Prevalence of aeroallergen sensitization in children in Northern China.

OBJECTIVE: This study aimed to analyze the sensitization rate of different aeroallergens in children of different age, sex, and disease groups, describe the changing trend of different aeroallergens in different ages, and analyze the sensitization risk factors for asthma. METHODS: Children (<18 years old) with suspected atopic diseases who visited the Department of Allergy of Children's Hospital Affiliated to Capital Institute of Pediatrics and underwent a skin prick test (SPT) were retrospectively enrolled from January 2019 to November 2021. RESULTS: A total of 5465 patients (3514 boys, 1951 girls; mean age, 7 ± 3 years) were enrolled. Of them, 3703 patients (67.8%) were sensitized to at least one aeroallergen. Before 4 years of age, mold was the most prevalent aeroallergen (103/380 [27.1%]), whereas after 4 years of age, weed pollen was the most prevalent aeroallergen. After 6 years of age, tree pollen became the second most prevalent aeroallergen. After 12 years of age, the sensitization rate of indoor aeroallergens was lower than that of outdoor aeroallergens. Logistic regression showed that sensitization to mold (odds ratio [OR]:1.4, 95% confidence interval (CI): 1.2-1.7, p < 0.001), animal dander (OR: 1.6, 95% CI: 1.4-1.9, p < 0.001), and polysensitization (OR: 1.4, 95% CI: 1.0-1.8, p = 0.038) were potential sensitization risk factors for asthma. CONCLUSIONS: Mold is an important allergen in early life. Different kinds of allergens affect different age groups. Patients who are sensitized to mold or animal dander or experience polysensitization should be carefully monitored for asthma risk.

Serum levels of specific IgE to cow's milk and its components as predictors of anaphylaxis in Chinese children with cow's milk allergy.

BACKGROUND: Cow's milk allergy (CMA) is one of the most common food allergies in young children. As improved diagnostic tools, allergic tests are inconsistent and limited in predicting anaphylaxis. OBJECTIVE: To explore risk factors for anaphylaxis and to determine practical cut-offs for allergic tests in predicting anaphylaxis. METHODS: This is a prospective cohort study. Children with IgE-mediated CMA were enrolled and divided into three groups (Group 1: non-anaphylaxis; Group 2: GRADE I anaphylaxis; Group 3: GRADE II-IV anaphylaxis that warranted epinephrine). Prick-to-prick tests (PTPs) using fresh cow's milk (CM) were performed. Serum specific IgE (sIgE) against CM and its components, including casein, alpha-lactalbumin, beta-lactoglobulin, and bovine serum albumin were measured. The 90% and 95% positive predictive value (PPV) decision points for predicting anaphylaxis were determined. Potential predictors of anaphylaxis were evaluated in logistic regression models. RESULTS: This study included 134 CMA patients with a median age of 14.4 months. The sensitization rate to any CM component was 89%. Group 3 was more likely to be sensitized to multiple CM components and have higher sIgE levels. The 95% PPV diagnostic decision points of casein-sIgE in predicting anaphylaxis was 13.0 kUA/L. For GRADE II-IV anaphylaxis, casein-sIgE ≥ 54.9 kUA/L could provide a PPV of 88.9%. The elevated casein-sIgE level (OR 14.0, P=0.025) and complicating respiratory allergic diseases (OR 4.8, P=0.022) were independent risk factors for GRADE II-IV anaphylaxis. CONCLUSION: High casein-sIgE levels are strongly associated with CM anaphylaxis. Detection of casein-sIgE may offer an additional value for the prediction of CM anaphylaxis.

Profile of Tissue Immunoglobulin E in Eosinophilic Chronic Rhinosinusitis with Nasal Polyps.

INTRODUCTION: Eosinophilic chronic rhinosinusitis with nasal polyps (eCRSwNP) exhibits a poorer prognosis than noneCRSwNP. The aim of this study was to analyze the potential of total immunoglobulin E (tIgE) and specific IgE (sIgE) levels in tissues for distinguishing and assessing eCRSwNP. METHODS: We enrolled 10 control and 88 CRSwNP patients. The clinical data of patients were collected before surgery. Nasal mucosa tissues were taken during surgery for measurements of tIgE, sIgE (weed pollen, epidermal and animal protein, mold, house dust, tree pollen), and subepithelial eosinophil (EOS) counts. The predictive significance of the potential predictors for eCRSwNP was assessed with receiver operating characteristic (ROC) curves. RESULTS: Nasal polyps tIgE and mold-sIgE were positively correlated with blood and tissue EOSs, comorbid allergic rhinitis and asthma, ethmoid score/total maxillary score ratio, visual analog scale, and CT score. The ROC curve analysis showed that tissue tIgE (p = 0.0004), mold-sIgE (p = 0.0030), blood EOS percentage (p = 0.0003), and absolute blood EOS count (p = 0.0010) acted as predictive factors for eCRSwNP. According to the cutoff value of tissue tIgE of 34.55 ku/L, patients with a high level were more likely to suffer from asthma (p = 0.016) and showed a significantly higher EOS count (p = 0.022), EOS percentage (p = 0.029), and tIgE (p = 0.002) in blood. CONCLUSION: Tissue tIgE and mold-sIgE had a significant relationship with the clinical and pathological characteristics of CRSwNP patients and might be reliable for distinguishing and assessing eCRSwNP.

Atypical asthma in children who present with isolated chest tightness: risk factors and clinical features.

ObjectiveAsthmatic children presenting with chest tightness as the only symptom have not been widely recognized. This study attempted to find risk factors, summarize clinical features and offer some suggestions for the diagnosis of this atypical asthma.Methods: We studied 94 children, aged 6 to 14 years, who complained only of chest tightness. Data from clinical manifestations and laboratory tests were analyzed. The atypical asthma group (n = 58) showed positive bronchial challenge tests, and symptoms either improved or resolved in response to the bronchodilator. The control group (n = 36) had negative results on the bronchial challenge, diurnal PEF, and BDR tests, and no response to asthma treatment with bronchodilator.Results: Pollution, weather, recent house renovation, and air-conditioning use may be risk factors for children with atypical asthma. These children had more accompanying symptoms of rhinitis and rhinitis family history (P < 0.05), and a higher positive detection rate of inhaled allergens and multiple sensitizations. Parameters of the pulmonary function test were lower in the atypical asthma group than in the control group, and they also had higher FeNO values. If a cutoff value of improvement in FEV1 of BDR were set at 8.9%, sensitivity would be 48.2%, which is higher than a 12% cutoff.Conclusions: Environmental factors appeared to cause development of the isolated chest tightness symptom. Clinical history and laboratory tests could provide partial values for this diagnosis. In the absence of a bronchial challenge test, a margin of improvement in FEV1 of BDR set at 8.9% may be helpful.

Artificial neural network for cytocompatibility and antibacterial enhancement induced by femtosecond laser micro/nano structures.

The failure of orthopedic and dental implants is mainly caused by biomaterial-associated infections and poor osseointegration. Surface modification of biomedical materials plays a significant role in enhancing osseointegration and anti-bacterial infection. In this work, a non-linear relationship between the micro/nano surface structures and the femtosecond laser processing parameters was successfully established based on an artificial neural network. Then a controllable functional surface with silver nanoparticles (AgNPs) to was produced to improve the cytocompatibility and antibacterial properties of biomedical titanium alloy. The surface topography, wettability, and Ag+ release were carefully investigated. The effects of these characteristics on antibacterial activity and cytocompatibilty were also evaluated. Results show that the prepared surface is hydrophobic, which can prevent the burst release of Ag+ in the initial stage. The prepared surface also shows both good cytocompatibility toward the murine calvarial preosteoblasts MC3T3-E1 cells (derived from Mus musculus (mouse) calvaria) and good antibacterial effects against Gram-negative (E. coli) and Gram-positive (S. aureus) bacteria, which is caused by the combined effect of appropriate micro/nano-structured feature and reasonable Ag+ release rate. We do not only clarify the antibacterial mechanism but also demonstrate the possibility of balancing the antibacterial and osteointegration-promoting properties by micro/nano-structures. The reported method offers an effective strategy for the patterned surface modification of implants.

[Evaluation of Mental Workload in Working Memory Tasks with Different Information Types Based on EEG].

OBJECTIVE: Exploring the effectiveness of using EEG linear and nonlinear features for accessing mental workload in different tasks. METHODS: Working memory tasks with different information types and various mental loads were designed based on N-Back paradigm. EEG signals from 18 normal adults were acquired when tasks were being performed. Linear and nonlinear features of EEGs were then extracted. Indices that can effectively reflect mental workload levels were selected by using multivariate analysis of variance statistical approach. RESULTS: With the increment of task load, power of frontal Theta, Theta/Alpha ratio, and sample entropies (scales>10) in parietal regions increased significantly first and decreased slightly then, while the power of central-parietal Alpha decreased significantly first and increased slightly then. No difference in power of frontal Theta, central-parietal Alpha, and sample entropies (scales>10) of parietal regions were found between verbal and object tasks, as well as between two spatial tasks. No difference of frontal Theta/Alpha ratio was found in all the four tasks. CONCLUSIONS: The results can provide evidence for the mental workload evaluation in tasks with different information types.

Grating-enabled high-speed high-efficiency surface-illuminated silicon photodiodes.

High-speed, high-efficiency silicon photodetectors play important roles in the optical communication links that are used increasingly in data centers to handle the increasing volumes of data traffic and higher bandwidths required as use of big data and cloud computing continues to grow exponentially. Monolithic integration of the optical components with signal processing electronics on a single silicon chip is of paramount importance in the drive to reduce costs and improve performance. Here we report grating-enhanced light absorption in a silicon photodiode. The absorption efficiency is determined theoretically to be as high as 77% at 850 nm for the optimal structure, which has a thin intrinsic absorption layer with a thickness of 220 nm. The fabricated devices demonstrate a high bandwidth of 11.3 GHz and improved radio-frequency output power of more than 14 dB, thus making them suitable for use in data center optical communications.

Retrospective analysis of epidemic thunderstorm asthma in children in Yulin, northwest China.

BACKGROUND: An epidemic of thunderstorm asthma in pediatric patients occurred in Yulin, a northwest city of China, on 11 September 2018. We described the epidemic and retrospectively analyzed the demographic and clinical aspects of the involved children. METHODS: The caseload data of patients were collected from the hospital information system in Yulin Pediatric Hospital. The detailed document of hospitalized children with thunderstorm asthma was sourced from the medical records. RESULTS: The mean number of daily visits to emergency/outpatient department and the daily admission to hospital were 2.7 and 16 times, respectively, than on the other days of September. A gender prominence of males was observed in both emergency/outpatient and inpatient department. Among the 51 hospitalized children with detailed medical records, 56% of them had never experienced or were diagnosed with asthma and 25% had confirmed diagnosis of asthma. Sixty-seven percent had a history of allergic rhinitis during August and September. Seventy-six percent of the hospitalized children presented as moderate asthma. Ninety-four percent of the pediatric patients had positive IgE against mugwort pollen and 78% were monosensitized to pollen. CONCLUSION: Thunderstorm asthma can affect children, especially who has allergic rhinitis or asthma without preventive management. Mugwort is also an aeroallergen in thunderstorm asthma attacks. IMPACT: Thunderstorm can induce asthma attacks in children with allergic rhinitis owing to mugwort and aggravate symptoms in children with confirmed diagnosis of asthma. Children with mugwort allergy are susceptible to thunderstorm asthma and a preponderance of boys was observed. Better identification of allergic children to mugwort, giving suitable protective measures during thunderstorm and standard therapy to existing allergic situation could be a benefit for children at risk of thunderstorm asthma.

Levels of nasal exhaled hydrogen sulfide in the general population and allergic rhinitis patients.

BACKGROUND: Objective measures used for the differential diagnosis and severity assessment of allergic rhinitis (AR) are still lacking. The involvement of hydrogen sulfide (H2 S) in the development of AR indicates that nasal exhaled H2 S (NeH2 S) has potential as a biomarker to be used in AR patients. This study aimed to evaluate the application value of NeH2 S measurement in the diagnosis and assessment of AR. METHODS: This study was a multi-center cross-sectional survey conducted in Northwestern China. Demographic information collection and rhinitis assessment were completed through questionnaires. The level of NeH2 S and serum immunoglobulin E were measured. RESULTS: The level of NeH2 S in general population ranged from 0 to 35 ppb, with a median value of 2 ppb. The NeH2 S levels in seasonal allergic rhinitis (SAR) patients were significantly lower than those in general population (2 [1, 2.75] vs. 2 [2, 3] ppb; p = .023), and the NeH2 S value of the SAR group tended to be lower than that of the non-allergic rhinitis (NAR) group (2 [1, 2.75] vs. 2 [2, 3] ppb; p = .094). The subgroup of AR patients with symptoms lasting longer than 2 weeks per month had a lower NeH2 S level compared with the subgroup of patients with symptoms lasting less than 2 weeks per month (2 [1, 2] vs. 2 [2, 3] ppb; p = .015). CONCLUSION: This study described the distribution range of NeH2 S levels in the general population. Further study with larger sample size was needed to clarify the relationship between NeH2 S level and AR.

The deadly coronaviruses: The 2003 SARS pandemic and the 2020 novel coronavirus epidemic in China.

The 2019-nCoV is officially called SARS-CoV-2 and the disease is named COVID-19. This viral epidemic in China has led to the deaths of over 1800 people, mostly elderly or those with an underlying chronic disease or immunosuppressed state. This is the third serious Coronavirus outbreak in less than 20 years, following SARS in 2002-2003 and MERS in 2012. While human strains of Coronavirus are associated with about 15% of cases of the common cold, the SARS-CoV-2 may present with varying degrees of severity, from flu-like symptoms to death. It is currently believed that this deadly Coronavirus strain originated from wild animals at the Huanan market in Wuhan, a city in Hubei province. Bats, snakes and pangolins have been cited as potential carriers based on the sequence homology of CoV isolated from these animals and the viral nucleic acids of the virus isolated from SARS-CoV-2 infected patients. Extreme quarantine measures, including sealing off large cities, closing borders and confining people to their homes, were instituted in January 2020 to prevent spread of the virus, but by that time much of the damage had been done, as human-human transmission became evident. While these quarantine measures are necessary and have prevented a historical disaster along the lines of the Spanish flu, earlier recognition and earlier implementation of quarantine measures may have been even more effective. Lessons learned from SARS resulted in faster determination of the nucleic acid sequence and a more robust quarantine strategy. However, it is clear that finding an effective antiviral and developing a vaccine are still significant challenges. The costs of the epidemic are not limited to medical aspects, as the virus has led to significant sociological, psychological and economic effects globally. Unfortunately, emergence of SARS-CoV-2 has led to numerous reports of Asians being subjected to racist behavior and hate crimes across the world.

In vitro evaluation of ultrafast laser drilling large-size holes on sheepshank bone.

Bone drilling has been widely used in medical surgeries such as repair and fixation in orthopedics. Traditional drilling method using drill-bits inevitably causes significant thermal and mechanical trauma in the adjacent bone tissues. This paper demonstrates the feasibility of femtosecond laser drilling in vitro large-size holes on the sheepshank bone with high efficiency and minimal collateral damage. A Yb:KGW femtosecond laser was utilized to drill millimeter-scale holes on the bone under different cooling conditions including gas- and water-assisted processes. Scanning electron microscopy, confocal laser scanning microscopy and infrared thermographic imaging system were used to investigate the residual debris, removal rate, bone temperature variation and hole morphology. Histological examination, Fourier transform infrared spectroscopy and Raman spectroscopy were employed to study thermal damage. Results show that a 4 mm hole with smooth and clean surface was successfully drilled on the bone, and the highest removal rate of 0.99 mm3/s was achieved, which was twenty times higher than the previous study of 0.05 mm3/s. Moreover, bone and bone marrow were distinguished by real-time monitoring system during laser drilling. This work demonstrates the potential for clinical applications using an ultrafast laser to produce crack-free large-size bone holes.

Yersinia YopT inhibits RLH-mediated NF-κB and IRF3 signal transduction.

The Gram-negative bacterial pathogen Yersinia delivers six effector proteins into the host cells to block the host innate immune response. One of the effectors, YopT, is a potent cysteine protease that causes the disruption of the actin cytoskeleton to inhibit phagocytosis of the pathogen; however, its molecular mechanism and relevance to pathogenesis need further investigation. In this report, we show that RIG-I is a novel target of the YopT protein. Remarkably, YopT interacts with RIG-I and inhibits rat liver homogenate-mediated nuclear factor-κB and interferon regulatory factor-3 activation. Further studies revealed a YopT-dependent increase in the K48-polymerized ubiquitination of RIG-I. These findings suggest that YopT negatively regulates RIG-I-mediated cellular antibacterial response by targeting RIG-I.

Thermal tolerance of dried shoots of the moss Bryum argenteum.

We conducted laboratory experiments to determine the lethal temperatures of the shoots of dried Bryum argenteum and to determine how this restoration species responds to extreme environments. We specifically assessed changes in gene expression levels in the shoots of dried B. argenteum plants that were subjected to sudden heat shock (control (20 ± 2°C), 80°C, 100°C, 110°C or 120°C) followed by exposure to heat for an additional 10, 20, 30 or 60 min. After they were exposed to heat, the samples were placed in wet sand medium, and their survival and regeneration abilities were evaluated daily for 56 days. The results showed that lethal temperatures significantly reduced the shoot regeneration potential, delayed both shoot and protonemal emergence times and reduced the protonemal emergence area. In addition, the expression of nine genes (HSF3, HSP70, ERF, LEA, ELIP, LHCA, LHCB, Tr288 and DHN) was induced by temperature stress, as assessed after 30 min of exposure. Additionally, a new thermal tolerance level for dried B. argenteum - 120°C for 20 min - was determined, which was the highest temperature recorded for this moss; this tolerance exceeded the previous record of 110°C for 10 min. These findings help elucidate the survival mechanism of this species under heat shock stress and facilitate the recovery and restoration of destroyed ecosystems.

Clinical efficacy of targeted injection of drugs in combination with ozone in treatment of lumbar disc protrusion.

To investigate the clinical efficacy of targeted injection of drugs surrounding the protruded lumbar disc in combination with the ozone in treatment of lumbar disc protrusion. Between January 2017 and January 2019, a total of 120 patients with lumbar disc protrusion were recruited in this study and divided into the control group and observation group, with 60 patients in each group. Patients in the control group received the ozone treatment, while those in the observation group additionally took the targeted injection of betamethasone surrounding the protruded lumbar disc. Following one month of treatment, we compared the short-term efficacy, joint range of motion in bending forward or backward of the lumbar disc, limb function, life quality and functional disturbance before and after treatment. In the observation group, the short-term effectiveness rate was higher than that in the control group (P<0.05), while after treatment, the joint range of motion in bending forward or backward of lumbar disc in the observation group was improved when comparing to the control group (P<0.05). After treatment, BI and Fugl-Meyer scale were all higher in the observation than those in the control group (P<0.05), with a lower Oswestry score (P<0.05). Targeted injection of betamethasone surrounding the protruded lumbar disc in combination with the ozone performs well in short-term efficacy, conducive to the improvement of the lumbar disc function and limb function and alleviation in function disturbance. Thus, this strategy is worthy of being promoted in clinical practice.

Metal-Organic Coordination Strategy for Obtaining Metal-Decorated Mo-Based Complexes: Multi-dimensional Structural Evolution and High-Rate Lithium-Ion Battery Applications.

Multi-dimensional metal oxides have attracted great attention in diverse applications due to their intriguing performances. However, their structural design remains challenging, particularly that based on organic chelation chemistry. Although metal-organic complexes with different architectures have been reported, their structure formation mechanisms are not well understood because of the complex chelation processes. Herein, we introduce a new metal-organic coordination strategy to construct metal-decorated (Ni, Co, Mn) Mo-based complexes ranging from 2D nanopetals to 3D microflowers. The chelating process of the metal-organic complex can be tuned by a surfactant, giving rise to different structures, and then a further metal can be appended. Thus, different metal (oxide)-decorated MoO2 /C-N structures were designed, enabling an extremely high lithium storage capability of 1018 mA h g-1 and rate capacities of up to 10 A g-1 over 1000 cycles. Relationships between electrochemical behavior and structure have been analyzed kinetically. A high-rate lithium-ion battery has been assembled from Ni-MoO2 /C-N and an Ni-rich layered oxide as the anode and cathode, respectively. We believe that this general metal-organic coordination strategy should be applicable to other multi-functional materials with superior capabilities.

Carrier Tuning in ZnSnN2 by Forming Amorphous and Microcrystalline Phases.

ZnSnN2 (ZTN), an earth-abundant element semiconductor, is a potential candidate for photovoltaic applications. However, the excessively high n-type carrier concentration caused by intrinsic defects hinders its progress. In this work, a series of Zn1± xSnN2 thin films are fabricated by RF-magnetron sputtering deposition. The zinc-rich composition is found to promote the crystallization of ZTN. As a main source of n-type carriers in the zinc-rich thin films, the interstitial Zn dominates the change of carrier concentration with an increase in the Zn/Sn ratio. Near the stoichiometric ratio, amorphous ZTN (a-ZTN) thin films are fabricated, and the n-type carrier concentration is suppressed to 1016 cm-3. With an increase in the Zn/Sn ratio from 0.9 to 1.3, the n-type carrier concentration can be tuned in the range 1016-1019 cm-3, accompanied by the phase-transition from a-ZTN to microcrystalline ZTN (µc-ZTN). For the a-ZTN thin film, the carrier mobility reaches up to 7 cm2 V-1 s-1, and the photoresponse covers almost the whole visible band. The above properties demonstrate that a-ZTN and µc-ZTN are potential candidates for photovoltaic applications.

A comparative study on short-term therapeutic effects of percutaneous transforaminal endoscopic discectomy and microendoscopic discectomy on lumbar disc herniation.

OBJECTIVE: To find out the short-term effects of percutaneous transforaminal endoscopic discectomy (PTED) and microendoscopic discectomy (MED) on lumbar disc herniation (LDH). METHODS: Ninety LDH patients treated in PLA Army General Hospital from July 2015 to July 2016 were selected and randomly divided into an MED group and a PTED group. Length of incision, amount of intraoperative bleeding, surgical time, number of times using intraoperative fluoroscopy, postoperative bedridden time, hospital stay, together with visual analogue scale (VAS) and Oswestry disability index (ODI) scores before surgery, three days, three months and six months after surgery were analyzed. RESULTS: As regards the length of surgical incision, amount of bleeding, postoperative bedridden time and hospital stay, the PTED group was significantly superior to the MED group ((P=0.000, 0.000, 0.000, 0.001, respectively)). Compared with the PTED group, the MED group used less fluoroscopy and had shorter surgical time (P=0.001, 0.000, respectively). The postoperative VAS and ODI scores of both groups were significantly improved compared with those before surgery (P<0.000, 0.000, respectively). The short-term postoperative low back pain (LBP) VAS score of PTED group was lower than that of MED group (P=0.001). The two groups had similar leg pain (LP) VAS score three and six months after surgery, postoperative and follow-up LP VAS and ODI scores, and surgical improvement rate (P=0.093, 0.097, respectively). CONCLUSION: LDH was effectively treated by both PTED and MED. Compared with MED, PTED had less trauma, less blood loss, and faster recovery after surgery.

Coexistence of rectangular and Gaussian-shape noise-like pulses in a figure-eight fiber laser.

We experimentally report the coexistence of the rectangular noise-like pulse (NLP) and the Gaussian-shape NLP in a figure-eight fiber laser. Benefiting from the strengthened nonlinear effect of a segment of highly nonlinear fiber (HNLF) in the cavity, the coexistent NLPs with various patterns, i.e. one rectangular pulse with one Gaussian-shape pulse, one rectangular pulse with two Gaussian-shape pulses and two rectangular pulses with one Gaussian-shape pulse, are formed depending on the cavity parameters setting. In particular, the evolution of these coexistent NLPs properties with pump power is investigated. It is found that the duration of the rectangular pulse always increases, while the Gaussian-shape pulse has almost no changes with the increasing pump power. The achieved results demonstrated for the first time, to the best of our knowledge, the pulses with different shapes can coexist under the NLP regime, which contributes to further understanding the fundamental characteristics of the NLPs and multiple pulses.

Bacterial E3 Ubiquitin Ligase IpaH4.5 of Shigella flexneri Targets TBK1 To Dampen the Host Antibacterial Response.

IFN regulatory factors play a pivotal role in many cellular processes, including inflammatory and immune responses. Their activation is tightly regulated by TANK-binding kinase 1 (TBK1). In response to microbial components, TBK1 activates IFN regulatory factor 3 (IRF3) and cytokine expression. In this article, we show that TBK1 is a novel target of the IpaH4.5 protein, a Shigella type III effector possessing E3 ubiquitin ligase activity. Remarkably, IpaH4.5 interacts with TBK1 and promotes its K48-linked polyubiquitylation. Consequently, polyubiquitylated TBK1 undergoes proteasome-dependent degradation, which perturbs the phosphorylation, nuclear translocation, and activation of IRF3. Because IRF3 and TBK1 are required for restricting Shigella growth, we propose that the polyubiquitylation and degradation of TBK1 during Shigella infection are new bacterial strategies to modulate the host antibacterial responses.

Yersinia YopJ negatively regulates IRF3-mediated antibacterial response through disruption of STING-mediated cytosolic DNA signaling.

The Yersinia outer protein J (YopJ) plays a pivotal role in evading the host immune response and establishes a persistent infection in host cells after bacterial infection. YopJ is a cysteine protease and can act as a deubiquitinating enzyme that deubiquitinates several targets in multiple signaling pathways. Stimulator of interferon genes (STING) is a critical adapter for the induction of interferon regulatory factor 3 (IRF3) phosphorylation and subsequent production of the cytokines in response to nucleic acids in the cytoplasm. Our studies demonstrate that YopJ targets STING to inhibit IRF3 signaling. Specially, YopJ interacts with STING to block its ER-to-Golgi traffic and remove its K63-linked ubiquitination chains. Deubiquited STING perturbs the formation of STING-TBK1 complex and the activation of IRF3. The 172th cysteine of YopJ mediated STING deubiquitination and IRF3 signaling inhibition. Consequently, mice infected with WT and ΔYopJ/YopJ bacteria induced lower levels of IRF3 and IFN-ß, decreased inflammation and reduced staining of STING as compared to ΔYopJ and ΔYopJ/YopJ C172A strains infection. The data herein reveal a previously unrecognized mechanism by which YopJ modulates innate immune signaling.