Spatially resolved transcriptomic profiling of placental development in dairy cow.

The placenta plays a crucial role in successful mammalian reproduction. Ruminant animals possess a semi-invasive placenta characterized by a highly vascularized structure formed by maternal endometrial caruncles and fetal placental cotyledons, essential for full-term fetal development. The cow placenta harbors at least two trophoblast cell populations: uninucleate (UNC) and binucleate (BNC) cells. However, the limited capacity to elucidate the transcriptomic dynamics of the placental natural environment has resulted in a poor understanding of both the molecular and cellular interactions between trophoblast cells and niches, and the molecular mechanisms governing trophoblast differentiation and functionalization. To fill this knowledge gap, we employed Stereo-seq to map spatial gene expression patterns at near single-cell resolution in the cow placenta at 90 and 130 days of gestation, attaining high-resolution, spatially resolved gene expression profiles. Based on clustering and cell marker gene expression analyses, key transcription factors, including YBX1 and NPAS2, were shown to regulate the heterogeneity of trophoblast cell subpopulations. Cell communication and trajectory analysis provided a framework for understanding cell-cell interactions and the differentiation of trophoblasts into BNCs in the placental microenvironment. Differential analysis of cell trajectories identified a set of genes involved in regulation of trophoblast differentiation. Additionally, spatial modules and co-variant genes that help shape specific tissue structures were identified. Together, these findings provide foundational insights into important biological pathways critical to the placental development and function in cows.

Quantification and Characterization of Fine Plastic Particles as Considerable Components in Atmospheric Fine Particles.

The negative effects of air pollution, especially fine particulate matter (PM2.5, particles with an aerodynamic diameter of ≤2.5 µm), on human health, climate, and ecosystems are causing significant concern. Nevertheless, little is known about the contributions of emerging pollutants such as plastic particles to PM2.5 due to the lack of continuous measurements and characterization methods for atmospheric plastic particles. Here, we investigated the levels of fine plastic particles (FPPs) in PM2.5 collected in urban Shanghai at a 2 h resolution by using a novel versatile aerosol concentration enrichment system that concentrates ambient aerosols up to 10-fold. The FPPs were analyzed offline using the combination of spectroscopic and microscopic techniques that distinguished FPPs from other carbon-containing particles. The average FPP concentrations of 5.6 µg/m3 were observed, and the ratio of FPPs to PM2.5 was 13.2% in this study. The FPP sources were closely related to anthropogenic activities, which pose a potential threat to ecosystems and human health. Given the dramatic increase in plastic production over the past 70 years, this study calls for better quantification and control of FPP pollution in the atmosphere.

Research on the Changes in Catecholamine and Other Indicators during Different Training Phases in Female Volleyball Players.

Objective: This study seeks to assess the functional status and central fatigue state of athletes in the Shanghai women's volleyball team during the training phase of the 2021 Shaanxi National Games. Employing a comprehensive methodology involving functional status assessment and catecholamine index analysis, the research aims to establish a scientific foundation for preparing for the 2025 National Games. Additionally, it aims to provide valuable insights for preventing excessive fatigue and promoting the rational elimination of fatigue. Methods: (1) Participants: Twelve adult female volleyball players from Shanghai participated in the study. The average age of the participants was 26.23±3.39 years, and they had an average training period of 11.92±3.73 years. (2) Training Period: The study spanned a duration of 21 consecutive weeks, during which the training regimen was divided into eight distinct stages based on specific content and tasks. (3) Testing Procedures: Various tests were conducted at specific intervals throughout the training period. These included assessments performed at the conclusion of each upper training stage and the Metamorphosis stage. Additionally, comprehensive testing was carried out before and after both the preliminaries and championship matches of the National Games. Fasting elbow venous blood samples were collected for assessing functional status indicators, including Hemoglobin (HGB), Blood Urea Nitrogen (BUN), Creatine Kinase (CK), Serum Ferritin (SF), Testosterone (T), Cortisol (C), Testosterone/Cortisol ratio (T/C). Moreover, blood catecholamine indicators (Dopamine (DA), Norepinephrine (NE), Epinephrine (E) were analyzed before the National Games, at the end of Metamorphosis stage 2, and at the conclusion of upper phase 3. (4)Data Analysis: The collected data underwent rigorous statistical processing using SPSS 25.0 statistical software package and Microsoft Excel software. This comprehensive analysis was essential for deriving meaningful conclusions and identifying significant patterns in the athletes' functional status and central fatigue states. Results: (1) HGB, T, and T/C showed the same trend throughout the whole period. The upper phase 1 drops significantly to the lowest value and the Metamorphosis stage increases. The training stage 2 fell again, but the decline was less than the training stage 1, and the Metamorphosis stage 2 increased significantly, and there was a significant difference between the basic value and the training stages (P < .05). Testosterone increased significantly to the maximum before the final of the National Games, and there was a significant difference between the baseline and the pre-match (P < .05). (2) At the end of the training stage, DA, and E decreased significantly, and there was no significant difference in NE decline. During the preliminaries of the National Games, DA, NE, and E all declined, but there was no significant difference. In the championship stage, DA, NE, and E both increased, but only NE was significantly different from the Metamorphosis stage and the championship (P < .05). Conclusion: (1) Performance Enhancement: Recognizing and addressing performance dips in the training stage through targeted adjustments can optimize athlete performance. Athletes exhibit improved competitiveness during actual games, indicating the effectiveness of tailored interventions (2) Strategic Fatigue Management: Distinguishing between body and central fatigue is vital. Monitoring sensitive markers like blood dopamine and adrenaline in the training stage enables timely fatigue management. Understanding the relationship between blood testosterone and dopamine offers insights into energy levels and mental resilience, aiding in effective training strategies. (3) Efficient Evaluation Tools: Hemoglobin and blood testosterone serve as efficient markers for evaluating athletes' states. Regular assessment of these indicators allows for proactive adjustments in training, preventing excessive fatigue and promoting overall well-being.

Chronotype characteristics of professional athletes in China: a comprehensive descriptive study.

BACKGROUND: Chronotype has gained recognition as a significant factor in enhancing athletic performance. This study aimed to deepen our understanding of athletes' sleep chronotypes and provide a foundation for developing evidence-based training and competition programs. By comprehensively describing and analyzing the chronotype characteristics of Chinese professional athletes, considering individual and sports factors, sleep quality and habits, and mental energy, this research aimed to contribute valuable insights to the field. METHODS: A sample of 1069 professional athletes from sports teams in Shanghai completed the Athlete Sleep Screening Questionnaire and the Athlete Mental Energy Scale to assess chronotype, sleep quality, sleep-influencing habits, and mental energy. RESULTS: Among athletes, sleep typology fell within the intermediate range, slightly leaning toward morningness. Male athletes and those who engaged in static sports displayed a greater propensity for morningness. Age correlated with a preference for eveningness. High-level athletes exhibited a stronger inclination toward eveningness. Sleep quality issues were associated with an inclination toward eveningness. Daily caffeine intake and the habit of using electronic devices before bedtime are also linked to eveningness. Chronotype demonstrated the ability to predict various dimensions of athletes' mental energy. It was the strongest predictor of vigor, but the loadings were smaller than those of sleep quality. CONCLUSION: Chinese athletes' chronotypes primarily exhibit distinct characteristics related to individual factors such as gender, sports discipline, and ranking, as well as habits like caffeine consumption and electronic device use. Moreover, these sleep patterns demonstrate predictive capabilities across all dimensions of athletes' mental energy. This study sheds light on Chinese athletes' unique sleep chronotype attributes, enriching our understanding of sleep patterns among professional athletes under various systems. These insights offer an initial basis for enhancing the effectiveness of athlete scheduling and training management.

Value of C-Reactive Protein-Triglyceride Glucose Index in Predicting Cancer Mortality in the General Population: Results from National Health and Nutrition Examination Survey.

BACKGROUND: Cancer is one of the leading causes of death. The current work aims to investigate the association between C-reactive protein-triglyceride glucose index (CTI) and the risk of incident cancer mortality and to evaluate the usefulness of CTI to refine the risk stratification of cancer mortality. METHODS: The study enrolled 19,957 subjects from American National Health and Nutrition Examination Survey. CTI was defined as 0.412*Ln(CRP) + ln[T.G. (mg/dL) × FPG (mg/dL)/2]. Cox regression was performed to investigate the association. RESULTS: During a follow-up of 215417.52 person-years, 736 subjects died due to malignant tumors, and the incidence of cancer mortality was 3.42 per 1,000 person-years. Kaplan-Meier curve revealed that the fourth quartile group had the lowest cancer mortality-free rate (Log-Rank p < 0.001). After full adjustment, each SD increase of CTI cast a 32.7% additional risk of incident cancer mortality. Furthermore, cancer mortality risk elevated proportionally with the increase of CTI. Finally, ROC and reclassification analyses supported the usefulness of CTI in improving the risk stratification of incident cancer mortality. CONCLUSION: The study revealed a significant association between CTI and cancer mortality risk, suggesting the value of CTI in improving the risk stratification of incident cancer mortality. KEY MESAGESC-reactive protein-triglyceride glucose index (CTI) is positively associated with cancer mortality risk in the general population.The association was linear in the whole range of CTI.CTI could improve the risk prediction of cancer mortality in the general population.

Kinematic and electromyography characteristics of performing butterfly stroke with different swimming speeds in flow environment.

Objective: To investigate effect of flow speeds on the upper limb muscular activity of butterfly swimmers training in a flow environment. A comparison of kinematic characteristics and muscular activity of upper limbs were made when the swimmers training with different flow speeds in a swimming flume. The purpose was to provide a basis for scientifically formulating special swimming training advice for athletes' training in flow environment. Methods: Ten youth female butterfly swimmers participated in the study with the speed of 70%, 80%, and 90% level of their max speeds. A stroke cycle was divided into four phases (entry, pull, push, and recovery). The kinematic parameters of upper limbs (stroke rate, stroke length, duration of each phase in a stroke cycle) and muscular activity (onset timing, integrated electromyography (iEMG), contribution ratio) of four muscles (Biceps brachii (BB), Triceps brachii (TB), Pectoralis major (PM), and Latissimus dorsi (LD)) were collected and analyzed in different stroke phases. Results: There was no significant difference between stroke rate and stroke length with different flow speeds. There were significant differences among the duration of the four stroke phases. The entry phase had the longest duration, the pull phase had the shortest duration, the push phase was longer than the recovery phase, and the recovery phase was shorter than the entry phase. The BB and PM were activated significantly earlier at 90% of target speed than at 80% of target speed, while the TB was activated significantly later than other two speeds. The muscular contribution ratio of the PM was highest in the pull phase and lowest in the pushing phase. The muscular contribution ratio of the BB was significantly lower in the pushing phase than in other three stroke phases. The muscular contribution of the TB was significantly higher in the recovery phase than in other three stroke phases. The muscular contribution ratio of the LD was highest in the pushing phase, and it was significantly higher in pushing phase and recovery phase than in pull phase. Conclusions: (1) When butterfly athletes training with 70%, 80% and 90% of their max speed in a flow environment, it didn't make significant differences between the kinematic or muscle activation characteristics of the upper limbs movement except the muscle onset timing. (2) Stroke phase was the main factor of the duration and the muscle contribution ratio during butterfly arm stroke for young athletes.

Psychological interventions for the prevention of depression relapse: systematic review and network meta-analysis.

Depression is highly prevalent and easily relapses. Psychological interventions are effective for the prevention of depression relapse. This systematic review and network meta-analysis aimed to compare the efficacy at the same follow-up time points of psychological interventions in depression. We searched PubMed, Embase, and PsycINFO via OVID, and the Cochrane Library published up to December 12, 2021, and PubMed up to July 1, 2022. The primary outcome was depression relapse, considering the same time points that were extracted on survival curves or relapse curves. The study protocol was registered with PROSPERO, CRD42022343327. A total of 2,871 patients were included from 25 RCTs. Mindfulness-based cognitive therapy (MBCT) was significantly better than placebo at the 3 months, the 6 months, and the 9 months at follow-up. Cognitive behavioral therapy (CBT) was significantly better than treatment as usual at the 3 months, the 9 months, the 12 months, and the 15 months at follow-up. CBT was significantly better than placebo at the 21 months and the 24 months at follow-up. Behavioral activation therapy was significantly better than placebo at the 21 months and the 24 months at follow-up. Interpersonal psychotherapy was significantly better than placebo at the 24-month follow-up. All psychological interventions included in the study were significantly better than supportive counseling most of the time. The results were robust in various sensitivity and subgroup analyses. In conclusion, MBCT had a continuous effect in preventing relapse of depression. CBT had the longest but not continuous effect in preventing relapse of depression. The effects of behavioral activation therapy and interpersonal therapy for the prevention of depression appeared late. All psychological interventions included in the study were more effective than supportive counseling. More evidence is needed from large comparative trials that provide long-term follow-up data.

MSINGB: A Novel Computational Method Based on NGBoost for Identifying Microsatellite Instability Status from Tumor Mutation Annotation Data.

Microsatellite instability (MSI), a vital mutator phenotype caused by DNA mismatch repair deficiency, is frequently observed in several tumors. MSI is recognized as a critical molecular biomarker for diagnosis, prognosis, and therapeutic selection in several cancers. Identifying MSI status for current gold standard methods based on experimental analysis is laborious, time-consuming, and costly. Although several computational methods based on machine learning have been proposed to identify MSI status, we need to further understand which machine learning model would favor identification for MSI and which feature subset is strongly related to MSI. On this basis, more effective machine learning-based methods can be developed to improve the performance of MSI status identification. In this work, we present MSINGB, an NGBoost-based method for identifying MSI status from tumor somatic mutation annotation data. MSINGB first evaluates the prediction performance of 11 popular machine learning algorithms and 9 deep learning models to identify MSI. Among 20 models, NGBoost, a novel natural gradient boosting method, achieves the overall best performance. MSINGB then introduces two feature selection strategies to find the compact feature subset, which is strongly related to MSI, and employs the SHAP approach to interpreting how selected features impact the model prediction. MSINGB achieves a better prediction performance on both the tenfold cross-validation test and independent test compared with state-of-the-art methods.

Case report: Plasma cell leukemia secondary to multiple myeloma successfully treated with anti-BCMA CAR-T cell therapy.

Chimeric antigen receptor (CAR)-T cell therapy provides an effective salvage treatment for relapsed/refractory multiple myeloma (RRMM) patients. End-stage RRMM with plasma cell leukemia (PCL) transformation is highly aggressive and resistant to conventional therapy. There is an urgent need for new therapeutics and CAR-T therapy may play an important role. We report a case of PCL secondary to RRMM successfully treated with CAR-T cell therapy targeting B-cell maturation antigen (BCMA). A woman was diagnosed as having MM 4 years ago and progressed to secondary PCL (sPCL) of five prior lines of treatment including proteasome inhibitors, an immunomodulatory agent, cytotoxic drugs, and an anti-CD38 monoclonal antibody. After receiving a BCMA CAR-T therapy, she achieved a stringent complete response that lasted 9 months. Then, the patient irregularly took venetoclax 10 mg per day due to a slightly higher λ FLC concentration, which did not meet the criteria for progression. She maintained a complete response for the following 7 months. In conclusion, BCMA CAR-T therapy may be a promising therapeutic approach in PCL patients. More studies are needed to evaluate the benefit of anti-BCMA CAR-T therapy in PCL patients. Clinical Trial Registration: www.chictr.org.cn, ChiCTR1900024388, Registered 9 July 2019.

Unexpected significance of a minor reaction pathway in daytime formation of biogenic highly oxygenated organic compounds.

Secondary organic aerosol (SOA), formed by oxidation of volatile organic compounds, substantially influence air quality and climate. Highly oxygenated organic molecules (HOMs), particularly those formed from biogenic monoterpenes, contribute a large fraction of SOA. During daytime, hydroxyl radicals initiate monoterpene oxidation, mainly by hydroxyl addition to monoterpene double bonds. Naturally, related HOM formation mechanisms should be induced by that reaction route, too. However, for α-pinene, the most abundant atmospheric monoterpene, we find a previously unidentified competitive pathway under atmospherically relevant conditions: HOM formation is predominately induced via hydrogen abstraction by hydroxyl radicals, a generally minor reaction pathway. We show by observations and theoretical calculations that hydrogen abstraction followed by formation and rearrangement of alkoxy radicals is a prerequisite for fast daytime HOM formation. Our analysis provides an accurate mechanism and yield, demonstrating that minor reaction pathways can become major, here for SOA formation and growth and related impacts on air quality and climate.

Effective Radiative Forcings Due To Anthropogenic Emission Changes Under Covid-19 and Post-Pandemic Recovery Scenarios.

With the continuation of the Coronavirus Disease 2019 (Covid-19) pandemic, the impacts of this catastrophe on anthropogenic emissions are no longer limited to its early stage. This study quantitatively estimates effective radiative forcings (ERFs) due to anthropogenic well-mixed greenhouse gases (WMGHGs) and aerosols for the period 2020-2050 under the three latest Covid-19 economic-recovery scenarios using an aerosol-climate model. The results indicate that reductions in both WMGHG and aerosol emissions under the Covid-19 green recoveries lead to increases ranging from 0 to 0.3 W m-2 in global annual mean anthropogenic ERF over the period 2020-2050 relative to the Shared Socioeconomic Pathway 2-4.5 scenario (the baseline case). These positive ERFs are mainly attributed to the rapid and dramatic decreases in atmospheric aerosol content that increase net shortwave radiative flux at the top of atmosphere via weakening the direct aerosol effect and low cloud cover. At the regional scale, reductions in aerosols contribute to positive ERFs throughout the Northern Hemisphere, while the decreased WMGHGs dominate negative ERFs over the areas away from aerosol pollution, such as the Southern Hemisphere oceans. This drives a strong interhemispheric contrast of ERFs. In contrast, the increased anthropogenic emissions under the fossil-fueled recovery scenario lead to an increase of 0.3 W m-2 in global annual mean ERF in 2050 compared with the baseline case, primarily due to the contribution of WMGHG ERFs. The regional ERF changes are highly dependent on local cloud radiative effects.

Molecular cloning, characterization, and tissue distribution of c-Myc from blood clam Tegillarca granosa and its role in cadmium-induced stress response.

Cadmium (Cd) pollution threatens the cultivation of the blood clam Tegillarca granosa (T. granosa) in coastal regions of the East China Sea. The molecular mechanisms regulating Cd stress response and detoxification in blood clams are largely unclear. In the present study, the full-length T. granosa c-Myc (Tgc-Myc) cDNA was cloned for the first time. The 3063-bp cDNA consisted of a 129-bp 5' untranslated region (UTR), a 1746-bp 3' UTR, and a 1188-bp open reading frame encoding a predicted protein of 395 amino acid residues. The predicted protein had a calculated molecular weight of 44.9 kDa and an estimated isoelectric point of 6.82. The predicted protein contained an N-terminal transactivation domain and a C-terminal basic helix-loop-helix leucine zipper domain, which are conserved functional domains of c-Myc proteins. Tgc-Myc showed broad tissue distribution in blood clams, with the highest expression detected in the gill and hepatopancreas. Exposure to Cd, a major heavy metal pollutant in coastal regions of the East China Sea, induced Tgc-Myc expression in gill tissues. Tgc-Myc knockdown led to reduced expression of a variety of stress response/detoxification genes in blood clams cultivated in Cd-contaminated seawater. Tgc-Myc knockdown also led to decreased expression of IGF1R, a proto-oncogene that promotes cell proliferation. These findings indicated that Tgc-Myc regulates Cd-induced stress response and detoxification in blood clams. The upregulation of Tgc-Myc may serve as an approach to generate strains with an enhanced detoxification response and consequently a low heavy metal buildup.

Humanized CD19 CAR-T cells in relapsed/refractory B-ALL patients who relapsed after or failed murine CD19 CAR-T therapy.

BACKGROUND: For CD19-positive relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL) after treatment with murine CD19 (mCD19) CAR-T, the reinfusion of mCD19 CAR-T cells may be ineffective due to anti-mouse single-chain variable fragment (scFv) antibody caused by mCD19 CAR. To overcome this immunogenicity, we applied humanized CD19 (hCD19) CAR-T cells to treat r/r B-ALL patients with prior mCD19 CAR-T therapy. METHODS: Nineteen pediatric and adult patients were included, 16 relapsed after and 3 were primarily resistant to mCD19 CAR-T. All patients presented with more than 5% blasts in bone marrow and/or extramedullary disease, and still showed CD19 antigen expression. Humanized CD19-CARs were lentiviral vectors carrying a second generation CAR with 4-1-BB co-stimulatory and CD3ζ signaling domains. Patient-derived cells were collected for producing CAR-T cells, the median dose of infused hCD19 CAR-T cells was 2.4 × 105/kg (range, 1.0-18.0 × 105/kg). RESULTS: hCD19 CAR-T resulted in a complete remission (CR) rate of 68% (13/19). Among 13 remission patients, 11 underwent allogeneic hematopoietic cell transplantation (allo-HCT) (3 were second HCT) and 10 remained in CR; the event-free survival rates at 12-18 months were 91% in 11 patients received following allo-HCT and 69% in all CR patients. Six cases had no response to hCD19 CAR-T, 3 died of disease progression; another 3 received salvage second transplantation, of them, 2 relapsed again (one died). Cytokine release syndrome (CRS) occurred in 95% (18/19) of patients, most CRS events were grade 1 and grade 2 (n = 17), there was only one grade 4 CRS. Two cases experienced grade 1 neurotoxicity. CONCLUSIONS: Humanized CD19 CAR-T cell therapy could be a treatment option for CD19-positive B-ALL patients who relapsed after or resisted prior murine CD19 CAR-T, hCD19 CAR-T followed by allo-HCT provided a longer remission in CR patients. Nevertheless, the prognosis of non-responders to hCD19 CAR-T remained dismal. TRIAL REGISTRATION: Chinese Clinical Trial Registry/WHO International Clinical Trial Registry ( ChiCTR1900024456 , URL: www.chictr.org.cn ); registered on July 12, 2019.

Development of GRAPES-CUACE adjoint model version 2.0 and its application in sensitivity analysis of ozone pollution in north China.

We presented the development of the gaseous chemistry adjoint module of the meteorological-chemical model system GRAPES-CUACE (Global/Regional Assimilation and PrEdiction System coupled with CMA Unified Atmospheric Chemistry Environmental Forecasting System) on the basis of the previously constructed aerosol adjoint module. The latest version of the GRAPES-CUACE adjoint model mainly includes the adjoint of the physical and chemical processes, the adjoint of the transport processes, and the adjoint of interface programs, of both gas and aerosol. The adjoint implementation was validated for the full model, and adjoint results showed good agreement with brute force sensitivities. We also applied the newly developed adjoint model to the sensitivity analysis of an ozone episode occurred in Beijing on July 2, 2017, as well as the design of emission-reduction strategies for this episode. The relationships between the ozone concentration and precursor emissions were well captured by the adjoint model. It is indicated that for a case used here, the Beijing peak ozone concentration was influenced mostly by local emissions (6.2-24.3%), as well as by surrounding emissions, including Hebei (4.4-16.8%), Tianjin (1.8-6.6%), Shandong (1.8-2.6%), and Shanxi (<1%). In addition, reduction of NOx, VOCs, and CO emissions in these regions would effectively decrease the Beijing peak ozone concentration. This study highlights the capability of GRAPES-CUACE adjoint model in quantifying "emission-concentration" relationship and in providing guidance for environmental control policy.

Highly Oxygenated Organic Nitrates Formed from NO3 Radical-Initiated Oxidation of ß-Pinene.

The reactions of biogenic volatile organic compounds (BVOC) with the nitrate radicals (NO3) are major night-time sources of organic nitrates and secondary organic aerosols (SOA) in regions influenced by BVOC and anthropogenic emissions. In this study, the formation of gas-phase highly oxygenated organic molecules-organic nitrates (HOM-ON) from NO3-initiated oxidation of a representative monoterpene, ß-pinene, was investigated in the SAPHIR chamber (Simulation of Atmosphere PHotochemistry In a large Reaction chamber). Six monomer (C = 7-10, N = 1-2, O = 6-16) and five accretion product (C = 17-20, N = 2-4, O = 9-22) families were identified and further classified into first- or second-generation products based on their temporal behavior. The time lag observed in the peak concentrations between peroxy radicals containing odd and even number of oxygen atoms, as well as between radicals and their corresponding termination products, provided constraints on the HOM-ON formation mechanism. The HOM-ON formation can be explained by unimolecular or bimolecular reactions of peroxy radicals. A dominant portion of carbonylnitrates in HOM-ON was detected, highlighting the significance of unimolecular termination reactions by intramolecular H-shift for the formation of HOM-ON. A mean molar yield of HOM-ON was estimated to be 4.8% (-2.6%/+5.6%), suggesting significant HOM-ON contributions to the SOA formation.

Post-stroke Anxiety Analysis via Machine Learning Methods.

Post-stroke anxiety (PSA) has caused wide public concern in recent years, and the study on risk factors analysis and prediction is still an open issue. With the deepening of the research, machine learning has been widely applied to various scenarios and make great achievements increasingly, which brings new approaches to this field. In this paper, 395 patients with acute ischemic stroke are collected and evaluated by anxiety scales (i.e., HADS-A, HAMA, and SAS), hence the patients are divided into anxiety group and non-anxiety group. Afterward, the results of demographic data and general laboratory examination between the two groups are compared to identify the risk factors with statistical differences accordingly. Then the factors with statistical differences are incorporated into a multivariate logistic regression to obtain risk factors and protective factors of PSA. Statistical analysis shows great differences in gender, age, serious stroke, hypertension, diabetes mellitus, drinking, and HDL-C level between PSA group and non-anxiety group with HADS-A and HAMA evaluation. Meanwhile, as evaluated by SAS scale, gender, serious stroke, hypertension, diabetes mellitus, drinking, and HDL-C level differ in the PSA group and the non-anxiety group. Multivariate logistic regression analysis of HADS-A, HAMA, and SAS scales suggest that hypertension, diabetes mellitus, drinking, high NIHSS score, and low serum HDL-C level are related to PSA. In other words, gender, age, disability, hypertension, diabetes mellitus, HDL-C, and drinking are closely related to anxiety during the acute stage of ischemic stroke. Hypertension, diabetes mellitus, drinking, and disability increased the risk of PSA, and higher serum HDL-C level decreased the risk of PSA. Several machine learning methods are employed to predict PSA according to HADS-A, HAMA, and SAS scores, respectively. The experimental results indicate that random forest outperforms the competitive methods in PSA prediction, which contributes to early intervention for clinical treatment.

Using Micro-Raman Spectroscopy to Investigate Chemical Composition, Mixing States, and Heterogeneous Reactions of Individual Atmospheric Particles.

Measuring the chemical composition of individual atmospheric aerosol particles can provide direct evidence of their heterogeneous reactions and mixing states in the atmosphere. In this study, micro-Raman spectroscopy was used to measure the chemical composition of 1200 individual atmospheric particles in 11 samples collected in Beijing air. (NH4)2SO4, NH4NO3, various minerals, carbonaceous species (soot and organics), and NaNO3 were identified in the measured particles according to their characteristic Raman peaks. These species represented the main components of aerosol particles. In individual particles, NH4NO3 and (NH4)2SO4 either existed separately or were internally mixed. Possible reaction pathways of CaCO3 particles in the atmosphere were proposed based on the results of this study and laboratory simulations on heterogeneous reactions in the literature. CaCO3 reacted with N- and S-containing (nitrogen- and sulfur-containing) acidic gases to produce Ca(NO3)2 and CaSO4. Ca(NO3)2 further reacted with S-containing acidic gases and oxidants to produce CaSO4. Of the soot-containing particles, 23% were internal mixtures of soot and inorganic material. Of the organics-containing particles, 57% were internal mixtures of organic and inorganic materials. Micro-Raman spectroscopy directly identified functional groups and molecules in individual atmospheric particles under normal ambient conditions, rendering it a powerful tool for measuring the chemical composition of individual atmospheric particles with a diameter of ≥1.0 µm.

Pseudogene ACTBP2 increases blood-brain barrier permeability by promoting KHDRBS2 transcription through recruitment of KMT2D/WDR5 in Aß1-42 microenvironment.

The blood-brain barrier (BBB) has a vital role in maintaining the homeostasis of the central nervous system (CNS). Changes in the structure and function of BBB can accelerate Alzheimer's disease (AD) development. ß-Amyloid (Aß) deposition is the major pathological event of AD. We elucidated the function and possible molecular mechanisms of the effect of pseudogene ACTBP2 on the permeability of BBB in Aß1-42 microenvironment. BBB model treated with Aß1-42 for 48 h were used to simulate Aß-mediated BBB dysfunction in AD. We proved that pseudogene ACTBP2, RNA-binding protein KHDRBS2, and transcription factor HEY2 are highly expressed in ECs that were obtained in a BBB model in vitro in Aß1-42 microenvironment. In Aß1-42-incubated ECs, ACTBP2 recruits methyltransferases KMT2D and WDR5, binds to KHDRBS2 promoter, and promotes KHDRBS2 transcription. The interaction of KHDRBS2 with the 3'UTR of HEY2 mRNA increases the stability of HEY2 and promotes its expression. HEY2 increases BBB permeability in Aß1-42 microenvironment by transcriptionally inhibiting the expression of ZO-1, occludin, and claudin-5. We confirmed that knocking down of Khdrbs2 or Hey2 increased the expression levels of ZO-1, occludin, and claudin-5 in APP/PS1 mice brain microvessels. ACTBP2/KHDRBS2/HEY2 axis has a crucial role in the regulation of BBB permeability in Aß1-42 microenvironment, which may provide a novel target for the therapy of AD.

Hydrogen in Patients With Corticosteroid-Refractory/Dependent Chronic Graft-Versus-Host-Disease: A Single-Arm, Multicenter, Open-Label, Phase 2 Trial.

Chronic graft-versus-host-disease (cGVHD) is the leading cause of late non-relapse mortality after allogeneic hematopoietic stem cell transplantation(HSCT). There is no standard therapy for patients refractory or dependent to corticosteroid treatment. We hypothesized that hydrogen may exert therapeutic effects on cGVHD patients with few side effects. A prospective open-label phase 2 study of hydrogen was conducted. Patients received hydrogen-rich water 4ml/kg orally three times a day. Responses were graded in the skin, mouth, Gastrointestinal(GI), liver, eyes, lungs and joints and fascia every 3 months. A total of 24 patients (median age 27) were enrolled. Of the 24 patients, 18 (75%; 95% CI, 55.1% to 88%) had an objective response. No significant toxicity was observed. The estimated 4-year overall survival rate was 74.7%(95% CI, 54.9%-94.5%). The survival time was significantly prolonged in the response group. The survival rate at 4 years in the response group is significantly higher than the nonresponse group (86.6% vs 0%; p= 0.000132). Hydrogen showed great efficacy on cGVHD patients and long-term administration of hydrogen was not associated with significant toxic effects. The trial was registered at www.ClinicalTrials.Gov, NCT02918188.

Extensive multifocal and pleomorphic pulmonary lesions in Waldenström macroglobulinemia: A case report.

BACKGROUND: Waldenström macroglobulinemia (WM) is a type of small lymphocytic lymphoma that mainly affects the bone marrow, spleen, and lymph nodes. A subset of patients with WM demonstrates extramedullary involvement (4.4%), and the most frequent extramedullary disease site involved is the lungs (30%). CASE SUMMARY: A 60-year-old male patient who experienced intermittent breath-holding for 6 mo was admitted on August 14, 2017. Chest computed tomography indicated multiple pulmonary cavities in the upper lobes of both lungs, with pulmonary consolidation, ground-glass opacities, patchy infiltrates, fibrous bands, large bullae, and enlarged lymph nodes in the mediastinum. The patient was a heavy smoker (20 cigarettes/d for 40 years). Diagnostic fiberoptic bronchoscopy revealed normal findings. Serological examination revealed a remarkable increase in serum immunoglobulin M levels (30.24 g/L; normal: 0.4-2.30 g/L). A computed tomography-guided percutaneous pulmonary biopsy was performed in the left lower lobe of the lung with pulmonary consolidation and indicated that the alveolar structure disappeared and that a large amount of amyloid-like deposition was present along with the infiltration of very few lymphocytes and plasma cells. The patient was treated with the combined treatment of dexamethasone + rituximab + lenalidomide over four courses. Serum immunoglobulin M did not normalize, and he received ibrutinib + dexamethasone. CONCLUSION: This patient with WM and lung amyloidosis had a wide range of pulmonary lesions and a variety of morphological features, which was a rare case. Yet, some changes might be ascribed to heavy smoking.