-M2, and alpha-fetoprotein of ≥200 ng/mL were independent risk factors for RFS (P < .05), and history of alcohol use disorder was an independent risk factor for OS (P = .022). CONCLUSION: Postoperative lenvatinib + PD-1 blockade improved the RFS in patients with HCC with MVI and was particularly beneficial for specific individuals.

Transcriptomics coupled with proteomics reveals osimertinib-induced myocardial mitochondrial dysfunction.

Osimertinib, an irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) used for cancer treatment, can cause significant cardiac toxicity. However, the specific mechanism of osimertinib-induced cardiotoxicity is not fully understood. In this study, we administered osimertinib to mice and neonatal rat ventricular myocytes (NRVMs). We observed significant structural and functional damage to the hearts of these mice, along with a marked increase in cardiac injury biomarkers and accompanying ultrastructural damage to mitochondria. We integrated 4D label-free protein quantification and RNA-Seq methods to analyze the sequencing data of NRVMs under osimertinib treatment (0 and 2.5 µM). Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis evidenced that differentially expressed genes (DEGs)and differentially expressed proteins (DEPs) were distinctly enriched for oxidative phosphorylation (OXPHOs). Simultaneously, osimertinib primarily affected the contents of adenosine triphosphate (ATP). Further investigations revealed that osimertinib disrupts the functions of the ATP synthase (complex V), leading to a reduction in ATP production. Taken together, our data demonstrated that osimertinib causes mitochondrial dysfunction, which in turn leads to the onset of cardiac toxicity.

Nomograms based on ratio indexes to predict severity and prognosis in immune checkpoint inhibitors-related myocarditis: a retrospective analysis.

PURPOSE: Immune checkpoint inhibitors-related myocarditis (ICI-M) is one of the immune-related adverse events (irAEs), which is rare and highly lethal. This study aimed to establish nomograms based on ratio biomarkers to predict the severity and prognosis of ICI-M. METHODS: We retrospectively examined patients with advanced cancers who were also diagnosed with ICI-M at the Fourth Hospital of Hebei Medical University. The patients of ICI-M were divided into mild and severe groups and a 40-day following up was carried out. The major adverse cardiovascular events(MACEs) were regarded as the endpoint. Nomogram-based models were established and validated. RESULTS: Seventy-seven patients were involved, including 31 severe cases(40.3%). Lactate dehydrogenase-to-albumin ratio(LAR) combined with the change rate from baseline to onset of LAR( ▵ LAR) which performed best to diagnose the severe ICI-M was identified to establish the nomogram-based model. The bootstrap-corrected concordance index [0.752 95% confidence interval (CI): 0.635 - 0.866] and calibration plot with good degree of fitting confirmed this diagnostic model. Neutrophil-to-high-density lipoprotein cholesterol ratio(NHR) and LAR were also screened into the nomogram-based model for 40-day MACEs after ICI-M, which performed well by validating for concordance index(0.779 95% CI: 0.677 - 0.865)and calibration plots after being bootstrap-corrected. Moreover, a  ≥ 101% increase in LAR significantly separated patients in MACE-free survival. CONCLUSION: Ratio indexes at onset and their change rates from baseline showed good diagnostic value for the severity of ICI-M and prognostic value for subsequent MACEs, particularly LAR, NHR and their change rates. The nomogram-based models of ratio indexes could provide a potential choice for early detection and monitor of the severe ICI-M and subsequent MACEs.

SCF/C-kit drives spermatogenesis disorder induced by abscopal effects of cranial irradiation in mice.

Cranial radiotherapy is a major treatment for leukemia and brain tumors. Our previous study found abscopal effects of cranial irradiation could cause spermatogenesis disorder in mice. However, the exact mechanisms are not yet fully understood. In the study, adult male C57BL/6 mice were administrated with 20 Gy X-ray cranial irradiation (5 Gy per day for 4 days consecutively) and sacrificed at 1, 2 and 4 weeks. Tandem Mass Tag (TMT) quantitative proteomics of testis was combined with bioinformatics analysis to identify key molecules and signal pathways related to spermatogenesis at 4 weeks after cranial irradiation. GO analysis showed that spermatogenesis was closely related to oxidative stress and inflammation. Severe oxidative stress occurred in testis, serum and brain, while serious inflammation also occurred in testis and serum. Additionally, the sex hormones related to hypothalamic-pituitary-gonadal (HPG) axis were disrupted. PI3K/Akt pathway was activated in testis, which upstream molecule SCF/C-Kit was significantly elevated. Furthermore, the proliferation and differentiation ability of spermatogonial stem cells (SSCs) were altered. These findings suggest that cranial irradiation can cause spermatogenesis disorder through brain-blood-testicular cascade oxidative stress, inflammation and the secretory dysfunction of HPG axis, and SCF/C-kit drive this process through activating PI3K/Akt pathway.

Behavioural and neuropsychological outcomes in children exposed in utero to maternal labour epidural analgesia.

BACKGROUND: Recent studies report conflicting results regarding the relationship between labour epidural analgesia (LEA) in mothers and neurodevelopmental disorders in their offspring. We evaluated behavioural and neuropsychological test scores in children of mothers who used LEA. METHODS: Children enrolled in the Raine Study from Western Australia and delivered vaginally from a singleton pregnancy between 1989 and 1992 were evaluated. Children exposed to LEA were compared with unexposed children. The primary outcome was the parent-reported Child Behaviour Checklist (CBCL) reporting total, internalising, and externalising behavioural problem scores at age 10 yr. Score differences, an increased risk of clinical deficit, and a dose-response based on the duration of LEA exposure were assessed. Secondary outcomes included language, motor function, cognition, and autistic traits. RESULTS: Of 2180 children, 850 (39.0%) were exposed to LEA. After adjustment for covariates, exposed children had minimally increased CBCL total scores (+1.41 points; 95% confidence interval [CI] 0.09 to 2.73; P=0.037), but not internalising (+1.13 points; 95% CI -0.08 to 2.34; P=0.066) or externalising (+1.08 points; 95% CI -0.08 to 2.24; P=0.068) subscale subscores. Increased risk of clinical deficit was not observed for any CBCL score. For secondary outcomes, score differences were inconsistently observed in motor function and cognition. Increased exposure duration was not associated with worse scores in any outcomes. CONCLUSIONS: Although LEA exposure was associated with slightly higher total behavioural scores, there was no difference in subscores, increased risk of clinical deficits, or dose-response relationship. These results argue against LEA exposure being associated with consistent, clinically significant neurodevelopmental deficits in children.

Significance of Pre-Treatment CALLY Score Combined with EBV-DNA Levels for Prognostication in Non-Metastatic Nasopharyngeal Cancer Patients: A Clinical Perspective.

Background: The C-reactive protein-albumin-lymphocyte (CALLY) score is a novel indicator associated with inflammation, immunity, and nutrition, utilized for cancer prognostic stratification. This study aimed to evaluate the integrated prognostic significance of the pre-treatment CALLY score and Epstein-Barr virus (EBV) DNA levels in nasopharyngeal carcinoma (NPC) patients and to develop prognostic models. Patients and Methods: A total of 1707 NPC patients from September 2015 to December 2017 were retrospectively enrolled. The cut-off point for the CALLY score, determined by maximum selected rank statistics, integrates with the published cut-off point for pre-EBV DNA to develop a comprehensive index. Subsequently, patients were randomly allocated in a 1:1 ratio into training and validation cohorts. Survival analysis was conducted using the Kaplan-Meier method with Log rank tests, and the Cox proportional hazards model was applied to identify independent prognostic factors for constructing predictive nomograms. The predictive ability of the nomograms were assessed through the concordance index (C-index), calibration curves, and decision curve analysis. Results: By integrating CALLY scores and EBV-DNA levels, patients were categorized into three risk clusters. Kaplan-Meier curves reveal significant differences in overall survival (OS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS) outcomes among different risk groups (all P values < 0.05). Multivariate analysis revealed that CALLY-EBV DNA index serves as an independent prognostic factor for the OS, DMFS, and LRRFS. The prognostic nomograms based on the CALLY-EBV DNA index provided accurate predictions for 1-year, 3-year, and 5-year OS, DMFS, and LRRFS. Additionally, compared to the traditional TNM staging system, the nomograms exhibited enhanced discriminatory power, calibration capability, and clinical applicability. All results were in agreement with the validation cohort. Conclusion: The CALLY-EBV DNA index is an independent prognostic biomarker. The nomogram prediction models, constructed based on the CALLY-EBV DNA index, demonstrates superior predictive performance compared to the traditional TNM staging.

Neoseiulus mites as biological control agents against Megalurothrips usitatus (Thysanoptera: Thripidae) and Frankliniella intonsa (Thysanoptera: Thripidae) on cowpea crop: laboratory to field.

Megalurothrips usitatus (Bagnall) (Thysanoptera: Thripidae) and Frankliniella intonsa (Trybom) (Thysanoptera: Thripidae) have been detrimental to cowpea production in many countries. Laboratory experiments were conducted to determine the prey stage preference and functional response of 2 predatory mites species, Neoseiulus barkeri (Hughes) (Acari: Phytoseiidae), and Neoseiulus californicus (McGregor) (Acari: Phytoseiidae), towards 2 thrips species (TS), M. usitatus, and F. intonsa, at varying densities and life stages on cowpea. Results shown that Neoseiulus species had a preference for different life stages of prey. Neoseiulus barkeri consumed more M. usitatus nymphs, while N. californicus consumed more F. intonsa (second-instar nymphs). The functional response of the 2 Neoseiulus spp. to nymphs of 2 TS was Type II on cowpea. The higher attack rate coefficient (a') and shorter handling time (Th) values were found on N. barkeri against M. usitatus, and a similar trend was found for those in N. californicus against F. intonsa. Field-caged trials were conducted to evaluate the effectiveness of Neoseiulus spp. in controlling 2 TS. The results have shown that Neoseiulus spp. was effective in controlling the 2 TS, with varying control efficacies at high or low release rates. The study provided valuable information on using Neoseiulus spp. as biological control agents against M. usitatus and F. intonsa in cowpea crops.

Biomimetic hydrogels with mesoscale collagen architecture for patient-derived tumor organoids culture.

Patient-derived tumor organoids (PDTOs) shows great potential as a preclinical model. However, the current methods for establishing PDTOs primarily focus on modulating local properties, such as sub-micrometer topographies. Nevertheless, they neglect to capture the global millimeter or intermediate mesoscale architecture that have been demonstrated to influence tumor response to therapeutic treatment and tumor progression. In this study, we present a rapid technique for generating collagen bundles with an average length of 90 ± 27 µm and a mean diameter of 5 ± 1.5 µm from tumor tissue debris that underwent mechanical agitation following enzymatic digestion. The collagen bundles were subsequently utilized for the fabrication of biomimetic hydrogels, incorporating microbial transglutaminase (mTG) crosslinked gelatin. These biomimetic hydrogels, referred to as MC-gel, were specifically designed for patient-derived tumor organoids. The lung cancer organoids cultured in MC-gel exhibited larger diameters and higher cell viability compared to those cultured in gels lacking the mesoscale collagen bundle; moreover, their irregular morphology more closely resembled that observed in vivo. The MC-gel-based lung cancer organoids effectively replicated the histology and mutational landscapes observed in the original donor patient's tumor tissue. Additionally, these lung cancer organoids showed a remarkable similarity in their gene expression and drug response across different matrices. This recently developed model holds great potential for investigating the occurrence, progression, metastasis, and management of tumors, thereby offering opportunities for personalized medicine and customized treatment options.

Repetitive transcranial magnetic stimulation ameliorates cognitive deficits in mice with radiation-induced brain injury by attenuating microglial pyroptosis and promoting neurogenesis via BDNF pathway.

BACKGROUND: Radiation-induced brain injury (RIBI) is a common and severe complication during radiotherapy for head and neck tumor. Repetitive transcranial magnetic stimulation (rTMS) is a novel and non-invasive method of brain stimulation, which has been applied in various neurological diseases. rTMS has been proved to be effective for treatment of RIBI, while its mechanisms have not been well understood. METHODS: RIBI mouse model was established by cranial irradiation, K252a was daily injected intraperitoneally to block BDNF pathway. Immunofluorescence staining, immunohistochemistry and western blotting were performed to examine the microglial pyroptosis and hippocampal neurogenesis. Behavioral tests were used to assess the cognitive function and emotionality of mice. Golgi staining was applied to observe the structure of dendritic spine in hippocampus. RESULTS: rTMS significantly promoted hippocampal neurogenesis and mitigated neuroinflammation, with ameliorating pyroptosis in microglia, as well as downregulation of the protein expression level of NLRP3 inflammasome and key pyroptosis factor Gasdermin D (GSDMD). BDNF signaling pathway might be involved in it. After blocking BDNF pathway by K252a, a specific BDNF pathway inhibitor, the neuroprotective effect of rTMS was markedly reversed. Evaluated by behavioral tests, the cognitive dysfunction and anxiety-like behavior were found aggravated with the comparison of mice in rTMS intervention group. Moreover, the level of hippocampal neurogenesis was found to be attenuated, the pyroptosis of microglia as well as the levels of GSDMD, NLRP3 inflammasome and IL-1ß were upregulated. CONCLUSION: Our study indicated that rTMS notably ameliorated RIBI-induced cognitive disorders, by mitigating pyroptosis in microglia and promoting hippocampal neurogenesis via mediating BDNF pathway.

Respiratory syncytial virus seasonality, transmission zones, and implications for seasonal prevention strategy in China: a systematic analysis.

BACKGROUND: Respiratory syncytial virus (RSV) represents a substantial global health challenge, with a disproportionately high disease burden in low-income and middle-income countries. RSV exhibits seasonality in most areas globally, and a comprehensive understanding of within-country variations in RSV seasonality could help to define the timing of RSV immunisation programmes. This study focused on China, and aimed to describe the geographical distribution of RSV seasonality, identify distinct RSV transmission zones, and evaluate the potential suitability of a seasonal RSV prevention strategy. METHODS: We did a systematic analysis of RSV seasonality in China, with use of data on RSV activity extracted from a systematic review of studies published on Embase, MEDLINE, Web of Science, China National Knowledge Infrastructure, Wanfang Data, Chongqing VIP Information, and SinoMed, from database inception until May 5, 2023. We included studies of any design in China reporting at least 25 RSV cases, which aggregated RSV case number by calendar month or week at the province level, and with data covering at least 12 consecutive months before the year 2020 (prior to the COVID-19 pandemic). Studies that used only serology for RSV testing were excluded. We also included weekly data on RSV activity from open-access online databases of the Taiwan National Infection Disease Statistics System and Hong Kong Centre for Health Protection, applying the same eligiblity requirements. Across all datasets, we excluded data on RSV activity from Jan 1, 2020, onwards. We estimated RSV seasonal epidemic onset and duration using the annual average percentage (AAP) approach, and summarised seasonality at the provincial level. We used Pearson's partial correlation analysis to assess the correlation between RSV season duration and the latitude and longitude of the individual provinces. To define transmission zones, we used two independent approaches, an infant-passive-immunisation-driven approach (the moving interval approach, 6-month interval) and a data-driven approach (k-means), to identify groups of provinces with similar RSV seasonality. The systematic review was registered on PROSPERO, CRD42022376993. FINDINGS: A total of 157 studies were included along with the two online datasets, reporting data on 194 596 RSV cases over 442 study-years (covering the period from Jan 1, 1993 to Dec 31, 2019), from 52 sites in 23 provinces. Among 21 provinces with sufficient data (≥100 reported cases), the median duration of RSV seasonal epidemics was 4·6 months (IQR 4·1-5·4), with a significant latitudinal gradient (r=-0·69, p<0·0007), in that provinces on or near the Tropic of Cancer had the longest epidemic duration. We found no correlation between longitude and epidemic duration (r=-0·15, p=0·53). 15 (71%) of 21 provinces had RSV epidemics from November to March. 13 (62%) of 21 provinces had clear RSV seasonality (epidemic duration ≤5 months). The moving interval approach categorised the 21 provinces into four RSV transmission zones. The first zone, consisting of five provinces (Fujian, Guangdong, Hong Kong, Taiwan, and Yunnan), was assessed as unsuitable for seasonal RSV immunisation strategies; the other three zones were considered suitable for seasonal RSV immunisation strategies with the optimal start month varying between September (Hebei), October (Anhui, Chongqing, Henan, Hubei, Jiangsu, Shaanxi, Shandong, Shanghai, Sichuan, and Xinjiang), and November (Beijing, Gansu, Guizhou, Hunan, and Zhejiang). The k-means approach identified two RSV transmission zones, primarily differentiated by whether the province was on or near the Tropic of Cancer (Fujian, Guangdong, Hong Kong, Taiwan, Yunan, and Hunan) or not (the remaining 15 provinces). INTERPRETATION: Although substantial variations in RSV seasonality were observed across provinces of China, our study identified distinct transmission zones with shared RSV circulating patterns. These findings could have important implications for decision making on RSV passive immunisation strategy. Furthermore, the methodological framework in this study for defining RSV seasons and identifying RSV transmission zones is potentially applicable to other countries or regions. FUNDING: Nanjing Medical University. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Thoracic spine infection caused by Pseudomonas fluorescens: A case report and review of literature.

BACKGROUND: The clinical incidence of spinal infection is gradually increasing, and its onset is insidious, easily leading to missed diagnosis and misdiagnosis, which may lead to serious complications such as nervous system dysfunction, spinal instability and/or deformity, and cause a huge burden on society and families. Early identification of the causative agent and precision medicine will greatly reduce the suffering of patients. At present, the main pathogenic bacteria that cause spinal infection are Staphylococcus aureus, Streptococcus, Pneumococcus, Escherichia coli, and Klebsiella. There are no reports of spinal infection caused by Pseudomonas fluorescens. CASE SUMMARY: We report a 32-year-old female patient with spinal infection. She presented with flank pain, initially thought to be bone metastases or bone tuberculosis, and had a family background of tumors. Her clinical features and changes in imaging and laboratory tests led to the suspicion of thoracic spine infection. Histopathology of the lesion showed inflammation, tissue culture of the lesion was negative several times, and the possible pathogen - Pseudomonas fluorescens was found after gene sequencing of the lesion. The patient recovered completely after a full course of antibiotic treatment. CONCLUSION: This report increases the range of pathogens involved in spinal infections, highlights the unique advantages of gene sequencing technology in difficult-to-diagnose diseases, and validates conservative treatment with a full course of antibiotics for spinal infections without complications.