Assessment of sedation by automated pupillometry in critically ill patients: a prospective observational study.

BACKGROUND: Quantitative measurement of pupil change has not been assessed against the Richmond Agitation and Sedation Scale (RASS) and spectral edge frequency (SEF) during sedation. The aim of this study was to evaluate pupillometry against these measures in sedated critically ill adult patients. METHODS: In ventilated and sedated patients, pupillary variables were measured by automated pupillometry at each RASS level from -5 to 0 after discontinuation of hypnotics, while processed electroencephalogram variables were displayed continuously and SEF was recorded at each RASS level. Correlations were made between percentage pupillary light reflex (%PLR) and RASS, and between %PLR and SEF. The ability of %PLR to differentiate light sedation (RASS ≥-2), moderate (RASS =-3), and deep sedation (RASS ≤-4) was assessed by areas under receiver operating characteristic (ROC) curves. RESULTS: A total of 163 paired measurements were recorded in 38 patients. With decreasing sedation depth, median %PLR increased progressively from 20% (interquartile range 17-25%) to 36% (interquartile range 33-40%) (P<0.001). Strong correlations were found between %PLR and RASS (Rho=0.635) and between %PLR and SEF (R=0.641). Area under the curve (AUC) of 0.87 with a %PLR threshold of 28% differentiated moderate/light sedation from deep sedation with sensitivity of 83% and specificity of 83%. An AUC of 0.82 with a threshold of 31% distinguished light sedation from moderate/deep sedation with a sensitivity of 81% and a specificity of 75%. CONCLUSIONS: Quantitative assessment of %PLR correlates with other indicators of sedation depth in critically ill patients.

Bbhox2 is a key regulator for conidiation and virulence in Beauveria bassiana.

Beauveria bassiana, a well-known filamentous biocontrol fungus, is the main pathogen of numerous field and forest pests. To explore the potential factors involved in the fungal pathogenicity, Bbhox2, an important and conserved functional transcription factor containing homeodomain was carried out by functional analysis. Homologous recombination was used to disrupt the Bbhox2 gene in B.bassiana. The conidia yield of the deletant fungal strain was significantly reduced. The conidial germination was faster, and stress tolerance to Congo red and high osmotic agents were decreased compared with that in the wildtype. Additionally, ΔBbhox2 showed a dramatic reduction in virulence no matter in topical inoculations or in intra-hemolymph injections against Galleria mellonella larvae, which is likely due to the failure of appressorium formation and the defect in producing hyphal body. These results indicate that the Bbhox2 gene markedly contributes to conidiation and pathogenicity in B. bassiana.

[Clinical analysis of endoscopic esophageal dilation for the treatment of corrosive esophageal strictures in children]. / å† é•œä¸‹é£Ÿç®¡æ‰©å¼ æ²»ç–—å„¿ç«¥è èš€æ€§é£Ÿç®¡ç‹­çª„çš„ä¸´åºŠåˆ†æž.

OBJECTIVES: To investigate the clinical application of endoscopic esophageal dilation in the treatment of corrosive esophageal strictures in children. METHODS: A retrospective analysis was performed on the clinical data of 15 children with corrosive esophageal strictures who underwent endoscopic esophageal dilation in Children's Hospital, Zhejiang University School of Medicine. The clinical features, treatment modality of endoscopic esophageal dilation, number of dilations, complications, and prognosis were reviewed. RESULTS: A total of 96 esophageal dilations were performed in the 15 children with corrosive esophageal strictures, with a median of 6 dilations per child. Among them, 9 children (60%) underwent 6 or more dilations. The children with a stricture length of >3 cm had a significantly higher number of dilations than those with a stricture length of ≤3 cm (P<0.05). The children with strictures in a single segment had a significantly better treatment outcome than those with strictures in multiple segments (P=0.005). No complication was observed during all sessions of dilation. The overall effective rate (including significant improvement and improvement) of endoscopic esophageal dilation treatment was 87%, with 2 cases of failure. CONCLUSIONS: Endoscopic esophageal dilation is an effective and relatively safe treatment method for corrosive esophageal strictures in children, and children with strictures in a single segment tend to have a better treatment outcome than those with strictures in multiple segments.

[Analysis of Characteristics and Sensitivity of Photochemical Pollution During High Ozone Season in Shanghai from 2016 to 2020].

The sensitivity analysis of ozone generation in key ozone-polluted regions and cities is an important basis for the prevention and control of near-surface ozone （O3） pollution. Based on the five-year data of ozone, VOCs, and NOx from three typical stations in Shanghai, namely Dianshan Lake Station （suburban area）, Pudong Station （urban area）, and Xinlian Station （industrial area） from 2016 to 2020, the nonlinear relationship between ozone and precursors （VOCs and NOx） during the high-ozone season in the five years was quantitatively analyzed using an observation model. The results showed that the peak months of near-surface ozone in Shanghai were from April to September during 2016 to 2020, with the highest values appearing from June to August. The volume fraction of VOCs and NO2 concentration had a strong indicative significance for the O3 concentration at Pudong Station. The O3 concentration at Dianshan Lake Station was mainly influenced by regional environment, meteorological factors, and cross-regional transmission. The ozone concentration at Xinlian Station was a combination of environmental background concentration and industrial area photochemical pollution. Pudong Station and Dianshan Lake Station were in the VOCs control zone. Xinlian Station was gradually closer to the NOx control zone from 2016 to 2019, transitioning to the VOCs control zone since 2020. The L·OH of Pudong Station, Dianshan Lake Station, and Xinlian Station were： NOx control area>collaborative control area>VOCs control area.

Expression of a viral ecdysteroid UDP-glucosyltransferase enhanced the insecticidal activity of the insect pathogenic fungus Beauveria bassiana.

BACKGROUND: Entomopathogenic fungi, such as Beauveria bassiana, hold promise as biological control agents against insect pests. However, the efficacy of these fungi can be hindered by insect immune responses. One strategy to enhance fungal virulence is to manipulate host immune by targeting key regulatory molecules like 20-hydroxyecdysone (20E). RESULTS: In this study, we engineered B. bassiana strains to constitutively express the enzyme ecdysteroid UDP-glucosyltransferase (EGT), which inactivates 20E, a crucial insect molting hormone. The engineered strain Bb::EGT-1 exhibited robust expression of EGT, leading to a significant reduction in insect 20E levels upon infection. Moreover, infection with Bb::EGT-1 resulted in accelerated larval mortality. Immune responses analysis revealed repression of insect immune response genes and decreased phenoloxidase (PO) activity in larvae infected with Bb::EGT-1. Microbiome analysis indicated alterations in bacterial composition within infected insects, with increased abundance observed during infection with Bb::EGT-1. Additionally, the presence of bacteria hindered hyphal emergence from insect cadavers, suggesting a role for microbial competition in fungal dissemination. CONCLUSIONS: Constitutive expression of EGT in B. bassiana enhances fungal virulence by reducing insect 20E levels, suppressing immune responses, and altering the insect microbiome. These findings highlighted the potential of engineered fungi as effective biocontrol agents against insect pests and provide insights into the complex interactions between entomopathogenic fungi, their hosts, and associated microbes. © 2024 Society of Chemical Industry.

An efficient visual screening of gene knockout mutants in the insect pathogenic fungus Beauveria bassiana.

Beauveria bassiana is an entomopathognic fungus, which is widely employed in the biological control of pests. Gene disruption is a common method for studying the functions of genes involved in fungal development or its interactions with hosts. However, generating gene deletion mutants was a time-consuming work. The transcriptional factor OpS3 has been identified as a positive regulator of a red secondary metabolite oosporein in B. bassiana. In this study, we have designed a new screening system by integrating a constitutive OpS3 expression cassette outside one of the homologous arms of target gene. Ectopic transformants predominantly exhibit a red colour with oosporein production, while knockout mutants appear as white colonies due to the loss of the OpS3 expression cassette caused by recombinant events. This screening strategy was used to obtain the deletion mutants of both tenS and NRPS genes. Correct mutants were obtained by screening fewer than 10 mutants with a positive efficiency ranging from 50% to 75%. This system significantly reduces the workload associated with DNA extraction and PCR amplification, thereby enhancing the efficiency of obtaining correct transformants in B. bassiana.

In Vivo Mouse Models for Adult Brain Tumors: Exploring Tumorigenesis and Advancing Immunotherapy Development.

Brain tumors, particularly glioblastoma (GBM), are devastating and challenging to treat, with a low 5-year survival rate of only 6.6%. Mouse models are established to understand tumorigenesis and develop new therapeutic strategies. Large-scale genomic studies have facilitated the identification of genetic alterations driving human brain tumor development and progression. Genetically engineered mouse models (GEMMs) with clinically relevant genetic alterations are widely used to investigate tumor origin. Additionally, syngeneic implantation models, utilizing cell lines derived from GEMMs or other sources, are popular for their consistent and relatively short latency period, addressing various brain cancer research questions. In recent years, the success of immunotherapy in specific cancer types has led to a surge in cancer immunology-related research which specifically necessitates the utilization of immunocompetent mouse models. In this review, we provide a comprehensive summary of GEMMs and syngeneic mouse models for adult brain tumors, emphasizing key features such as model origin, genetic alteration background, oncogenic mechanisms, and immune-related characteristics. Our review serves as a valuable resource for the brain tumor research community, aiding in the selection of appropriate models to study cancer immunology.

Experimental study on the effect of freeze-thaw cycles to the cohesion and moisture content of geogrid reinforced silty clay.

The freezing and thawing cycle is one of the primary causes of damage and instability to buildings in seasonal frost regions. During this process, the mechanical properties of soil are affected, leading to settlement, cracking, or deformation of infrastructure. Mitigating or reducing the occurrence of building frost damage in seasonal frost regions has become an important subject of study. Freeze-thaw (F-T) action will influence the distribution of moisture inside the reinforced soil and change the strength of thawing soil, which is closely related to the main influencing factors, such as initial moisture content, compaction degree, reinforced spacing, number of freeze-thaw cycles (FTC), freezing temperature, and effective vertical stress. Cohesion is an important index to determine the shear strength of clay, which is important to analyze the change in cohesion after F-T. Meanwhile, cohesion is closely related to soil moisture content. This study conducted orthogonal experiments on these primary influencing factors (6 factors at 5 levels) through FTC tests, triaxial tests, and moisture content tests to determine the undrained cohesion and moisture content of the clay after FTC, thereby establishing the influence of reinforcement on soil strength under freeze-thaw conditions. Based on the experimental results, SPSS software was used to fit the regression equations of undrained cohesion and moisture content expressed by the main influencing factors at different heights of the clay. Optimization options for the main influencing factors were obtained with Matlab software when the highest undrained cohesion values 6.8, 10.6, 8.9 kPa and lowest moisture content values 24.0%, 24.3%, 26.2% appeared in upper, middle and lower parts of the testing clay structure respectively, in conditions of - 15 °C freezing temperature and 5 times FTC. And determined the optimal combinations of moisture content, reinforcement spacing, compaction density, and vertical load at different heights. Decreasing reinforced spacing in silty clay was beneficial for liquid underwater seepage after F-T. The redistribution of internal moisture in the soil sample strengthened its undrained cohesion, thereby increasing the soil's shear strength. Comparing reinforcement conditions at different locations, it was found that when there were 3 layers of reinforcement with a spacing of 150 mm between them, this spacing was optimal. It played a significant role in improving the soil's shear strength and enhancing its bearing capacity. For reinforced clay itself, the order of the main factors influencing the undrained cohesion of soil after F-T, from high to low, was initial moisture content, reinforced spacing, and compaction degree.

Epidural ropivacaine versus bupivacaine for cesarean sections: a system review and meta-analysis.

INTRODUCTION: It is still no consensus on the use of ropivacaine or bupivacaine in epidural anesthesia for cesarean section (CS), because their anesthetic potency and relative complications remains controversial. This system review and meta-analysis aimed to compare the efficacy of epidural ropivacaine and bupivacaine for elective CSs and investigate relative complications for parturients and neonates. METHODS: We searched PubMed, MEDLINE, Embase, Cochrane Library, Science-Direct, and Google Scholar to June 30, 2023 for randomized controlled trials (RCTs), which compared epidural ropivacaine with bupivacaine for elective CSs. The success rate of epidural anesthesia (EA) was primary outcome. The secondary outcomes included onset times of sensory block, maternal side effects, neonatal Apgar scores and umbilical artery pH. RESULTS: We analyzed 8 RCTs with 532 parturients. 0.75% ropivacaine is associated with a shorter onset time of sensory block than 0.5% bupivacaine (SMD = -0.43, 95% CI: -0.70 to -0.17; p = .001). 0.5% ropivacaine resulted in a reduced nausea than 0.5% bupivacaine (RR = 0.49, 95% CI: 0.28 to 0.83; p = .008). In addition, there were no significant difference between ropivacaine and bupivacaine groups in terms of success rate of epidural anesthesia, maternal side effects (hypotension, bradycardia, shivering), and neonatal Apgar scores and umbilical artery pH. CONCLUSIONS: The findings suggest that there were no significant difference between epidural ropivacaine and bupivacaine for elective CSs in terms of the success rate (85.9% vs. 83.5), maternal side effects (hypotension, bradycardia, shivering), and neonatal Apgar scores and umbilical artery pH. But compared with 0.5% bupivacaine, epidural 0.75% ropivacaine was mildly effective for reducing onset time of sensory block and 0.5% ropivacaine reduced the incidence of maternal nausea.

Bioactive chitosan/polydopamine nanospheres coating on carbon fiber towards strengthening epoxy composites.

This paper initially examines the feasibility and effectiveness on interfacial adhesion of composites when grafting nanoparticle-structured polydopamine (PDA) and chitosan around carbon fiber periphery. The resulting interfacial shear strength was maximized as 92.3 MPa, delivering 50.1 % and 15.7-16.2 % gains over those of control fiber and only polydopamine nanospheres (PDANPs) or only chitosan modified fiber composites. Measuring surface morphology and thermal stability of fibers found that abundant PDANPs well adhered with the help of chitosan, highlighting nanoscale size effects and intrinsic adhesiveness of PDA. Under good wettability, rich and dense interfacial interactions (covalent and hydrogen bond, electrostatic interaction, and π conjugation) caused by PDANPs/chitosan coating provides impetus for effective stress transfer. Additionally, the stable "soft-rigid" combination of chitosan and PDANPs adds the efficiency of crack passivation. As such, it is hoped that this work could fully explore the possibility of PDA geometry in interphase engineering of fiber composites.

An Oxidoreductase-like Protein is Required for Verticillium dahliae Infection and Participates in the Metabolism of Host Plant Defensive Compounds.

Verticillium dahliae, a notorious phytopathogenic fungus, is responsible for vascular wilt diseases in numerous crops. Uncovering the molecular mechanisms underlying pathogenicity is crucial for controlling V. dahliae. Herein, we characterized a putative oxidoreductase-like protein (VdOrlp) from V. dahliae that contains a functional signal peptide. While the expression of VdOrlp was low in artificial media, it significantly increased during host infection. Deletion of VdOrlp had minimal effects on the growth and development of V. dahliae but severely impaired its pathogenicity. Metabolomic analysis revealed significant changes in organic heterocyclic compounds and phenylpropane compounds in cotton plants infected with ΔVdOrlp and V991. Furthermore, VdOrlp expression was induced by lignin, and its deletion affected the metabolism of host lignin and phenolic acids. In conclusion, our results demonstrated that VdOrlp plays an important role in the metabolism of plant phenylpropyl lignin and organic heterocyclic compounds and is required for fungal pathogenicity in V. dahliae.

Synergistic Effects of Chemotherapy and Phototherapy on Ovarian Cancer Using Follicle-Stimulating Hormone Receptor-Mediated Liposomes Co-Loaded with SN38 and IR820.

We have developed an ovarian cancer-targeted drug delivery system based on a follicle-stimulating hormone receptor (FSHR) peptide. The lipophilic chemotherapeutic drug SN38 and the photosensitizer IR820 were loaded into the phospholipid bilayer of liposomes. The combination of chemotherapy and phototherapy has become a promising strategy to improve the therapeutic effect of chemotherapy drugs on solid tumors. IR820 can be used for photodynamic therapy (PDT), effectively converting near-infrared light (NIR) into heat and producing reactive oxygen species (ROS), causing damage to intracellular components and leading to cell death. In addition, PDT generates heat in near-infrared, thereby enhancing the sensitivity of tumors to chemotherapy drugs. FSH liposomes loaded with SN38 and IR820 (SN38/IR820-Lipo@FSH) were prepared using thin-film hydration-sonication. FSH peptide binding was analyzed using 1H NMR spectrum and Maldi-Tof. The average size and zeta potential of SN38/IR820-Lipo@FSH were 105.1 ± 1.15 nm (PDI: 0.204 ± 0.03) and -27.8 ± 0.42 mV, respectively. The encapsulation efficiency of SN38 and IR820 in SN38/IR820-Lipo@FSH liposomes were 90.2% and 91.5%, respectively, and their release was slow in vitro. FSH significantly increased the uptake of liposomes, inhibited cell proliferation, and induced apoptosis in A2780 cells. Moreover, SN38/IR820-Lipo@FSH exhibited better tumor-targeting ability and anti-ovarian cancer activity in vivo when compared with non-targeted SN38/IR820-Lipo. The combination of chemotherapy and photodynamic treatment based on an FSH peptide-targeted delivery system may be an effective approach to treating ovarian cancer.

Impact of thermal ultrasound on enzyme inactivation and flavor improvement of sea cucumber hydrolysates.

In this study, the effects of the thermal ultrasonic enzyme inactivation process on flavor enhancement in sea cucumber hydrolysates (SCHs) and its impact on the inactivation of neutral proteases (NPs) were investigated. The body wall of the sea cucumber was enzymatically hydrolyzed with NPs. On the one hand, the structure of NPs subjected to different enzyme inactivation methods was analyzed using ζ-potential, particle size, and Fourier transform infrared (FT-IR) spectroscopy. On the other hand, the microstructure and flavor changes of SCHs were examined through scanning electron microscopy, E-nose, and gas chromatography-ion mobility spectrometry (GC-IMS). The results indicated that thermal ultrasound treatment at 60 °C could greatly affect the structure of NPs, thereby achieving enzyme inactivation. Furthermore, this treatment generated more pleasant flavor compounds, such as pentanal and (E)-2-nonenal. Hence, thermal ultrasound treatment could serve as an alternative process to traditional heat inactivation of enzymes for improving the flavor of SCHs.

Comprehensive repair of the alveolar cleft using cortical and cancellous bone layers: A retrospective study.

To retrospectively review the clinical effect of comprehensive treatment of alveolar cleft (CTAC) using the mandible as the bone source. Patients with alveolar clefts who met the inclusion criteria were subjected to a CTAC protocol that included the following: (1) preoperative orthodontic treatment for creating good soft-tissue conditions; (2) 'area-like grafting' with subperiosteal osteogenic chin bone instead of cartilaginous osteogenic iliac bone; (3) simulation of normal bone anatomy via a sandwich-like bone graft consisting of 'cortical bone + cancellous bone + cortical bone'; and (4) strong internal fixation to ensure initial bone block stability. At 6 months postoperatively, the titanium plate was removed and cone-beam computed tomography was performed to evaluate the surgical results. A total of 54 patients underwent treatment with the CTAC protocol. The average age at the initial operation was 10.3 ± 2.1 years, and the average hospital stay was 2.8 ± 0.6 days. At 6 months postoperatively, 49 patients (90.7%) showed good clinical results. The transplanted bone block formed a 'cortical bone + cancellous bone + cortical bone' structure similar to that of the normal jawbone. A mature bone bridge formed, and the impacted permanent teeth continued to erupt and enter the bone graft area. CTAC is a comprehensive restorative solution for alveolar cleft repair that integrates multiple concepts, including orthodontics, embryology, anatomy, and improvements to surgical methods. The method is easy to perform, causes little surgical trauma, and shows a stable success rate, and is thus worth promoting.

Deep Learning Imaging Reconstruction Algorithm for Carotid Dual Energy CT Angiography: Opportunistic Evaluation of Cervical Intervertebral Discs-A Preliminary Study.

Thus, the aim of this study is to evaluate the performance of deep learning imaging reconstruction (DLIR) algorithm in different image sets derived from carotid dual-energy computed tomography angiography (DECTA) for evaluating cervical intervertebral discs (IVDs) and compare them with those reconstructed using adaptive statistical iterative reconstruction-Veo (ASiR-V). Forty-two patients who underwent carotid DECTA were included in this retrospective analysis. Three types of image sets (70 keV, water-iodine, and water-calcium) were reconstructed using 50% ASiR-V and DLIR at medium and high levels (DLIR-M and DLIR-H). The diagnostic acceptability and conspicuity of IVDs were assessed using a 5-point scale. Hounsfield Units (HU) and water concentration (WC) values of the IVDs; standard deviation (SD); and coefficient of variation (CV) were calculated. Measurement parameters of the 50% ASIR-V, DLIR-M, and DLIR-H groups were compared. The DLIR-H group showed higher scores for diagnostic acceptability and conspicuity, as well as lower SD values for HU and WC than the ASiR-V and DLIR-M groups for the 70 keV and water-iodine image sets (all p < .001). However, there was no significant difference in scores and SD among the three groups for the water-calcium image set (all p > .005). The water-calcium image set showed better diagnostic accuracy for evaluating IVDs compared to the other image sets. The inter-rater agreement using ASiR-V, DLIR-M, and DLIR-H was good for the 70 keV image set, excellent for the water-iodine and water-calcium image sets. DLIR improved the visualization of IVDs in the 70 keV and water-iodine image sets. However, its improvement on color-coded water-calcium image set was limited.

Machine Learning-Directed Conversion of Glioblastoma Cells to Dendritic Cell-like Antigen-Presenting Cells as Cancer Immunotherapy.

Immunotherapy has limited efficacy in glioblastoma (GBM) due to the blood-brain barrier and the immunosuppressed or "cold" tumor microenvironment (TME) of GBM, which is dominated by immune-inhibitory cells and depleted of cytotoxic T lymphocytes (CTL) and dendritic cells (DC). Here, we report the development and application of a machine-learning precision method to identify cell fate determinants (CFD) that specifically reprogram GBM into induced antigen-presenting cells with DC-like functions (iDC-APC). In murine GBM models, iDC-APCs acquired DC-like morphology, regulatory gene expression profile, and functions comparable to natural DCs. Among these acquired functions were phagocytosis, direct presentation of endogenous antigens, and cross presentation of exogenous antigens. The latter endowed the iDC-APCs with the ability to prime naïve CD8+ CTLs, a hallmark DC function critical for antitumor immunity. Intratumor iDC-APCs reduced tumor growth and improved survival only in immunocompetent animals, which coincided with extensive infiltration of CD4+ T cells and activated CD8+ CTLs in the TME. The reactivated TME synergized with an intratumor soluble PD-1 decoy immunotherapy and a DC-based GBM vaccine, resulting in robust killing of highly resistant GBM cells by tumor-specific CD8+ CTLs and significantly extended survival. Lastly, we defined a unique CFD combination specifically for the human GBM to iDC-APC conversion of both glioma stem-like cells (GSC) and non-GSC GBM cells, confirming the clinical utility of a computationally directed, tumor-specific conversion immunotherapy for GBM and potentially other solid tumors.

BpAFP, a Broussonetia papyrifera latex chitinase, exhibits a dual role in resisting to both Verticillium wilt disease and lepidopterous pests, Plutella xylostella and Prodenia litura.

Paper mulberry (Broussonetia papyrifera) is a fast-growing tree known for its tolerance to diverse biotic and abiotic stresses. To explore genes combating Verticillium wilt, a devasting and formidable disease damage to cotton and many economically significant crops, we purified an antifungal protein, named BpAFP, from the latex of paper mulberry. Based on peptide fingerprint, we cloned the full cDNA sequence of BpAFP and revealed that BpAFP belongs to Class I chitinases, sharing 74 % identity with B. papyrifera leaf chitinase, PMAPII. We further introduced BpAFP into Arabidopsis, tobacco, and cotton. Transgenic plants exhibited significant resistance to Verticillium wilt. Importantly, BpAFP also demonstrated insecticidal activity against herbivorous pests, Plutella xylostella, and Prodenia litura, when feeding the larvae with transgenic leaves. Our finding unveils a dual role of BpAFP in conferring resistance to both plant diseases and lepidopterous pests.

Disease burden of COPD attributable to PM2.5 in China, Japan and South Korea from 1990 to 2019: a comparative study based on Global Burden of Disease Study 2019.

OBJECTIVE: We hope to reveal the changing trends of chronic obstructive pulmonary disease (COPD) burden attributable to particulate matter pollution (PM2.5) and its age, period and cohort effects in China, Japan and Korea. DESIGN: We analysed the trend of COPD disease burden attributable to PM2.5 from 1990 to 2019 based on the latest Global Burden of Disease Database (GBD 2019) using JoinPoint model and analysed the effect of age, period and cohort on COPD burden attributable to PM2.5 in China, Japan and Korea from 1990 to 2019 using age-period-cohort model (model). SETTING: GBD data from 1990 to 2019. PARTICIPANTS: Data were publicly available and individuals were not involved. MAIN OUTCOMES: Outcomes included the age standardised mortality rate (ASMR), the age-standardised disability-adjusted life year (DALY), average annual per cent change (AAPC), net drift, local drift, longitudinal age curves, period (cohort) rate ratios, age (period, cohort) bias coefficient. RESULTS: From 1990 to 2019, the ASMR of COPD attributable to PM2.5 in China (AAPC=-5.862), Japan (AAPC=-1.715) and Korea (AAPC=-1.831) showed a downward trend. The age-standardised DALY of COPD attributable to PM2.5 in China (AAPC=-5.821), Japan (AAPC=-1.39) and Korea (AAPC=-1.239) showed a downward trend. Mortality of COPD attributable to PM2.5 increased slowly with age in Korea and Japan. Mortality of COPD attributable to PM2.5 in China decreased after rising (95% CI: 404.66 to 466.01). Mortality of COPD attributable to PM2.5 decreased over time in China and Korea, while it increased in Japan from 2015 to 2019. In China and Japan, mortality of COPD attributable to PM2.5 was approximately lower the later the birth, while in Korea it decreased after an increase (95% CI: 2.13 to 2.40) in the 1900-1910. CONCLUSIONS: Most COPD burden attributable to PM2.5 is on the decline; COPD mortality attributable to PM2.5 both increased with age and decreased with time and cohort. Countries with high burden should develop targeted measures to control PM2.5.

Tas2R143 regulates the expression of the Blood-Testis Barrier tight junction protein in TM4 cells through the NF-κB signaling pathway.

Although bitter receptors, known as Tas2Rs, have been identified in the testes and mature sperm, their expression in testicular Sertoli cells (SCs) and their role in recognizing harmful substances to maintain the immune microenvironment remain unknown. To explore their potential function in spermatogenesis, this study utilized TM4 cells and discovered the high expression of the bitter receptor Tas2R143 in the cells. Interestingly, when the Tas2R143 gene was knocked down for 24 and 48 h, there was a significant downregulation (P < 0.05) in the expression of tight junction proteins (occludin and ZO-1) and NF-κB. Additionally, Western blot results demonstrated that the siRNA-133+NF-κB co-treatment group displayed a significant downregulation (P < 0.05) in the expression of occludin and ZO-1 compared to both the siRNA-133 transfection group and the NF-κB inhibitors treatment group. These findings suggest that Tas2R143 likely regulates the expression of occludin and ZO-1 through the NF-κB signaling pathway and provides a theoretical basis for studying the regulatory mechanism of bitter receptors in the reproductive system, aiming to attract attention to the chemical perception mechanism of spermatogenesis.