Gut microbial co-metabolite 2-methylbutyrylcarnitine exacerbates thrombosis via binding to and activating integrin α2ß1.

Thrombosis represents the leading cause of death and disability upon major adverse cardiovascular events (MACEs). Numerous pathological conditions such as COVID-19 and metabolic disorders can lead to a heightened thrombotic risk; however, the underlying mechanisms remain poorly understood. Our study illustrates that 2-methylbutyrylcarnitine (2MBC), a branched-chain acylcarnitine, is accumulated in patients with COVID-19 and in patients with MACEs. 2MBC enhances platelet hyperreactivity and thrombus formation in mice. Mechanistically, 2MBC binds to integrin α2ß1 in platelets, potentiating cytosolic phospholipase A2 (cPLA2) activation and platelet hyperresponsiveness. Genetic depletion or pharmacological inhibition of integrin α2ß1 largely reverses the pro-thrombotic effects of 2MBC. Notably, 2MBC can be generated in a gut-microbiota-dependent manner, whereas the accumulation of plasma 2MBC and its thrombosis-aggravating effect are largely ameliorated following antibiotic-induced microbial depletion. Our study implicates 2MBC as a metabolite that links gut microbiota dysbiosis to elevated thrombotic risk, providing mechanistic insight and a potential therapeutic strategy for thrombosis.

C-to-G editing generates double-strand breaks causing deletion, transversion and translocation.

Base editors (BEs) introduce base substitutions without double-strand DNA cleavage. Besides precise substitutions, BEs generate low-frequency 'stochastic' byproducts through unclear mechanisms. Here, we performed in-depth outcome profiling and genetic dissection, revealing that C-to-G BEs (CGBEs) generate substantial amounts of intermediate double-strand breaks (DSBs), which are at the centre of several byproducts. Imperfect DSB end-joining leads to small deletions via end-resection, templated insertions or aberrant transversions during end fill-in. Chromosomal translocations were detected between the editing target and off-targets of Cas9/deaminase origin. Genetic screenings of DNA repair factors disclosed a central role of abasic site processing in DSB formation. Shielding of abasic sites by the suicide enzyme HMCES reduced CGBE-initiated DSBs, providing an effective way to minimize DSB-triggered events without affecting substitutions. This work demonstrates that CGBEs can initiate deleterious intermediate DSBs and therefore require careful consideration for therapeutic applications, and that HMCES-aided CGBEs hold promise as safer tools.

Relationship between SLC6A2 gene polymorphisms and brain volume in Han Chinese adults who lost their sole child.

BACKGROUND: Norepinephrine transporter (NET) is encoded by the SLC6A2 gene and is a potential target for studying the pathogenesis of PTSD. To the best of our knowledge, no prior investigations have examined SLC6A2 polymorphism-related neuroimaging abnormalities in PTSD patients. METHODS: In 218 Han Chinese adults who had lost their sole child, we investigated the association between the T-182 C SLC6A2 genotype and gray matter volume (GMV). Participants included 57 PTSD sufferers and 161 non-PTSD sufferers, and each group was further separated into three subgroups based on each participant's SLC6A2 genotype (TT, CT, and CC). All participants received magnetic resonance imaging (MRI) and clinical evaluation. To assess the effects of PTSD diagnosis, genotype, and genotype × diagnosis interaction on GMV, 2 × 3 full factorial designs were used. Pearson's correlations were used to examine the association between GMV and CAPS, HAMD, and HAMA. RESULTS: The SLC6A2 genotype showed significant main effects on GMV of the left superior parietal gyrus (SPG) and the bilateral middle cingulate gyrus (MCG). Additionally, impacts of the SLC6A2 genotype-diagnosis interaction were discovered in the left superior frontal gyrus (SFG). The CAPS, HAMA, and HAMD scores, as well as the genotype main effect and diagnostic SLC6A2 interaction, did not significantly correlate with each other. CONCLUSION: These findings indicate a modulatory effect that the SLC6A2 polymorphism exerts on the SPG and MCG, irrespective of PTSD diagnosis. We found evidence to suggest that the SLC6A2 genotype-diagnosis interaction on SFG may potentially contribute to PTSD pathogenesis in adults who lost their sole child.

Disorganized Functional Connectivity of Anterior Insular Subnetworks in Adults with Executive Dysfunction after Trauma Exposure.

There is increasing evidence that major trauma can adversely affect the brain and cognition. In some cases, trauma may lead to deficits in executive function (EF). The anterior insula may be a causal outflow hub acting to coordinate EF-related brain networks. To clarify the neural underpinnings of EF deficits (EFD) after trauma, we performed a resting-state functional magnetic resonance imaging (rs-fMRI) study of anterior insular subnetworks in adults who have lost their only child. A total of 167 participants completed various psychological and cognitive assessments to assess EF-related deficits. Correlations were computed between abnormal connectivity and cognitive/post-traumatic stress symptoms. The results showed abnormal anterior insular subregion connectivity in the default mode network (DMN), prefrontal lobe, and cerebellum lobe in participants with EFD. No correlation was found between abnormal connectivity and cognitive/post-traumatic stress symptoms in participants with EFD. These results suggest that excessive connections between the insula and DMN could contribute to EFD after trauma. Overall, this study provides novel references into the neural mechanisms of EF status after trauma exposure.

Epidemiological and laboratory characteristics of Omicron infection in a general hospital in Guangzhou: a retrospective study.

The COVID-19 pandemic caused by SARS-CoV-2 has emerged as a major global public health concern. In November 2022, Guangzhou experienced a significant outbreak of Omicron. This study presents detailed epidemiological and laboratory data on Omicron infection in a general hospital in Guangzhou between December 1, 2022, and January 31, 2023. Out of the 55,296 individuals tested, 12,346 were found to be positive for Omicron. The highest prevalence of positive cases was observed in the 20 to 39 age group (24.6%), while the lowest was in children aged 0 to 9 years (1.42%). Females had a higher incidence of infection than males, accounting for 56.6% of cases. The peak time of Omicron infection varied across different populations. The viral load was higher in older adults and children infected with Omicron, indicating age-related differences. Spearman's rank correlation analysis revealed positive correlations between Ct values and laboratory parameters in hospitalized patients with Omicron infection. These parameters included CRP (rs = 0.059, p = 0.009), PT (rs = 0.057, p = 0.009), INR (rs = 0.055, p = 0.013), AST (rs = 0.067, p = 0.002), LDH (rs = 0.078, p = 0.001), and BNP (rs = 0.063, p = 0.014). However, EO (Eosinophil, rs = -0.118, p < 0.001), BASO (basophil, rs = -0.093, p < 0.001), and LY (lymphocyte, rs = -0.069, p = 0.001) counts showed negative correlations with Ct values. Although statistically significant, the correlation coefficients between Ct values and these laboratory indices were very low. These findings provide valuable insights into the epidemiology of Omicron infection, including variations in Ct values across gender and age groups. However, caution should be exercised when utilizing Ct values in clinical settings for evaluating Omicron infection.

Altered brain degree centrality and functional connectivity in adults with executive dysfunction after trauma exposure.

Losing an only child is undoubtedly a huge blow that can adversely affect the prefrontal lobe, a highly sensitive brain region. Neuropsychological evidence emphasizes that executive function (EF) is closely related to the optimal functioning of the frontal cortex. However, the characteristics and potential mechanisms underlying changes in executive function following the huge shock of losing an only child remain insufficiently studied and understood. In this study, we performed degree centrality (DC) and functional connectivity (FC) analyses to explore the organization of the executive function deficits (EFD) network among adults who have lost their only child. In addition, we performed correlation analyses to establish an association between abnormal DC and FC values and post-traumatic stress symptoms. Finally, we used support vector machine analyses to assess the accuracy of abnormal DC and FC values in distinguishing adults with EFD who have lost their only child from those without EFD. Our findings revealed increased DC in the left superior frontal gyrus and right angular gyrus (ANG), whereas decreased DC in the left superior occipital gyrus among adults with EFD. Further FC analysis revealed that the altered FC primarily involved the prefrontal and temporal lobes and cerebellum. Notably, the altered FC between the right ANG and left inferior temporal gyrus exhibited a negative correlation with irritability symptoms (R = -0.047, p = 0.003) in the EFD group. A combined model incorporating altered DC and FC values enabled the classification of 96.69% of adults with EFD, with a sensitivity of 0.8837 and specificity of 0.9558. These findings provide valuable insights into the neural mechanisms underlying distinct EF statuses following trauma exposure, distinguishing adults with and without EFD.

Persistence of post-traumatic stress disorder in Chinese Shidu parents is associated with combined gray and white matter abnormalities.

Post-traumatic stress disorder (PTSD) is one of the most common mental health disorders among Shidu parents. Identification of gray and white matter differences between persistence of PTSD (P-PTSD) and remission of PTSD (R-PTSD) is crucial to determine their prognosis. A total of 37 Shidu parents with PTSD were followed for five years. Surface-based morphometry and diffusion tensor imaging were carried out to analyze the differences in gray and white matter between P-PTSD and R-PTSD. Finally, 30 patients with PTSD were enrolled, including 12 with P-PTSD and 18 with R-PTSD. Compared with patients with R-PTSD, patients with P-PTSD exhibited lower fractional anisotropy (FA) in Cluster 1 (including body of the corpus callosum, superior longitudinal fasciculus, corticospinal tract) and Cluster 2 (including inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, splenium of the corpus callosum) in the left cerebral hemisphere and higher cortical thickness in the right lateral occipital cortex (LOC). In patients with P-PTSD, FA values of Cluster 2 were negatively correlated with cortical thickness of the right LOC. These results suggest that among Shidu parents, differences were observed in gray and white matter between P-PTSD and R-PTSD. Moreover, some certain gray and white matter abnormalities were often present simultaneously in P-PTSD.

Role of serum cytokines in the prediction of heart failure in patients with coronary artery disease.

AIMS: Coronary artery disease (CAD) is the most common cause of heart failure (HF). This study aimed to identify cytokine biomarkers for predicting HF in patients with CAD. METHODS AND RESULTS: Twelve patients with CAD without HF (CAD-non HF), 12 patients with CAD complicated with HF (CAD-HF), and 12 healthy controls were enrolled for Human Cytokine Antibody Array, which were used as the training dataset. Then, differentially expressed cytokines among the different groups were identified, and crucial characteristic proteins related to CAD-HF were screened using a combination of the least absolute shrinkage and selection operator, recursive feature elimination, and random forest methods. A support vector machine (SVM) diagnostic model was constructed based on crucial characteristic proteins, followed by receiver operating characteristic curve analysis. Finally, two validation datasets, GSE20681 and GSE59867, were downloaded to verify the diagnostic performance of the SVM model and expression of crucial proteins, as well as enzyme-linked immunosorbent assay was also used to verify the levels of crucial proteins in blood samples. In total, 12 differentially expressed proteins were overlapped in the three comparison groups, and then four optimal characteristic proteins were identified, including VEGFR2, FLRG, IL-23, and FGF-21. After that, the area under the receiver operating characteristic curve of the constructed SVM classification model for the training dataset was 0.944. The accuracy of the SVM classification model was validated using the GSE20681 and GSE59867 datasets, with area under the receiver operating characteristic curve values of 0.773 and 0.745, respectively. The expression trends of the four crucial proteins in the training dataset were consistent with those in the validation dataset and those determined by enzyme-linked immunosorbent assay. CONCLUSIONS: The combination of VEGFR2, FLRG, IL-23, and FGF-21 can be used as a candidate biomarker for the prediction and prevention of HF in patients with CAD.

Effect of inactivated COVID-19 vaccine on the negative conversion of nucleic acid in asymptomatic or mild patients with COVID-19.

BACKGROUND: Negative conversion of nucleic acid was a key factor in deciding discharge or the end of isolation of asymptomatic or mild COVID-19 patients. We aimed to explore the effect of vaccination on the time to negative conversion after Omicron infection. METHODS: This retrospective cohort study included asymptomatic or mild patients with COVID-19 admitted to Fangcang shelter Hospital from November 10, 2022 to December 2, 2022. The relationship between vaccination status and the time to negative conversion was analyzed by multiple linear regression. RESULTS: A total of 2,104 asymptomatic or mild COVID-19 patients were included in the analysis, of whom 1,963 were vaccinated. The mean time to negative conversion of no vaccination, one dose, two doses, and three doses were 12.57 (5.05), 12.18 (3.46), 11.67 (4.86) and 11.22 (4.02) days, respectively (p = 0.002). Compared with no vaccination, two doses (ß=-0.88, 95% CI: -1.74, -0.02, p = 0.045), and three doses (ß=-1.51, 95% CI: -2.33, -0.70, p < 0.001) were both associated with shorter time to negative conversion. Comparing with two doses, booster dose was associated significantly with shorter time to negative conversion (ß=-0.63, 95% CI: -1.07, -0.20, p = 0.004). Age was positively correlated with the time to negative conversion (ß = 0.04, 95% CI: 0.02, 0.05, p < 0.001). CONCLUSION: Vaccination with inactivated vaccine and booster dose can shorten the time to negative conversion of asymptomatic or mild COVID-19 patients. The significant prolongation of time to negative conversion with increasing age suggests the promotion of vaccination, especially booster dose, particularly in the elderly.

Longitudinal changes in brain structure and their relationship with subclinical psychiatric symptoms in parents who lost their only child in China.

BACKGROUND: Losing an only child (Shidu) is a grievous traumatic event that may affect brain structure, even if it does not lead to psychiatric disorders. However, longitudinal changes in brain structure and their relationship to subclinical psychiatric symptoms (SPS) have not been well investigated in Shidu parents without any psychiatric disorders (SDNP). OBJECTIVES: This study aimed to investigate cross-sectional and longitudinal changes in cortical thickness and surface area in SDNP, and to explore their relationship with SPS. METHODS: A total of 50 SDNP and 40 matched healthy controls (HC) were enrolled. All participants underwent structural MRI scans and clinical assessment at baseline and at the 5-year follow-up. Differences in brain structural phenotypes (cortical thickness, surface area, and their annual rate of change) between the SDNP and HC groups were compared using FreeSurfer. Correlations between significant brain structural phenotypes and SPS in the SDNP group were evaluated using multiple linear regressions. RESULTS: The SDNP group showed a smaller surface area in the left inferior parietal cortex than the HC group at baseline and follow-up. The SDNP group showed slower rates of cortical thinning and surface area loss in several brain regions than the HC group from baseline to follow-up. Moreover, slower rates of cortical thinning in the left insula, superior frontal cortex, and superior temporal cortex were associated with greater reductions in avoidance, depression, and trauma re-experiencing symptoms scores over time in the SDNP group, respectively. CONCLUSIONS: Shidu trauma-induced structural abnormalities in the inferior parietal cortex may persist over time and be independent of the severity of psychiatric symptoms. The expansion of prefrontal, temporal, and insular cortex implicated in emotional regulation may contribute to improvements in psychiatric symptoms in Shidu parents.

This study focused on longitudinal changes in cortical thickness and surface area and their relationship with subclinical psychiatric symptoms in Shidu parents without any psychiatric disorders.Shidu trauma-induced structural abnormalities in the inferior parietal cortex may persist over time and be independent of the severity of psychiatric symptoms.The expansion of prefrontal, temporal, and insular cortex implicated in emotional regulation may contribute to improvements in psychiatric symptoms in Shidu parents.

Hypofractionated Radiotherapy followed by Hypofractionated Boost with weekly concurrent chemotherapy for Unresectable Stage III Non-Small Cell Lung Cancer: Results of A Prospective Phase II Study (GASTO-1049).

PURPOSE: We launched a prospective phase 2 clinical trial to explore the safety and efficacy of hypofractionated radiation therapy (hypo-RT) followed by hypofractionated boost (hypo-boost) combined with concurrent weekly chemotherapy in patients with unresectable locally advanced non-small cell lung cancer (LA-NSCLC). METHODS AND MATERIALS: Patients with newly diagnosed LA-NSCLC with unresectable stage III disease were recruited between June 2018 and June 2020. Patients were treated with hypo-RT (40 Gy in 10 fractions) followed by hypo-boost (24-28 Gy in 6-7 fractions) combined with concurrent weekly chemotherapy (docetaxel 25 mg/m2 and nedaplatin 25 mg/m2). The primary endpoint of the study was progression-free survival (PFS), and the secondary endpoints included overall survival (OS), locoregional failure-free survival (LRFS), distant metastasis-free survival (DMFS), objective response rate (ORR), and toxicities. RESULTS: From June 2018 to June 2020, 75 patients were enrolled with a median follow-up duration of 28.0 months. The ORR of the whole cohort was 94.7%. Disease progression or death was recorded in 44 (58.7%) patients, with a median PFS of 21.6 months (95% confidence interval [CI], 15.6-27.6 months). The 1- and 2-year PFS rates were 81.3% (95% CI, 72.5%-90.1%) and 43.3% (95% CI, 31.5%-55.1%), respectively. The median OS, DMFS, and LRFS had not been reached at the time of the last follow-up. The 1- and 2-year OS rates were 94.7% (95% CI, 89.6%-99.8%) and 72.4% (95% CI, 62.0%-82.8%), respectively. The most frequent acute nonhematologic toxicity was radiation esophagitis. Grade (G) 2 and G3 acute radiation esophagitis were observed in 20 (26.7%) and 4 (5.3%) patients, respectively. Thirteen patients (13/75, 17.3%) had G2 pneumonitis and no G3-G5 acute pneumonitis occurred during follow-up. CONCLUSIONS: Hypo-RT followed by hypo-boost combined with concurrent weekly chemotherapy could yield satisfactory local control and survival outcomes with moderate radiation-induced toxicity in patients with LA-NSCLC. The new potent hypo-CCRT regimen significantly shortened treatment time and provided the potential opportunity for the combination of consolidative immunotherapy.

Kaempferol has potential anti-coronavirus disease 2019 (COVID-19) targets based on bioinformatics analyses and pharmacological effects on endotoxin-induced cytokine storm.

COVID-19 has infected 272 million patients and caused 5.33 million deaths around the world, and it remains the main global threat. Previous studies revealed that Chinese traditional medicine is an effective treatment for COVID-19 infection. This study aims to reveal the pharmacological effects of kaempferol, which is the active component of Radix Bupleuri and Tripterygii Radix, and potential mechanisms for the treatment of COVID-19. Here, we employed the bioinformatics methods to filter the anti-COVID-19 candidate genes of kaempferol, which mainly enriched in inflammation (TNF, JUN, etc.) and virus infection (AKT1, JNK, etc.). The Transcription levels of AKT1, JNK and JUN were significantly reduced by kaempferol treatment in the LPS-activated macrophages. In addition, kaempferol reduced the secretion of inflammatory factors by LPS-stimulated macrophages, inhibited MAPK/NF-κB signaling and regulated macrophage polarization to M2 type in vitro, and suppressed endotoxin-induced cytokine storm and improved survival in mice. Molecular docking analysis demonstrated that kaempferol was probable to bind the COVID-19 protein 5R84 and formatted hydrogen bond with the residues, the free binding energy of which was lower than the original ligand. In summary, our current work indicates that kaempferol has anti-COVID-19 potential through the reduction of COVID-19-induced body dysfunction and molecule-protein interaction, and bioinformatics results clarify that some of these key target genes might serve as potential molecular markers for detecting COVID-19.

Extracting Tissue Optical Properties and Detecting Bruised Tissue in Pears Quickly and Accurately Based on Spatial Frequency Domain Imaging and Machine Learning.

Recently, Spatial Frequency Domain Imaging (SFDI) has gradually become an alternative method to extract tissue optical properties (OPs), as it provides a wide-field, no-contact acquisition. SFDI extracts OPs by least-square fitting (LSF) based on the diffuse approximation equation, but there are shortcomings in the speed and accuracy of extracting OPs. This study proposed a Long Short-term Memory Regressor (LSTMR) solution to extract tissue OPs. This method allows for fast and accurate extraction of tissue OPs. Firstly, the imaging system was developed, which is more compact and portable than conventional SFDI systems. Next, numerical simulation was performed using the Monte Carlo forward model to obtain the dataset, and then the mapping model was established using the dataset. Finally, the model was applied to detect the bruised tissue of 'crown' pears. The results show that the mean absolute errors of the absorption coefficient and the reduced scattering coefficient are no more than 0.32% and 0.21%, and the bruised tissue of 'crown' pears can be highlighted by the change of OPs. Compared with the LSF, the speed of extracting tissue OPs is improved by two orders of magnitude, and the accuracy is greatly improved. The study contributes to the rapid and accurate extraction of tissue OPs based on SFDI and has great potential in food safety assessment.

Spectral Reflectance Reconstruction from Red-Green-Blue (RGB) Images for Chlorophyll Content Detection.

Chlorophyll is one of the most important pigments in plants, and the measurement of chlorophyll levels enables real-time monitoring of plant growth, which is of great importance to the vegetation monitoring. Compared with the high cost and time-consuming operation of hyperspectral imaging technique, the spectral reflectance reconstruction technique based on RGB images has the advantages of being inexpensive and fast. In this study, using the example of ginkgo leaves, the spectra were reconstructed from red-green-blue (RGB) images taken by smartphones based on a back propagation (BP) neural network and pseudo-inverse method. Based on a BP neural network, the maximum absolute error between the reconstructed spectra and the reference spectra acquired by the hyperspectral camera was less than 0.038. A partial least squares regression (PLSR) prediction model for chlorophyll content estimation was established using the reconstructed spectra. The R2 and root mean square error (RMSE) of the validation set were 0.8237 and 1.1895%, respectively, there was a high correlation between predicted and measured values. Compared with the pseudo-inverse method, the maximum absolute error of the reconstructed spectra was reduced by 10.9%, the R2 in the chlorophyll prediction results was improved by 12.7%, and the RMSE was reduced by 19.3%. This research showed that reconstructing spectral reflectance based on RGB images can realize real-time measurement of chlorophyll content. It provided a reliable tool for fast and low-cost monitoring of plant physiology and growth conditions.

CT radiomics-based long-term survival prediction for locally advanced non-small cell lung cancer patients treated with concurrent chemoradiotherapy using features from tumor and tumor organismal environment.

BACKGROUND: Definitive concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced non-small cell lung cancer (LANSCLC) patients, but the treatment response and survival outcomes varied among these patients. We aimed to identify pretreatment computed tomography-based radiomics features extracted from tumor and tumor organismal environment (TOE) for long-term survival prediction in these patients treated with CCRT. METHODS: A total of 298 eligible patients were randomly assigned into the training cohort and validation cohort with a ratio 2:1. An integrated feature selection and model training approach using support vector machine combined with genetic algorithm was performed to predict 3-year overall survival (OS). Patients were stratified into the high-risk and low-risk group based on the predicted survival status. Pulmonary function test and blood gas analysis indicators were associated with radiomic features. Dynamic changes of peripheral blood lymphocytes counts before and after CCRT had been documented. RESULTS: Nine features including 5 tumor-related features and 4 pulmonary features were selected in the predictive model. The areas under the receiver operating characteristic curve for the training and validation cohort were 0.965 and 0.869, and were reduced by 0.179 and 0.223 when all pulmonary features were excluded. Based on radiomics-derived stratification, the low-risk group yielded better 3-year OS (68.4% vs. 3.3%, p < 0.001) than the high-risk group. Patients in the low-risk group had better baseline FEV1/FVC% (96.3% vs. 85.9%, p = 0.046), less Grade ≥ 3 lymphopenia during CCRT (63.2% vs. 83.3%, p = 0.031), better recovery of lymphopenia from CCRT (71.4% vs. 27.8%, p < 0.001), lower incidence of Grade ≥ 2 radiation-induced pneumonitis (31.6% vs. 53.3%, p = 0.040), superior tumor remission (84.2% vs. 66.7%, p = 0.003). CONCLUSION: Pretreatment radiomics features from tumor and TOE could boost the long-term survival forecast accuracy in LANSCLC patients, and the predictive results could be utilized as an effective indicator for survival risk stratification. Low-risk patients might benefit more from radical CCRT and further adjuvant immunotherapy. TRIAL REGISTRATION: retrospectively registered.

Metagenomic next-generation sequencing for the detection of pathogenic microorganisms in patients with pulmonary infection.

OBJECTIVE: To explore the clinical value of metagenomic next-generation sequencing (mNGS) in diagnosing pulmonary infectious diseases. METHODS: A retrospective analysis was performed on 82 patients with pulmonary infection who were admitted to the Eighth Affiliated Hospital of Guangxi Medical University & Guigang City People's Hospital from January 2020 to December 2021. The pathogens were detected by mNGS and conventional methods (culture and PCR). Then, the type and number of detected pathogens, as well as the specificity and sensitivity, were compared between the two methods. In addition, the positive rates of bacteria, fungi, tubercle bacillus, and mixed infection in bronchoalveolar lavage fluid, sputum, pleural effusion, and blood detected by mNGS, and the advantage in required test time were evaluated. RESULTS: More types and numbers of pathogens were detected by mNGS with a higher sensitivity but a lower specificity, as compared to the conventional detection methods (all P<0.05). The positive rates and integrity rates of bacteria, fungi, and tubercle bacillus detected by mNGS were higher than those by conventional methods (all P<0.05). Moreover, there was no difference in the overall sensitivity of mNGS among different sample types, but the sensitivities of mNGS in bronchoalveolar lavage fluid and sputum samples were significantly higher than those of conventional methods (both P<0.05). The average test time for mNGS was shorter than that of conventional methods. CONCLUSION: mNGS can detect more types and numbers of pathogenic microorganisms, improve the detection sensitivity, and reduce the detection time in patients with pulmonary infection.

[Influence of Optimal Land Use Allocation on Phosphorus Loss in the Process of Rainfall and Runoff].

In order to explore the impact of optimized land use allocation on phosphorus loss in the runoff process of a small watershed in the Three Gorges Reservoir area, a traditional agricultural model catchment area (CG) and a catchment area after optimized land use allocation in the Shipanqiu watershed in Zhong County, Chongqing (EG) were selected as the research object, sampling at the outlets of the two catchment areas, respectively, to monitor the runoff process and different forms of phosphorus in rainfall events and to analyze the influence of land use configuration on the law of phosphorus loss. The results showed that:① in the 10 monitored rainfall and runoff processes, the ρ[total phosphorus (TP)] of EG was lower than that of CG, and the ranges of the two were 0.09-0.75 mg·L-1 and 0.13-2.82 mg·L-1, respectively. Compared with that of CG, EG significantly reduced the peak value of TP. ② The average EMC of TP, total dissolved phosphorus (TDP), dissolved inorganic phosphorus (DIP), and particulate phosphorus (PP) in the process of rainfall and runoff was lower than that of CG, and EG and CG showed significant differences in EMC of TP, TDP, and DIP (P<0.05); the main form of phosphorus loss in the two catchment areas in the process of rainfall and runoff was TDP, but the average TDP/TP of EG was larger. ③ The output load of EG was 45%, 43%, 57%, and 47% lower than that of the TP, TDP, DIP, and PP in CG. The output load of EG and CG of various forms of phosphorus was significantly correlated with the total runoff (P<0.01). In addition, the slope of the linear fitting of various phosphorus forms in the CG catchment area to the total amount of runoff was 1.66 to 1.75 times that of EG. The output load of various phosphorus forms of CG was more sensitive to runoff than that of EG, and the output per unit area in the process of rainfall and runoff was more sensitive than that of EG. The amount of sand could have caused the difference in phosphorus concentration and output load more than the output per unit area. Optimizing land use configuration can effectively reduce the loss of various forms of phosphorus and provide a reference for the prevention and control of phosphorus loss in small watersheds in the Three Gorges Reservoir area.

Efficacy of Thymosin α1 in Management of Radiation Pneumonitis in Patients With Locally Advanced Non-Small Cell Lung Cancer Treated With Concurrent Chemoradiotherapy: A Phase 2 Clinical Trial (GASTO-1043).

PURPOSE: To evaluate the efficacy of thymosin α1 in management of radiation pneumonitis (RP) in patients with locally advanced non-small cell lung cancer (LANSCLC) treated with concurrent chemoradiotherapy (CCRT). METHODS AND MATERIALS: This phase 2, single-arm trial enrolled patients with unresectable LANSCLC of 18 to 75 years' old and an Eastern Cooperative Oncology Group performance status of 0 to 1. Eligible patients received definitive CCRT and weekly thymosin α1 from the start of CCRT until 2 months after CCRT. Patients were administered 51 Gy in 17 daily fractions or 40 Gy in 10 daily fractions in the first course followed by a re-evaluation and those patients without disease progression had an adaptive plan of 15 Gy in 5 daily fractions or 24 Gy in 6 daily fractions as a boost. Concurrent chemotherapy consisted of weekly docetaxel (25 mg/m2) and nedaplatin (25 mg/m2) during radiation therapy. The primary endpoint was the incidence of Grade (G) ≥2 RP. Secondary endpoints included the incidence of late pulmonary fibrosis, total lymphocyte count (TLC), serum C-reactive protein (CRP) levels, and the composition of gut microbiota. TLC and CRP data were collected at baseline, 2 to 3 weeks during CCRT, the end of CCRT, 2 and 6 months after CCRT. Fecal samples were collected at baseline and the end of CCRT. Patients treated with CCRT but without thymosin α1 intervention during the same period were selected as the control group by the propensity score matching method. RESULTS: Sixty-nine patients were enrolled in the study, and another 69 patients were selected as the control group. The incidence of G≥2 RP was lower in the study group compared with control cases (36.2% vs 53.6%, P = .040). G1 late pulmonary fibrosis occurred in 2 (3.7%) patients of the control group compared with no event in the study group (P = .243). Compared with the control group, the incidence of G3 to G4 lymphopenia (19.1% vs 62.1%, P < .001) was lower, and the median TLC nadir (0.51 k/µL vs 0.30 k/µL, P < .001) was higher in the study group. The proportion of patients with maximum CRP ≥100 mg/L was lower in the study group (13.8% vs 29.7% P = .029). The diversity and community composition of the gut microbiota were not significantly different between the 2 groups. CONCLUSIONS: Administration of thymosin α1 during and after CCRT was associated with significant reductions in G≥2 RP and G3 to G4 lymphopenia in patients with LANSCLC compared with historic controls.

RORA rs8042149 polymorphism moderates the association between PTSD symptom severity and transverse temporal gyrus thickness in Han Chinese adults who lost their only child.

BACKGROUND: The G allele in retinoid-related orphan receptor alpha (RORA, rs8042149) gene is associated with post-traumatic stress disorder (PTSD) diagnosis and more severe symptoms, reported in the first genome-wide association study of PTSD and subsequent replication studies. Although recent MRI studies identified brain structural deficits in RORA rs8042149 risk G allele carriers, the neural mechanism underlying RORA-related brain structural changes in PTSD remains poorly understood. METHODS: This study included 227 Han Chinese adults who lost their only child. Cortical thickness and subcortical volume were extracted using FreeSurfer, and PTSD severity was assessed using the Clinician-Administered PTSD Scale. Hierarchical linear regression was used to assess the interaction effect between RORA genotypes (T/T, G/T, and G/G) and PTSD severity on cortical and subcortical structures. RESULTS: Significant genotype × PTSD symptom severity interaction effects were found for bilateral transverse temporal gyrus thickness. For individuals with the homozygous T/T genotype, current PTSD symptom severity was positively associated with bilateral transverse temporal gyrus thickness. For individuals with heterozygous G/T genotype, current PTSD symptom severity was negatively associated with the left transverse temporal gyrus thickness. No significant main or interaction effects were found in any subcortical regions. LIMITATION: Cross-sectional design of this study. CONCLUSION: These findings suggest that the non-risk T/T genotype - but not the risk G allele carriers - has a potentially protective or compensatory role on temporal gyrus thickness in adults who lost their only child. These results highlight the moderation effect of RORA polymorphism on the relationship between PTSD symptom severity and cortical structural changes.

UBR3 promotes inflammation and apoptosis via DUSP1/p38 pathway in the nucleus pulposus cells of patients with intervertebral disc degeneration.

Intervertebral disc disease (IDD) is a primary cause of low back pain, affecting 5% of individuals. Previous study have shown that dual-specificity (Thr/Tyr) phosphatase 1 (DUSP1) regulates p38 MAPK activity and DUSP1 level is regulated by ubiquitination. As an E3 ubiquitin-protein ligase, UBR3 has been shown to regulate a variety of biological processes through ubiquitination. However, the role of UBR3/DUSP1/p38 in IDD remains to be elucidated. In the current study, we found that UBR3 was significantly increased in the nucleus pulposus tissues of IDD patients and was correlated with IDD severity. Silencing UBR3 promoted the growth, inhibited apoptosis, and inhibited inflammation in primary NPCs. Mechanism study suggested that UBR3 exerted its effects through p38. Co-immunoprecipitation assay indicated that UBR3 promoted DUSP1 ubiquitination. Overexpression of DUSP1 reversed the effect of UBR3 overexpression. Our data also supported that UBR3 was positively correlated with p-p38, but negatively correlated with DUSP1 in IDD. In summary, UBR3 promotes inflammation and apoptosis via inhibiting the p38 signaling pathway by DUSP1 ubiquitination in the NPCs of IDD patients. These findings highlight the importance of UBR3/DUSP1/p38 signaling pathway in IDD and provide new insights for the prevention and treatment of IDD.