The ETI-dependent receptor-like kinase 1 positively regulates effector-triggered immunity by stabilizing NLR-required for cell death 4 in Nicotiana benthamiana.

Leucine-rich repeat receptor-like kinases (LRR-RLKs) comprise the largest class of membrane-localized receptor-like kinases in plants. Leucine-rich repeat receptor-like kinases are key immune sectors contributing to pattern-triggered immunity (PTI), but whether LRR-RLK mediates effector-triggered immunity (ETI) in plants remains unclear. In this study, we evaluated the function of LRR-RLKs in regulating ETI by using a virus-induced gene silencing (VIGS)-based reverse genetic screening assay, and identified a LRR-RLK named ETI-dependent receptor-like kinase 1 (EDK1) required for ETI triggered by the avirulence effector AVRblb2 secreted by Phytophthora infestans and its cognate receptor Rpi-blb2. Silencing or knockout of EDK1 compromised immunity mediated by Rpi-blb2 and the cell death triggered by recognition of AVRblb2. NLR-required for cell death 4 (NRC4), a signaling component acts downstream of Rpi-blb2, was identified that interacts with EDK1 using the LC-MS analysis and the interaction was further evaluated by co-immunoprecipitation. EDK1 promotes protein accumulation of NRC4 in a kinase-dependent manner and positively regulates resistance to P. infestans in Nicotiana benthamiana. Our study revealed that EDK1 positively regulates plant ETI through modulating accumulation of the NLR signaling component NRC4, representing a new regulatory role of the membrane-localized LRR-RLKs in plant immunity.

CYP8B1 Catalyzes 12alpha-hydroxylation of C27 Bile Acid: In Vitro Conversion of Dihydroxycoprostanic Acid into Trihydroxycoprostanic Acid.

CYP8B1 is the unique P450 enzyme with sterol 12-oxidation activity, playing an exclusive role in 12α-hydroxylating intermediates along the bile acid (BA) synthesis pathway. Despite the long history of BA metabolism studies, it is unclear whether CYP8B1 catalyzes 12α-hydroxylation of C27 BAs, the key intermediates shuttling between mitochondria and peroxisomes. This work provides robust in vitro evidence that both microsomal and recombinant CYP8B1 enzymes catalyze the 12α-hydroxylation of dihydroxycoprostanic acid (DHCA) into trihydroxycoprostanic acid (THCA). On the one hand, DHCA 12α-hydroxylation reactivity is conservatively detected in liver microsomes of both human and preclinical animals. The reactivity of human tissue fractions conforms well with the selectivity of CYP8B1 mRNA expression, while the contribution of P450 enzymes other than CYP8B1 is excluded by reaction phenotyping in commercial recombinant enzymes. On the other hand, we prepared functional recombinant human CYP8B1 proteins according to a recently published protocol. Titration of the purified CYP8B1 proteins with either C4 (7α-hydroxy-4-cholesten-3-one) or DHCA yields expected blue shifts of the heme Soret peak (type I binding). The recombinant CYP8B1 proteins efficiently catalyze 12α-hydroxylation of both DHCA and C4, with Km of 3.0 and 1.9 µM and kcat of 3.2 and 2.6 min-1, respectively. In summary, the confirmed role of CYP8B1 in 12α-hydroxylation of C27 BAs has furnished the forgotten passageway in the BA synthesis pathway. The present finding might have opened a new window to consider the biology of CYP8B1 in glucolipid metabolism and to evaluate CYP8B1 inhibition as a therapeutic approach of crucial interest for metabolic diseases. Significance Statement Academic community has spent about 90 years interpreting the synthesis of bile acids. However, the 12α-hydroxylation of intermediates catalyzed by CYP8B1 is not completely mapped on the classic pathway, particularly for the C27 bile acids, the pivotal intermediates shuttling between mitochondria and peroxisomes. This work discloses the forgotten 12α-hydroxylation pathway from dihydroxycoprostanic acid into trihydroxycoprostanic acid. The present finding may facilitate evaluating CYP8B1 inhibition as a therapeutic approach of crucial interest for metabolic diseases.

Gut Dysbiosis Promotes Preeclampsia by Regulating Macrophages and Trophoblasts.

BACKGROUND: Preeclampsia is one of the leading causes of maternal and perinatal morbidity and is characterized by hypertension, inflammation, and placental dysfunction. Gut microbiota plays key roles in inflammation and hypertension. However, its roles and mechanisms in preeclampsia have not been fully elucidated. METHODS: 16S rRNA gene sequencing and targeted metabolomics were conducted on stool samples from 92 preeclamptic patients and 86 normal late-pregnant women. Then, fecal microbiota transplantation and in vitro and in vivo functional experiments were performed to explore the roles and mechanisms of gut microbiota in preeclampsia development. RESULTS: We revealed the gut microbiota dysbiosis in preeclamptic patients, including significant reductions in short-chain fatty acid-producing bacteria and short-chain fatty acids. The gut microbiota of preeclamptic patients significantly exacerbated pathologies and symptoms of preeclamptic rats, whereas the gut microbiota of healthy pregnant women had significant protective effects. Akkermansia muciniphila, propionate, or butyrate significantly alleviated the symptoms of preeclamptic rats. Mechanistically, they significantly promoted autophagy and M2 polarization of macrophages in placental bed, thereby suppressing inflammation. Propionate also significantly promoted trophoblast invasion, thereby improved spiral arterial remodeling. Additionally, we identified a marker set consisting of Akkermansia, Oscillibacter, and short-chain fatty acids that could accurately diagnose preeclampsia. CONCLUSIONS: Our study revealed that gut microbiota dysbiosis is an important etiology of preeclampsia. Gut microbiota and their active metabolites have great potential for the treatment and diagnosis of preeclampsia. Our findings enrich the gut-placenta axis theory and contribute to the development of microecological products for preeclampsia.

Establishment and validation of a CT-based prediction model for the good dissolution of mild chronic subdural hematoma with atorvastatin treatment.

PURPOSE: To develop and validate a prediction model based on imaging data for the prognosis of mild chronic subdural hematoma undergoing atorvastatin treatment. METHODS: We developed the prediction model utilizing data from patients diagnosed with CSDH between February 2019 and November 2021. Demographic characteristics, medical history, and hematoma characteristics in non-contrast computed tomography (NCCT) were extracted upon admission to the hospital. To reduce data dimensionality, a backward stepwise regression model was implemented to build a prognostic prediction model. We calculated the area under the receiver operating characteristic curve (AUC) of the prognostic prediction model by a tenfold cross-validation procedure. RESULTS: Maximum thickness, volume, mean density, morphology, and kurtosis of the hematoma were identified as the most significant predictors of good hematoma dissolution in mild CSDH patients undergoing atorvastatin treatment. The prediction model exhibited good discrimination, with an area under the curve (AUC) of 0.82 (95% confidence interval [CI], 0.74-0.90) and good calibration (p = 0.613). The validation analysis showed the AUC of the final prognostic prediction model is 0.80 (95% CI 0.71-0.86) and it has good prediction performance. CONCLUSION: The imaging data-based prediction model has demonstrated great prediction accuracy for good hematoma dissolution in mild CSDH patients undergoing atorvastatin treatment. The study results emphasize the importance of imaging data evaluation in the management of CSDH patients.

The impact of unmet community service demand on the loneliness of older adults: based on CLHLS (2008-2018).

PURPOSE: To explore the impact of unmet community service demands on loneliness among older adults. METHODS: Based on the longitudinal tracking data of CLHLS (2008-2018), latent growth curve model (LGCM) was used to describe the trajectory of loneliness among older adults. Panel regression was used to analyze the impact of unmet community service demands on loneliness, and latent classification analysis (LCA) was used to classify the older adults and analyze the differences in loneliness among different types of older adults. RESULTS: A total of 1445 older people participated in all four surveys, and 22.4% of them reported feeling lonely. From 2008 to 2018, there was a significant non-linear increase in loneliness, with average values of 1.77, 1.81, 1.83, and 1.96, respectively. The level of community service supply (1.31) was far from meeting the demand level (5.11). Unmet community service demands were associated with a higher prevalence of loneliness (ß = 0.012, P = 0.003, 95% CI = [0.004, 0.020]). In addition, according to the demand difference for community services, older adults were classified into the comprehensive demand type (Type I) and the medical demand type (Type II). The loneliness of Type I older adults was significantly higher than that of Type II (P < 0.05). CONCLUSIONS: With the passage of time, loneliness of older adults is showing an accelerating upward trend. Unmet community services can lead to enhanced loneliness among older adults, and the higher the demand for community services, the stronger the loneliness. The government should increase the supply of community services to meet the basic and socio-emotional needs of the older adults to reduce loneliness.

Effect of MVF Combined with FES on Limb Function Recovery and Fine Function Rehabilitation of Hemiplegic Patients after ACI.

Background: This study assesses the efficacy of mirror visual feedback (MVF) combined with functional electrical stimulation (FES) in rehabilitating limb function and fine motor skills in hemiplegic patients after acute cerebral infarction (ACI). Given the limited research in this area, this study aims to provide insights into innovative rehabilitation techniques. Methods: A randomized controlled trial was conducted on 106 post-ACI hemiplegic patients, split into two groups of 53 each. One group received conventional training plus FES, while the other group underwent MVF combined with FES. Key metrics like walking parameters, the modified Lindmark score, center of gravity movement speed, Fugl-Meyer Motor function (FMA) score, fall index, Berg score, and Time-Up-Go Time (TUGT) were measured to evaluate the effectiveness. Results: In the study, significant improvements were observed in the observation group compared to the control group. The Modified Lindmark Scores for sensory function, motor coordination, and total scores in the observation group improved to 6.85±0.72, 15.77±2.25, and 22.62±2.78 respectively post-treatment, surpassing the control group's scores of 5.77±0.68, 13.92±1.87, and 19.69±2.45. In terms of FMA score, fall index, Berg score, and TUGT time, the observation group showed remarkable improvement: the FMA score increased from 43.69±4.51 to 67.25±7.04, the fall index decreased from 55.74±8.76 to 42.08±5.97, the Berg score rose from 31.03±6.28 to 43.11±6.71, and the TUGT time was reduced from 30.78±6.59s to 18.57±3.26s. These changes were significantly better than those in the control group, with all P = .000, indicating statistically significant improvements. Conclusion: The results indicate that the combination of MVF and FES is more effective in improving limb function, hand fine movements, and balance in hemiplegic patients post-ACI compared to FES alone. This suggests that integrating MVF with FES may be a more beneficial approach in stroke rehabilitation. Future research is advised to explore larger sample sizes and long-term effects, offering guidance for developing more effective treatment and rehabilitation plans. This study suggests that integrating mirror visual feedback and functional electrical stimulation into stroke rehabilitation could significantly enhance recovery, potentially influencing clinical practices and rehabilitation policies. Future studies should explore the long-term effects, applicability to diverse patient groups, and cost-effectiveness of these combined therapies.

CCP5 and CCP6 retain CP110 and negatively regulate ciliogenesis.

BACKGROUND: The axonemal microtubules of primary cilium undergo a conserved protein posttranslational modification (PTM) - polyglutamylation. This reversible procedure is processed by tubulin tyrosine ligase-like polyglutamylases to form secondary polyglutamate side chains, which are metabolized by the 6-member cytosolic carboxypeptidase (CCP) family. Although polyglutamylation modifying enzymes have been linked to ciliary architecture and motility, it was unknown whether they also play a role in ciliogenesis. RESULTS: In this study, we found that CCP5 expression is transiently downregulated upon the initiation of ciliogenesis, but recovered after cilia are formed. Overexpression of CCP5 inhibited ciliogenesis, suggesting that a transient downregulation of CCP5 expression is required for ciliation initiation. Interestingly, the inhibitory effect of CCP5 on ciliogenesis does not rely on its enzyme activity. Among other 3 CCP members tested, only CCP6 can similarly suppress ciliogenesis. Using CoIP-MS analysis, we identified a protein that potentially interacts with CCP - CP110, a known negative regulator of ciliogenesis, whose degradation at the distal end of mother centriole permits cilia assembly. We found that both CCP5 and CCP6 can modulate CP110 level. Particularly, CCP5 interacts with CP110 through its N-terminus. Loss of CCP5 or CCP6 led to the disappearance of CP110 at the mother centriole and abnormally increased ciliation in cycling RPE-1 cells. Co-depletion of CCP5 and CCP6 synergized this abnormal ciliation, suggesting their partially overlapped function in suppressing cilia formation in cycling cells. In contrast, co-depletion of the two enzymes did not further increase the length of cilia, although CCP5 and CCP6 differentially regulate polyglutamate side-chain length of ciliary axoneme and both contribute to limiting cilia length, suggesting that they may share a common pathway in cilia length control. Through inducing the overexpression of CCP5 or CCP6 at different stages of ciliogenesis, we further demonstrated that CCP5 or CCP6 inhibited cilia formation before ciliogenesis, while shortened the length of cilia after cilia formation. CONCLUSION: These findings reveal the dual role of CCP5 and CCP6. In addition to regulating cilia length, they also retain CP110 level to suppress cilia formation in cycling cells, pointing to a novel regulatory mechanism for ciliogenesis mediated by demodifying enzymes of a conserved ciliary PTM, polyglutamylation.

Dimension compensation of printed master molds by a desktop LCD 3D printer for high-precision microfluidic applications.

Recent advances in low-cost liquid crystal display (LCD) 3D printing have popularized its use in creating microfluidic master molds and complete devices. However, the quality and precision of these fabrications often fall short of the rigorous standards required for advanced microfluidic applications. This study introduces a novel approach to enhance the dimensional accuracy of microchannels produced using a desktop LCD 3D printer. We propose a method for dimension compensation, optimize the printing parameters, and provide a straightforward post-treatment technique to ensure high-quality curing of polydimethylsiloxane (PDMS) in master molds made from photosensitive resin. Our investigation assesses the precision of 3D printing across three different scales of square cross-section microchannels by measuring their widths and heights, leading to the determination of optimal printing parameters that minimize dimensional errors. The dimensional errors are further reduced by introducing a series of dimension compensation factors, which correct the nominal dimensions of the microchannels by using the compensation factors in 3D printing. The dimensional accuracy is significantly improved after compensation even in fabricating complex microchannels of triangular cross-sections. Finally, a spiral channel of trapezoidal-like cross-section with tilted edges is fabricated for microfluidic application, and highly efficient particle separation is realized in the channel. The proposed method provides new insights for utilizing desktop LCD 3D printers to achieve high-accuracy microstructures necessary for advanced microfluidic applications.

Spiral microchannels with concave cross-section for enhanced cancer cell inertial separation.

Inertial microfluidic technologies have proven effective for particle focusing and separation in many microchannels, typically the channels with the rectangular and trapezoidal shapes. To advance particle focusing in complex channels, we propose a spiral channel combining rectangular and concave cross-sections for high-resolution particle and cell focusing and separation. Numerical simulations were conducted to illustrate the effects of channel geometry on secondary flow distribution and particle focusing positions. The simulation shows the concave cross-section generates two asymmetrical Dean vortices skewing towards the inner and outer channel walls, resulting to stronger flow velocity magnitudes near the walls than the channel center. Consequently, larger particles focus near the inner wall, while smaller particles are trapped closer to the outer wall under the influence of the stronger velocity magnitude near the walls. A microfluidic chip with the proposed channel geometry, along with a traditional rectangular channel, was fabricated by 3D printing and PDMS casting. Fluorescent microbeads were used to investigate inertial focusing and separation behaviors in the microfluidic chips. Experimental results show that the concave channel facilitates particle focusing or trapping much closer to the walls than the traditional rectangular channel, achieving better separation resolution. Finally, the proposed channel was applied to separate lung cancer A549 cells from human blood, achieving a cancer cell recovery rate of ~ 84.78% (enrichment ratio over 820-fold) and a blood cell rejection rate of ~ 99.88%. This innovative channel design in inertial microfluidics offers new insights for enhanced particle focusing and holds significant promise for cell manipulation with improved separation resolution.

Translation, Cultural Adaptation and Validation of the Standardized Cosmesis and Health Nasal Outcomes Survey (SCHNOS) in Chinese.

BACKGROUND: Rhinoplasty requires balanced consideration of function and aesthetics, necessitating a precise evaluation tool. A reliable and validated patient-reported measure, the Standardized Cosmesis and Health Nasal Outcomes Survey (SCHNOS) evaluates both aspects but was previously unavailable in Chinese. This study fills that gap by providing a Chinese version. OBJECTIVES: This study aims to translate, culturally adapt, and validate a Chinese iteration of the SCHNOS (C-SCHNOS) for appraising the functional and aesthetic outcomes among Chinese patients post-rhinoplasty, furnishing a reliable and efficacious assessment tool for Chinese users. METHODS: Following international guidelines, the SCHNOS questionnaire was translated and culturally adapted for Chinese use. Its psychometric properties, including internal consistency, correlations, and reproducibility, were evaluated among Chinese natives in Sichuan Province from March 2022 to January 2023. RESULTS: The C-SCHNOS was administered to 110 Chinese natives, showing high internal consistency, Cronbach's α of 0.81 for SCHNOS-O (Obstructive domain), 0.92 for SCHNOS-C (Cosmetic domain). Spearman correlations for SCHNOS-O (0.36-0.65) and SCHNOS-C (0.51-0.74) were positive and significant. Test-retest reliability analyses revealed strong Spearman correlations for SCHNOS-O (r=0.87) and SCHNOS-C (r=0.90). Responsiveness was statistically significant for SCHNOS-O (P < 0.001) but not for SCHNOS-C (P=0.222). Exploratory factor analysis and parallel tests indicated that C-SCHNOS maintained a single-factor structure, with eigenvalues exceeding the critical values (2.55 for SCHNOS-O and 4.35 for SCHNOS-C), reflecting excellent unidimensionality. CONCLUSIONS: The SCHNOS questionnaire was successfully translated into Chinese and culturally adapted. The C-SCHNOS is a dependable and valid instrument for use in Chinese population undergoing functional or cosmetic rhinoplasty.

[Integrated strategy for mechanism of Shenling Baizhu San in treating ulcerative colitis based on colonic metabolomics and network pharmacology].

Shenling Baizhu San(SLBZS) is a commonly used medicine for the treatment of ulcerative colitis(UC). This study aims to explore the mechanism of SLBZS in treating UC by using colonic metabolomics and network pharmacology. BALB/c mice were randomly divided into four groups: a blank group, a model group, an SLBZS group, and a sulfasalazine group. UPLC-Q-TOF-MS/MS technology was utilized to analyze the metabolic profiles of colonic tissue in mice, and differential metabolites and related metabolic pathways were screened. Based on the online database, active ingredients, action targets, and UC disease targets of SLBZS were screened. The protein-protein interaction(PPI) network of core targets of SLBZS in treating UC was constructed using STRING and Cytoscape 3.9.1. Gene Ontology(GO) functional and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were performed using the DAVID database. A "metabolite-reaction-enzyme-gene" network was constructed to conduct a combined analysis of metabolomics and network pharmacology. SLBZS reversed the levels of 25 metabolites involved in various pathways such as D-glutamine and D-glutamate metabolism, caffeine metabolism, sphingolipid metabolism, arginine biosynthesis, lysine degradation, alanine, aspartate, and glutamate metabolism, glycerophospholipid metabolism, and pyrimidine metabolism in UC colonic tissue. 47 core targets of SLBZS in treating UC were involved in pathways including the MAPK signaling pathway, TNF signaling pathway, Toll-like receptor signaling pathway, lipid and atherosclerosis, inflammatory bowel disease, and Th17 cell differentiation. Integrated analysis showed that glycerophospholipid metabolism and pyrimidine metabolism were key metabolic pathways in the treatment of UC with SLBZS. The results suggested that SLBZS improved colonic mucosal morphology by regulating colonic metabolites, down-regulated the expression of inflammation-related core target genes to reduce inflammation levels, and alleviated lipid metabolism disorders, thereby exerting a therapeutic effect on UC.

Rtr1 is required for Rpb1-Rpb2 assembly of RNAPII and prevents their cytoplasmic clump formation.

RNA polymerase II (RNAPII) is an essential machinery for catalyzing mRNA synthesis and controlling cell fate in eukaryotes. Although the structure and function of RNAPII have been relatively defined, the molecular mechanism of its assembly process is not clear. The identification and functional analysis of assembly factors will provide new understanding to transcription regulation. In this study, we identify that RTR1, a known transcription regulator, is a new multicopy genetic suppressor of mutants of assembly factors Gpn3, Gpn2, and Rba50. We demonstrate that Rtr1 is directly required to assemble the two largest subunits of RNAPII by coordinating with Gpn3 and Npa3. Deletion of RTR1 leads to cytoplasmic clumping of RNAPII subunit and multiple copies of RTR1 can inhibit the formation of cytoplasmic clump of RNAPII subunit in gpn3-9 mutant, indicating a new layer function of Rtr1 in checking proper assembly of RNAPII. In addition, we find that disrupted activity of Rtr1 phosphatase does not trigger the formation of cytoplasmic clump of RNAPII subunit in a catalytically inactive mutant of RTR1. Based on these results, we conclude that Rtr1 cooperates with Gpn3 and Npa3 to assemble RNAPII core.

The hepatoprotective effects of plant-based foods based on the "gut-liver axis": a prospective review.

The importance of the "gut-liver axis" in the pathogenesis of liver diseases has been revealed recently; which promotes the process of developing preventive and therapeutic strategies. However, considering that there are still many challenges in the medical treatment of liver diseases, potential preventive dietary intervention may be a good alternative choice. Plant-based foods have received much attention due to their reported health-promoting effects in targeting multiple pathways involved in the pathogenesis of liver diseases as well as the relative safety for general use. Based on the PubMed and Web of Science databases, this review emphatically summarizes the plant-based foods and their chemical constituents with reported effects to impact the LPS/TLR4 signaling pathway of gut-liver axis of various liver diseases, reflecting their health benefits in preventing/alleviating liver diseases. Moreover, some plant-based foods with potential gut-liver effects are specifically analyzed from the reported studies and conclusions. This review intends to provide readers an overview of the current progress in the field of this research topic. We expect to see more hepatoprotective measures for alleviating the current prevalence of liver diseases.

Separation and identification of terpene-conjugated curcuminoids based on liquid chromatography-tandem mass spectrometry and their in vitro anti-inflammatory activities.

Terpene-conjugated curcuminoids are conjugates of curcuminoids and bisabolanes in the rhizomes of Curcuma longa L. The fragmentation pathways of known three terpene-conjugated curcuminoids (bisabolocurcumin-ether, bisabocurcumin, and demethoxybisabolocurcumin ether) and curcumin, demethoxycurcumin, and bisdemethoxycurcumin were investigated using high-performance liquid chromatography-electrospray ionization tandem mass spectrometry in negative mode to rapidly search and discover similar unknown compounds of the acetone fraction of turmeric. Subsequently, compounds 1-3 were founded in the acetone fraction based on molecular weight and above fragmentation pathways (the characteristic fragment ions, the most and second most abundant fragment ions produced in MS2 spectra). Terpecurcumin X (1) and terpecurcumin Y (3) were further separated by liquid chromatography-tandem mass spectrometry guided isolation technique to verify their structures by nuclear magnetic resonance, electrospray ionization high-resolution mass spectroscopy, ultraviolet and visible spectra and infrared spectra. Interestingly, 1 and 3 were new compounds. The results indicate the feasibility and significant advantages of liquid chromatography-tandem mass spectrometry for the rapid discovery and analysis of new constituents in traditional Chinese medicine. In vitro, Terpene-conjugated curcuminoids had better nitric oxide inhibitory activity than the other seven curcuminoids (demethoxycurcumin, bisdemethoxycurcumin, curdione, curcumenone, bisacurone, curcumenol, and germacron).

[Predictive value of peripheral blood lymphocyte subsets for children with intravenous immunoglobulin-resistant Kawasaki disease]. / å¤–å‘¨è¡€æ·‹å·´ç»†èƒžäºšç¾¤å¯¹é™è„‰æ³¨å°„å ç–«çƒè›‹ç™½æ— ååº”åž‹å·å´Žç— æ‚£å„¿çš„é¢„æµ‹ä»·å€¼.

OBJECTIVES: Based on peripheral blood lymphocyte subsets and common laboratory test indexes, this study aimed to construct a predictive scoring system for intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD). METHODS: Children hospitalized in Tianjin Children's Hospital from January 2021 to March 2023 were included in the study (185 cases of IVIG-sensitive KD and 41 cases of IVIG -resistant KD). Forty-six healthy children matched for age and gender were selected as controls. The relative percentage and absolute counts of peripheral lymphocyte subsets were measured by flow cytometry. Multivariate logistic regression was used to identify the predictive factors for IVIG-resistant KD and to construct a predictive scoring system for predicting IVIG-resistant KD. RESULTS: The multivariate logistic regression analysis showed that CD4+ T cell absolute count, natural killer cell absolute count, serum sodium level, globulin level, and total bilirubin level were identified as predictive factors for IVIG-resistant KD (P<0.05). The predictive scoring system based on these factors achieved a sensitivity of 70.7% and a specificity of 83.8% in predicting IVIG-resistant KD. CONCLUSIONS: Peripheral blood lymphocyte subsets can serve as predictive indicators for IVIG-resistant KD in children. The introduction of this indicator and the establishment of a scoring system based on it can provide a higher accuracy in predicting IVIG-resistant KD in children.

A Versatile Method for the End-Functionalization of Polycarbenes.

End-functionalization is an effective strategy for constructing functional materials. A method for chain-end functionalization of helical polycarbenes is herein developed that relied on Sonogashira coupling reaction. In this work, a family of helical polycarbenes with controlled molecular mass (Mn ) and low polydispersity (Mw /Mn ) is readily prepared using Pd(II) and the Wei-Phos ligand as initiator. The Pd(II) complex is confirmed to remain at the chain end of polycarbene. Subsequently, a series of terminal alkyne derivatives with interesting functional groups, including the F atom, aldehyde, or anthracene groups, are synthesized. They could be installed at the chain end of polycarbene through Sonogashira coupling reaction catalyzed by the Pd(II) complex at the chain end. Moreover, a couple of hybrid block copolymers are easily obtained by installing terminal alkynes modified by another type of polymer. The structures of the isolated polymers are confirmed by 1 H nuclear magnetic resonance (1 H NMR), 19 F nuclear magnetic resonance (19 F NMR), 31 P nuclear magnetic resonance (31 P NMR), and Fourier transform infrared spectroscopy (FT-IR), respectively. The self-assembly properties of the hybrid block copolymers are also investigated by atomic force spectroscopy analysis. By the hereby developed method, various functional groups can be introduced at the chain end of helical polycarbenes for constructing functional polymer materials, moreover, the transition metal residues at the end of polymer chains can be easily removed.

Relative acquisition evaluation of health poverty alleviation project: a quantitative study of data from different regions of China.

BACKGROUND: Poverty is the greatest obstacle to the realization of human rights, among which illness is the leading cause in China. In 2015, China began to implement the health poverty alleviation project (HPAP). By 2020, all rural households living below the current poverty level (2300 yuan per person per year) have been lifted out of poverty. METHODS: This study introduces the concept of relative acquisition and constructs a scale based on the capability approach to measure the relative acquisition and compares its fairness of HPAP. RESULTS: The findings show that the values of the relative acquisition of HPAP in survey areas are all reached middle level (0.4-0.6), with 0 indicating the worst level and 1 indicating the best level. Specifically, the values of the functional activities of "health care", "health ability", "equal treatment opportunities" and "social support" are all above 0.4, while the values of "economic conditions" and "health education" are below 0.4. CONCLUSIONS: The HPAP plays a significant role in reducing the economic burden of disease on patients. However, due to insufficient social support and health education, the HPAP objects lack endogenous motivation to fight against poverty, and the fairness also needs to be improved.

The inflammatory cellular feature in the peripheral blood of chronic subdural hematoma patients.

BACKGROUND: Chronic subdural hematoma (CSDH) is a common neurosurgical disease with an increasing incidence. The absorption route of CSDH is not clear. Whether inflammatory factors enter the peripheral blood and cause systemic reactions is unknown. METHODS: We screened 105 CSDH patients and 105 control individuals. Their clinical characteristics and blood routine results were collected and compared. The blood routine changes of CSDH patients before and after treatment were compared. Age-stratified analysis was performed due to age may affect the inflammatory markers. RESULTS: The white blood cell count, absolute neutrophil count, neutrophil percentage, neutrophil-lymphocyte count ratio (NLR), and platelet to lymphocyte count ratio (PLR) of CSDH patients before treatment were within the normal range, while were significantly higher than the control individuals (p < 0.001). The absolute lymphocyte count and lymphocyte percentage of control individuals were higher than those of patients (p < 0.001). The inflammatory cells in patients of different age groups were similar. After the patient was cured, the white blood cell count, the absolute value and percentage of neutrophils decreased (p < 0.05), while the number of monocytes increased. CONCLUSIONS: CSDH caused slight systemic inflammatory responses in the peripheral blood, implying that there is a non-hematologic route for the absorption of hematoma.

[Analysis of gene variant in an infant with succinic semialdehyde dehydrogenase deficiency].

OBJECTIVE: To explore the genetic basis for a child with succinate semialdehyde dehydrogenase deficiency. METHODS: Peripheral blood samples of the proband and his parents were collected and subjected to Sanger sequencing. High-throughput sequencing was used to verify the gene variants. Bioinformatic software was used to analyze the pathogenicity of the variant sites. RESULTS: Sanger sequencing showed that the proband carried a homozygous c.1529C>T (p.S510F) variant of the ALDH5A1 gene, for which his mother was a carrier. The same variant was not detected in his father. However, high-throughput sequencing revealed that the child and his father both had a deletion of ALDH5A1 gene fragment (chr6: 24 403 265-24 566 986). CONCLUSION: The c.1529C>T variant of the ALDH5A1 gene and deletion of ALDH5A1 gene fragment probably underlay the disease in the child. High-throughput sequencing can detect site variation as well as deletion of gene fragment, which has enabled genetic diagnosis and counseling for the family.

Deep sequencing reveals the skewed B-cell receptor repertoire in plaques and the association between pathogens and atherosclerosis.

The immune/inflammatory responses regulated by B cells are the critical determinants of atherosclerosis. B-cell receptor (BCR) plays pivotal roles in regulating B cell function. However, the composition and molecular characteristics of the BCR repertoire in atherosclerotic patients have not been fully elucidated. Herein we analyzed BCR repertoire in circulation and plaques of atherosclerotic patients by sequencing the BCR heavy chain complement determining region 3 (BCRH CDR3). Our data showed that in plaques, BCR repertoire was dramatically skewed and their combinations and diversity were significantly decreased, while the frequency of public and dominant B-cell clones was markedly increased. Additionally, BCRH CDR3 in plaques had higher positive selection pressure than that in the peripheral blood of normal subjects and atherosclerotic patients. Moreover, the BCRH CDR3 of some B cell clones specifically expanded in plaques were similar to that of antibodies which recognized certain pathogens including Influenza A virus, implying the possibility of the association between pathogens and atherosclerosis. The present study contributed to understand the roles of B cells in atherosclerosis. The design of specific antibodies based on the B cell clones specifically expanded in plaques might yield useful tools to reveal the pathogenesis of atherosclerosis, assess or alleviate the progression of atherosclerosis.