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Although the immune systems of patients with systemic lupus erythematosus (SLE) are affected by both personal characteristics and environmental factors, the effects of parabens on patients with SLE have not been well studied. We investigated the indirect effects of four parabens-methylparaben (MP), ethylparaben (EP), propylparaben (n-PrP), and butylparaben (n-BuP)-on several immunological markers.We assessed the serum levels of MP, EP, n-PrP, and n-BuP in 25 SLE patients and correlated the concentration of each paraben with available clinical and laboratory markers, including intracellular markers of antiviral immunity and apoptosis.The expression of aryl hydrocarbon receptor (AhR) was significantly negatively correlated with n-PrP levels (p = 0.03, r = -0.434). In monocytes, APO2.7 was significantly positively correlated with n-BuP levels (p = 0.019, r = 0.467). Glutathione levels were significantly negatively correlated with n-BuP levels (p = 0.019, r = -0.518). Anti- β2 glycoprotein I IgM was significantly positively correlated with both MP (p = 0.011, r = 0.585) and EP levels (p = 0.032, r = 0.506). Anti-cardiolipin IgA was significantly positively correlated with both MP (p = 0.038, r = 0.493) and n-PrP levels (p = 0.031, r = 0.508). On CD8 T cells, the early apoptotic marker annexin V was significantly negatively correlated with both MP (p0.05, r = -0.541) and n-BuP levels (p = 0.02, r = -0.616), and L-selectin was significantly positively correlated with both MP (p0.05, r = 0.47) and n-PrP levels (p = 0.02, r = 0.556).Our findings suggest that higher parabens levels were associated with lower AhR expression in leukocytes, increased monocyte apoptosis, lower serum glutathione levels, reduced annexin V expression on CD8 T cells, and higher L-selectin levels on leukocytes.

Background Triggering receptor expressed on myeloid cells 2 (TREM2) is upregulated in activated microglia and may be related to cognitive decline in patients with Alzheimer’s disease (AD). There is conflicting evidence regarding the association of peripheral levels of TREM2 mRNA expression and soluble TREM2 (the extracellular domain of TREM2) with cognitive function in patients with AD. The correlation between peripheral TREM2 mRNA expression and neuroinflammation is unclear. Methods We recruited subjects with mild dementia due to AD (clinical dementia rating = 0.5 or 1) and healthy controls. Quantitative real-time polymerase chain reaction analysis was performed using two types of primers. One detects all peripheral TREM2 mRNA isoforms, and the other is specific for TREM2alt. In a subgroup of patients with AD, magnetic resonance spectroscopy (MRS) was used to measure the myo-inositol (mI) level in the posterior cingulate cortex, which is considered a marker for microglial activation. We analyzed the difference in mRNA expression between the two groups and the association between mRNA expression and cognition and mI levels. Results We recruited 61 patients with AD and 51 healthy controls. A one-way analysis of covariance adjusted for covariates showed higher TREM2 and TREM2alt mRNA expression levels in the AD group than in the control group (p = 0.013 and p = 0.001, respectively). Correlation analysis and linear regression examining the association between the mRNA expression levels and mini-mental state examination score showed a positive correlation in patients with AD (TREM2, rs = 0.305, p = 0.017, adjusted p = 0.001; TREM2alt, rs = 0.302, p = 0.018, adjusted p = 0.009) but not in the control group. Subgroup analysis of 25 AD patients with MRS showed a negative correlation between mRNA expression and mI levels (TREM2, rs = -0.426, p = 0.034, adjusted p = 0.032; TREM2alt, rs = -0.447, p = 0.025, adjusted p = 0.028). Conclusions Increased TREM2 and TREM2alt mRNA expression is associated with AD pathogenesis at the mild dementia stage, thereby serving as a potential biomarker for the early symptomatic stage of AD. TREM2 may exert protective effects on both cognition and microglia-mediated neuroinflammation.

Obstructive sleep apnea syndrome (OSAS) has mostly been examined using in-laboratory polysomnography (Lab-PSG), which may overestimate severity. This study compared sleep parameters in different environments and investigated the association between the plasma levels of neurochemical biomarkers and sleep parameters.Thirty Taiwanese participants underwent Lab-PSG while wearing a single-lead electrocardiogram patch. Participants' blood samples were obtained in the morning immediately after the recording. Participants wore the patch for the subsequent three nights at home. Sleep disorder indices were calculated, including the apnea-hypopnea index (AHI), chest effort index, and cyclic variation of heart rate index (CVHRI). The 23 eligible participants' derived data were divided into the normal-to-moderate (N-M) group and the severe group according to American Association of Sleep Medicine (AASM) guidelines (Lab-PSG) and the recommendations of a previous study (Rooti Rx). Spearman's correlation was used to examine the correlations between sleep parameters and neurochemical biomarker levels.The mean T-Tau protein level was positively correlated with the home-based CVHRI (r = 0.53, p 0.05), whereas no significant correlation was noted between hospital-based CVHRI and the mean T-tau protein level (r = 0.25, p = 0.25). The home-based data revealed that the mean T-Tau protein level in the severe group was significantly higher than that in the N-M group (severe group: 24.75 ± 6.16 pg/mL, N-M group: 19.65 ± 3.90 pg/mL; p 0.05). Furthermore, the mean in-hospital CVHRI was higher than the mean at-home values (12.16 ± 13.66 events/h).Severe OSAS patients classified by home-based CVHRI demonstrated the higher T-Tau protein level, and CVHRI varied in different sleep environments.

Both insects and pathogens release effectors that are transferred into plant cells and weaken the host defense or immune response. While the imports of some bacterial and fungal effectors into plants have been reported, how caterpillar effectors enter plant cells remains a mystery. Here, using live cell imaging and real-time protein tracking, we show that HARP1, an effector from oral secretions of cotton bollworm (Helicoverpa armigera) which is previously reported to interfere with defense hormone jasmonate (JA) signaling output in host plants, enters plant cells via protein-mediated endocytosis. The interactions of HARP1 with vesicle trafficking components including CTL1, PATL2 and TET8 are essential for its entry. Notably, JA restricts HARP1 import by inhibiting endocytosis and HARP1 loading on endosomes. Taken together, the effector and JA set up a defense and counter-defense loop in the arm race between plants and insects. Our study unveils a new paradigm for the plant-insect interaction.

Background: Croup caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging disease, and data on the risk factors associated with disease severity are still limited. The Westley croup score (WS) is widely used to assess croup severity. The current study aimed to analyze biomarkers associated with the WS and clinical outcomes in patients with croup and coronavirus disease 2019 in the pediatric emergency department (PED). Population and Method: Patients diagnosed with croup caused by SARS-CoV-2 were admitted at two PEDs. Clinical data including age, WS, length of hospital stay, initial laboratory data, and treatment were analyzed. Clinical parameters were evaluated via multivariate logistic regression analysis. The best cutoff values for predicting croup severity and outcomes were identified using the receiver operating characteristic curve. Result: In total, 250 patients were assessed. Moreover, 128 (51.2%) patients were discharged from the PED, and 122 (48.8%) were admitted to the hospital. Mild, moderate, and severe croup accounted for 63.6% (n = 159), 32% (n = 80), and 4.4% (n = 11) of all cases, respectively. A high mean age (years), neutrophil count (%), neutrophil-to-lymphocyte ratio (NLR), ALT (U/L), procalcitonin (ng/mL), and hemoglobin (g/dL) level, and length of hospital stay (days), and a low lymphocyte count (%) and blood pH were associated with croup severity and need for intensive care. Based on the multivariate logistic regression model, the NLR remained independent factors associated with croup severity and prognosis. Further, NLR was significantly correlated with WS. The area under the receiver operating characteristic curve of NLR for predicting a WS of ≥ 3 was 0.895 (0.842–0.948, p < 0.001), and that for predicting ICU admission was 0.795 (0.711–0.879, p < 0.001). The best cutoff values for a WS of ≥3 and ICU admission were 1.65 and 2.06, respectively. Conclusion: WS is associated with the severity of croup caused by SARS-CoV-2. Furthermore, NLR is correlated with WS and is a cost effective, easily accessible prognostic biomarker in the PED.

The structures of biomacromolecules are conventionally characterized by crystallography and cryogenic electron microscopy . The requirements of sample preparation limit the understanding of the specimens in their native states. Small-angle x-ray scattering (SAXS) has the capability of obtaining structural information from biological specimens in solution. However, resolving the structure from the acquired one-dimensional (1D) diffraction data requires the prior knowledge of the sample, and no unique solution can be guaranteed. Coherent diffraction imaging (CDI) provides excellent uniqueness in 2D/3D phase retrieval while the resolution is restricted by the poor signal-to-noise ratio at high-angle scattering. Here we combine CDI and SAXS to directly image a 19-nm-sized nodavirus particle in solution and determine the core-shell density distribution at a 1.3 nm pixel resolution. With 77,170 diffraction patterns summarized from randomly distributed nodavirus particles, the structural information can be obtained from the diffraction intensity alone without preknowledge. The hollow density distribution of a nodavirus particle revealed by our reconstruction is consistent with the structural determinations from crystallography and cryogenic electron microscopy. We believe this work represents a new protocol for characterizing the structures of macromolecules in solution from accumulated x-ray scattering data.

Welding in the world (2022). doi:10.1007/s40194-022-01428-9, Published by Springer, Heidelberg

Purpose Emergency endotracheal intubations outside the operating room (OR) are associated with high complications. We compare the outcome of emergency endotracheal intubation in the general ward, the intensive care unit (ICU) and the emergency department (ED). Materials and methods We retrospectively analyzed adult patients requiring emergency endotracheal intubation that called for anesthesiologists at our tertiary care institution from January 1, 2015 to December 31, 2016. We evaluated the outcomes, including aspiration, hemodynamic collapse, pneumothorax, emergency tracheostomy, and survival to hospital discharge in the general ward, ICU, and ED. Results There were 416 non-OR emergency endotracheal intubation calls for the anesthesiologist. Among these areas, the ED had the highest proportion of difficult endotracheal (DET) intubation (n = 144 [80.4%]), followed by the general ward (n = 85 [66.4%]), and then the ICU (n = 65 [59.6%]). The incidence of hemodynamic collapse was higher in the general ward (n = 44 [34.4%]) than the ICU (n = 18 [16.5%]) or the ED (n = 16 [9.0%]). We reported the survival rate of the general ward (55.5%), which was lower than the ICU (63.3%) and the ED (80.4%). Among these locations, the ED had the highest rate of neurologically intact (91%) to hospital discharge, compared to the ICU (56.6%) and the general ward (55%). As for the ED, although there was no difference in survival between non-preventive and preventive intubations, preventive intubations was associated with high neurological intact with hospital discharge. Conclusion Emergency and DET intubation in the general ward and ICU resulted in a higher incidence of hemodynamic collapse and mortality than those performed in the ED. Early calls for the anesthesiologist for DET intubation without medications in the ED resulted in a higher rate of neurologically intact survival to hospital discharge.

Chronic kidney disease (CKD) is a global burden in the world. Low protein diet (LPD) recommendation is suggested in CKD patients to avoid or defer dialysis initiation and slow down CKD progression. However, nutritional imbalance and protein energy wasting represent key worries. The amino acid-based metabolic profile may provide a sensitive biomarker to evaluate CKD patients' nutrition status with LPD recommendations.We conducted a cross-sectional study in CKD stage 3-5 patients who had received LPD recommendation to evaluate the association between LPD and traditional markers (including plasma levels of albumin, pre-albumin, transferrin, total iron-binding capacity), inflammation markers (including peripheral leukocyte count and plasma levels of high-sensitivity C-reactive protein), body composition, muscle strength, and physical function, and novel nutrition markers (including amino acid-based metabolic profile) in CKD stage 3-5 patients.In our study CKD stage 3-5 patients with the total number of 73, the mean age was around 71 ± 10 years old. The mean daily protein intake (DPI) was around 0.9 ± 0.3 g/kg/day and 25 (34%) patients met the recommended goal of DPI0.8 g/kg/day. The mean daily calorie intake (DCI) was around 23 ± 6 kcal/kg/day, with only 11 (15%) patients met the recommend DCI with 30-35 kcal/kg/day. Compared to CKD patients with non-LPD, patients with LPD had significantly lower hemoglobin and albumin levels, shorter 6-min walking distance (6MWD), and lower leucine levels. Multivariable analysis found that lower hemoglobin and leucine levels, and shorter 6MWD were negatively and independently associated with LPD (all p 0.05). Then ROC curve analysis found that the optimal cut-off value of leucine plasma levels was 95.5 μM with 60% sensitivity and 71% specificity to predict those CKD patients with LPD with the area under the curve of 0.646 (95% CI: 0.512-0.780).LPD attainment was noted in 34% patients and most of CKD stage 3-5 patients (around 85%) had inadequate daily calorie intake although receiving standard dietary counseling routinely. A low protein diet and inadequate daily calorie intake in CKD patients were associated with shorter 6MWD, and lower hemoglobin and leucine levels. Plasma leucine levels lower than 95.5 μM may be a herald for muscle wasting and malnutrition in these CKD stage 3-5 patients with inadequate calorie intake.

Whole exome sequencing (WES) has been used to detect rare causative variants in neurological diseases. However, the efficacy of WES in genetic diagnosis of clinically heterogeneous familial stroke remains inconclusive. We prospectively searched for disease-causing variants in unrelated probands with defined familial stroke by candidate gene/hotspot screening and/or WES, depending on stroke subtypes and neuroimaging features at a referral center. The clinical significance of each variant was determined according to the American College of Medical Genetics guidelines. Among 161 probands (mean age at onset 53.2 ± 13.7 years; male 63.4%), 33 participants (20.5%) had been identified with 19 pathogenic/likely pathogenic variants (PVs; WES applied 152/161 = 94.4%). Across subtypes, the highest hit rate (HR) was intracerebral hemorrhage (ICH, 7/18 = 38.9%), particularly with the etiological subtype of structural vasculopathy (4/4 = 100%, PVs in ENG, KRIT1, PKD1, RNF213); followed by ischemic small vessel disease (SVD, 15/48 = 31.3%; PVs in NOTCH3, HTRA1, HBB). In contrast, large artery atherosclerosis (LAA, 4/44 = 9.1%) and cardioembolism (0/11 = 0%) had the lowest HR. NOTCH3 was the most common causative gene (16/161 = 9.9%), presenting with multiple subtypes of SVD (n = 13), ICH (n = 2), or LAA (n = 1). Importantly, we disclosed two previously unreported PVs, KRIT1 p.E379* in a familial cerebral cavernous malformation, and F2 p.F382L in a familial cerebral venous sinus thrombosis. The contribution of monogenic etiologies was particularly high in familial ICH and SVD subtypes in our Taiwanese cohort. Utilizing subtype-guided hotspot screening and/or subsequent WES, we unraveled monogenic causes in 20.5% familial stroke probands, including 1.2% novel PVs. Genetic diagnosis may enable early diagnosis, management and lifestyle modification. Graphical Abstract Among 161 familial stroke probands, 33 (20.5%) had been identified pathogenic or likely pathogenic monogenic variants related to stroke. The positive hit rate among all subtypes was high in intracerebral hemorrhage (ICH) and ischemic small vessel disease (SVD). Notably, two previously unreported variants, KRIT1 p.E379* in a familial cerebral cavernous malformation and F2 p.F382L in familial cerebral venous sinus thrombosis, were disclosed. CVT cerebral venous thrombosis; HTN Hypertensive subtype; LAA large artery atherosclerosis; SV structural vasculopathy; U Undetermined.

Background The WALANT (wide-awake local anesthesia with no tourniquet) technique was based on local infiltration of lidocaine and epinephrine. This technique has rapidly gained popularity in recent years and can perform most hand operations. This study aimed to investigate the time spent on anesthesia and operation and perform an economic analysis among general anesthesia, wrist block with a tourniquet, and the WALANT technique for the internal fixation of metacarpal fractures. Methods We retrospectively reviewed all the single metacarpal fractures managed with the same procedure, open reduction, and internal fixation with the plate between January 2015 and December 2019. They were divided into three groups according to the method of anesthesia: (1) general anesthesia (GA group), (2) wrist block with a tourniquet (WB group), and (3) WALANT technique (WALANT group). We collected and analyzed patient demographic data, perioperative or postoperative complications, number of hospital days, and postoperative functional recovery assessment. Results A total of 63 patients met the inclusion criteria, including 24 in the GA group, 28 in the wrist block group using a tourniquet, and 11 in the WALANT group. There were no complications during the operation and follow-up in each group. The GA group had an average of 32.8 min of anesthesia time, significantly longer than the other two groups. However, there is no significant difference regarding surgical time among the presenting three groups. The discomfort of vomiting and nausea after surgery occurred in 20 patients in the GA group (38.1%). Nevertheless, there was no postoperative vomiting and nausea present in both the WB and WALANT groups. Most patients achieved full recovery of pre-injury interphalangeal and metacarpophalangeal motion at the final assessment of functional recovery. Conclusions The patients undergoing metacarpal fixation surgery under WALANT or WB had significantly less anesthesia time and postoperative vomiting and nausea. Moreover, there was no difference in surgical time and intraoperative complications. The time-related reduction improved the utilization of the operation room for additional cases. The reduction of the preoperative examination, anesthesia fee, postoperative recovery room observation, and hospitalization can effectively reduce medical costs. Furthermore, the WALANT group is more acceptable because of no tourniquet, which commonly causes discomfort.

非專長授課是教學現場中實際存在的問題，第二專長班即是為此因應而生的教師專業發展途徑。本研究的目的在於探討修習生活科技第二專長課程的教師在投入科技教育時，其自身之動機、課程意識建構及教學實踐的轉化，以期能作為未來推動科技領域師資培訓與教師專業發展之參考。本研究採問卷調查與半結構深度訪談之個案研究法，針對參與第二專長班的教師進行研究，先以問卷調查全體29位學員對實施生活科技課程意願之觀點，再以個人與小組訪談的形式，邀請其中九位學員進行深度訪談。訪談時間為2018年10月，每次訪談時間約60分鐘。研究者運用質性分析軟體進行資料的編碼與分析後，對應量化問卷的分析結果， 歸納以下研究發現：一、參與第二專長班之動機，主要源於自身對於實作之興趣與學校教學需求；二、參與第二專長班對其課程意識建構之影響，包含有助於提升對生活科技課程之專業覺知、形塑實施科技教育之信念，並對任教生活科技建立正向的自我覺知；三、教學實踐會促使第二專長班教師快速吸收及轉化專業知識，但在過程中容易因外在環境因素的干擾與自覺專業知識不足，而影響教學信心；四、校內外教師社群與學校行政的支持，是協助第二專長班教師克服教學困難的重要關鍵。 Background Technology education plays an increasingly vital role in ensuring students’ technological literacy under the new Curriculum Guidelines of 12-Year Basic Education, which was introduced in 2019. However, because of the low importance assigned to living technology courses, most schools do not have sufficient qualified teachers in this field. This poses a hurdle in the implementation of the technology curriculum of Taiwan’s 12-year basic education. Moreover, because of declining birthrates, many teachers have no students to teach and the number of teachers in junior high schools have consequently shrunk. The Ministry of Education established a second-specialty course to provide teachers with a second professional certificate to meet the teaching needs of schools. Living technology is based on hands-on learning, problem-solving, and design thinking. Therefore, in addition to the conceptual knowledge of technology and engineering, living technology teachers should possess diverse practical skills and engineering design thinking and problem-solving abilities. Unlike other traditional disciplines, the living technology course attaches great importance to practical hands-on skills for solving technical problems, which is a major challenge faced by teachers of the second specialty. On the basis of this background, this research explored different means of helping teachers with second specialty to teach living technology more effectively. Purpose The purpose of this study is to explore the transformation of teachers, who have taken the second specialty course in living technology. These teachers’ motivation, beliefs, curricular awareness construction, and teaching practices were examined. Understanding the dynamic relationship among multiple factors that can be used as a reference for the future promotion of teacher training and professional development in the field of technology is imperative. Theoretical Framework The theoretical framework of the study is based on teachers’ beliefs, curricular consciousness, the Theory of Planned Behavior (TPB) (Ajzen, 1985, 1991), curricular awareness, and teaching practices. This study evaluated (1) teachers’ motivation to participate in professional development learning and (2) teachers’ curricular consciousness. First, this study investigated teachers’ motivation from the perspective of their beliefs and self-efficacy. Teachers’ self-efficacy refers to their belief in their abilities to teach effectively and is assessed according to whether the students have acquired real knowledge and abilities (Thoonen et al., 2011). When teachers regard teaching as a mission but feel that they lack professional competence and face pressure from changes in the educational environment, they are motivated to invest in continuing education. However, most teachers engage in continuing education because of several motivating factors. Second, teachers’ curriculum consciousness is a dynamic process of awareness. It includes internal reflection, beliefs in their teaching, reflection on curriculum implementation, and interpretation and organization of the environment (Fang & Feng, 2017). Specifically, curricular awareness includes awareness of professional knowledge, awareness of self-beliefs, and awareness of the environment (Chen, 2003; Fang & Feng, 2017; Kung & Lin, 2009). Professional knowledge includes content knowledge, pedagogical knowledge, pedagogical content knowledge, knowledge of the teaching environment, and knowledge of students (Shulman, 1986, 1987). Professional knowledge should have a positive connection with teaching practice, which, in turn, modifies curriculum consciousness. Self-belief awareness refers to the self-evaluation of the results of applying certain teaching activities and teaching strategies. This can be explained in conjunction with the “attitude” aspect of the TPB (Ajzen, 1985, 1991). Environmental factors, such as hardware and software equipment, school culture, parents, and community, may present limitations and challenges to teachers but may also be perceived as opportunities related to the “subjective norm” and “perceived behavior control” factors in the TPB (Ajzen, 1985, 1991). Design/Methods On the basis of a review of the existing literature, this study investigated the factors that affect teachers’ motivation for and effectiveness in participating in a second-specialty course and subsequently constructed the outline of a semi-structured interview. A case study was employed along with semi-structured, in-depth interviews with nine teachers from various junior high schools in southern Taiwan. Both individual and group interviews were conducted. The second-specialty course of living technology started in July 2018. To elucidate the changes in the participants’ curricular consciousness after the second-specialty course, the interviews were conducted after the first stage of the course (following the completion of eleven credits). The interviews, each lasting approximately 60 minutes, were conducted in October 2018. The transcripts of the interviews were imported into NVivo qualitative analysis software, and the data were analyzed through the following steps: First, preliminary coding and classification was conducted on the basis of the aspects of investment motivation, curriculum awareness, teaching practices. Second, two researchers discussed the preliminary inductive findings, identified common or disparate views, and focused on further establishing concepts. Third, the summarized concepts were compared with related literature, and, if necessary, the interviewees were invited to verify the accuracy of the analysis results or provide auxiliary reference materials. Triangulation was used to ensure the validity of the study. Finally, in-depth discussions were held according to the research purpose, and the research findings were summarized. Results The encoding and analysis of the data using NVivo produced the following research findings: (1) The motivation of teachers to participate in the second-specialty course of living technology primarily came from their interest in hands-on implementation and their schools’ teaching needs. All teachers reported that before teaching living technology courses, they believed that this subject involved handicrafts or industrial arts, which they had previously learned. Most knowledge of technology was derived from self-learning and the experience of using technology in daily life. Most of the participants indicated that fully understanding and transforming the subject into teaching activities was difficult. (2) The effect of teachers’ participation in the second-specialty course on the development of their curricular consciousness included the promotion of their professional awareness of living technology courses, the transformation of their beliefs concerning technology education, and the establishment of positive self-awareness regarding teaching living technology. (3) Teaching practice prompted teachers of the second-specialty course to rapidly absorb and transform professional knowledge. However, in the process, their teaching confidence was affected by external environmental factors and a lack of professional knowledge. (4) The support available to teacher communities from inside and outside the school and from the school administration are critical to enabling teachers in the second-specialty course to overcome their teaching difficulties. Conclusion This study explored the transformation of second-specialty teachers involved in technology education, including their motivation, beliefs, curricular awareness construction, and teaching practices. On the basis of a literature review and interview analysis, the researchers proposed a framework to highlight the dynamic relationship between teachers’ curricular consciousness and their teaching practices. The results demonstrated that substantial professional growth occurs between learning in the second-specialty course and teaching living technology in junior high school. Teachers’ learning motivation, knowledge construction, and real-life teaching situations influence each other and affect teachers’ self-awareness, professional awareness, and environmental awareness, respectively. These dynamic interactions help form teachers’ curricular awareness. The interviews revealed that external change factors may motivate teachers to expand their knowledge. However, the most critical factors involve teachers independently generating learning motivation and curricular consciousness and desiring real changes that prompts them to invest in continual learning and teaching practices. Furthermore, teachers must establish their own teaching beliefs and curricular awareness to strengthen their teaching confidence in new fields and face external pressure, which is the core focus of curricular reform.

Six previously undescribed components, bis(4-glycosyloxybenzyl) 2-isobutyltartrate derivatives (pholidotoside A-E) and phenolic glycoside (pholidotosin A), together with twenty known compounds were isolated from the pseudobulbs of Pholidota chinensis. Their structures and absolute configuration were elucidated and established through various spectroscopic and chemical methods. The anti-inflammatory potential of selected compounds was examined using a human neutrophil cell model activated by N-formyl-methionyl-leucyl-phenylalanine/cytochalasin B (fMLP/CB). Among these, dihydrophenanthrenes exhibited potent inhibitory effect on both superoxide anion generation and elastase release assays with IC

Associations between hepatitis C virus (HCV) and chronic kidney disease (CKD) have been reported; however, differences of renal progression between general and CKD population remain to be elucidated in prospective studies. A total of 1179 participants, who have tested for anti-HCV antibody, were enrolled and prospectively followed for 3 years. The risks associated with HCV infection, in terms of incidence of CKD, annual estimated glomerular filtration rate (eGFR) changes and 50% decline of eGFR at 3-year from baseline, were compared between normal renal function subjects and CKD patients. Overall, 111 of 233 (47.6%) CKD patients and 167 of 946 (17.7%) non-CKD subjects had HCV infection. The crude incidence rates of CKD were 226.9 per 1000 person-years and 14.8 per 1000 person-years in in HCV and non-HCV infected patients, respectively. The adjusted hazard ratio of HCV infection for incident CKD was 7.9 (95% CI 5–12.7). The HCV-infected normal renal function subjects were independently associated with increased risks of eGFR decline in the 1-year, 2-year and 3-year, respectively. The risk associations remained significant in 50% decline of eGFR at 3 years models and in different subgroup analyses. The increases of risks of eGFR decline were also notorious among overall HCV-infected CKD patients. However, the risk associations were less prominent in subgroup analyses (elderly, women and diabetic patients). The findings highlighted the importance of viral diagnosis with not only prognostic but also public health implications for preserving kidney function.

Skin photoaging is exogenous aging caused by long-term ultraviolet radiation, which not only affects skin appearance, but also has a close relationship with the development of skin cancer. Saponins, flavonoids, polyphenols, polysaccharides, and extracts of Chinese medicine have been found to have anti-skin photoaging effects in recent studies. Various mechanisms such as anti-oxidative stress damage, inhibition of matrix metalloproteinase expression, promotion of collagen synthesis, inhibition of inflammatory response, DNA damage repair, enhancement of cell autophagy, and inhibition of melanin synthesis can improve the symptoms of skin photoaging and delay the photoaging process. With the active ingredients of Chinese medicine for anti-skin photoaging as the entry point, the study systematically discussed the research progress of the mechanisms underlying the anti-photoaging effects of active ingredients of Chinese medicine in recent years, in order to provide theoretical reference for the development of new anti-photoaging drugs and methods.

T cells redirected to cancer cells either via a chimeric antigen receptor (CAR-T) or a bispecific molecule have been breakthrough technologies; however, CAR-T cells require individualized manufacturing and bispecifics generally require continuous infusions. We created an off-the-shelf, single-dose solution for achieving prolonged systemic serum levels of protein immunotherapeutics via adeno-associated virus (AAV) gene transfer. We demonstrate proof of principle in a CD19 + lymphoma xenograft model using a single intravenous dose of AAV expressing a secreted version of blinatumomab, which could serve as a universal alternative for CD19 CAR-T cell therapy. In addition, we created an inducible version using an exon skipping strategy and achieved repeated, on-demand expression up to at least 36 weeks after AAV injection. Our system could be considered for short-term and/or repeated expression of other transgenes of interest for noncancer applications.

We previously showed that intraosseous (IO) delivery of factor VIII (FVIII, gene F8) lentiviral vector (LV) driven by the megakaryocyte-specific promoter Gp1bα (G-F8-LV) partially corrected the bleeding phenotype in hemophilia A (HemA) mice for up to 5 months. In this study, we further characterized and confirmed the successful transduction of self-regenerating hematopoietic stem and progenitor cells (HSPCs) in treated mice. In addition, secondary transplant of HSPCs isolated from G-F8-LV–treated mice corrected the bleeding phenotype of the recipient HemA mice, indicating the potential of long-term transgene expression following IO-LV therapy. To facilitate the translation of this technology to human applications, we evaluated the safety and efficacy of this gene transfer therapy into human HSPCs. In vitro transduction of human HSPCs by the platelet-targeted G-F8-LV confirmed megakaryocyte-specific gene expression after preferential differentiation of HSPCs to megakaryocyte lineages. Lentiviral integration analysis detected a polyclonal integration pattern in G-F8-LV–transduced human cells, profiling the clinical safety of hemophilia treatment. Most importantly, IO delivery of G-F8-LV to humanized NBSGW mice produced persistent FVIII expression in human platelets after gene therapy, and the megakaryocytes differentiated from human CD34+ HSPCs isolated from LV-treated humanized mice showed up to 10.2% FVIII expression, indicating efficient transduction of self-regenerating human HSPCs. Collectively, these results indicate the long-term safety and efficacy of the IO-LV gene therapy strategy for HemA in a humanized model, adding further evidence to the feasibility of translating this method for clinical applications.

Considering that SF $_6$ is a potent greenhouse gas, SF $_{6}$ /N $_2$ gas mixtures are preferred to serve as the insulating gas for its environmental friendliness and good insulation. Since heat transfer analysis is very useful for ascertaining the appropriate temperature rise range, which can ensure the safe operation and extension of remaining useful life of GIL, it is essential to study the thermal properties of SF $_{6}$ /N $_2$ gas mixtures. Nevertheless, very few studies investigate on the temperature field of SF $_{6}$ /N $_2$ gas mixtures under ideal conditions. To reflect the heat transfer characteristics accurately, in this paper, by using the finite-element method and multi-physics coupling, the heat transfer properties in the GIL is analyzed by using a three-dimensional (3-D) axisymmetric GIL model. By varying the SF $_{6}$ /N $_2$ mixing ratio and observing the corresponding heat transfer characteristics, the mapping between SF $_{6}$ /N $_2$ mixing ratio and the temperature rise is obtained by using the model. Furthermore, the mappings are studied under different gas pressures, line currents and ambient temperatures, which correspond to different real-life operating conditions. The proposed strategies can effectively give guidance of choosing proper SF $_{6}$ /N $_2$ mixing ratio for desired temperature rise, and thus having great values of practical applications.

PURPOSE OF REVIEW Thunderclap headache (TCH) is an abrupt-onset of severe headache that needs to be thoroughly investigated because the most common secondary cause is subarachnoid hemorrhage (SAH). There has been no consensus guideline regarding the diagnostic workup. This review aims to provide an update on the evaluation of TCH. RECENT FINDINGS The most important update in the 2019 American College of Emergency Physicians guideline for evaluation of acute headache in the emergency department is that negative noncontrast brain computed tomography (CT) findings within 6 h from ictus essentially excludes SAH. Additionally, the updated guideline recommends that after a negative brain CT, CT angiogram is a reasonable alternative to lumbar puncture if clinical suspicion of an intracranial source of SAH is high. An important update of reversible vasoconstriction syndrome (RCVS), the second most common etiology of TCH, is the RCVS2 score development based on clinical and radiological features, providing high specificity and sensitivity for distinguishing RCVS from other intracranial arteriopathies. SUMMARY Although the evaluation of TCH is exhaustive, the potentially catastrophic consequence of a missed diagnosis of sentinel headache justifies the efforts. Awareness of the clinical features and application of diagnostic tools specific for different pathological conditions can facilitate the diagnostic workup.