Recombinase polymerase amplification combined with lateral flow dipstick assay for rapid visual detection of A.simplex (s. s.) and A.pegreffii in sea foods.

Anisakiasis is a food-borne parasitic disease mainly caused by the third stage of Anisakis simplex (s. s.) and Anisakis pegreffii. Traditional methods for detecting of Anisakis involve morphology identification such as visual inspection, enzyme digestion, and molecular methods based on PCR, but they have certain limitations. In this study, the internal transcribed spacer 1 (ITS 1) regions of Anisakis were targeted to develop a visual screening method for detecting A. simplex (s. s.) and A. pegreffii in fish meat based on recombinase polymerase amplification (RPA) combined with lateral flow dipstick (LFD). Specific primers and probes were designed and optimized for temperature, reaction time, and detection threshold. LFD produced clear visual results that were easily identifiable after a consistent incubation of 10-20 min at 37 °C. The whole process of DNA amplification by RPA and readout by LFD did not exceed 30 min. In addition, the detection limit is up to 9.5 × 10-4 ng/µL, and the detection of the artificially contaminated samples showed that the developed assay can effectively and specifically detect A. simplex (s. s.) and A. pegreffii, which fully meet the market's requirements for fish food safety supervision.

Assessment of urban ecosystem health and its influencing factors: a case study of Zibo City, China.

Urban ecosystem health is the foundation of sustainable urban development. It is important to know the health status of urban ecosystem and its influencing factors for formulating scientific urban development planning. Taking Zibo city as the study area, the indicators were selected from five aspects: ecosystem vigor, structure, resilience, service function and population health to establish an assessment index system of urban ecosystem health. The health level of urban ecosystem was assessed, and its changing trend was analyzed from 2006 to 2018 in Zibo. Furthermore, obstacle degree analysis and sensitivity analysis were used to quantitatively analyze the main obstacle factors and sensitivity factors affecting urban ecosystem health, so as to provide references for improving urban ecosystem health. The results showed that the health level of urban ecosystem in Zibo showed an upward trend from 2006 to 2018. The poor structure and ecological environment quality were the main obstacle factors to urban ecosystem health. The impact of changes in a single indicator on urban ecosystem health gradually decreased, but the sensitivity index of indicators had obvious differences. Urban ecosystem health was sensitive to changes in ecosystem structure and resilience. In the future, Zibo should strengthen ecological construction, optimize the industrial structure, and develop green economy to promote urban ecosystem healthy.

Direct Observation of Circularly Polarized Nonlinear Optical Activities in Chiral Hybrid Lead Halides.

Circularly polarized light emission is a crucial application in imaging, sensing, and photonics. However, utilizing low-energy photons to excite materials, as opposed to high-energy light excitation, can facilitate deep-tissue imaging and sensing applications. The challenge lies in finding materials capable of directly generating circularly polarized nonlinear optical effects. In this study, we introduce a chiral hybrid lead halide (CHLH) material system, R/S-DPEDPb3Br8·H2O (DPED = 1,2-diphenylethylenediammonium), which can directly produce circularly polarized second harmonic generation (CP-SHG) through linearly polarized infrared light excitation, exhibiting a polarization efficiency as high as 37% at room temperature. To understand the spin relaxation mechanisms behind the high polarization efficiency, we utilized two models, so-called D'yakonov-Perel' (DP) and Bir-Aronov-Pikus (BAP) mechanisms. The unique zigzag inorganic frameworks within the hybrid structure are believed to reduce the dielectric confinement and exciton binding energy, thus enhancing spin polarization, especially in regions with a high excitation pump fluence based on the DP mechanism. In the case of low excitation pump fluence, the BAP mechanism dominates, as evidenced by the observed decrease in the polarization ratio from CP-SHG measurement. Using density functional theory analysis, we elucidate how the distinctive 8-coordination environment of lead bromide building blocks effectively suppresses spin-orbit coupling at the conduction band minimum. This suppression significantly diminishes spin-splitting, thereby slowing the spin relaxation rate.

Near-infrared and mid-infrared light emission of boron-doped crystalline silicon.

The bottleneck in achieving fully integrated silicon photonics lies in silicon-based light-emitting devices that are compatible with standard CMOS technology. Dislocation loops created by implanting boron into silicon and annealing represent an enticing strategy to transform highly inefficient silicon into a luminescent material. However, the emission at telecommunication wavelength suffers from the strong thermal quenching effect, resulting in low efficiency at room temperature. Here, we applied a new deep cooling process to address this issue. Interestingly, we find that electrons and holes recombine through defects emitting two photons, one in near infrared (NIR, 1.3∼1.6 µm) and the other in mid-infrared band (MIR, around 3.5 µm). The photoluminescence intensity at NIR increases three fold when the temperature increases from 77 K to 300 K. Furthermore, the NIR light emission of reverse biased silicon diodes was significantly enhanced compared to forward bias, emitting the maximum output power of 42 nW at 60 mA. The results offer new opportunities for the development of infrared light sources in integrated circuits.

Inhibition of co-occurring weeds and young sugarcane seedling growth by perennial sugarcane root extract.

Allelopathy is a process whereby a plant directly or indirectly promotes or inhibits growth of surrounding plants. Perennial sugarcane root extracts from various years significantly inhibited Bidens pilosa, Digitaria sanguinalis, sugarcane stem seedlings, and sugarcane tissue-cultured seedlings (P < 0.05), with maximum respective allelopathies of - 0.60, - 0.62, - 0.20, and - 0.29. Allelopathy increased with increasing concentrations for the same-year root extract, and inhibitory effects of the neutral, acidic, and alkaline components of perennial sugarcane root extract from different years were significantly stronger than those of the control for sugarcane stem seedlings (P < 0.05). The results suggest that allelopathic effects of perennial sugarcane root extract vary yearly, acids, esters and phenols could be a main reason for the allelopathic autotoxicity of sugarcane ratoons and depend on the type and content of allelochemicals present, and that allelopathy is influenced by other environmental factors within the rhizosphere such as the presence of old perennial sugarcane roots. This may be a crucial factor contributing to the decline of perennial sugarcane root health.

Identification of a multidrug resistance genomic island harboring a nonfunctional optrA gene in Campylobacter coli of chicken origin.

Campylobacter spp., such as Campylobacter jejuni and Campylobacter coli, are important zoonotic Gram-negative pathogens that cause acute intestinal diseases in humans. In this study, a retrospective analysis was conducted on previously collected Campylobacter isolates from antimicrobial resistance surveillance. A total of 29 optrA-positive C. coli strains were identified and subjected to second-generation sequencing. Multilocus sequence typing and single nucleotide polymorphism analyses demonstrated that the 29 optrA-positive isolates were genetically homogeneous. Notably, among the 29 isolated strains, the ΔoptrA variants exhibit a nonsense mutation at position 979 where the base C is substituted by T, leading to the formation of a premature termination codon. The alignment of sequences and genetic environmental characteristics suggested that ΔoptrA located on a chromosomally carried multidrug-resistant genomic island. There are other resistant genes on the multidrug resistance genomic island, such as aph(2'')-If, aph(3')-III, aadE, tet(O), tet(L), cat, erm(A), optrA and blaOXA-61. As a result, the 29 ΔoptrA-positive strains displayed susceptibility to both florfenicol and linezolid. The ΔoptrA gene is linked to the erm(A) gene, resulting in the formation of translocatable unit (TU) that are encompassed by two copies of IS1216 mobile elements. Multiple occurrences of similar TUs have been documented in numerous C. coli and provided evidence for the significance of TUs in facilitating the transfer of drug resistance genes in C. coli.

Route planning of mobile robot based on improved RRT star and TEB algorithm.

This paper presents a fusion algorithm based on the enhanced RRT* TEB algorithm. The enhanced RRT* algorithm is utilized for generating an optimal global path. Firstly, proposing an adaptive sampling function and extending node bias to accelerate global path generation and mitigate local optimality. Secondly, eliminating path redundancy to minimize path length. Thirdly, imposing constraints on the turning angle of the path to enhance path smoothness. Conducting kinematic modeling of the mobile robot and optimizing the TEB algorithm to align the trajectory with the mobile robot's kinematics. The integration of these two algorithms culminates in the development of a fusion algorithm. Simulation and experimental results demonstrate that, in contrast to the traditional RRT* algorithm, the enhanced RRT* algorithm achieves a 5.8% reduction in path length and a 62.5% decrease in the number of turning points. Utilizing the fusion algorithm for path planning, the mobile robot generates a superior, seamlessly smooth global path, adept at circumventing obstacles. Furthermore, the local trajectory meticulously conforms to the kinematic constraints of the mobile robot.

CDK12 Loss Promotes Prostate Cancer Development While Exposing Vulnerabilities to Paralog-Based Synthetic Lethality.

Biallelic loss of cyclin-dependent kinase 12 (CDK12) defines a unique molecular subtype of metastatic castration-resistant prostate cancer (mCRPC). It remains unclear, however, whether CDK12 loss per se is sufficient to drive prostate cancer development-either alone, or in the context of other genetic alterations-and whether CDK12-mutant tumors exhibit sensitivity to specific pharmacotherapies. Here, we demonstrate that tissue-specific Cdk12 ablation is sufficient to induce preneoplastic lesions and robust T cell infiltration in the mouse prostate. Allograft-based CRISPR screening demonstrated that Cdk12 loss is positively associated with Trp53 inactivation but negatively associated with Pten inactivation-akin to what is observed in human mCRPC. Consistent with this, ablation of Cdk12 in prostate organoids with concurrent Trp53 loss promotes their proliferation and ability to form tumors in mice, while Cdk12 knockout in the Pten-null prostate cancer mouse model abrogates tumor growth. Bigenic Cdk12 and Trp53 loss allografts represent a new syngeneic model for the study of androgen receptor (AR)-positive, luminal prostate cancer. Notably, Cdk12/Trp53 loss prostate tumors are sensitive to immune checkpoint blockade. Cdk12-null organoids (either with or without Trp53 co-ablation) and patient-derived xenografts from tumors with CDK12 inactivation are highly sensitive to inhibition or degradation of its paralog kinase, CDK13. Together, these data identify CDK12 as a bona fide tumor suppressor gene with impact on tumor progression and lends support to paralog-based synthetic lethality as a promising strategy for treating CDK12-mutant mCRPC.

The effect of single low-dose primaquine treatment for uncomplicated Plasmodium falciparum malaria on hemoglobin levels in Ethiopia: a longitudinal cohort study.

Background: To interrupt residual malaria transmission and achieve successful elimination of P. falciparum in low-transmission settings, the World Health Organization (WHO) recommends the administration of a single dose of 0.25 mg/kg (or 15 mg/kg for adults) primaquine (PQ) combined with artemisinin-based combination therapy (ACT) without glucose-6-phosphate dehydrogenase (G6PD) testing. However, due to the risk of hemolysis in patients with G6PD deficiency (G6PDd), PQ use is not as common. Thus, this study aimed to assess the safety of a single low dose of PQ administered to patients with G6PD deficiency. Methods: An observational cohort study was conducted with patients treated for uncomplicated P. falciparum malaria with either single-dose PQ (0.25 mg/kg) (SLD PQ) + ACT or ACT alone. Microscopy-confirmed uncomplicated P. falciparum malaria patients visiting public health facilities in Arjo Didessa, Southwest Ethiopia, were enrolled in the study from September 2019 to November 2022. Patients with uncomplicated P. falciparum malaria were followed up for 28 days through clinical and laboratory diagnosis, such as measurements of G6PD levels and hemoglobin (Hb) concentrations. G6PD levels were masured by a quantiative biosensor machine. Patient interviews were also conducted, and the type and frequency of clinical complaints were recorded. Hb data were taken on days (D) 7, 14, 21, and 28 following treatment with SLD-PQ + ACT or ACT alone. Results: A total of 249 patients with uncomplicated P. falciparum malaria were enrolled in this study. Of these, 83 (33.3%) patients received ACT alone, and 166 (66.7%) received ACT combined with SLD-PQ treatment. The median age of the patients was 20 (IQR 14) years. G6PD deficiency was found in 17 (6.8%) patients, 14 males and 3 females. There were 6 (7.2%) and 11 (6.6%) phenotypic G6PD-deficient patients in the ACT alone and ACT + SLD-PQ arms, respectively. The mean Hb levels in patients treated with ACT + SLD-PQ were reduced by an average of 0.45 g/dl (95% CI = 0.39 to 0.52) in the posttreatment phase (D7) compared to a reduction of 0.30 g/dl (95% CI = 0.14 to -0.47) in patients treated with ACT alone (P = 0.157). A greater mean Hb reduction was observed on day 7 in the G6PD deficiency group (-0.56 g/dL) than in the G6PD normal group (-0.39 g/dL); however, there was no statistically significant difference (P = 0.359). Overall, D14 losses were 0.10 g/dl (95% CI = -0.00 to 0.20) and 0.05 g/dl (95% CI = -0.123 to 0.22) in patients with and without SLD-PQ, respectively (P = 0.412). Conclusions: Our findings showed that single low-dose primaquine (SLD-PQ) treatment for uncomplicated P. falciparum malaria is safe and does not increase the risk of hemolysis in G6PDd patients. This evidence suggests that the wider deployment of SLD-PQ for P. falciparum is part of a global strategy for eliminating P. falciparum malaria.

Expressions of CXCR3 and PD-1 on T cells and their clinical relevance in colorectal cancer.

PURPOSE: Clinical application of immunotherapy represented by Programmed Death-1 (PD-1) monoclonal antibody has changed the treatment paradigm for colorectal cancer (CRC), and tumor-infiltrating T lymphocytes are critical for anti-PD-1 therapy in CRC. However, there are few studies on the relationship between the expression CXCR3 on T lymphocytes and the clinical aspects of CRC. In this study, we analyzed the expression levels of CXCR3 and PD-1 in CD8+ and CD4+ T lymphocytes in healthy donors (HDs) and patients with CRC. METHODS: We detected the expressions of CXCR3 and PD-1 on T lymphocytes in peripheral blood of healthy donors as well as peripheral blood, tumor tissue and para-cancerous tissues of patients with CRC using flow cytometry. We also analyzed the relationship between the expressions of CXCR3 and PD-1 on T lymphocytes and the pathological characteristics of CRC using t test. RESULTS: Expression of CXCR3 on tumor-infiltrating T lymphocytes was lower, whereas the expression of PD-1 was higher than that on para-cancerous tissues and PB in patients with CRC. In patients with lymph node metastasis of CRC, the expressions levels of CXCR3+ PD-1+ on tumor-infiltrating CD8+ and CD4+ T lymphocytes were higher than those in patients without lymph node metastasis. The levels of CXCR3+ PD-1+ expressions differed depending on the primary tumor site. CONCLUSION: Expressions of CXCR3 and PD-1 on tumor-infiltrating T lymphocytes are related to the development of CRC and metastasis, providing clues for exploring the pathogenesis of CRC and developing new strategies for tumor immunotherapy.

Peripheral nerve injury associated with JEV infection in high endemic regions, 2016-2020: a multicenter retrospective study in China.

ABSTRACTPreviously, we have reported a cohort of Japanese encephalitis (JE) patients with Guillain-Barré syndrome. However, the evidence linking Japanese encephalitis virus (JEV) infection and peripheral nerve injury (PNI) remains limited, especially the epidemiology, clinical presentation, diagnosis, treatment, and outcome significantly differ from traditional JE. We performed a retrospective and multicenter study of 1626 patients with JE recorded in the surveillance system of the Chinese Center for Disease Control and Prevention, spanning the years 2016 to 2020. Cases were classified into type 1 and type 2 JE based on whether the JE was combined with PNI or not. A comparative analysis was conducted on demographic characteristics, clinical manifestations, imaging findings, electromyography data, laboratory results, and treatment outcomes. Among 1626 laboratory confirmed JE patients, 230 (14%) were type 2 mainly located along the Yellow River in northwest China. In addition to fever, headache, and disturbance of consciousness, type 2 patients experienced acute flaccid paralysis of the limbs, as well as severe respiratory muscle paralysis. These patients presented a greater mean length of stay in hospital (children, 22 years [range, 1-34]; adults, 25 years [range, 0-183]) and intensive care unit (children, 16 years [range, 1-30]; adults, 17 years [range, 0-102]). The mortality rate was higher in type 2 patients (36/230 [16%]) compared to type 1 (67/1396 [5%]). The clinical classification of the diagnosis of JE may play a crucial role in developing a rational treatment strategy, thereby mitigating the severity of the disease and potentially reducing disability and mortality rates among patients.

MicroRNA-485-5p targets keratin17 to regulate pancreatic cancer cell proliferation and invasion via the FAK / SRC / ERK pathway.

Background: It is crucial to probe into the biological effect and mechanism of miRNA-485-5p regulating keratin 17 (KRT17) in pancreatic cancer (PC) to understand its pathogenesis and identify potential biological targets. Methods: The bioinformatics means were used to evaluate the clinical significance of KRT17 expression in the Cancer Genome Atlas (TCGA) database. TargetScan database analysis in conjunction with dual luciferase and RNA Immunoprecipitation (RIP) experiments was used to probe the interaction relationship of miRNA-485-5p with KRT17. The expression of miRNA-485-5p and KRT17 in PC tissue and cancer cell lines was detected by Q-PCR paired with western blot assay. The biological function of miRNA-485-5p in regulating KRT17 was investigated in the PC cell line via gene silencing/overexpression technique. A western blot experiment was utilized to investigate the regulatory effect of KRT17 on cell cycle-related proteins and the FAK/Src/ERK signal pathway. Results: The level of KRT17 was increased in PC tissues and this significantly decreased the survival rate of PC patients. TargetScan in combination with dual luciferase and RIP experiments verified the miRNA-485-5p target KRT17. The expression of KRT17 was high in the PC cell line, although the expression of miRNA-485-5p was low. Silencing KRT17 or overexpression of miRNA-485-5p significantly inhibited PC cell viability, proliferation, invasion, and colony formation, while promoting apoptosis. Overexpression of KRT17 drastically reversed the function of miRNA-485-5p. The silenced KRT17 remarkably downregulated the expression of cyclinD1, Cyclin Dependent Kinase 1 (CDK1), CDK2, Phospho-Focal Adhesion Kinase (p-FAK), p-Src, and p-ERK proteins in the PC cells. Conclusion: Generally, an essential signaling cascade of miRNA-485-5p/KRT17/FAK/Src/ERK influences the biological functions of PC cells.

Reduced Surface Trap States of PbS Quantum Dots by Acetonitrile Treatment for Efficient SnO2-Based PbS Quantum Dot Solar Cells.

The solution-phase ligand-exchange strategy offers a simple pathway to prepare PbS quantum dots (QDs) and their corresponding solar cells. However, the production of high-quality PbS QDs with reduced surface trap state density for efficient PbS QD solar cells (QDSCs) still faces challenges. As the hydroxyl group (-OH) has been demonstrated to be the primary source of the surface trap states on PbS QDs in the general oleic acid method, here, we present an effective and facile strategy for reducing the surface -OH content of PbS QDs by using acetonitrile (ACN) as precipitant to wash the surface of QDs, which significantly decreases the trap state density and enables the preparation of superior PbS QDs. The resulting solar cell with an ITO/SnO2/n-PbS/p-PbS/Au structure obtained an improved photoelectric conversion efficiency (PCE) from 8.53 to 10.49% with an enhanced air storage stability, realizing a high PCE for SnO2-based PbS QDSCs.

Malaria transmission heterogeneity in different eco-epidemiological areas of western Kenya: a region-wide observational and risk classification study for adaptive intervention planning.

BACKGROUND: Understanding of malaria ecology is a prerequisite for designing locally adapted control strategies in resource-limited settings. The aim of this study was to utilize the spatial heterogeneity in malaria transmission for the designing of adaptive interventions. METHODS: Field collections of clinical malaria incidence, asymptomatic Plasmodium infection, and malaria vector data were conducted from 108 randomly selected clusters which covered different landscape settings including irrigated farming, seasonal flooding area, lowland dryland farming, and highlands in western Kenya. Spatial heterogeneity of malaria was analyzed and classified into different eco-epidemiological zones. RESULTS: There was strong heterogeneity and detected hot/cold spots in clinical malaria incidence, Plasmodium prevalence, and vector abundance. The study area was classified into four zones based on clinical malaria incidence, parasite prevalence, vector density, and altitude. The two irrigated zones have either the highest malaria incidence, parasite prevalence, or the highest malaria vector density; the highlands have the lowest vector density and parasite prevalence; and the dryland and flooding area have the average clinical malaria incidence, parasite prevalence and vector density. Different zones have different vector species, species compositions and predominant species. Both indoor and outdoor transmission may have contributed to the malaria transmission in the area. Anopheles gambiae sensu stricto (s.s.), Anopheles arabiensis, Anopheles funestus s.s., and Anopheles leesoni had similar human blood index and malaria parasite sporozoite rate. CONCLUSION: The multi-transmission-indicator-based eco-epidemiological zone classifications will be helpful for making decisions on locally adapted malaria interventions.

Variation of peripheral blood-based biomarkers for response of anti-PD-1 immunotherapy in non-small-cell lung cancer.

PURPOSE: Immune checkpoint inhibitors (ICIs) for non-small-cell lung cancer (NSCLC) are on the rise, but unfortunately, only a small percentage of patients benefit from them in the long term. Thus, it is crucial to identify biomarkers that can forecast the efficacy of immunotherapy. METHODS: We retrospectively studied 224 patients with NSCLC who underwent anti-PD-1 therapy. The role of biomarkers and clinical characteristics were assessed in a prognostic model. RESULTS: Only 14.3% of patients had both programmed death ligand 1 (PD-L1) and tumor mutational burden (TMB) outcomes, highlighting the need to investigate more available biomarkers. Our analysis found a correlation between histological PD-L1 TPS and hematological PD-1 expression. Analysis of hematological biomarkers revealed that elevated expression of CD4/CD8 and LYM% are positively associated with effective immunotherapy, while PD-1+ on T cells, NLR, and MLR have a negative impact. Moreover, high level of ΔCEA%, CYFRA21-1 and LDH may suggest ineffective ICIs. We also observed that disparate immunotherapy drugs didn't significantly impact prognosis. Lastly, by comparing squamous carcinoma and adenocarcinoma cohorts, ΔCEA%, CD3+PD-1+, CD4+PD-1+, and CD4/CD8 are more important in predicting the prognosis of adenocarcinoma patients, while age is more significant for squamous carcinoma patients. CONCLUSION: Our research has yielded encouraging results in identifying a correlation between immunotherapy's response and clinical characteristics, peripheral immune cell subsets, and biochemical and immunological biomarkers. The screened hematological detection panel could be used to forecast an NSCLC patient's response to anti-PD-1 immunotherapy with an accuracy rate of 76.3%, which could help customize suitable therapeutic decision-making.

A genotyping array for the globally invasive vector mosquito, Aedes albopictus.

BACKGROUND: Although whole-genome sequencing (WGS) is the preferred genotyping method for most genomic analyses, limitations are often experienced when studying genomes characterized by a high percentage of repetitive elements, high linkage, and recombination deserts. The Asian tiger mosquito (Aedes albopictus), for example, has a genome comprising up to 72% repetitive elements, and therefore we set out to develop a single-nucleotide polymorphism (SNP) chip to be more cost-effective. Aedes albopictus is an invasive species originating from Southeast Asia that has recently spread around the world and is a vector for many human diseases. Developing an accessible genotyping platform is essential in advancing biological control methods and understanding the population dynamics of this pest species, with significant implications for public health. METHODS: We designed a SNP chip for Ae. albopictus (Aealbo chip) based on approximately 2.7 million SNPs identified using WGS data from 819 worldwide samples. We validated the chip using laboratory single-pair crosses, comparing technical replicates, and comparing genotypes of samples genotyped by WGS and the SNP chip. We then used the chip for a population genomic analysis of 237 samples from 28 sites in the native range to evaluate its usefulness in describing patterns of genomic variation and tracing the origins of invasions. RESULTS: Probes on the Aealbo chip targeted 175,396 SNPs in coding and non-coding regions across all three chromosomes, with a density of 102 SNPs per 1 Mb window, and at least one SNP in each of the 17,461 protein-coding genes. Overall, 70% of the probes captured the genetic variation. Segregation analysis found that 98% of the SNPs followed expectations of single-copy Mendelian genes. Comparisons with WGS indicated that sites with genotype disagreements were mostly heterozygotes at loci with WGS read depth < 20, while there was near complete agreement with WGS read depths > 20, indicating that the chip more accurately detects heterozygotes than low-coverage WGS. Sample sizes did not affect the accuracy of the SNP chip genotype calls. Ancestry analyses identified four to five genetic clusters in the native range with various levels of admixture. CONCLUSIONS: The Aealbo chip is highly accurate, is concordant with genotypes from WGS with high sequence coverage, and may be more accurate than low-coverage WGS.

Asymmetric Deoxygenative Functionalization of Secondary Amides with Vinylpyridines Enabled by a Triple Iridium-Photoredox-Chiral Phosphoric Acid System.

An enantioselective deoxygenative functionalization of secondary amides with vinylpridines is developed by merging relay iridium catalysis and cooperative photoredox-chiral Brønsted acid catalysis, affording a series of valuable chiral amines in moderate to good yields with good enantioselectivities. The intriguing multiple catalytic system invoking triple-catalysis was found to be the key to the success of the current reactions, which may stimulate further development of catalytic methodologies for asymmetric deoxygenative transformations of amides.

Tiam1 regulates proliferation, invasion, and differentiation in neuroblastoma through the Tiam1/Rac1 signaling pathway.

Neuroblastoma is the most common extracranial solid tumor in children. The purpose of the present study is to detect the prognostic role and potential therapeutic efficacy of the T lymphoma invasion and metastasis 1 (Tiam1) in neuroblastoma. The overexpression of Tiam1 protein is frequently observed in neuroblastoma. Tiam1 expression is closely associated with adverse prognosis of neuroblastoma and risk group classification. Knockdown of TIAM1 by lentivirus expressing short hairpin RNA against TIAM1 (sh-TIAM1) inhibited the proliferation, invasion and cell-cycle progression, and promoted apoptosis of the neuroblastoma cell lines SH-SY5Y and SK-N-AS. Additionally, downregulation of the differentiation-related protein expression and decreased Rac1 expression was observed in the sh-TIAM1-transfected SH-SY5Y cells. In vivo, nude mice bearing TIAM1 knockdown SH-SY5Y cells showed improved overall survival and tumor growth suppression. The results demonstrate that inhibition of Tiam1 expression is a potential strategy for targeted therapy in neuroblastoma.

Bilateral Endoscopic Debridement Combined with Local Antituberculosis Drugs for Thoracic Tuberculosis with Large Paravertebral Abscess: A Multicenter Study with 4-year Follow-Up.

BACKGROUND: Paravertebral abscess represents a prevalent manifestation of thoracic tuberculosis, often necessitating surgical intervention. In this study, we introduced a novel approach by employing bilateral endoscopic debridement (BED) to address large Paravertebral abscesses associated with thoracic tuberculosis, a method not previously proposed in the literature. The clinical efficacy was examined through a comprehensive 4-year follow-up. METHODS: We conducted a retrospective analysis on patients diagnosed with thoracic tuberculosis and paravertebral abscess who underwent BED combined with local antituberculosis drugs (BED + LAD) between February 2015 and February 2019. A total of 29 eligible patients (12 males and 17 females) with a median (interquartile ranges) of 59.0(16.5) years were included in the study. All patients received the BED + LAD treatment. After the surgery, the patients were treated with a 4-drug antituberculosis therapy (Rifampicin, Isoniazid, Pyrazinamide, and Ethambutol). All relevant indicators were meticulously recorded and analyzed. RESULTS: The surgical procedures were successfully completed for all subjects, with an average intraoperative bleeding volume of (25.2 ± 8.9) ml, an average surgical time of (68.4 ± 14.0) minutes, an average fluoroscopy frequency of (21.7 ± 8.2) times, an average hospital stay of (14.2 ± 4.3) days, and an average medication period of (42.1 ± 9.6) weeks. All subjects completed at least a 4-year follow-up period. At the final follow-up, ESR and CRP levels returned to normal, and there was no significant increase in the Cobb angle (P>0.05). CONCLUSIONS: The application of BED + LAD in the treatment of thoracic tuberculosis and paravertebral abscess proved to be a safe, effective, and feasible approach.