[Quantitative HER2 mRNA assay in breast cancer with HER2 immunohistochemistry 0].

Objective: To investigate HER2 mRNA expression in breast cancer with HER2 immunohistochemistry (IHC) 0 and to analyze the feasibility of distinguishing between the tumor with HER2 µltra-low expression and the one without expression of HER2 (no staining by IHC) by HER2 mRNA level preliminarily. Methods: HER2 mRNA was analyzed by reverse transcription digital PCR in 41 cases of formalin-fixed paraffin-embedded surgical tissue samples of invasive breast cancer obtained between January 2020 and March 2023 at Peking Union Medical College Hospital. The cohort included 21 HER2 IHC 1+ and 20 IHC 0 (12 ultra-low and 8 non-expression of HER2). HER2 mRNA expression level was quantitatively evaluated by the FAM (HER2)/VIC (reference gene) ratio. Results: The expression of HER2 mRNA for the cases with 1+, ultra-low, and non-expression of HER2 by IHC was 0.30 to 1.78 (average 0.90, median 0.82), 0.55 to 1.51 (average 0.93, median 0.90) and 0.22 to 0.78 (average 0.41, median 0.36), respectively. For the mean and median HER2 mRNA levels, there was no significant difference between HER2 IHC 1+ and HER2 ultra-low expression diseases (P=0.757). A remarkable difference in HER2 gene expression was found between the tumors with 1+ and non-expression of HER2 by IHC (P=0.002). And, HER2 ultra-low cases contained statistically higher levels of HER2 mRNA compared with non-expression of HER2 subgroup by IHC (P=0.001). Conclusions: Based on HER2 mRNA, HER2 non-expression and HER2 weak expression (including HER2 IHC 1+ and ultra-low) belong to two different types of the tumor and the disease with HER2 IHC 1+ and HER2 ultra-low expression may be the same. It is necessary to further test the performance of HER2 mRNA detection for stratifying the HER2 weak expression subgroup and to determine the threshold.

[Progress in research of self-sampling for detection of genital chlamydia trachomatis and related factors in men who have sex with men].

Laboratory testing is a vital chain in the prevention and control of genital chlamydia trachomatis infection. The prevalence of genital chlamydia trachomatis infection is high, but the detection rate of the infection is low in men who have sex with men (MSM) in China. Self-sampling for genital chlamydia trachomatis detection by MSM is a new option to address this problem, which would play a significant role in expanding genital chlamydia trachomatis infection screening in this population. This paper summarizes the progress in research of self-sampling for the detection of genital chlamydia trachomatis and the related factors in MSM both at home and abroad to provide reference for the promotion of self-sampling for the detection of genital chlamydia trachomatis in this population.

Tuning Plant Promoters Using a Simple Split Luciferase Method to Assess Transcription Factor-DNA Interactions.

Sequence features, including the affinity of binding motifs for their cognate transcription factors, are important contributors to promoter behavior. The ability to predictably recode affinity enables the development of synthetic promoters with varying levels of response to known cellular signals. Here we describe a luminescence-based microplate assay for comparing the interactions of transcription factors with short DNA probes. We then demonstrate how these data can be used to design synthetic plant promoters of varying strengths that respond to the same transcription factor.

[Characteristics of serum autoantibodies in patients with lupus nephritis and tubulointerstitial damage].

OBJECTIVE: To observe the tubulointerstitial damage (TID) in lupus nephritis (LN) and investigate the relationship between autoantibodies and TID in lupus nephritis. METHODS: This cross-sectional study was conducted in a comprehensive tertiary hospital in Peking University Shenzhen Hospital. From March 2012 to July 2021, LN patients who performed renal biopsy were enrolled in the study. Clinical, laboratory and pathology data were collected. We classified the patients into none-or-mild group and moderate-to-severe groups according to the severity of interstitial fibrosis (IF) /tubular atrophy (TA) or tubulointerstitial inflammation (TII). The t test, U test and Chi-square test were used for statistical analysis as appropriate. RESULTS: A total of 226 patients were included, of who 190 (84%) were female with a median age of 32 (26, 39) years. 89% (201/226) of the patients who pathologically proved to be proliferative LN by renal biopsy. The frequency of moderate-to-severe TII and moderate-to-severe IF/TA was 30% (67/226) and 34% (76/226) respectively. For autoantibodies, the patients with moderate-to-severe TII had a lower rate of positive serum anti-ribonucleoprotein (anti-RNP) antibodies than the patients with none-or-mild TII (34% vs. 51%), and moderate-to-severe IF/TA had a lower rate of positive anti-ribosomal P protein (anti-P) antibodies than patients with none-or-mild IF/TA (19% vs. 33%). For other clinical indicators, the patients with moderate-to-severe TII and moderate-to-severe IF/TA were more often combined with proliferative LN, hypertension and anemia than the patients with none-or-mild TII and none-or-mild IF/TA, respectively. The patients with moderate-to-severe TII had higher serum creatinine values and lower glomerular filtration rates than the patients with none-or-mild TII. The patients with moderate-to-severe IF/TA had higher serum creatinine values, and lower glomerular filtration rates than the patients with none-or-mild IF/TA. CONCLUSION: In patients with LN in Southern China, anti-RNP antibodies and anti-P antibodies may be potential protective factors for TII and IF/TA, respectively. More studies are needed to identify the risk factors of lupus patients with TID and investigate the correlation between autoantibodies and TID, which are critical for developing better preventive and therapeutic strategies to improve the survival rate of LN.

[Chlamydia trachomatis infection and its associated factors among asymptomatic outpatients attending sexually transmitted disease-related clinics].

Objective: To understand the prevalence of Chlamydia trachomatis (CT) infection and its associated factors among asymptomatic outpatients attending sexually transmitted disease (STD)-related clinics in Shenzhen and provide evidence for development of future interventions. Methods: From April 15 to May 16, 2018, a cross-sectional study was conducted and patients attending STD-related Clinics were recruited from 22 medical institutions in Nanshan, Luohu, Bao'an, Longgang, Yantian, and Longhua districts of Shenzhen. After the informed consent from each participant was obtained, social-demographic information was collected through a structured questionnaire and urine samples were collected for CT nucleic acid detection. In addition, logistic regression was used to explore associated factors of CT infection. Results: In asymptomatic outpatients, the prevalence of CT infection was 7.16% (250/3 492). Being single (aOR=2.29, 95%CI:1.65-3.16), without registered Shenzhen residency (aOR=1.49, 95%CI:1.04-2.13), and without previous CT testing in the past year (aOR=2.04, 95%CI:1.03-4.05) were the risk factors of CT infection in asymptomatic outpatients. Among participants without registered Shenzhen residency, 89.25% (2 176/2 438) were college-degree or below, and 51.29% (1 255/2 447) were aged ≤30 years, and the risk of CT infection among those ≤30 years old was 1.73 times higher than those >30 years old (95%CI:1.28-2.34). Conclusions: The prevalence of CT infection was high among asymptomatic outpatients attending STD-related clinics in Shenzhen. Routine CT screening should be carried out for this population, especially for those with sexually active age, being single, with low educational level, and without previous CT testing in the past year. Also, raising their awareness of knowledge and adverse outcomes of CT infection should be considered to promote routine CT screening and timely treatment.

[The meaning and indication of "Rou Ji"].

"Rou Ji", as a name of disease syndrome, played an important role with its relevant theories and clinical experiences in historical recordings. However, it was treasured neither in modern archives nor by clinical physicians. The concept of "Rou Ji" started in the Spring and Autumn Period and the Warring States Period (770 B.C. - 221 B.C.), and its name was first found in Shan Fan Fang in the Southern and Northern Dynasties (420-589). The symptoms of this disease mainly suggested weakness of limbs caused by exogenous factors. It was gradually developed into following symptoms, such like emaciation or muscle atrophy, fatigue, skin color change, abnormal skin sensation, poor digestion and absorption function of spleen and stomach. Its etiology was changed from exogenous factors into internal injuries and deficiency of congenital Qi. Its treatment was also changed with the change of the understanding of diseases. The dialectical thinking in its treatment in ancient medical materials may have reference value for current clinical diagnosis and treatment.

[Analysis of cervical instability and clinical characteristics in treatment-naive rheumatoid arthritis patients].

OBJECTIVE: To study the proportion of cervical spine instability in treatment-naive rheumatoid arthritis (RA) patients, to investigate the associated neck symptoms, and to analyze the clinical characteristics in treatment-naive RA patients and treated RA patients. METHODS: RA patients who underwent cervical spine X-ray imaging from the Department of Rheumatology and Immunology of Peking University Third Hospital and Peking University Shenzhen Hospital from August 2015 to October 2019 and had clinical records of medication administration were included. Clinical and laboratory data including cervical symptoms and X-ray imaging data of cervical spine were collected. The constituent ratio of cervical spine instability in treatment-naive RA patients was statistically analyzed. The clinical data and laboratory data were analyzed by t-test, u-test and chi square to explore the clinical characteristics of the treatment-naive RA patients with cervical instability. RESULTS: Of the 408 RA patients, 105 patients were treatment-naive. Of the 105 treatment-naive patients, 82.9% (87/105) were female, with an average age of (52±14) years, the median duration of the disease was 24 months, the shortest history was 2 weeks, and the longest history was 30 years. 28.6% (30/105) of the treatment-naive RA patients showed cervical spine instability. The prevalence of cervical instability was 13.6% in the treatment-naive RA patients with disease duration less than 24 months. Among them, there were no significant differences in neck symptoms between cervical spine instability group and none cervical spine instability group. The patients with cervical spine instability had a longer duration of disease [60 (18, 180) months vs.16 (8, 51) months], a higher proportion of peripheral joint deformity (63.3%vs.21.3%), and a lower hemoglobin [(106.90±21.61) g/L vs. (115.77±14.69) g/L]. There was no significant difference in the occurrence of cervical instability in the treatment-naive RA patients compared with treated RA patients. Among the RA patients with cervical instability, there was no statistically significant difference in the composition of each type between the patients with treatment-naive RA and patients with treated RA, except for a shorter duration of disease [120.0 (72.0, 240.0) months vs. 60.0 (27.0, 167.5) months]. CONCLUSION: 28.6% of treatment-naive RA patients showed cervical spine instability. Cervical instability was also common in RA patients with a duration less than 24 months. There was no significant correlation between cervical instability and neck symptoms. Patients with cervical spine instability had a long-term disease, a higher proportion of peripheral joint deformity and a lower hemoglobin. Controlling the condition of RA early may help to control the progression of cervical involvement in patients with RA.

Automated Radiographic Evaluation of Adenoid Hypertrophy Based on VGG-Lite.

Adenoid hypertrophy is a pathological hyperplasia of the adenoids, which may cause snoring and apnea, as well as impede breathing during sleep. The lateral cephalogram is commonly used by dentists to screen for adenoid hypertrophy, but it is tedious and time-consuming to measure the ratio of adenoid width to nasopharyngeal width for adenoid assessment. The purpose of this study was to develop a screening tool to automatically evaluate adenoid hypertrophy from lateral cephalograms using deep learning. We proposed the deep learning model VGG-Lite, using the largest data set (1,023 X-ray images) yet described to support the automatic detection of adenoid hypertrophy. We demonstrated that our model was able to automatically evaluate adenoid hypertrophy with a sensitivity of 0.898, a specificity of 0.882, positive predictive value of 0.880, negative predictive value of 0.900, and F1 score of 0.889. The comparison of model-only and expert-only detection performance showed that the fully automatic method (0.07 min) was about 522 times faster than the human expert (36.6 min). Comparison of human experts with or without deep learning assistance showed that model-assisted human experts spent an average of 23.3 min to evaluate adenoid hypertrophy using 100 radiographs, compared to an average of 36.6 min using an entirely manual procedure. We therefore concluded that deep learning could improve the accuracy, speed, and efficiency of evaluating adenoid hypertrophy from lateral cephalograms.

[Population distribution and clinical characteristics in rheumatoid arthritis patients with cervical spine instability].

OBJECTIVE: To investigate the population distribution of cervical spine instability in rheumatoid arthritis (RA) patients, and to analyze the clinical characteristics in RA patients with cervical spine instability. METHODS: A total of 439 RA patients who had completed cervical spine X-ray examination from Department of Rheumatology and Immunology of Peking University Shenzhen Hospital and Peking University Third Hospital from August 2015 to March 2019 were enrolled. The clinical data, laboratory data and cervical radiographic data were collected and analyzed by t-test, rank sum test and Chi-square test to clarify the clinical characteristics in the RA patients with cervical spine instability. RESULTS: Of the 439 RA patients, 80.9% (355/439) were female, with an average age of (52.9±13.9) years, a median duration of the disease was 60 months, the shortest history was 2 weeks, and the longest history was up to 46 years. 29.6% (130/439) of the RA patients showed cervical spine instability. Among them, 20 RA patients were complicated with two different types of cervical instability, the atlantoaxial subluxation (AAS) accounted for 24.6% (108/439), the vertical subluxation (VS) accounted for 7.3% (32/439) and the subluxial subluxations (SAS) accounted for 2.3% (10/439). The patients with cervical spine instability had a longer duration of disease [120 (36, 240) months vs. 48 (12, 120) months], a higher proportion of peripheral joint deformity (56.9% vs. 29.9%), and a higher visual analog scale (VAS) measuring general health score (4.89±2.49 vs. 3.93±2.38), a lower hemoglobin [(111.31±19.44) g/L vs. (115.56±16.60) g/L] and a higher positive rate of anti-cyclic citrullina-ted peptide (CCP) antibody (90.8% vs. 76.6%). There were no significant differences in gender, age, number of swollen joints, number of tenderness joints, erythrocyte sedimentation rate, rheumatoid factor level, 28-joint disease activity score, positive rate of anti keratin antibody, duration of glucocorticoid use and duration of disease modifying anti-rheumatic drugs use between the two groups. CONCLUSION: In the study, 29.6% of the RA patients showed cervical spine instability. RA patients with cervical spine instability had a long-term disease, a higher proportion of peripheral joint deformity, a higher VAS measuring general health score, a lower hemoglobin and a higher positive rate of anti-CCP antibody.

[Analysis on Neisseria gonorrhoeae infection status and related factors in outpatients of sexually transmitted diseases in Shenzhen].

Objective: To understand the prevalence of Neisseria gonorrhoeae (NG) infection and related factors in outpatients of sexually transmitted disease (STD) in Shenzhen and provide scientific evidence for targeted intervention. Methods: A cross-sectional study was conducted in STD outpatients who were aged 18-49 years, had had sexual intercourse, had not received antibiotics in the last 2 weeks and sought medical cares in 22 medical institutions in 6 districts of Shenzhen from 15 April, 2018 to 16 May, 2018, their basic information and urine samples were collected, and NG in urine sample was detected by nucleic acid amplification test. Logistic regression analysis was conducted to identify the related factors for NG infection. Results: The information collection and sample collection were completed for 8 324 STD outpatients, among these STD outpatients, 196 were NG positive, with a positive rate of 2.4% (196/8 324). The positive rate of NG in men (5.8%, 148/2 567) was higher than that in women (0.8%, 47/5 742) (χ(2)=189.43, P<0.05). Aged 24 years or below (OR=2.11, 95%CI: 1.44-3.09), single/divorced/widowed (OR=1.98, 95%CI:1.38-2.84), having casual sex in the last 3 months (OR=1.77, 95%CI:1.29-2.43) were the related factors for NG infection. Conclusions: We found that NG infection rate was high in STD outpatients in Shenzhen. The infection rates in men and in women differed obviously. It is necessary to conduct gonorrhea screening and intervention in STD outpatients with high-risk behaviors, such as extramarital and casual sex behaviors, and standardize the treatment to reduce the incidence and spread of gonorrhea and other STDs.

Time series analysis and forecasting of chlamydia trachomatis incidence using surveillance data from 2008 to 2019 in Shenzhen, China.

Chlamydia trachomatis (CT) infection has been a major public health threat globally. Monitoring and prediction of CT epidemic status and trends are important for programme planning, allocating resources and assessing impact; however, such activities are limited in China. In this study, we aimed to apply a seasonal autoregressive integrated moving average (SARIMA) model to predict the incidence of CT infection in Shenzhen city, China. The monthly incidence of CT between January 2008 and June 2019 in Shenzhen was used to fit and validate the SARIMA model. A seasonal fluctuation and a slightly increasing pattern of a long-term trend were revealed in the time series of CT incidence. The monthly CT incidence ranged from 4.80/100 000 to 21.56/100 000. The mean absolute percentage error value of the optimal model was 8.08%. The SARIMA model could be applied to effectively predict the short-term CT incidence in Shenzhen and provide support for the development of interventions for disease control and prevention.

[Pay attention to the exposure risk of patients with chronic wounds on the way to hospital during coronavirus disease 2019 epidemic prevention and control].

Statistics show that 76.74% (4 688) of 6 109 patients with chronic wounds are over 50 years of age; the proportion of patients with underlying diseases in all age groups above 50 years ranges from 78.25% to 100.00%. Among the underlying diseases of chronic wound patients, the top four diseases are diabetes mellitus, cardiovascular and cerebrovascular diseases, hypertension, and respiratory diseases. The above underlying diseases and ages of patients are the susceptibility factors of coronavirus disease 2019 released by National Health Commission of China. It is an unavoidable fact that the patients with chronic wounds have to go to the hospital for treatment prescribed by the physician. At the same time, we found that quite a few patients preferred going far afield in choosing hospital for treatment due to various reasons. During the prevention and control of coronavirus epidemic, this " go far afield" style of seeking medical treatment may increase the exposure risk during travelling. Accordingly, we convened 36 wound care clinics in different regions in Shanghai to implement the " Five Measures" encouraging the patients with chronic wounds to seek medical treatment nearby. The principle of this operation is that when seeking medical treatment, patients with chronic wounds should try their best to reduce the travel distance as much as possible to minimize the exposure risk during the epidemic period, which will in turn support the campaign of epidemic prevention and control.

Correction to: Inhibition of cathepsin B by caspase-3 inhibitors blocks programmed cell death in Arabidopsis.

We thank D Nicholson for initial advice on caspase activity purification and B Turk for advice on recombinant cathepsin B. We thank N Atanasova for cell death assays. The Bioimaging Facility microscopes used in this study were purchased with grants from BBSRC, Wellcome Trust and the University of Manchester Strategic Fund. Special thanks go to D Knight in the Faculty Biomolecular Analysis facility. We thank P Birch and M Kim for improving the manuscript. The project was partially funded by BBSRC Grants 34/P14516, BB/K009478/1 and China National High-Tech Research and Development Programme(863 programme)NO. 2015AA020903.

[Factors associated with syphilis/HIV infection among men who have sex with men in Shenzhen,2011-2016].

Objective: To investigate the factors associated with syphilis/HIV infection among men who have sex with men (MSM) maintaining a single sexual partner in Shenzhen. Methods: Respondent driven sampling and snowball sampling method were used to recruit MSM receiving voluntary counseling and testing in Shenzhen Rainbow clinic from 2011 to 2016. INCLUSION CRITERIA: aged 18 years and above; reported having one or more anal sexual partners in the recent 6 months. A total of 3 109 men who have sex with men (MSM) were involved in the study. Questionnaire-based interviews were conducted on a one-on-one basis. Data were collected including socio-demographic information, human immunodeficiency virus (HIV) testing history, history of blood donation and drug abuse in the recent two years, self-identified sexual orientation, role in homosexual behavior, ever being money boys (MB) and clients of MB, female sexual partners in the recent 6 months. 5 ml blood samples were taken after questionnaires. Syphilis was screened using toluidine red unheated serum test for the antibody of treponema pallidum and then confirmed by treponema pallidum particle assay. The enzyme-linked immunosorbent assay (ELISA) was used for screening HIV and western blot was used to confirm the HIV screening results. The difference of condom use among MSM between female sexual partners and male sexual partners were compared. Multivariate unconditional stepwise logistic regression model was used to analyze factors associated with syphilis infection and HIV positive among MSM. Results: A total of 3 109 eligible participants with mean (SD) age of 31.49 (8.64) years were enrolled in this study. Among them, 565 cases were infected with syphilis (18.17%), 330 cases were infected with HIV (10.61%), and 165 cases (5.31%) were syphilis co-infected with HIV. 791 (25.44%) reported maintaining a single sexual partners in the recent 6 months. Compared to MSM with multiple sexual partners, the prevalence of syphilis and HIV infection among MSM with a single sexual partner were lower, and the OR (95%CI) were 0.64 (0.51-0.81) and 0.66 (0.49-0.90), respectively. Conclusion: The proportion of fixed single sexual partner was much lower among MSM in Shenzhen. Maintaining a single sexual partners can reduce the risk of syphilis/HIV infection among MSM.

[Factors associated with commercial sexual behavior among men who have sex with men in Shenzhen, China, in 2011-2015].

Objective: To investigate the status and factors associated with commercial sexual behavior among men who have sex with men (MSM) in Shenzhen. Methods: A convenience sampling method was used to recruit MSM in Shenzhen from 2011 to 2015. Questionnaire-based interviews were conducted on a one-on-one basis. Data were collected, including socio-demographic information, HIV testing history, history of blood donation and drug abuse in the last 2 years, self-reported sexual orientation, role in homosexual behavior, and experience serving as a male sex worker and/or as a client of male sex workers. Blood samples (5 ml) were taken and tested for treponema pallidum and HIV antibodies. The rate of MSM serving as male sex workers among different age groups was analyzed using the Cochran-Armitage trend test. Factors associated with commercial sexual behavior were analyzed by univariate logistic regression and multivariate unconditional logistic regression. Results: Among the 3 040 MSM recruited, 341 (11.2%) reported having served as male sex worker. The prevalence rates of syphilis, HIV, and syphilis-HIV co-infection among all recruited MSM were 18.3% (556/3 040), 9.8% (297/3 040), and 5.1% (154/3 040), respectively. The prevalence rates of syphilis, HIV, and syphilis-HIV co-infection among those who served as male sex worker were 27.0% (92/341), 16.4% (56/341), and 8.8% (30/341), respectively, and the prevalence rates among MSM with no experience as male sex worker were 17.2% (464/2 699), 8.9% (241/2 699), and 4.6% (124/2 699), respectively. Compared with non-male sex worker MSM, male sex worker had a significantly higher prevalence rates of syphilis, HIV, and syphilis-HIV co-infection (with χ2 values of 19.41, 19.28, and 11.12, and P-values of <0.001,<0.001, 0.001, respectively). The results of the multivariate logistic regression analysis indicate that>30-year-old MSM or education level of college or above, reside in Shenzhen for 0.5-3.0 years or the living years above 3.0 years are less likely to serve as male sex worker compared with<30-year-old MSM, education level of high school or below, who reside in Shenzhen for less than 0.5 years; the OR (95%CI) values were 0.55 (0.42-0.71), 0.10 (0.06-0.14), 0.46 (0.31-0.68), and 0.23 (0.16-0.33), respectively. MSM having a monthly income of >5 000 yuan, drug abuse history, experience as male sex worker clients, and self-reported insertive and receptive anal sex behaviors were more likely to have experience serving as male sex worker compared with those having a monthly income of <3 000 yuan (OR=2.57, 95%CI: 1.85-3.57), no drug abuse history (OR=3.23, 95% CI: 2.14-4.87), no experience as male sex worker clients (OR =1.50, 95% CI: 1.04-2.15) and who engage in predominantly insertive anal sex behaviors (OR=1.77, 95% CI: 1.34-2.35). Conclusion: Age, education level, duration of residence in Shenzhen, monthly income, history of drug abuse, role in homosexual activity, and had experience commercial sex activity were associated with serving as a male sex worker among MSM. These factors need to be considered when designing syphilis/HIV prevention programs for MSM.

Antibody detection tests for early diagnosis in tuberculous meningitis.

BACKGROUND: Tuberculous meningitis (TBM) is the most severe form of tuberculosis. Microbiological confirmation is rare and treatment is often delayed. Early diagnosis and immediate initiation of treatment are essential for effective TBM control. A systematic review was performed in this study to assess the diagnostic accuracy of detecting antibodies against Mycobacterium tuberculosis in the cerebrospinal fluid (CSF), according to standard methods. Test performance was summarized using a bivariate random-effects meta-analysis. METHODS: Studies were identified by a search of the literature, up to July 25, 2015, in the EMBASE and MEDLINE databases via Ovid SP and PubMed. The Cochrane Library was also searched for original, peer-reviewed molecular epidemiology studies that reported the diagnosis of TBM based on antibody detection in the CSF. RESULTS: Thirty-six articles (58 studies) were identified. The sensitivity of antibody detection was 0.75 (95% confidence interval (CI) 0.66-0.82), specificity was 0.98 (95% CI 0.96-0.99), and the area under the receiver operating characteristic curve (AUROC) was 0.97 (95% CI 0.95-0.98). By subgroup analysis, the detection of anti-M37Ra was the highest (AUROC 0.99, 95% CI 0.98-1.00), followed by anti-antigen 5 (AUROC 0.99, 95% CI 0.97-0.99) and anti-M37Rv (AUROC 0.97, 95% CI 0.95-0.98). CONCLUSIONS: For the early diagnosis of TBM based on antibodies in the CSF, the detection of anti-M37Ra, anti-antigen 5, or anti-M37Rv provides the greatest sensitivity and specificity.

Inhibition of cathepsin B by caspase-3 inhibitors blocks programmed cell death in Arabidopsis.

Programmed cell death (PCD) is used by plants for development and survival to biotic and abiotic stresses. The role of caspases in PCD is well established in animal cells. Over the past 15 years, the importance of caspase-3-like enzymatic activity for plant PCD completion has been widely documented despite the absence of caspase orthologues. In particular, caspase-3 inhibitors blocked nearly all plant PCD tested. Here, we affinity-purified a plant caspase-3-like activity using a biotin-labelled caspase-3 inhibitor and identified Arabidopsis thaliana cathepsin B3 (AtCathB3) by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Consistent with this, recombinant AtCathB3 was found to have caspase-3-like activity and to be inhibited by caspase-3 inhibitors. AtCathepsin B triple-mutant lines showed reduced caspase-3-like enzymatic activity and reduced labelling with activity-based caspase-3 probes. Importantly, AtCathepsin B triple mutants showed a strong reduction in the PCD induced by ultraviolet (UV), oxidative stress (H2O2, methyl viologen) or endoplasmic reticulum stress. Our observations contribute to explain why caspase-3 inhibitors inhibit plant PCD and provide new tools to further plant PCD research. The fact that cathepsin B does regulate PCD in both animal and plant cells suggests that this protease may be part of an ancestral PCD pathway pre-existing the plant/animal divergence that needs further characterisation.