Rapid determination of 54 dye components in hair dyes by liquid chromatography coupled to quadrupole orbitrap high-resolution mass spectrometry.

Chemical hair dye components can have allergenic, reproductive, and carcinogenic risks. Detecting restricted and prohibited ingredients in these products is challenging due to product diversity, isomer separation, instability, and wide polarity range. A method was developed using HPLC-high-resolution mass spectrometry for the qualitative and quantitative analysis of 54 hair dye components in various products. Samples were extracted with a 70% methanol solution, ultrasonicated in an ice bath, centrifuged, filtered, diluted with 25% methanol solution and 25% methanol solution containing 0.05% D-isoascorbic acid. Separation was achieved using an ACE Excel 3 C18 column (2.1 mm × 150 mm, 3 µm) with analysis conducted via quadrupole Orbitrap mass spectrometry. It showed good linear correlations, with detection limits of 0.1-23.5 ng mL-1, and quantitation limits of 0.2-78.1 ng mL-1. Average recovery ranged from 60.0% to 118.4%, with repeatability from 4.0% to 14.9%. Stability was confirmed within 48 hours. When applied to 20 batches of commercially available hair dyes, 24 hair dye components were found within permissible levels. The method is crucial for quality control of hair dyes, covering 10 common prohibited and 44 permissible hair dye components outlined in the Safety and Technical Standards for Cosmetics (2015 Edition). Compared to the standard methods, it can separate isomers in a single mobile phase system within 15 minutes in positive ion mode while maintaining sensitivity for phenol, hydroquinone, and other components in negative ion mode. Moreover, the pre-treatment strategy significantly improved stability and accuracy, enabling precise analysis of the 54 hair dye components.

Combined DeRitis ratio and alkaline phosphatase on the prediction of portal vein tumor thrombosis in patients with hepatocellular carcinoma.

Portal vein tumor thrombosis (PVTT) is one of the common complications of HCC and represents a sign of poor prognosis. PVTT signifies advanced liver cancer, deteriorating liver function, and heightened susceptibility to intrahepatic dissemination, systemic metastasis, and complications related to portal hypertension. It is important to seek novel strategies for PVTT arising from HCC. Portal vein tumor thrombus (PVTT) in hepatocellular carcinoma (HCC) represents a worse liver function, less treatment tolerance, and poor prognosis. This study aimed to investigate the diagnostic value of the combination of the DeRitis ratio (AST/ALT) and alkaline phosphatase (ALP) index (briefly named DALP) in predicting the occurrence risk of PVTT in patients with HCC. We performed a retrospective study enrolling consecutive patients with HCC from January 2017 to December 2020 in Hebei Medical University Third Hospital. ROC analysis was performed to estimate the predictive effectiveness and optimal cut-off value of DALP for PVTT occurrence in patients with HCC. Kaplan-Meier analysis revealed the survival probabilities in each subgroup according to the risk classification of DALP value. Univariate and multivariate Logistics regression analyses were applied to determine the independent risk for poor prognosis. ROC analysis revealed that the optimal cut-off value for DALP was 1.045, with an area under the curve (AUC) of 0.793 (95% CI 0.697-0.888). Based on the DALP classification (three scores: 0-2) with distinguishable prognoses, patients in the score 0 group had the best prognosis with a 1-year overall survival (OS) of 100%, whereas score 2 patients had the worst prognosis with 1-year OS of 72.4%. Similarly, there was a statistically different recurrence-free survival among the three groups. Besides, this risk classification was also associated with PVTT progression in HCC patients (odds ratio [OR] 5.822, P < 0.0001). Pathologically, patients in the score 2 group had more advanced tumors considering PVTT, extrahepatic metastasis, and ascites than those in score 0, 1 groups. Moreover, patients with a score of 2 had more severe hepatic inflammation than other groups. Combination of DeRitis ratio and ALP index presented a better predictive value for PVTT occurrence in patients with HCC, contributing to the tertiary prevention.

Use of Metagenomic Next-Generation Sequencing to Identify Pathogens Involved in Central Nervous System Infections.

Purpose: Application of metagenomic next-generation sequencing (mNGS) in identifying nosocomial central nervous system (CNS) infections in critical care units remains understudied. Methods: We conducted a retrospective analysis of microbiological results through both mNGS and routine examination of cerebrospinal fluid (CSF) samples from patients with nosocomial CNS infections. The aim of this study was to assess the clinical diagnostic effect of nosocomial mNGS in this population. Results: The study included 26 cases of nosocomial CNS infections in total. A total of 69.2% (18/26) of the samples tested positive for mNGS, which is substantially greater than the 7.7% (2/26; p<0.05) detected through conventional techniques. Administration of antibiotics before culture is most likely the cause of the low CSF culture rate. Twenty-five pathogenic strains that were missed by standard testing. Three pathogens that were consistent with the mNGS results were positive by routine tests. Eight cases were negative by mNGS due to low pathogen CSF titres. Compared to traditional testing, mNGS demonstrated 100% sensitivity and 33.3% specificity in diagnosing CNS infections. The thirty-day mortality rate was 26.9% (7/26). Conclusion: Routine microbiologic testing frequently falls short of detecting all neuroinvasive pathogens. Our research suggests that mNGS offers an alternative means of detecting nosocomial CNS infections. By applying mNGS to CSF samples from patients with meningitis or encephalitis, we were able to improve the ability to diagnose nosocomial neurologic infections.

Development of an Ion Mobility Spectrometer Based on a Pulsed Photoelectric Effect Ionization Source.

Ion mobility spectrometry (IMS) is a compact and sensitive trace gas analysis instrument that ionizes the sample into ions for detection. Typically, an ion gate is used to cut the continuous ion beam into ion packets for separation and detection. However, commonly used ion gates suffer from complex structures or low ion transmission rates, making the gateless IMS a viable alternative. In this study, an IMS based on a pulsed photoelectric effect ionization source was designed. The photoelectrons were generated by irradiating a photoelectric material with a back-illuminated pulsed xenon lamp. This allows for low-energy photoelectron generation and the production of simple reactant ions (O2-(H2O)n) and thus negative product ions. The photoelectron current generated by this ionization source was analyzed, which can reach an intensity of a few microamperes and can be converted into an ion signal exceeding 10 nA. The introduction of the pulsed photoelectric effect ionization source makes it possible to generate separate ion packets and complete ion injection when a constant electric field is maintained in the ionization region. And with an assisted pulsed electric field in the ionization region, the resolving power of the system can be effectively improved to 1.85 times that of the constant electric field. The IMS developed in this study was used for the detection of common volatile hazardous chemicals, yielding effective results. The detection limit for phenol was below 1 ppb, and the dynamic response range exceeded 1 order of magnitude, which implies the potential applications of this IMS to detect substances with high electron affinity, such as explosives detection in public safety.

Effect of ezetimibe-statin combination therapy vs. statin monotherapy on coronary atheroma phenotype and lumen stenosis in patients with coronary artery disease: a meta-analysis and trial sequential analysis.

Background: Evidence indicates that the addition of ezetimibe to statin therapy reduces cardiovascular events. However, the impact of ezetimibe-statin combination therapy on coronary plaque regression, plaque stabilization, and diameter stenosis remains a matter of controversy. Methods: We performed electronic searches in PubMed, Web of Knowledge, and the Cochrane Central Register of Controlled Trials to identify eligible trials assessing the effects of ezetimibe-statin combination therapy versus statin monotherapy reporting at least one outcome among total atheroma volume (TAV), minimum fibrous cap thickness (FCT), lumen volume (LV), and lumen area (LA) derived from intravascular imaging modalities of intravascular ultrasound (IVUS) and optical coherence tomography (OCT). We used the random-effects model and performed trial sequential analysis (TSA) during this meta-analysis. Results: Eleven articles with a total of 926 individuals (460 in the dual-lipid-lowering therapy group and 466 in the statin monotherapy group) were included in the final meta-analysis. Compared to statin monotherapy, ezetimibe-statin combination therapy was associated with significantly decreased TAV [WMD = -3.17, 95% CI (-5.42 to -0.92), and p = 0.006], with no effect on the LV of the coronary artery [WMD = -0.52, 95% CI (-2.24 to 1.21), and p = 0.56], the LA of the coronary artery [WMD = 0.16, 95% CI (-0.10-0.42), and p = 0.22], or minimum FCT thickness [WMD = 19.11, 95%CI (-12.76-50.97)]. Conclusion: In patients with coronary artery disease, ezetimibe-statin combination therapy resulted in a significant regression in TAV compared to statin monotherapy, whereas no overall improvements of minimum FCT or lumenal stenosis were observed.

Large-Scale Alternative Polyadenylation-Wide Association Studies to Identify Putative Cancer Susceptibility Genes.

Alternative polyadenylation (APA) modulates mRNA processing in the 3'-untranslated regions (3' UTR), affecting mRNA stability and translation efficiency. Research into genetically regulated APA has the potential to provide insights into cancer risk. In this study, we conducted large APA-wide association studies to investigate associations between APA levels and cancer risk. Genetic models were built to predict APA levels in multiple tissues using genotype and RNA sequencing data from 1,337 samples from the Genotype-Tissue Expression project. Associations of genetically predicted APA levels with cancer risk were assessed by applying the prediction models to data from large genome-wide association studies of six common cancers among European ancestry populations: breast, ovarian, prostate, colorectal, lung, and pancreatic cancers. A total of 58 risk genes (corresponding to 76 APA sites) were associated with at least one type of cancer, including 25 genes previously not linked to cancer susceptibility. Of the identified risk APAs, 97.4% and 26.3% were supported by 3'-UTR APA quantitative trait loci and colocalization analyses, respectively. Luciferase reporter assays for four selected putative regulatory 3'-UTR variants demonstrated that the risk alleles of 3'-UTR variants, rs324015 (STAT6), rs2280503 (DIP2B), rs1128450 (FBXO38), and rs145220637 (LDHA), significantly increased the posttranscriptional activities of their target genes compared with reference alleles. Furthermore, knockdown of the target genes confirmed their ability to promote proliferation and migration. Overall, this study provides insights into the role of APA in the genetic susceptibility to common cancers. Significance: Systematic evaluation of associations of alternative polyadenylation with cancer risk reveals 58 putative susceptibility genes, highlighting the contribution of genetically regulated alternative polyadenylation of 3'UTRs to genetic susceptibility to cancer.

Co-occurrence of depressive and anxious symptoms and their influence on self-rated health: a national representative survey among Chinese older adults.

OBJECTIVES: The prevalence of the co-occurrence of depressive and anxious symptoms (CO) and their influence on perceived overall health were not clear in community dwelling Chinese older adults. The aims of the study were to investigate the prevalence of CO and to explore its influence on self-rated health (SRH). METHOD: This study included 12301 individuals aged ≥65 years from the 2018 wave of the Chinese Longitudinal Healthy Longevity Survey (CLHLS), a nationally representative survey of older adults in mainland China. Participants received face-to-face interviews and assessments of depressive symptoms and anxious symptoms via 10-item of the Center for Epidemiologic Studies Depression Scale (CES-D-10) and 7-item Generalized Anxiety Disorder Questionnaire (GAD-7), respectively. SRH was measured by self-reported. A logistic regression model was used to examine the association between CO and SRH after adjusting for confounding variables. RESULTS: The average age was 83.4 (SD: 11.0) years and there were 6576 (53.5%) females. The age- and sex-standardized prevalence of depressive symptoms only (DSO) was 38.6%, anxious symptoms only (ASO) was 1.5%, and CO was 10.8%. Compared with those without depressive and anxious symptoms, the older adults with DSO or ASO were more likely to have significant influence on SRH. And particularly, CO was likely to produce the greatest decrement in the level of SRH. CONCLUSION: CO was not rare in Chinese older adults nationwide. The older adults having CO had increased risk for lower level of SRH than having DSO or ASO. More attention should be given to CO among the older adults.

FraHMT: A Fragment-Oriented Heterogeneous Graph Molecular Generation Model for Target Proteins.

The molecular generation task stands as a pivotal step in the domains of computational chemistry and drug discovery, aiming to computationally generate molecular structures for specific properties. In contrast to previous models that focused primarily on SMILES strings or molecular graphs, our model placed a special emphasis on the substructure information on molecules, enabling the model to learn richer chemical rules and structure features from fragments and chemical reaction information on molecules. To accomplish this, we fragmented the molecules to construct heterogeneous graph representations based on atom and fragment information. Then our model mapped the heterogeneous graph data into a latent vector space by using an encoder and employed a self-regressive generative model as a decoder for molecular generation. Additionally, we performed transfer learning on the model using a small set of ligand molecules known to be active against the target protein to generate molecules that bind better to the target protein. Experimental results demonstrate that our model is highly competitive with state-of-the-art models. It can generate valid and diverse molecules with favorable physicochemical properties and drug-likeness. Importantly, they produce novel molecules with high docking scores against the target proteins.

Higher disease burden and lower utilization in Mongolian with breast cancer: a 9-year retrospective cohort study of 18.19 million adults in China.

BACKGROUND: Whether health inequalities of disease burden and medical utilization exist by ethnicity in Asian breast cancer (BC) patients remains unclear. The authors aim to measure ethnic disparities in disease burden and utilization among Mongolian and Han female BC patients in China. MATERIALS AND METHODS: Based on data extracted from Inner Mongolia Regional Health Information Platform, a retrospective cohort study was established during 2012-2021. Disease burden including incidence, 5-year prevalence, mortality, survival rate, and medical cost were analyzed and compared between Han and Mongolian patients. RESULTS: A total of 34 878 female patients [mean (SD) age, 52.34 (10.93) years] were included among 18.19 million Chinese, and 4315 (12.03%) participants were Mongolian. Age-standardized rates of incidence are 32.68 (95% CI: 20.39-44.98) per 100 000. Higher age-specific incidence and 5-year prevalence were observed in Mongolian than in Han. The cost of BC annually per capita was significantly lower for Mongolian than Han [$1948.43 (590.11-4 776.42) vs. $2227.35 (686.65-5929.59), P <0.001]. Mongolian females showed higher all-cause mortality [30.92 (95% CI: 28.15-33.89) vs. 27.78 (95% CI: 26.77-28.83) per 1000, P =0.036] and BC-specific mortality [18.78 (95% CI: 16.64-21.13) vs. 15.22 (95% CI: 14.47-16.00) per 1000, P =0.002] than Han females. After adjusting covariates, Mongolian were associated with increased all-cause mortality [HR, 1.21, (95% CI: 1.09-1.34); P <0.001] and BC-specific mortality [HR, 1.31, (95% CI: 1.14-1.49); P <0.001]. CONCLUSION: The findings of this cohort study highlight a higher level of disease burden with unmet medical demand in Mongolian patients, suggesting that more practical efforts should be made for the minority. Further research is needed to explore the concrete mechanisms of the disparities as well as eliminate health disproportion.

α-HBDH is a superior to LDH in predicting major adverse cardiovascular events in patients with acute aortic dissection.

Objective: Acute aortic dissection (AAD) with a high mortality and postoperative complications remains presently no effective indicators to conjunctly predict the short-term mortality and the prognosis. This study aimed to investigate the predictive role of α-HBDH on in-hospital mortality and postoperative Major adverse cardiovascular events (MACE) in patients with AAD. Methods: In this retrospective study, a total of 369 enrolled patients from 2015 to 2021 were divided into three groups (T1: low, T2: medium and T3: high) based on the tertiles of α-HBDH levels on admission. In terms of the preoperative, intraoperative and postoperative indicators among 3 groups, the relationship between α-HBDH and studying endpoints was determined by logistic regression models, along with the consolidation using Kaplan-Meier and restricted cubic spline (RCS) analysis for predicting the in-hospital death and MACE complications. Last, subgroup analysis further verified the predictive value of α-HBDH. Results: Logistic regression analysis showed that α-HBDH was independently associated with in-hospital mortality of patients with AAD [OR(95CI): 4.771(1.043-21.832), P = 0.044] and MACE [OR(95CI): 9.869(2.148-45.349), P = 0.003]. Moreover, Kaplan-Meier analysis also showed an increased α-HBDH levels associated with poor survival within 30 days (log rank test, P < 0.01), especially in acute Stanford A dissection. RCS presented that 204 U/L was the optimal cut-off value of α-HBDH for in-hospital mortality and postoperative MACE, which facilitated clinical stratification of patients with AAD. Subgroup analysis confirmed a stable correlation between α-HBDH level and hospital mortality and MACE (P > 0.05). Conclusions: α-HBDH is a predictor of the in-hospital mortality and postoperative MACE, guiding admission stratification of patients with AAD.

The residues and health risk assessment of polychlorinated biphenyls (PCBs) in Pheretima (an earthworm-derived traditional medicine) from southeastern China.

Minimal research exists on polychlorinated biphenyl (PCB) exposure from traditional Chinese medicines (TCMs), despite their significant contributions to domestic and international health protection. This study is the first to investigate the levels, profiles, and health risks of PCB residue in Pheretima, a typical TCM produced from earthworm. Seventy-seven Pheretima samples from different regions of China were analyzed for 45 PCB congeners. PCBs were found in all samples exhibiting species-dependent discrepancies. ∑45PCBs was ranging from 0.532 to 25.2 µg/kg (mean 4.46 µg/kg), with CB-11 being the most abundant congener contributing 71.8% ± 10.8% to ∑45PCBs, followed by CB-47, which were all non-Aroclor congeners called unintentionally produced PCBs (UP-PCBs). The average estimated daily intake of ∑45PCBs, ∑7ID-PCBs (indicative polychlorinated biphenyls), and CB-11 were 0.71, 0.04, and 0.51 ng/kg bw/d, respectively. The ∑HQ of PCBs in Pheretima samples was 2.97 × 10-4-2.46 × 10-2 (mean 2.77 × 10-3, 95th 4.21 × 10-3), while the ∑RQ ranged from 1.19 × 10-8 to 2.88 × 10-6 (mean 4.87 × 10-7, 95th 2.31 × 10-6). These findings indicate that Pheretima ingestion does not pose significant non-carcinogenic risks. However, certain individual samples exhibit an acceptable level of potential risks, particularly when considering that PCBs are recognized as endocrine disruptors and classified as probable carcinogens. These results contribute to the safety evaluation of traditional medicines and suggest the potential use of Pheretima as a bioindicator for PCB pollution. It is advisable to monitor UP-PCBs as indicator congeners and gather additional toxicological data.

Safety and efficacy of balloon pulmonary angioplasty for technically operable chronic thromboembolic pulmonary hypertension.

Balloon pulmonary angioplasty (BPA) has been proven effective for addressing technically inoperable chronic thromboembolic pulmonary hypertension (CTEPH). However, the effectiveness of BPA in technically operable CTEPH patients who, for various reasons, did not undergo the procedure remains an area requiring exploration. This study sought to assess the safety and efficacy of BPA in such cases. We collected and reviewed data from CTEPH patients who underwent BPA in a consecutive manner. Following multidisciplinary team (MDT) decisions, patients were classified into two groups: technically inoperable (group A) and operable (group B). Group B comprised patients deemed technically suitable for pulmonary endarterectomy (PEA) but who did not undergo the procedure for various reasons. All patients underwent a comprehensive diagnostic work-up, including right heart categorization at baseline and the last intervention. This study compared changes in hemodynamic parameters, functional capacity, and quality of life between the two groups. In total, 161 patients underwent 414 procedures at our center, with Group A comprising 112 patients who underwent 282 BPA sessions and group B comprising 49 patients who underwent 132 BPA sessions. Significantly, both groups exhibited improvements in hemodynamics, functional capacity, and quality of life. The occurrence rate of complications, including hemoptysis and lung injury, was similar [12 (63.2%) vs. 7 (36.8%), p = 0.68]. BPA demonstrated favorable outcomes in patients with proximal CTEPH who did not undergo pulmonary endarterectomy. However, the clinical impact of BPA in technically operable CTEPH was found to be less significant than in inoperable cases.

Direct Performance of Triple-Stage Tandem Mass Spectrometry Analysis Using Dual-Direction Dipolar Excitation in a Digital Linear Ion Trap.

The ion trap mass spectrometer offers a unique advantage over other mass spectrometers by enabling multistage tandem mass spectrometry analysis with a single mass analyzer. It is employed to generate fragment ions through collision-induced dissociation (CID) usually by applying alternating current (AC) signals to a pair of electrodes for dipole excitation. The process of achieving double-stage tandem mass spectrometry analysis (MS/MS) in the mass spectrometer involves successive stages of injection, cooling, isolation, excitation, and scanning. For triple-stage tandem mass spectrometry analysis (MS/MS/MS), additional stages of isolation, cooling, and excitation need to be added based on the MS/MS analysis, resulting in a complex and time-consuming mass spectrometry workflow. In this study, a digital ion trap technology with the method of simultaneously applying dipole excitation signals to two pairs of electrodes in the ion trap was developed. This allows fragmentation of the precursor ion in one direction while exciting the first-generation product ions in the other direction, enabling direct acquisition of MS/MS/MS spectra. This approach simplifies the process of tandem mass spectrometry, as demonstrated by experimental studies on methamphetamine, which show that dual-direction excitation effectively reduces workflow and enhances the intensity of product ions. Additionally, the method of direct MS/MS/MS spectra achieved through dual-direction excitation in a digital ion trap mass spectrometer allows for a lower q value of the precursor ion owing to a pseudopotential well depth that is 1.648 times greater than that of a traditional sinusoidal ion trap. The experiments of analyzing high concentration n-butyl acetate and isobutyl acetate have shown that the implementation of MS/MS/MS analysis using dual-direction excitation can provide more mass spectral information and effectively distinguish between the two isomeric samples. The results of direct triple-stage spectra obtained by this technique for several typical volatile hazardous chemicals demonstrate the method's capability for rapid analysis and detection of such substances. In summary, the developed method of dual-directional excitation coupled with digital ion trap technology enables direct performance of triple-stage tandem mass spectrometry analysis, improving fragment ion intensities and providing more valuable mass spectral information. It offers advantages such as simplified workflows, faster analysis, and enhanced accuracy for analyzing compounds with low mass fragment ions.

Comparative proteomics analysis of kidney in chicken infected by infectious bronchitis virus.

The gamma coronavirus infectious bronchitis virus (IBV) is known to cause an acute and highly contagious infectious disease in poultry. Here, this study aimed to investigate the impact of virulent or avirulent IBV infection on the avian host by conducting proteomics with data-independent acquisition mass spectrometry (DIA-MS) in the kidneys of IBV-infected chickens. The results revealed 267, 489, and 510 differentially expressed proteins (DEPs) in the chicken kidneys at 3, 5, and 7 days postinfection (dpi), respectively, when infected with the GD17/04 strain, which is a highly nephrogenic strain and belongs to the 4/91 genotype. In contrast, the attenuated 4/91 vaccine resulted in the identification of 144, 175, and 258 DEPs at 3, 5, and 7 dpi, respectively. Functional enrichment analyses indicated distinct expression profiles between the 2 IBV strains. Upon GD17/04 infection, metabolic pathways respond initially in the early stage (3 dpi) and immune-related signaling pathways respond in the middle and late stages (5 and 7 dpi). The 4/91 vaccine elicited a completely opposite response compared to the GD17/04 infection. Among all DEPs, 62 immune-related DEPs were focused on and found to be mainly enriched in the type I interferon (IFN-I) signaling pathway and involved in humoral and cellular immunity. Notably, key molecules in the IFN-I signaling pathway including MDA5, LGP2, and TBK1 may serve as regulatory targets of IBV. Overall, this study highlights similarities and discrepancies in the patterns of protein expression at different stages of infection with virulent and avirulent IBV strains, with the IFN-I signaling pathway emerging as a critical response to IBV infection.

Pharmacodynamics Research on Danggui-Shaoyao-San through Body Fluid Indexes of Spleen Deficiency-water Dampness Rats using Bioimpedance Technology.

BACKGROUND: Spleen deficiency-water dampness symptom is closely related to body fluid-mediated organism metabolism and circulation. However, previous clinical evaluation of spleen deficiency-water dampness model was based only on body weight, D-xylose excretion rate, serum gastrin content, etc. Therefore, we established a large sample of normal rats and model rats experiment to verify the scientific nature of bio-impedance measuring body fluid indexes for evaluation of the modeling state. Pharmacodynamics research on Danggui-Shaoyao- San (DSS) was conducted through body fluid index changes of rats using bio-impedance technology. METHODS: A spleen deficiency-water dampness symptom rat model was established through an inappropriate diet combined with excess fatigue. Experimental rats were divided into a normal control group, a model control group, a positive drug control group (hydrochlorothiazide), a blood-activating group, a water-disinhibiting group, and a DSS group. Total Body Water/Body Weight (TBW%), extracellular fluid/total body water content (ECF%), intracellular fluid/total body water content (ICF%), extracellular fluid/intracellular fluid (ECF/ICF), fat mass/body weight (FM%), fat-free mass/body weight (FFM%), and fat mass/fat-free mass (FM/FFM) of 150 rats were detected by a Bio-Imp Vet Body analyzer. RESULTS: The TBW% of the model control group increased significantly, and the FM/FFM was significantly reduced compared with the normal group (P < 0.05) (P < 0.01), showing symptoms of spleen deficiency and diarrhea; the TBW% of the blood-activating group, and the waterdisinhibiting group decreased significantly, and the FM/FFM increased significantly (P < 0.05) (P < 0.01). The TBW% and FM/FFM in the water-disinhibiting group had returned to nearnormal values compared with the model control group. The blood-activating and waterdisinhibiting split prescriptions in DSS are both effective in treating spleen deficiency-water dampness rats. Comparatively, the fluid-regulating effect of split prescriptions in DSS was even stronger than that of DSS as shown in the present study. CONCLUSIONS: These findings suggest that using bio-impedance technology to measure body fluid indexes can pave a road for further exploring the molecular mechanism of the reason why the blood-activating and disinhibit-water split prescriptions in DSS are both effective in treating spleen deficiency-water dampness rats.

Large-scale alternative polyadenylation (APA)-wide association studies to identify putative susceptibility genes in human common cancers.

Alternative polyadenylation (APA) modulates mRNA processing in the 3' untranslated regions (3'UTR), which affect mRNA stability and translation efficiency. Here, we build genetic models to predict APA levels in multiple tissues using sequencing data of 1,337 samples from the Genotype-Tissue Expression, and apply these models to assess associations between genetically predicted APA levels and cancer risk with data from large genome-wide association studies of six common cancers, including breast, ovary, prostate, colorectum, lung, and pancreas among European-ancestry populations. At a Bonferroni-corrected P □<□0.05, we identify 58 risk genes, including seven in newly identified loci. Using luciferase reporter assays, we demonstrate that risk alleles of 3'UTR variants, rs324015 ( STAT6 ), rs2280503 ( DIP2B ), rs1128450 ( FBXO38 ) and rs145220637 ( LDAH ), could significantly increase post-transcriptional activities of their target genes compared to reference alleles. Further gene knockdown experiments confirm their oncogenic roles. Our study provides additional insight into the genetic susceptibility of these common cancers.

Targeted glycan degradation potentiates cellular immunotherapy for solid tumors.

Immune cell-based cancer therapies, such as chimeric antigen receptor T (CAR-T)-cell immunotherapy, have demonstrated impressive potency against hematological tumors. However, the efficacy of CAR-T cells against solid tumors remains limited. Herein, we designed tumor-targeting molecule-sialidase conjugates that potently and selectively stripped different sialoglycans from a variety of cancer cells. Desialylation enhanced induced pluripotent stem cell-derived chimeric antigen receptor-macrophage (CAR-iMac) infiltration and activation. Furthermore, the combination of cancer cell desialylation and CAR-iMac adoptive cellular therapy exerted a dramatic therapeutic effect on solid tumors and significantly prolonged the survival of tumor-bearing mice; these effects were mainly dependent on blockade of the checkpoint composed of sialic acid-binding immunoglobulin-like lectin (Siglec)-5 and Siglec-10 on the macrophages, and knockout of the glycoimmune checkpoint receptors could construct a CAR-iMac cell with stronger anticancer activity. This strategy that reverts the immune escape state ("cold tumor") to a sensitive recognition state ("hot tumor") has great significance for enhancing the effect of cellular immunotherapy on solid tumors. Therefore, desialylation combined with CAR-iMac cellular immunotherapy is a promising approach to enhance treatment with cellular immunotherapy and expand the valid indications among solid tumors, which provides inspiration for the development of cellular immunotherapies with glycoimmune checkpoint inhibition for the treatment of human cancer.

Full-length genome sequence of porcine epidemic diarrhea virus strain SDTA13-2020.

We report here the complete genome sequence of porcine epidemic diarrhea virus (PEDV) strain SDTA13-2020, isolated from a suckling piglet with watery diarrhea in Shandong, China. The isolate is genetically close to other recent Chinese G2 genotype PEDVs and distinct from the classical PEDVs.

Genome Sequence of Chinese Porcine Parvovirus Strain BJ2.

Porcine parvovirus (PPV) strain BJ2 was isolated from a pig with symptoms consistent with PPV in Beijing, China. The analysis showed that the PPV genome sequence has the characteristics of a German cluster 27a strain and the virulent Kreese strain, which will facilitate understanding of the prevalence of PPV in China.