Transcription factors KNAT3 and KNAT4 are essential for integument and ovule formation in Arabidopsis.

Integuments form important protective cell layers surrounding the developing ovules in gymno- and angiosperms. Although several genes have been shown to influence the development of integuments, the transcriptional regulatory mechanism is still poorly understood. In this work, we report that the Class II KNOTTED1-LIKE HOMEOBOX (KNOX II) transcription factors KNOTTED1-LIKE HOMEBOX GENE 3 (KNAT3) and KNAT4 regulate integument development in Arabidopsis (Arabidopsis thaliana). KNAT3 and KNAT4 were co-expressed in inflorescences and especially in young developing ovules. The loss-of-function double mutant knat3 knat4 showed an infertility phenotype, in which both inner and outer integuments of the ovule are arrested at an early stage and form an amorphous structure as in the bell1 (bel1) mutant. The expression of chimeric KNAT3- and KNAT4-EAR motif repression domain (SRDX repressors) resulted in severe seed abortion. Protein-protein interaction assays demonstrated that KNAT3 and KNAT4 interact with each other and also with INNER NO OUTER (INO), a key transcription factor required for the outer integument formation. Transcriptome analysis showed that the expression of genes related with integument development is influenced in the knat3 knat4 mutant. The knat3 knat4 mutant also had a lower indole-3-acetic acid (IAA) content, and some auxin signaling pathway genes were downregulated. Moreover, transactivation analysis indicated that KNAT3/4 and INO activate the auxin signaling gene IAA INDUCIBLE 14 (IAA14). Taken together, our study identified KNAT3 and KNAT4 as key factors in integument development in Arabidopsis.

Construction and Hierarchical Self-Assembly of Multifunctional Coordination Cages with Triangular Metal-Metal-Bonded Units.

Herein, a series of face-capped (Tr2M3)4L4 (Tr = cycloheptatrienyl cationic ring; M = metal; L = organosulfur ligand) tetrahedral cages 1-3 functionalized with 12 appended crown ether moieties were designed and synthesized. The reversible binding of ammonium cations with peripheral crown ether moieties to adjust internal guest-binding was realized. Combination of a bisammonium linker and cage 3 led to the formation of a supramolecular gel SPN1 via host-guest interactions between the crown ether moieties and ammonium salts. The obtained supramolecular gel exhibited multiple-stimuli responsiveness, injectability, and excellent self-healing properties and could be further developed to a SPN1-based drug delivery system. In addition, the storage modulus of SPN1 was 20 times higher than that of the model gel without Pd-Pd bonded blocks, and SPN1 had better self-healing properties compared with the latter, demonstrating the importance of such cages in improving mechanical strength without losing the dynamic properties of the material. The cytotoxicity in vitro of the drug-loaded (doxorubicin or methotrexate) SPN1 was significantly improved compared to that of free drugs.

Construction and Hierarchical Self-Assembly of a Supramolecular Metal-Carbene Complex with Multifunctional Units.

Hierarchical combinations involving metal-ligand interactions and host-guest interactions can consolidate building blocks with unique functions into material properties. This study reports the construction and hierarchical self-assembly of multifunctional trinuclear AuI tricarbene complex containing three crown ether units and three ferrocene units. Host-guest interactions between the multifunctional trinuclear AuI tricarbene complex and organic ammonium salts were investigated, revealing that crown ether-based host-guest interactions can effectively regulate the electrochemical properties of the complex. Utilizing bisammonium salt as the cross-linker and multifunctional trinuclear AuI tricarbene complex as the core, a stimuli-responsive and self-healing supramolecular gel with different functional units was obtained.

A qualitative exploration of "empathic labor" in Chinese hospice nurses.

BACKGROUND: Hospice nurses may devote more emotional labor during the empathy process with patients, and this empathy can be used as a form of psychological behavior of emotional labor in the hospice care model. The aim of this study was to analyze hospice nurses' empathy characteristics in the context of emotional labor theory, and explore the impact of empathy on patient care. METHODS: We conducted semi-participant observations from three hospitals and multicenter in-depth interviews with n = 26 hospice nurses from eight cities. Interviews were transcribed, and directed content analysis was applied. RESULTS: Two categories with four sub-categories were extracted from the data analysis. Category 1 described the "empathic labor" process which covers cognitive empathy (including empathic imagination, empathic consideration, and empathic perception) and affective empathy (including natural empathy, surface empathy, and deep empathy). The second category concerns the outcome of nurses' "empathic labor" which incorporates both positive and negative effects. CONCLUSIONS: The findings indicated that hospice nurses' empathy process should be understood as emotional labor. Nursing managers should pay more attention to raising the ability of deep empathy with hospice nurses, and explore more sufficient active empowerment strategies to alleviate the negative impact of empathy on nurses and to strengthen nurses' deep empathy with terminal ill patients.

Mobile device use and the cognitive function and depressive symptoms of older adults living in residential care homes.

BACKGROUND: With the fast-paced aging and increasing digitalization of society, there has been a growing interest in the effect of mobile device use on cognitive function and depression in older adults. However, research examining this issue among older adults in residential care homes (RCHs) is scant. Therefore, this study aimed to examine the impact of mobile device use on the cognitive function and depressive symptoms of older adults living in RCHs. METHODS: A cross-sectional survey was conducted using a sociodemographic questionnaire, the Montreal Cognitive Assessment (MoCA) and the 15-item Geriatric Depression Scale (GDS-15). RESULTS: A total of 235 senior residents (aged 82.58 ± 5.54) in four RCHs were surveyed. Users of mobile devices had a significantly higher total MoCA score (25.02 ± 4.14) and a significantly lower GDS-15 score (3.28 ± 2.74) than non-users (MoCA: 19.34 ± 5.21, GDS-15: 4.69 ± 2.90). Multivariate linear regression indicate that mobile device use is significantly associated with total MoCA score, six of the seven sub-scores (visuospatial abilities and execution functions, attention, language, abstraction, delayed recall, and orientation)(P < 0.05). Logistic regression showed that mobile device use was significantly associated with the level of depressive symptoms (OR = 0.458, 95%CI = 0.249-0.845). CONCLUSIONS: Use of mobile devices has a significant association with the cognitive function and depressive symptoms of older adults living in RCHs, and thus should be encouraged as a measure to maintain and improve cognition and prevent depression.

Overexpression of GP73 promotes cell invasion, migration and metastasis by inducing epithelial-mesenchymal transition in pancreatic cancer.

Pancreatic cancer is one of the most difficult clinical cases to diagnose with a very low 5-year survival rate of 5%, regardless of the advances made in both the medical and surgical treatment of the disease. One of the contributing factors for the high mortality rate seen of pancreatic cancer patients is the lack of effective chemotherapies, which is believed to be due to drug-resistance. Based on recent evidence, epithelial-mesenchymal transition (ETM) of pancreatic cancer cells has been found to be associated with the development of drug resistance and an increase in cell invasion. Therefore, we conducted the present study in order to investigate the regulatory effects of Golgi protein-73 (GP73) on PC. GP73 and EMT-related gene expressions in PC, along with the adjacent and chronic pancreatitis tissues were determined by means of RT-qPCR and Western blot analysis. Cultured PC cells were treated with pAdTrack-CMV, si-NC, GP73 overexpression, Si-GP73, Snail-siRNA and GP73 + Snail-siRNA. Cell invasion, migration and metastasis were measured in vitro and in vivo. The results revealed that the PC tissues and chronic pancreatitis tissues exhibited diminished E-cadherin expression and amplified GP73, N-cadherin, Vimentin and Snail expression. In response to GP73 gene silencing, PC cells presented with increased E-cadherin expression and decreased N-cadherin, Vimentin, Snail expression in addition to the inhibition of the number of invasive cells, tumor volume and number of liver lesions. These findings highly indicated that the overexpression of GP73 promotes cell invasion, migration and metastasis by inducing EMT in PC.

The analgesic efficacy of subcostal transversus abdominis plane block with Mercedes incision.

BACKGROUND: Conventional perioperative analgesic modalities (e.g. opioids, epidural analgesia) have their own drawbacks, which limit their clinical application. This study investigated the opioid-sparing effectsof the oblique subcostal transversus abdominis plane (OSTAP) blockade with ropivacaine for the patients undergoing open liver resection with a Mercedes incision. METHODS: 126 patients who were scheduled for open liver resection were enrolled in this study. Patients were randomly assigned to receive bilateral ultrasound-guided OSTAPblocks with either 0.375% ropivacaine (groupT) or 0.9% isotonic saline (group C). Both groups also received intravenous patient-controlled analgesia and intravenous 40 mg parecoxib every 12 h for a total of 3 days. Preoperative and intraoperative parameters, plus intraoperative and postoperative cumulative sufentanil consumption, were recorded. RESULTS: 70 patients were enrolled in the study finally. There were no significant differences between the two groups with respect to preoperative parameters, and surgical and anesthetic characteristics. The intraoperative sufentanil use, cumulative sufentanil consumption at 5 min after extubation, 2 h, 4 h,12 h and 24 h after operation in group T was significantly less than that in group C (P = 0.001, 0.001, 0.000, 0.000, 0.001 and 0.044, respectively). Compared with group C, postoperative NRS pain scores at rest were significantly lower at 2 h and 4 h postoperatively in group T (P = 0.04and 0.02, respectively); NRS scores at the time of coughing were also significantly lower in group T than in group C at all time points except 5 min after extubation (all P < 0.001). Furthermore, compared with group C, the number of intraoperative vasodilator use, the extubation time and the incidence of nausea was reduced in group T. CONCLUSION: Ultrasound-guided OSTAP block with ropivacaine can significantly decrease the perioperative cumulative dosage of analgesics and improve analgesic effect without obvious side effects for the patients who underwent an open liver resection with Mercedes incision when compared tothe ultrasound-guided OSTAP block with saline. TRIAL REGISTRATION: The study protocol was registered at http://www.chictr.org.cn (ChiCTR-TRC- 14004827) on February 19, 2014.

KNAT7 positively regulates xylan biosynthesis by directly activating IRX9 expression in Arabidopsis.

Xylan is the major plant hemicellulosic polysaccharide in the secondary cell wall. The transcription factor KNOTTED-LIKE HOMEOBOX OF ARABIDOPSIS THALIANA 7 (KNAT7) regulates secondary cell wall biosynthesis, but its exact role in regulating xylan biosynthesis remains unclear. Using transactivation analyses, we demonstrate that KNAT7 activates the promoters of the xylan biosynthetic genes, IRREGULAR XYLEM 9 (IRX9), IRX10, IRREGULAR XYLEM 14-LIKE (IRX14L), and FRAGILE FIBER 8 (FRA8). The knat7 T-DNA insertion mutants have thinner vessel element walls and xylary fibers, and thicker interfascicular fiber walls in inflorescence stems, relative to wild-type (WT). KNAT7 overexpression plants exhibited opposite effects. Glycosyl linkage and sugar composition analyses revealed lower xylan levels in knat7 inflorescence stems, relative to WT; a finding supported by labeling of inflorescence walls with xylan-specific antibodies. The knat7 loss-of-function mutants had lower transcript levels of the xylan biosynthetic genes IRX9, IRX10, and FRA8, whereas KNAT7 overexpression plants had higher mRNA levels for IRX9, IRX10, IRX14L, and FRA8. Electrophoretic mobility shift assays indicated that KNAT7 binds to the IRX9 promoter. These results support the hypothesis that KNAT7 positively regulates xylan biosynthesis.

Activation of RAS/ERK alone is insufficient to inhibit RXRα function and deplete retinoic acid in hepatocytes.

Activation of RAS/ERK signaling pathway, depletion of retinoid, and phosphorylation of retinoid X receptor alpha (RXRα) are frequent events found in liver tumors and thought to play important roles in hepatic tumorigenesis. However, the relationships among them still remained to be elucidated. By exploring the transgenic mouse model of hepatic tumorigenesis induced by liver-specific expression of H-ras12V oncogene, the activation of RAS/ERK, the mRNA expression levels of retinoid metabolism-related genes, the contents of retinoid metabolites, and phosphorylation of RXRα were determined. RAS/ERK signaling pathway was gradually and significantly activated in hepatic tumor adjacent normal liver tissues (P) and hepatic tumor tissues (T) of H-ras12V transgenic mice compared with normal liver tissues (Wt) of wild type mice. On the contrary, the mRNA expression levels of retinoid metabolism-related genes were significantly reduced in P and T compared with Wt. Interestingly, the retinoid metabolites 9-cis-retinoic acid (9cRA) and all-trans-retinoic acid (atRA), the well known ligands for nuclear transcription factor RXR and retinoic acid receptor (RAR), were significantly decreased only in T compared with Wt and P, although the oxidized polar metabolite of atRA, 4-keto-all-trans-retinoic-acid (4-keto-RA) was significantly decreased in both P and T compared with Wt. To our surprise, the functions of RXRα were significantly blocked only in T compared with Wt and P. Namely, the total protein levels of RXRα were significantly reduced and the phosphorylation levels of RXRα were significantly increased only in T compared with Wt and P. Treatment of H-ras12V transgenic mice at 5-week-old or 5-month-old with atRA had no effect on the prevention of tumorigenesis or cure of developed nodules in liver. These events imply that the depletion of 9cRA and atRA and the inhibition of RXRα function in hepatic tumors involve more complex mechanisms besides the activation of RAS/ERK pathway.

Reversible T-wave inversions and neurogenic myocardial stunning in a patient with recurrent stress-induced cardiomyopathy.

A 72-year-old female was diagnosed as a stress-induced cardiomyopathy from apical ballooning pattern of left ventricular dysfunction without coronary artery stenosis after the mental stress. ECG showed the transient T-wave inversions after the ST-segment elevations. By the mental stress after 1 year, she showed a transient dysfunction with similar ECG changes again. T-wave inversions recovered earlier, and cardiac sympathetic dysfunction showed a lighter response corresponding to the less severe dysfunction than those after the first onset. Wellens' ECG pattern was associated with the degree of neurogenic myocardial stunning with sympathetic hyperinnervation caused by mental stress.

Engineering Pseudomonas chlororaphis HT66 for the Biosynthesis of Copolymers Containing 3-Hydroxybutyrate and Medium-Chain-Length 3-Hydroxyalkanoates.

Polyhydroxyalkanoates (PHAs) are promising alternatives to petroleum-based plastics, owing to their biodegradability and superior material properties. Here, the controllable biosynthesis of scl-co-mcl PHA containing 3-hydroxybutyrate (3HB) and mcl 3-hydroxyalkanoates was achieved in Pseudomonas chlororaphis HT66. First, key genes involved in fatty acid ß-oxidation, the de novo fatty acid biosynthesis pathway, and the phaC1-phaZ-phaC2 operon were deleted to develop a chassis strain. Subsequently, an acetoacetyl-CoA reductase gene phaB and a PHA synthase gene phaC with broad substrate specificity were heterologously expressed for producing and polymerizing the 3HB monomer with mcl 3-hydroxyalkanoates under the assistance of native ß-ketothiolase gene phaA. Furthermore, the monomer composition of scl-co-mcl PHA was regulated by adjusting the amount of glucose and dodecanoic acid supplemented. Notably, the cell dry weight and scl-co-mcl PHA content reached 14.2 g/L and 60.1 wt %, respectively, when the engineered strain HT11Δ::phaCB was cultured in King's B medium containing 5 g/L glucose and 5 g/L dodecanoic acid. These results demonstrated that P. chlororaphis can be a platform for producing scl-co-mcl PHA and has the potential for industrial application.

Measuring reliability and validity of a newly developed stress instrument: Newly Diagnosed Breast Cancer Stress Scale.

AIMS AND OBJECTIVES: To assess the reliability and validity of a developed instrument entitled Newly Diagnosed Breast Cancer Stress Scale. BACKGROUND: Distress, clinical anxiety and depression are evident in patients with cancer, leading to poor psychosocial and quality-of-life outcomes. DESIGN: Instrument development study with norm-referenced measurements. METHODS: Content validity was determined by expert review. Cronbach's α was used to assess internal consistency reliability and product-moment correlations were conducted. Exploratory factor analysis measured validity of items using varimax rotation method. Criterion-related validity testing used the Perceived Stress Scale and the convergent validity test of construct validity used the Hospital Anxiety and Depression Scale. A total of 125 women pathologically diagnosed with breast cancer were interviewed on the day prior to initial breast surgery. RESULTS: After testing, the Newly Diagnosed Breast Cancer Stress Scale consisted of four main factors with 17 items with acceptable reliability and good validity, and its length and time to complete the questionnaire were appropriate. Internal consistency reliability of the scale was shown by Cronbach's α = 0·84, the criterion validity of Perceived Stress Scale-10 was r = 0·46 (p < 0·001), the convergent validity of Hospital Anxiety and Depression Scale-14 was r = 0·57 (p < 0·001) for anxiety and r = 0·35 (p < 0·001) for depression. CONCLUSIONS: The Newly Diagnosed Breast Cancer Stress Scale has acceptable reliability and good validity to measure stress in newly diagnosed patients with breast cancer. RELEVANCE TO CLINICAL PRACTICE: The Newly Diagnosed Breast Cancer Stress Scale can provide healthcare workers with an instrument to better identify stress levels in newly diagnosed breast cancer patients and provide valuable information when defining psychosocial care interventions.

[Determination method for 17 pesticides in common in whole blood by gas chromatography coupled to mass spectrometry with solid-phase extraction sample cleanup].

OBJECTIVE: To establish a method for simultaneous determination of 17 common pesticides in whole blood by solid phase extraction-gas chromatography-mass spectrometry (SPE-GC-MS). METHODS: Whole blood samples were treated by extraction with acetonitrile, and the obtained extract was cleaned up using an Oasis HLB SPE cartridge; pesticides were separated by GC and quantitatively analyzed by MS with selected ion monitoring. RESULTS: The concentrations of 17 pesticides in whole blood were 1.0-5.0 mg/L, and the recovery rate was 41.3-102.1%, with a relative standard deviation of less than 10%in most pesticides. The 17 pesticides showed a good linear relationship between concentration and peak area within 0.5-5.0 mg/L, with a correlation coefficient of 0.9945-0.9994. The limit of detection and limit of quantification were 0.02-0.05 mg/L and 0.05-0.09 mg/L, respectively. CONCLUSION: With this method, 17 pesticides in whole blood can be well separated and determined. This method has high sensitivity, accuracy, and precision and can be used for identification and quantification of multiple pesticides in blood samples.

[Determination of lead and isotope ratios in whole blood by inductively coupled plasma mass spectrometry].

OBJECTIVE: To establish a method to determine lead and Isotope Ratios in whole blood by inductively coupled plasma mass spectrometry (ICP-MS). METHODS: The whole blood samples was removed protein by 5% nitric acid , Online join thallium (Tl) as internal standard substance, used lyophilized bovine blood lead and cadmium standard material (GBW09139h and GBW09140h) for quality control of blood lead concentrations. Lead isotope standard substances (GBW04426) is used to determine the correction factor, lead isotope ratios will lead isotope standard reference material NIST SRM981 by icp-ms with samples for testing. RESULTS: Optimize the detection method, detection of blood lead and lead isotope, and the method of linear range r >0.9999, GBW09139h and GBW09140h test results are within the scope of quality control. NIST SRM981 isotope determination precision RSD<1%, NIST SRM981 test results and the certificate of value close to. CONCLUSION: The method is simple and convenient data is reliable, can meet the total lead (pb) in blood and former isotope simultaneous determination.

[Relationship between early serum lipid profiles and respiratory distress syndrome in preterm infants].

OBJECTIVE: To investigate early serum lipid profiles in preterm infants and their relationship with neonatal respiratory distress syndrome (RDS). METHODS: Appropriate-for-gestational-age (AGA) preterm infants were grouped according to gestational age (GA) or birth weight (BW). AGA full-term infants were randomly selected as the control group. Venous blood samples were collected within 12 hours after birth for measurement of biochemical indices, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG). Blood lipid levels were compared between preterm infants with and without RDS in various groups. RESULTS: Plasma TG level rose as GA and BW increased. Plasma TG levels in the 28-30 week and 31-33 week GA groups were significantly lower than in the 34-36 week GA and control groups (P<0.01). Plasma TG levels in the ≤ 1499 g and 1500-2499 g BW groups were significantly lower than in the ≥ 2500 g BW and control groups (P<0.05), and the 1500-2499 g BW group had a significantly higher plasma TG level than the ≤ 1499 g BW group (P<0.01). There were no significant differences in plasma HDL-C, LDL-C and TC levels between all groups and between preterm infants with RDS and without RDS. In the 28-30 week GA group, the preterm infants with RDS had a significantly lower TG level than those without RDS (P<0.05); also, in the ≤ 1499 g BW group, preterm infants with RDS had a significantly lower TG level than those without RDS ( P<0.05). CONCLUSIONS: Blood lipid levels are related to GA and BW. Low TG level may be one of the causes of RDS in preterm infants with a gestational age of 28-30 weeks and a BW of ≤ 1499 g.

A new oncolytic adenoviral vector carrying dual tumour suppressor genes shows potent anti-tumour effect.

Cancer Targeting Gene-Viro-Therapy (CTGVT) is a promising cancer therapeutical strategy that strengthens the anti-tumour effect of oncolytic virus by expressing inserted foreign anti-tumour genes. In this work, we constructed a novel adenoviral vector controlled by the tumour-specific survivin promoter on the basis of the ZD55 vector, which is an E1B55KD gene deleted vector we previously constructed. Compared with the original ZD55 vector, this new adenoviral vector (ZD55SP/E1A) showed much better ability of replication and reporter gene expression. We then combined anti-tumour gene interleukine-24 (IL-24) with an RNA polymerase III-dependent U6 promoter driving short hairpin RNA (shRNA) that targets M-phase phosphoprotein 1 (MPHOSPH1, a newly identified oncogene) by inserting the IL-24 and the shRNA of MPHOSPH1 (shMPP1) expression cassettes into the new ZD55SP/E1A vector. Our results demonstrated excellent anti-tumour effect of ZD55SP/E1A-IL-24-shMPP1 in vitro on multiple cancer cell lines such as lung cancer, liver cancer and ovarian caner. At high multiplicity-of-infection (MOI), ZD55SP/E1A-IL-24-shMPP1 triggered post-mitotic apoptosis in cancer cells by inducing prolonged mitotic arrest; while at low MOI, senescence was induced. More importantly, ZD55SP/E1A-IL-24-shMPP1 also showed excellent anti-tumour effects in vivo on SW620 xenograft nude mice. In conclusion, our strategy of constructing an IL-24 and shMPP1 dual gene expressing oncolytic adenoviral vector, which is regulated by the survivin promoter and E1B55KD deletion, could be a promising method of cancer gene therapy.

[Measurement of 16 elements in blood by inductively coupled plasma mass spectrometry].

OBJECTIVE: To establish a method of determining more elements in whole blood by inductively coupled plasma mass spectrometry (ICP-MS). METHODS: The whole blood samples were treated by 5% nitric acid to remove the proteins, then were centrifuged. Sixteen elements (Be, Al, Mn, V, Cr, Co, Ni, As, Mo, Ag, Cd, Sb, Ba,Tl, Pb and U) in the supernatant were directly measured by ICP-MS. RESULTS: The detection limits of 16 elements were 0.01 ∼ 6.51 µg/L. The linear correlation coefficient was ≥ 0.999. The relative standard deviations were below 5 %. The recovery rates were 105% ∼ 115%. Seronorm Trace Elements SerumL-1 LOT 0903106 and GBW09139g or GBW09140g were used in the quality control, the detected results corresponded with the standard values. CONCLUSION: ICP-MS technique is a simple, rapid, accurate and reliable method, which can be used to measure several trace elements in whole blood samples.

Reduction of psychological cravings and anxiety in women compulsorily isolated for detoxification using autonomous sensory meridian response (ASMR).

OBJECTIVE: To explore the effects of the autonomous sensory meridian response (ASMR) on the psychological cravings and anxiety of women compulsorily isolated for detoxification. METHOD: Around 122 women were recruited in a female drug detoxification center. Except for the 12-week training of ASMR, the experimental conditions of the experimental group (n = 60) were the same as those of the control group (n = 62). The addiction Stroop task was used to assess the level of psychological cravings and the State-Trait Anxiety Inventory was used to assess the level of anxiety. RESULTS: After the training, the decrease in state anxiety of the experimental group was larger than that of the control group, and the reaction time of the experimental group in the Stroop was also significantly lower than before the training. CONCLUSIONS: ASMR could thus reduce to a certain extent the state anxiety and attentional bias for drug-related clues under signaling psychological cravings among women compulsorily isolated for detoxification. HIGHLIGHTS: Intervention effects on psychological cravings and anxiety of women isolated for detoxification Basis for role of ASMR in regulating psychological cravings and anxiety in forced abstainers ASMR intervention reduced forced abstainers' attentional bias to drug-related clues.

ACE2-independent infection of T lymphocytes by SARS-CoV-2.

SARS-CoV-2 induced marked lymphopenia in severe patients with COVID-19. However, whether lymphocytes are targets of viral infection is yet to be determined, although SARS-CoV-2 RNA or antigen has been identified in T cells from patients. Here, we confirmed that SARS-CoV-2 viral antigen could be detected in patient peripheral blood cells (PBCs) or postmortem lung T cells, and the infectious virus could also be detected from viral antigen-positive PBCs. We next prove that SARS-CoV-2 infects T lymphocytes, preferably activated CD4 + T cells in vitro. Upon infection, viral RNA, subgenomic RNA, viral protein or viral particle can be detected in the T cells. Furthermore, we show that the infection is spike-ACE2/TMPRSS2-independent through using ACE2 knockdown or receptor blocking experiments. Next, we demonstrate that viral antigen-positive T cells from patient undergone pronounced apoptosis. In vitro infection of T cells induced cell death that is likely in mitochondria ROS-HIF-1a-dependent pathways. Finally, we demonstrated that LFA-1, the protein exclusively expresses in multiple leukocytes, is more likely the entry molecule that mediated SARS-CoV-2 infection in T cells, compared to a list of other known receptors. Collectively, this work confirmed a SARS-CoV-2 infection of T cells, in a spike-ACE2-independent manner, which shed novel insights into the underlying mechanisms of SARS-CoV-2-induced lymphopenia in COVID-19 patients.

China rheumatoid arthritis registry of patients with Chinese medicine (CERTAIN): Rationale, design, and baseline characteristics of the first 11,764 enrollees.

BACKGROUND: Chinese medicine (CM) has become a popular interventional treatment for rheumatoid arthritis (RA). However, limited knowledge about general characteristics and long-term clinical outcomes hampers the development of CM for RA. PURPOSE: The main objectives of the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) were to describe the population of RA patients receiving CM treatment in multiple centers in China using different variables and compare these findings with internationally reported data. STUDY DESIGN: The CERTAIN is a prospective, multicenter, observational disease registry. METHODS: Adult RA patients who fulfilled the 2010 American College of Rheumatology/ European League Against Rheumatism classification criteria for RA and received CM treatment were recruited into the CERTAIN by rheumatologists from 145 hospitals across 30 provinces in China. Data on demographics, disease characteristics, comorbidities, treatments, and adverse events, with a 2-year follow-up, were collected and documented using a predefined protocol. RESULTS: In the 2 years since the study began in September 2019, 11,764 patients have been enrolled (enrolment is ongoing), and 13.10% of participants have completed the 6-month follow-up. We present the baseline characteristics of the first 11,764 enrollees. CONCLUSIONS: The CERTAIN is the first nationwide registry to document comprehensive data on CM treatment in patients with RA. The development of the CERTAIN resource is a significant step forward for Chinese RA patients, herbal medicine users, and research communities and will deepen our understanding of CM for RA. REGISTRATION: The study was registered at ClinicalTrials.gov (NCT05219214).