Legionella effector LnaB is a phosphoryl-AMPylase that impairs phosphosignalling

AMPylation is a post-translational modification in which AMP is added to the amino acid side chains of proteins1,2. Here we show that, with ATP as the ligand and actin as the host activator, the effector protein LnaB of Legionella pneumophila exhibits AMPylase activity towards the phosphoryl group of phosphoribose on PRR42-Ub that is generated by the SidE family of effectors, and deubiquitinases DupA and DupB in an E1- and E2-independent ubiquitination process3-7. The product of LnaB is further hydrolysed by an ADP-ribosylhydrolase, MavL, to Ub, thereby preventing the accumulation of PRR42-Ub and ADPRR42-Ub and protecting canonical ubiquitination in host cells. LnaB represents a large family of AMPylases that adopt a common structural fold, distinct from those of the previously known AMPylases, and LnaB homologues are found in more than 20 species of bacterial pathogens. Moreover, LnaB also exhibits robust phosphoryl AMPylase activity towards phosphorylated residues and produces unique ADPylation modifications in proteins. During infection, LnaB AMPylates the conserved phosphorylated tyrosine residues in the activation loop of the Src family of kinases8,9, which dampens downstream phosphorylation signalling in the host. Structural studies reveal the actin-dependent activation and catalytic mechanisms of the LnaB family of AMPylases. This study identifies, to our knowledge, an unprecedented molecular regulation mechanism in bacterial pathogenesis and protein phosphorylation.

Legionella effectors SidC/SdcA ubiquitinate multiple small GTPases and SNARE proteins to promote phagosomal maturation.

Protein ubiquitination is one of the most important posttranslational modifications (PTMs) in eukaryotes and is involved in the regulation of almost all cellular signaling pathways. The intracellular bacterial pathogen Legionella pneumophila translocates at least 26 effectors to hijack host ubiquitination signaling via distinct mechanisms. Among these effectors, SidC/SdcA are novel E3 ubiquitin ligases with the adoption of a Cys-His-Asp catalytic triad. SidC/SdcA are critical for the recruitment of endoplasmic reticulum (ER)-derived vesicles to the Legionella-containing vacuole (LCV). However, the ubiquitination targets of SidC/SdcA are largely unknown, which restricts our understanding of the mechanisms used by these effectors to hijack the vesicle trafficking pathway. Here, we demonstrated that multiple Rab small GTPases and target soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) proteins are bona fide ubiquitination substrates of SidC/SdcA. SidC/SdcA-mediated ubiquitination of syntaxin 3 and syntaxin 4 promotes their unconventional pairing with the vesicle-SNARE protein Sec22b, thereby contributing to the membrane fusion of ER-derived vesicles with the phagosome. In addition, our data reveal that ubiquitination of Rab7 by SidC/SdcA is critical for its association with the LCV membrane. Rab7 ubiquitination could impair its binding with the downstream effector Rab-interacting lysosomal protein (RILP), which partially explains why LCVs avoid fusion with lysosomes despite the acquisition of Rab7. Taken together, our study reveals the biological mechanisms employed by SidC/SdcA to promote the maturation of the LCVs.

Exercise Prescription in Individuals with Prehypertension and Hypertension: Systematic Review and Meta-Analysis.

Background: The prevalence of prehypertension and hypertension has been increasing over the years, and is closely related to cardiovascular and cerebrovascular diseases. Exercise is an effective method of lifestyle intervention, and it aims to lower blood pressure and control other risks. Studies have shown that different modes of exercise have varying effects on blood pressure, and individuals with prehypertension or hypertension need to carry out this intervention by using personalized modes of exercise. Methods: We conducted a systematic review and meta-analysis to evaluate the effects of different modes of exercise regimens on systolic blood pressure, diastolic blood pressure and heart rate in individuals with high-normal blood pressure and hypertension. We included 27 trials, and 2731 individuals were under 8 exercise regimens. Stata12.0 statistical software was used for statistical analysis. Results: Heat pools significantly reduced systolic blood pressure (SBP) by 15.62 mmHg (95% confidence interval [CI]: -23.83, -7.41), and cycling reduced SBP by 14.76 mmHg (-17.04, -12.48). Two to three types of aerobic exercise performed at the same time also significantly reduced diastolic blood pressure (DBP) by 5.61 mmHg (-7.71, -3.52), and isometric handgrip training exercise reduced DBP by 5.57 mmHg (-7.48, -3.66). Cycling also significantly reduced heart rate (HR) by 9.57 beats/minute (-11.25, -7.90). Conclusions: The existing literature suggests that different types of exercise can effectively reduce the levels of SBP, DBP and HR in individuals with prehypertension or hypertension.

Brain frailty associated with stroke events in anterior circulation large artery occlusion.

OBJECTIVE: To investigate the factors associated with brain frailty and the effect of brain frailty in patients with anterior circulation large artery occlusion (AC-LAO). METHODS: 1100 patients with AC-LVO consecutively admitted to the Second Hospital of Hebei Medical University, North China between June 2016 and April 2018 were retrospectively analyzed. The variables associated with brain frailty and stroke outcome were analyzed by ANOVA analysis, the Mann-Whitney U test and multiple linear regression. Based on previous research. Brain frailty score comprises 1 point each for white matter hyperintensity (WMH), old infarction lesions, and cerebral atrophy among 983 participants with baseline brain magnetic resonance imaging or computed tomography. RESULTS: Among AC-LAO participants, baseline brain frailty score ≥ 1 was common (750/983, 76.3%). Duration of hypertension > 5 years (mean difference [MD] 0.236, 95% CI 0.077, 0.395, p = 0.004), multiple vessel occlusion (MD 0.339, 95% CI 0.068, 0.611, p = 0.014) and basal ganglia infarction (MD -0.308, 95% CI -0.456, -0.160, p < 0.001) were independently associated with brain frailty score. Brain frailty score was independently associated with stroke events, and higher brain frailty scores were associated with higher rates of stroke events (p < 0.001). However, brain frailty has no independent effect on short-term outcome of ACI in AC-LAO patients. CONCLUSIONS: In AC-LAO patients, older age, duration of hypertension > 5 years, and multiple vessel occlusion influenced the brain frailty score. Brain frailty score was independently associated with the occurrence of stroke events in AC-LAO patients.

Feminization of the health workforce in China: exploring gendered composition from 2002 to 2020.

BACKGROUND: Feminization of health workforce has been globally documented, but it has not been investigated in China. This study aims to analyze changes in the gendered composition of health workforce and explore the trend in different types of health workforce, health organizations and majors within China's health system. METHODS: The data were collected from China Health Statistical Yearbook from 2002 to 2020. We focused on health professionals including doctors, nurses, and pharmacists in health organizations. Trend analysis was employed to examine the change in the ratio of female health workforce over 18 years. The estimated average annual percent change (AAPC) was estimated, and the reciprocals of variances for the female ratios were used as weights. RESULTS: In China, health professionals increased from 4.7 million in 2002 to 10.68 million in 2020. Health professionals per 1000 population increased from 3.41 in 2002 to 7.57 in 2020. The ratio of female health professionals significantly increased from 63.85% in 2002 to 72.4% in 2020 (AAPC = 1.04%, 95% CI 0.96-1.11%, P < 0.001). Female doctors and pharmacists increased 4.7 and 7.9 percentage points from 2002 to 2020. Female health workers at township health centers, village clinics, centers for disease control and prevention had higher annual increase rate (AAPC = 1.67%, 2.25% and 1.33%, respectively) than those at hospital (0.70%) and community health center (0.5%). Female doctors in traditional Chinese medicine, dentistry and public health had higher annual increase rate (AAPC = 1.82%, 1.53% and 1.91%, respectively) than female clinical doctor (0.64%). CONCLUSIONS: More women are participating in the healthcare sector in China. However, socially lower-ranked positions have been feminizing faster, which could be due to the inherent and structural gender norms restricting women's career. More collective and comprehensive system-level actions will be needed to foster a gender-equitable environment for health workforce at all levels.

Gender income differences among general practitioners with compulsory services in early career stage in underdeveloped areas: evidence from a prospective cohort study in China.

BACKGROUND: Gender equality and the gender income gap in medicine are long-standing global problems. Although gender-related differences have been widely studied in developed countries, they remain unclear in underdeveloped regions. In 2010, China initiated a national compulsory service program (CSP) to train qualified general practitioners in rural and remote areas. This study aimed to evaluate gender income differences for early career CSP and non-CSP (NCSP) graduates in underdeveloped areas. METHODS: A cohort study was conducted with 3620 CSP and NCSP graduates from four medical universities in Central and Western China. Baseline surveys and six follow-up surveys were conducted between 2015 and 2022. Incomes, including monthly mean income and proportion of performance-based income, were measured as the key outcome variables. Multivariate linear regression models were used to identify the gender income gap. RESULTS: NCSP graduates had higher average monthly incomes than CSP graduates. In the seventh year after graduation, the average monthly income for NCSP graduates was 7859 CNY while was 5379 CNY for CSP graduates. After controlling for demographic characteristics, the gender monthly income gap for CSP graduates was expanded from the fourth year (3.0%) to the sixth year (5.9%) after graduation, and that for NCSP graduates was expanded from the fifth year (11.9%) to the seventh year (16.3%) after graduation. Regarding performance-based income, it was 58.9% for NCSP graduates and 45.8% for CSP graduates in the seventh year after graduation. After controlling for performance-based income proportion, the gender income gap was reduced from 5.9 to 4.0% in the sixth year after graduation for CSP graduates, and from 16.3 to 14.4% for NCSP graduates in the seventh year after graduation. CONCLUSION: An extensive and ever-increasing gender income gap exists among young doctors in the early stages of their careers in underdeveloped areas of China. The high proportion of performance-based income among men is one of the main explanations for the observed difference. A more explicit compensation system must be established to enhance support for female health workers.

Effects of predictive nursing interventions on pressure ulcer in older bedridden patients: A meta-analysis.

To evaluate the effect of predictive nursing interventions on pressure ulcers in elderly bedridden patients by meta-analysis. Applied computer searches of PubMed, Embase, Google Scholar, Cochrane Library, China National Knowledge Infrastructure and Wanfang databases for randomised controlled trials (RCTs) on the effect of predictive nursing in preventing pressure ulcers in elderly bedridden patients from the database inception to November 2023. Two researchers independently screened the literature, extracted data and performed quality assessment based on inclusion and exclusion criteria. Stata 17.0 software was utilised for data analysis. Eighteen RCTs involving 6504 patients were finally included. The analysis revealed the implementation of predictive nursing interventions had a significant advantage in reducing the incidence of pressure ulcers in elderly bedridden patients compared with conventional nursing (odds ratio [OR] = 0.20, 95% confidence interval [CI]: 0.15-0.28, p < 0.001), while the patients' satisfaction with nursing care was higher (OR = 3.70, 95% CI: 2.99-4.57, p < 0.001). This study shows that the implementation of a predictive nursing interventions for elderly bedridden patients can effectively reduce the occurrence of pressure ulcers and significantly improve patients' satisfaction with nursing care, which is worthy of clinical promotion and application.

Clinical application of metagenomic next-generation sequencing in patients with different organ system infection: A retrospective observational study.

Microbiological identification is essential for appropriate treatment, but conventional methods are time-consuming and have a low sensitivity. In contrast, metagenomic next-generation sequencing (mNGS) is a culture-free and hypothesis-free technique that can detect a wide array of potential pathogens. This study aimed to reveal the overall diagnostic value of mNGS for infectious diseases of different organ systems and compare the sensitivity and specificity of mNGS with conventional methods. In a retrospective cohort study, 94 patients with mNGS results were enrolled, and clinical data were recorded and analyzed to compare the positive rate of mNGS with traditional methods including as smears, serological tests, and traditional PCR, etc. In this study, mNGS and culture were both positive in 12.77% cases and were both negative in 23.4% cases. There were positive results in 56 cases (54.26%) only by mNGS and 4 cases (4.26%) were positive only by culture. There were significant differences in sensitivity of pathogen detection between of ID and NID group for mNGS (χ2 = 10.461, P = .001)and conventional methods(χ2 = 7.963, P = .005). The positive predictive values and negative predictive values of diagnosing infectious disease by mNGS were 94.12% and 30.77%, respectively. mNGS increased the sensitivity rate by approximately 53.66% compared with that of culture (78.05% vs24.39%; χ2 = 47.248, P < .001) and decreased the specificity rate by 12.5% compared with that of culture (66.67% vs 100.0%; χ2 = 4.8, P = .028). mNGS can identify emerging or rare pathogen and further guide treatment regimens. mNGS has advantages in identifying overall pathogens and bacteria, however, there was no obvious advantage in identifying fungi, virus and tuberculosis. mNGS has higher specificity than conventional methods in identifying pathogens and advantages in detecting emerging or rare pathogens.

Dip effect on the orientation of rock failure plane under combined compression-shear loading.

Shear failure often occurs in engineering rock mass (such as inclined pillar) in gently inclined strata. Prediction and characterization the orientation of shear failure plane is the foundation of rock mass engineering reinforcement. In this paper, sandstone samples are used to perform uniaxial and shear tests to obtain the basic mechanical parameters. Then, by employing the numerical method, the combined compression-shear loading tests were carried out for inclined specimens varied from 0° to 25° at an interval of 5°, to obtain the dip effect on the orientation of rock failure plane. The results show that the failure plane of rock changes with the change of dip angle of rock sample. Based on the Mohr-Coulomb criterion, the ultimate stress state of rock was characterized under combined compression-shear loading. The ultimate strength of rock is equal to the ratio of the stress circle radius of rock under combined compression-shear condition to the stress circle radius of rock under uniaxial compression condition, multiplied by the uniaxial compressive strength. The fracture angle of rock was defined under combined compression-shear loading. A theoretical model was developed for predicting the fracture angle. The developed model could be characterized by internal friction angle, dip angle of rock sample and Poisson's ratio. Finally, the numerical results of the fracture angle were analyzed, which are consistent with the predicted results of the model. The investigation shows that the rock fracture angle has a dip effect, which decreases with the increase of the inclination angle of the sample. The research results provide a new means to identify the potential failure plane of engineering rock mass, and lay a theoretical foundation for calculating the orientation of rock fracture plane.

Prolonged post-washing in ethanol decreases bond strength of additively manufactured crown materials.

OBJECTIVES: This study aimed to investigate the effect of post-washing duration and crown thickness on the bond strength between additively manufactured crown materials and dental cement in vitro. METHODS: Rectangular-shaped specimens of two thicknesses (1.5 and 2.0 mm) were additively manufactured from permanent VarseoSmile Crown (VC) and long-term temporary NextDent (ND) materials. The specimens were post-washed (n = 160) in ethanol for 5 min, 10 min, 1 h, and 8 h then cemented with dual-cure resin cement. Twenty PMMA (TC) were milled as a control. A chevron-notch test was performed to measure the maximum load until failure (N). Interfacial bond strength (J/m2) was calculated and statistically analysed. The mode of failure was analysed by scanning electron microscopy (SEM). RESULTS: There was a significant difference in the bond strength between all groups (p < 0.01). VC at 1.5mm thickness post-washed for 10 min showed the highest mean bond strength (1.77 ±0.96 J/m2) while VC at 2.0mm thickness post-washed for 8 h showed the lowest (0.22 ±0.10 J/m2). Exposure to ethanol for 8 h resulted in lower bond strength. Within the type of material, there were no differences in bond strength between the thicknesses when post-washed for the same duration. CONCLUSIONS: Prolonged post-washing of AM crown materials can significantly decrease the bond strength to resin cement. There were no differences between the permanent and long-term temporary AM materials. When post-washed for 5 min, AM materials observed comparable or higher bond strength values compared to PMMA. CLINICAL SIGNIFICANCE: The output of this research serves as a guide for dental practitioners, emphasising the importance of adhering to correct post-washing procedures for optimal bond strength of additively manufactured crown materials.

Factors influencing the bond strength of additively manufactured crown materials in dentistry: A systematic review of in vitro studies.

OBJECTIVE: The purpose of this systematic review was to investigate how different interventions can impact the bond strength of additively manufactured crown materials after cementation. DATA/SOURCES: Four online databases Ovid MEDLINE, Scopus, Web of Science and Google Scholar were searched up to January 2023. Inclusion criteria were English-language publications, full-text, and in vitro studies only. Exclusion criteria were studies that did not assess the bonding of an additively manufactured crown material to cement or did not conduct any bond strength tests. An assessment of risk of bias was done in accordance with a modified Consolidated Standards of Reporting Trials (CONSORT) checklist. Each study was analysed and compared based on the interventions and bond strength results. STUDY SELECTION: Six studies satisfied the inclusion and exclusion criteria, five of which evaluated photopolymerised resin and one that tested zirconia manufacturing via 3D printing. All studies observed a low risk of bias. The interventions applied included the type of surface pretreatments, airborne-particle abrasion pressure, cement type, taper of crown, and artificial aging. Three studies compared the bonding performance to milled materials. CONCLUSIONS: The bond strength of crown materials additively manufactured from photopolymers presented high values and are comparable to milled materials. The systematic review demonstrated there was no definite superior cement type, but airborne-particle abrasion with alumina was generally recommended. There is a clear gap in the literature regarding the bond strength of additively manufactured crowns. Therefore, further research is necessary to evaluate its clinical applicability for permanent restorations. CLINICAL SIGNIFICANCE: Factors influencing the bond strength of additively manufactured crown materials should be evaluated so dental professionals can adopt procedures that promote the strongest bond.

Injectable extracellular matrix-mimetic hydrogel based on electrospun Janus fibers.

To date, the reported injectable hydrogels have failed to mimic the fibrous architecture of the extracellular matrix (ECM), limiting their biological effects on cell growth and phenotype. Additionally, they lack the micro-sized pores present within the ECM, which is unfavorable for the facile transport of nutrients and waste. Herein, an injectable ECM-mimetic hydrogel (IEMH) was fabricated by shortening and dispersing Janus fibers capable of self-curling at body temperature into pH 7.4 phosphate buffer solution. The IEMH could be massively prepared through a side-by-side electrospinning process combined with ultraviolet irradiation. The IEMHs with only 5 wt% fibers could undergo sol-gel transition at body temperature to become solid gels with desirable stability, sturdiness, and elasticity and self-healing ability. In addition, they possessed notable pseudoplasticity, which is beneficial to injection at room temperature. The results obtained from characterization analysis via scanning electron microscopy, total internal reflection fluorescence microscopy, nuclear magnetic resonance spectroscopy, and Fourier-transform infrared spectroscopy indicate that their sol-gel transition under physiological conditions stems from the synergistic action of the tight entanglements between thermally-induced self-curling fibers and the hydrophobic interaction between the fibers. An MTT assay using C2C12 myoblast cells was performed to examine the in vitro cytotoxicity of IEMHs for biomedical applications, and the cell viability was found to be more than 95%.

Influence of different post-processing methods on the dimensional accuracy of 3D-printed photopolymers for dental crown applications - A systematic review.

OBJECTIVES: To perform a systematic review that provides an overview of the current literature on the influence of different post-processing methods on the accuracy of additive-manufactured (3D-printed) photopolymer crown materials, and whether more research is needed. MATERIALS AND METHODS: The search used three online databases, Ovid (MEDLINE), Scopus and Web of Science which were screen for publications that involved assessing dimensional accuracy in post-processing of 3D printed dental crown materials. Publications that were literature reviews, abstracts, written in a language different from English, or publications that did not assess dimensional accuracy were excluded. RESULTS: The included articles were published between 1995 and 2023. After the removal of duplicates using Endnote, 135 studies remained for further screening, 13 were selected for full-text analysis, and 7 studies were included in the systematic review. A total of 7 articles were examined and categorised based on several factors, such as the type of material, number of specimens per group, print layer thickness, print angle of specimens, 3D printer used, properties of the specimens studied, and the method of analysing the accuracy of the specimens. CONCLUSION: It was found that post-processing washing times outside the prescribed instruction for use (IFU) may have an impact on the physical and biocompatibility characteristics of the material. Studies focusing on inert mediums during post-processing require more detailed investigation. The use of different post-curing conditions does not significantly affect the materials dimensional accuracy.

Comparison of the Biomechanical Properties between Healthy and Whole Human and Porcine Stomachs.

Gastric cancer poses a societal and economic burden, prompting an exploration into the development of materials suitable for gastric reconstruction. However, there is a dearth of studies on the mechanical properties of porcine and human stomachs. Therefore, this study was conducted to elucidate their mechanical properties, focusing on interspecies correlations. Stress relaxation and tensile tests assessed the hyperelastic and viscoelastic characteristics of porcine and human stomachs. The thickness, stress-strain curve, elastic modulus, and stress relaxation were assessed. Porcine stomachs were significantly thicker than human stomachs. The stiffness contrast between porcine and human stomachs was evident. Porcine stomachs demonstrated varying elastic modulus values, with the highest in the longitudinal mucosa layer of the corpus and the lowest in the longitudinal intact layer of the fundus. In human stomachs, the elastic modulus of the longitudinal muscular layer of the antrum was the highest, whereas that of the circumferential muscularis layer of the corpus was the lowest. The degree of stress relaxation was higher in human stomachs than in porcine stomachs. This study comprehensively elucidated the differences between porcine and human stomachs attributable to variations across different regions and tissue layers, providing essential biomechanical support for subsequent studies in this field.

Migrating foreign bodies of penis: a case report and literature review.

BACKGROUND: Only a few cases have been reported about active foreign body implantation in the cavernous body of the penis. CASE PRESENTATION: A 47-year-old man inserted two needles from the glans penis into the bilateral penile sponge body. Subsequently, two needles migrated through the penile cavernous body into the pelvic cavity. Attempts to remove the needles through the penis were unsuccessful. Eventually, after a duration exceeding one month, the displaced needles were removed in stages from the buttocks. CONCLUSION: A few cases of intracavernosal-injection-therapy-associated needle breakage and retention have been reported globally. And this is the first case in China documenting the migration of foreign bodies within the penile region. In this condition, it is of utmost importance to engage the expertise of experienced andrologists to minimize the risk of excessive manipulation, thereby ensuring that inadvertent deep penetration of the needle into the penile tissue is prevented. In case the foreign body has migrated deeper into the tissues and the patient does not exhibit any specific symptoms or risks of macrovascular injury-related bleeding, close surveillance of its movement can be implemented. Surgical intervention can be initiated once the foreign body has reached a suitable position. Moreover, a psychiatric evaluation should be recommended for patient to discover any underlying mental health disorders.

RéSUMé: CONTEXTE: Seuls quelques cas ont été rapportés concernant l'implantation active d'un corps étranger dans le corps caverneux du pénis. PRéSENTATION DU CAS: Un homme de 47 ans a inséré deux aiguilles, par le gland du pénis, dans les corps spongieux du pénis. Par la suite, les deux aiguilles ont migré à travers le corps caverneux du pénis jusque dans la cavité pelvienne. Les tentatives pour retirer les aiguilles à travers le pénis ont été infructueuses. Finalement, après une durée de plus d'un mois, les aiguilles déplacées ont été retirées, par étapes, au niveau des fesses. CONCLUSION: Quelques cas de rupture et de rétention d'aiguille associés au traitement par injection intracaverneuse ont été signalés dans le monde. Il s'agit ici du premier cas en Chine qui documente la migration de corps étrangers dans la région du pénis. Dans cette situation, il est de la plus haute importance de faire appel à l'expertise d'andrologues expérimentés pour minimiser le risque de manipulation excessive, garantissant ainsi que la pénétration profonde par inadvertance de l'aiguille dans le tissu pénien est prévenue. Dans le cas où le corps étranger a migré plus profondément dans les tissus et que le patient ne présente pas de symptômes spécifiques ou de risques de saignements liés à une lésion macrovasculaire, une surveillance étroite du mouvement du corps étranger peut être mise en œuvre. L'intervention chirurgicale peut être initiée une fois que le corps étranger a atteint une position appropriée. Enfin, une évaluation psychiatrique devrait être recommandée à la recherche de tout trouble sous-jacent de santé mentale.

Bacterial ubiquitin ligases hijack the host deubiquitinase OTUB1 to inhibit MTORC1 signaling and promote autophagy.

Many bacterial pathogens have evolved effective strategies to interfere with the ubiquitination network to evade clearance by the innate immune system. Here, we report that OTUB1, one of the most abundant deubiquitinases (DUBs) in mammalian cells, is subjected to both canonical and noncanonical ubiquitination during Legionella pneumophila infection. The effectors SidC and SdcA catalyze OTUB1 ubiquitination at multiple lysine residues, resulting in its association with a Legionella-containing vacuole. Lysine ubiquitination by SidC and SdcA promotes interactions between OTUB1 and DEPTOR, an inhibitor of the MTORC1 pathway, thus suppressing MTORC1 signaling. The inhibition of MTORC1 leads to suppression of host protein synthesis and promotion of host macroautophagy/autophagy during L. pneumophila infection. In addition, members of the SidE family effectors (SidEs) induce phosphoribosyl (PR)-linked ubiquitination of OTUB1 at Ser16 and Ser18 and block its DUB activity. The levels of the lysine and serine ubiquitination of OTUB1 are further regulated by effectors that function to antagonize the activities of SidC, SdcA and SidEs, including Lem27, DupA, DupB, SidJ and SdjA. Our study reveals an effectors-mediated complicated mechanism in regulating the activity of a host DUB.Abbreviations: BafA1: bafilomycin A1; BMDMs: bone marrow-derived macrophages; DUB: deubiquitinase; Dot/Icm: defective for organelle trafficking/intracellular multiplication; DEPTOR: DEP domain containing MTOR interacting protein; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; L. pneumophila: Legionella pneumophila; LCV: Legionella-containing vacuole; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MOI: multiplicity of infection; MTORC1: mechanistic target of rapamycin kinase complex 1; OTUB1: OTU deubiquitinase, ubiquitin aldehyde binding 1; PR-Ub: phosphoribosyl (PR)-linked ubiquitin; PTM: posttranslational modification; SDS-PAGE: sodium dodecyl sulfate-polyacrylamide gel electrophoresis; SidEs: SidE family effectors; Ub: ubiquitin.

Whole-course quality of tuberculosis (TB) care in rural China: a retrospective study based on chart abstraction.

OBJECTIVES: The aim of this study was to assess the quality of tuberculosis (TB) care for the whole course and assess factors that affect completing treatment. DESIGN: This is an observational retrospective study using chart abstraction for the whole course of TB care conducted at two underserved provinces in China. SETTING: The study was conducted from June 2021 to July 2021. All medical records (outpatient and inpatient) for the whole course (6-8 months) of patients with TB newly registered from July 2020 to December 2020 were reviewed and abstracted using predetermined checklists. PARTICIPANTS: A total of 268 outpatient medical records and 126 inpatient records were included. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome included diagnostic quality, treatment quality and management quality. The secondary outcome was completing treatment. RESULTS: For diagnostic quality, 94.2% of the diagnosis were based on adequate evidence. For treatment quality, 240 (91.6%) outpatients and 100 (85.5%) inpatients took the standard chemotherapy regimens. 234 (87.3%) patients completed treatment. 85.1% of the inpatients prescribed with second-line drugs were inappropriate. For management quality, 128 (47.9%) patients received midterm assessments, but only 47 (19.7%) received sufficient services for the whole course. Patients with TB symptoms were 1.8 times more likely to complete treatment (p=0.011). CONCLUSION: Patients with TB received high-quality diagnosis and treatment services, but low-quality whole-course management. Integration of medical and public health services should be strengthened to improve whole-course quality.

Data on hematological parameters and generalized severe periodontitis in the United States.

This article describes an ensemble of datasets used to understand the relationship between generalized severe periodontitis and hematological parameters. This dataset combines public periodontal examination data, hematological parameters data, and demographic data from the National Center for Health Statistics from 2009 to 2014. The stage of periodontitis was identified by attachment loss conducted by dental examiners, who were dentists (D.D.S./ D.M.D.) licensed in at least one U.S. state, while matching current classification criteria from the American Academy of Periodontology and the European Federation of Periodontology. Based on the NHANES database, information on age, gender, education level (< 9th grade, 9-11th grade, high school, college, graduate), race/ethnicity (Mexican American, Hispanic, non-Hispanic White, non-Hispanic Black, and other races), PIR (poverty income ratio) were acquired from the demographic data. Hematological parameters (including HB, HCT, mean cell volume, mean cell hemoglobin, mean cell hemoglobin concentration, red cell distribution width, platelet count, mean platelet volume, and red blood cell count) and glucose data had been obtained from laboratory data. Smoking data had been obtained from questionnaire data.

Targeting Notch signaling pathways with natural bioactive compounds: a promising approach against cancer.

Notch signaling pathway is activated abnormally in solid and hematological tumors, which perform essential functions in cell differentiation, survival, proliferation, and angiogenesis. The activation of Notch signaling and communication among Notch and other oncogenic pathways heighten malignancy aggressiveness. Thus, targeting Notch signaling offers opportunities for improved survival and reduced disease incidence. Already, most attention has been given to its role in the cancer cells. Recent research shows that natural bioactive compounds can change signaling molecules that are linked to or interact with the Notch pathways. This suggests that there may be a link between Notch activation and the growth of tumors. Here, we sum up the natural bioactive compounds that possess inhibitory effects on human cancers by impeding the Notch pathway and preventing Notch crosstalk with other oncogenic pathways, which provoke further study of these natural products to derive rational therapeutic regimens for the treatment of cancer and develop novel anticancer drugs. This review revealed Notch as a highly challenging but promising target in oncology.