Endoplasmic reticulum stress-related protein GRP78 and CHOP levels in synovial fluid correlate with disease progression of primary knee osteoarthritis: A cross-sectional study.

BACKGROUND: Endoplasmic reticulum (ER) stress has been shown to play an important role in osteoarthritis (OA). OBJECTIVE: This study was aimed at assessing the relationship of endoplasmic reticulum (ER) stress-related glucose-regulated protein 78 (GRP78) and CCAAT/enhancer-binding protein homologous protein (CHOP) concentrations in the serum/synovial fluid (SF) with disease severity of primary knee osteoarthritis (pkOA). METHODS: Patients with pkOA together with healthy individuals were consecutively recruited from our hospital. The levels of GRP78 and CHOP in serum / SF were detected using enzyme-linked immunosorbent assay. The levels of IL-6 and MMP-3 were also examined. Radiographic progression of pkOA was evaluated based on Kellgren-Lawrence (K-L) grades. Receiver Operating Characteristic (ROC) curves were used to assess the diagnostic value of GRP78/CHOP levels with regard to K-L grades. The assessment of clinical severity was conducted using the visual analogue scale (VAS), Oxford knee score (OKS), and Lequesne algofunctional index (LAI). RESULTS: A total of 140 pkOA patients and 140 healthy individuals were included. Serum GRP78 and CHOP levels in pkOA patients were not significantly different from those in healthy individuals. The SF GRP78 and CHOP levels in healthy controls were not detected due to ethical reasons. Compared to those with K-L grade 2 and 3, the pkOA patients with K-L grade 4 had higher GRP78 and CHOP levels in the SF with statistical significance. In addition, the pkOA patients with K-L grade 3 exhibited drastically upregulated GRP78 and CHOP concentrations in the SF compared to those with K-L grade 2. Positive correlations of GRP78 and CHOP levels with K-L grades, IL-6, and MMP-3 levels in the SF were observed. ROC curve analysis indicated that both GRP78 and CHOP levels may act as decent indicators with regard to OA. GRP78 and CHOP concentrations in the SF were positively correlated with VAS/LAI score and negatively associated with OKS score. CONCLUSION: The study indicated that GRP78 and CHOP levels in the SF but not the serum were positively correlated with disease severity of pkOA.

Recent trends in preparation and biomedical applications of iron oxide nanoparticles.

The iron oxide nanoparticles (IONPs), possessing both magnetic behavior and semiconductor property, have been extensively used in multifunctional biomedical fields due to their biocompatible, biodegradable and low toxicity, such as anticancer, antibacterial, cell labelling activities. Nevertheless, there are few IONPs in clinical use at present. Some IONPs approved for clinical use have been withdrawn due to insufficient understanding of its biomedical applications. Therefore, a systematic summary of IONPs' preparation and biomedical applications is crucial for the next step of entering clinical practice from experimental stage. This review summarized the existing research in the past decade on the biological interaction of IONPs with animal/cells models, and their clinical applications in human. This review aims to provide cutting-edge knowledge involved with IONPs' biological effects in vivo and in vitro, and improve their smarter design and application in biomedical research and clinic trials.

Single-worm quantitative proteomics reveals aging heterogeneity in isogenic Caenorhabditis elegans.

The heterogeneity of aging has been investigated at cellular and organic levels in the mouse model and human, but the exploration of aging heterogeneity at whole-organism level is lacking. C. elegans is an ideal model organism for studying this question as they are self-fertilized and cultured in the same chamber. Despite the tremendous progress made in single-cell proteomic analysis, there is few single-worm proteomics studies about aging. Here, we apply single-worm quantitative mass spectrometry to quantify the heterogenous proteomic changes during aging across individuals, a total of 3524 proteins from 157 C. eleagns individuals were quantified. A reconstructed C. elegans aging trajectory and proteomic landscape of fast-aging individuals were used to analyze the heterogeneity of C. elegans aging. We characterized inter-individual proteomic variation during aging and revealed contributing factors that distinguish fast-aging individuals from their siblings.

Betaine prevents cognitive dysfunction by suppressing hippocampal microglial activation in chronic social isolated male mice.

Chronic social isolation (SI) stress, which became more prevalent during the COVID-19 pandemic, contributes to abnormal behavior, including mood changes and cognitive impairment. Known as a functional nutrient, betaine has potent antioxidant and anti-inflammatory properties in vivo. However, whether betaine can alleviate the abnormal behavior induced by chronic SI in mice remains unknown. In this study, we investigated the efficacy of betaine in the treatment of behavioral changes and its underlying mechanism. Three-week-old male mice were randomly housed for 8 weeks in either group housing (GH) or SI. The animals were divided into normal saline-treated GH, normal saline-treated SI, and betaine-treated SI groups in the sixth week. The cognitive and depression-like behavior was determined in the eighth week. We found that long-term betaine administration improved cognitive behavior in SI mice but failed to prevent depression-like behavior. Moreover, long-term betaine administration inhibited hippocampal microglia over-activation and polarized microglia toward the M2 phenotype, which effectively inhibited the expression of inflammatory factors in SI mice. Finally, the protective effect of betaine treatment in SI mice might not be due to altered activity of the hypothalamic-pituitary-adrenal axis. Collectively, our findings reveal that betaine can improve SI-induced cognitive impairment, thus providing an alternative natural source for the prevention of memory loss caused by SI or loneliness.

IGF2/IGF2R/Sting signaling as a therapeutic target in DSS-induced ulcerative colitis.

Ulcerative colitis is an inflammatory bowel disease with increasing prevalence and incidence. Current treatments for ulcerative colitis are not generally applicative and are often accompanied by side effects. IGF2 is an endogenous protein that plays roles in anti-inflammation and stemness maintenance, but little is known about its mechanism and function in the progression of ulcerative colitis. In this study, mouse recombinant IGF2 was used in a mouse model of ulcerative colitis established by DSS. IGF2 expression was reduced in colon tissues but not plasma of DSS-induced colitis mice. IGF2R expression was also decreased in colitis colons, which was then elevated by recombinant IGF2. Recombinant IGF2 alleviated colon injury in colitis, which was evaluated by colon shortening, body weight loss and DAI score. IGF2 treatment also relieved the inflammatory response in colitis, which was assessed by the spleen weight index, MPO activity and proinflammatory cytokine expression and was also detected in LPS-stimulated RAW264.7 cells in vitro. Moreover, IGF2R was predicted and further verified to interact with the Sting protein, and the cGAS-Sting pathway as a key pathway for stemness regulation, was upregulated in colonic colons, which was blocked by IGF2 treatment. Additionally, IGF2 treatment can maintain colonic stemness and further repair colonic tight junction function in DSS-induced colitis. In conclusion, IGF2/IGF2R downregulated the cGAS-Sting pathway to sustain colonic stemness and barrier integrity to protect against ulcerative colitis induced by DSS.

Cell wall thickness has phylogenetically consistent effects on the photosynthetic nitrogen-use efficiency of terrestrial plants.

Leaf photosynthetic nitrogen-use efficiency (PNUE) diversified significantly among C3 species. To date, the morpho-physiological mechanisms and interrelationships shaping PNUE on an evolutionary time scale remain unclear. In this study, we assembled a comprehensive matrix of leaf morpho-anatomical and physiological traits for 679 C3 species, ranging from bryophytes to angiosperms, to comprehend the complexity of interrelationships underpinning PNUE variations. We discovered that leaf mass per area (LMA), mesophyll cell wall thickness (Tcwm ), Rubisco N allocation fraction (PR ), and mesophyll conductance (gm ) together explained 83% of PNUE variations, with PR and gm accounting for 65% of those variations. However, the PR effects were species-dependent on gm , meaning the contribution of PR on PNUE was substantially significant in high-gm species compared to low-gm species. Standard major axis (SMA) and path analyses revealed a weak correlation between PNUE and LMA (r2 = 0.1), while the SMA correlation for PNUE-Tcwm was robust (r2 = 0.61). PR was inversely related to Tcwm , paralleling the relationship between gm and Tcwm , resulting in the internal CO2 drawdown being only weakly proportional to Tcwm . The coordination of PR and gm in relation to Tcwm constrains PNUE during the course of evolution.

Comparison of the efficacy and safety of ultrasonic cycloplasty vs valve implantation and anti-VEGF for the treatment of fundus disease-related neovascular glaucoma.

AIM: To compare the clinical efficacy and safety of ultrasonic cycloplasty (UCP) vs Ahmed glaucoma drainage valve implantation (ADV) in addition to intravitreal anti-vascular endothelial growth factor (VEGF) for treatment of fundus disease-related neovascular glaucoma (NVG). METHODS: A total of 43 patients (45 eyes) with NVG secondary to fundus diseases underwent anti-VEGF combined with UCP or ADV from August 2020 to March 2022 were enrolled in this retrospective cohort study. Of them, 14 patients (15 eyes) were treated with both UCP and anti-VEGF as the UCP group and 29 patients (30 eyes) treated with both ADV and anti-VEGF as the ADV group. The success of the treatment was defined as intraocular pressure (IOP) between 11-20 mm Hg with or without using IOP-lowering drugs. IOP measurement, IOP lowering drugs at baseline and follow-ups period and complications were recorded. RESULTS: The average age was 63.03±9.95 and 52.27±12.89y in ADV and UCP groups, respectively (P=1.947). The fundus pathology included proliferative diabetic retinopathy in 42 eyes and retinal vein occlusion in 3 eyes. All eyes in both groups achieved successful treatment at 3mo. While the success rate was 90.0% (27/30) in the ADV group and 86.7% (13/15) in the UCP group at the last follow-up of 6mo (P>0.05). IOP was significantly lower with reduction of drug use than the baseline in both groups (both P<0.05). And the ADV group needed fewer anti-glaucoma drops than the UCP group from 1d to 3mo. The comfort scores of patients in the ADV group were significantly lower than those in the UCP group in the first week after the operation (P<0.05). CONCLUSION: UCP is an alternative to the ADV with the same efficacy but non-invasive for the treatment of NVG.

Tandem mass tag-based quantitative proteomics analyses of a chicken-original virulent and its attenuated Histomonas meleagridis strain in China.

Introduction: Histomonas meleagridis can cause histomonosis in poultry. Due to the prohibition of effective drugs, the prevention and treatment of the disease requires new strategies. Questions about its pathogenic mechanisms and virulence factors remain puzzling. Methods: To address these issues, a tandem mass tag (TMT) comparative proteomic analysis of a virulent strain and its attenuated strain of Chinese chicken-origin was performed. Results: A total of 3,494 proteins were identified in the experiment, of which 745 proteins were differentially expressed (fold change ≥1.2 or ≤0.83 and p < 0.05), with 192 up-regulated proteins and 553 down-regulated proteins in the virulent strain relative to the attenuated strain. Discussion: Surface protein BspA like, digestive cysteine proteinase, actin, and GH family 25 lysozyme were noted among the proteins up regulated in virulent strains, and these several proteins may be directly related to the pathogenic capacity of the histomonad. Ferredoxin, 60S ribosomal protein L6, 40S ribosomal protein S3, and NADP-dependent malic enzyme which associated with biosynthesis and metabolism were also noted, which have the potential to be new drug targets. The up-regulation of alpha-amylase, ras-like protein 1, ras-like protein 2, and involucrin in attenuated strains helps to understand how it is adapted to the long-term in vitro culture environment. The above results provide some candidate protein-coding genes for further functional verification, which will help to understand the molecular mechanism of pathogenicity and attenuation of H. meleagridis more comprehensively.

A Single Central Pattern Generator for the Control of a Locomotor Rolling Wave in Mollusc Aplysia.

Locomotion in mollusc Aplysia is implemented by a pedal rolling wave, a type of axial locomotion. Well-studied examples of axial locomotion (pedal waves in Drosophila larvae and body waves in leech, lamprey, and fish) are generated in a segmented nervous system via activation of multiple coupled central pattern generators (CPGs). Pedal waves in molluscs, however, are generated by a single pedal ganglion, and it is unknown whether there are single or multiple CPGs that generate rhythmic activity and phase shifts between different body parts. During locomotion in intact Aplysia, bursting activity in the parapedal commissural nerve (PPCN) was found to occur during tail contraction. A cluster of 20 to 30 P1 root neurons (P1Ns) on the ventral surface of the pedal ganglion, active during the pedal wave, were identified. Computational cluster analysis revealed that there are 2 phases to the motor program: phase I (centered around 168°) and phase II (centered around 357°). PPCN activity occurs during phase II. The majority of P1Ns are motoneurons. Coactive P1Ns tend to be electrically coupled. Two classes of pedal interneurons (PIs) were characterized. Class 1 (PI1 and PI2) is active during phase I. Their axons make a loop within the pedal ganglion and contribute to locomotor pattern generation. They are electrically coupled to P1Ns that fire during phase I. Class 2 (PI3) is active during phase II and innervates the contralateral pedal ganglion. PI3 may contribute to bilateral coordination. Overall, our findings support the idea that Aplysia pedal waves are generated by a single CPG.

Apomictic Malus plants exhibit abnormal pollen development.

Apomixis is the asexual reproduction through seeds that leads to the production of genetically uniform progeny. It has become an important tool in plant breeding because it facilitates the retention of genotypes with desirable traits and allows seeds to be obtained directly from mother plants. Apomixis is rare in most economically important crops, but it occurs in some Malus species. Here, the apomictic characteristics of Malus were examined using four apomictic and two sexually reproducing Malus plants. Results from transcriptome analysis showed that plant hormone signal transduction was the main factor affecting apomictic reproductive development. Four of the apomictic Malus plants examined were triploid, and pollen was either absent or present in very low densities in the stamen. Variation in the presence of pollen was associated with variation in the apomictic percentage; specifically, pollen was absent in the stamens of tea crabapple plants with the highest apomictic percentage. Furthermore, pollen mother cells failed to progress normally into meiosis and pollen mitosis, a trait mostly observed in apomictic Malus plants. The expression levels of meiosis-related genes were upregulated in apomictic plants. Our findings indicate that our simple method of detecting pollen abortion could be used to identify apple plants that are capable of apomictic reproduction.

Kounis syndrome caused by bee sting: a case report and literature review.

Kounis syndrome is defined as an acute coronary syndrome (ACS) secondary to allergic or hypersensitivity reactions. It can be further categorised into subtypes such as coronary vasospasms, acute myocardial infarction or stent thrombosis based on the pathogenesis. Kounis syndrome is most likely an underdiagnosed condition in China, given the many triggers reported in the literature. Herein, we report a case of Kounis syndrome, possibly triggered by a bee sting. The patient had late onset of angina symptoms with delayed diagnosis due to unfamiliarity with this condition. In patients with clinical signs of ACS that are superimposed on a hypersensitivity reaction, especially those with pre-existing cardiovascular risk factors, Kounis syndrome should be considered, so that appropriate assessment and treatment can be initiated. Prompt management of both the allergic reaction and the ACS is vital for Kounis syndrome.

Epigenetic modifications and metabolic memory in diabetic retinopathy: beyond the surface.

Epigenetics focuses on DNA methylation, histone modification, chromatin remodeling, noncoding RNAs, and other gene regulation mechanisms beyond the DNA sequence. In the past decade, epigenetic modifications have drawn more attention as they participate in the development and progression of diabetic retinopathy despite tight control of glucose levels. The underlying mechanisms of epigenetic modifications in diabetic retinopathy still urgently need to be elucidated. The diabetic condition facilitates epigenetic changes and influences target gene expression. In this review, we summarize the involvement of epigenetic modifications and metabolic memory in the development and progression of diabetic retinopathy and propose novel insights into the treatment of diabetic retinopathy.

Integrative genomic and transcriptomic profiling reveals distinct molecular subsets in adult mixed phenotype acute leukemia.

Mixed phenotype acute leukemia (MPAL) is a subtype of leukemia in which lymphoid and myeloid markers are co-expressed. Knowledge regarding the genetic features of MPAL is lacking due to its rarity and heterogeneity. Here, we applied an integrated genomic and transcriptomic approach to explore the molecular characteristics of 176 adult patients with MPAL, including 86 patients with T-lymphoid/myeloid MPAL (T/My MPAL-NOS), 42 with Ph+ MPAL, 36 with B-lymphoid/myeloid MPAL (B/My MPAL-NOS), 4 with t(v;11q23), and 8 with MPAL, NOS, rare types. Genetically, T/My MPAL-NOS was similar to B/T MPAL-NOS but differed from Ph+ MPAL and B/My MPAL-NOS. T/My MPAL-NOS exhibited higher CEBPA, DNMT3A, and NOTCH1 mutations. Ph+ MPAL demonstrated higher RUNX1 mutations. B/T MPAL-NOS showed higher NOTCH1 mutations. By integrating next-generation sequencing and RNA sequencing data of 89 MPAL patients, we defined eight molecular subgroups (G1-G8) with distinct mutational and gene expression characteristics. G1 was associated with CEBPA mutations, G2 and G3 with NOTCH1 mutations, G4 with BCL11B rearrangement and FLT3 mutations, G5 and G8 with BCR::ABL1 fusion, G6 with KMT2A rearrangement/KMT2A rearrangement-like features, and G7 with ZNF384 rearrangement/ZNF384 rearrangement-like characteristics. Subsequently, we analyzed single-cell RNA sequencing data from five patients. Groups G1, G2, G3, and G4 exhibited overexpression of hematopoietic stem cell disease-like and common myeloid progenitor disease-like signatures, G5 and G6 had high expression of granulocyte-monocyte progenitor disease-like and monocyte disease-like signatures, and G7 and G8 had common lymphoid progenitor disease-like signatures. Collectively, our findings indicate that integrative genomic and transcriptomic profiling may facilitate more precise diagnosis and develop better treatment options for MPAL.

Evaluation of Pelvic Floor Dysfunction by Pelvic Floor Ultrasonography after Total Hysterectomy for Cervical Cancer.

Objective: To study the value of pelvic floor ultrasonography in evaluating pelvic floor dysfunction (PFD) after total hysterectomy for cervical cancer. Methods: All the enrolled patients were given 4D pelvic floor ultrasound examination before and after surgery. The results of ultrasonic examination and the parameters of four-dimensional ultrasonic examination before and after surgery were analyzed, and the quality of life of the patients before and after surgery was evaluated. Results: Postoperatively, the posterior angle of bladder and urethra, the rotation angle of urethra, the decreased value of bladder neck, and the distance between bladder neck and pubic symphysis were (122.60 ± 9.53)°, (136.47 ± 14.67)°, (58.90 ± 18.19)°, (18.14 ± 7.32) mm, and (2.76 ± 0.46) cm, significantly greater than the preoperative (89.90 ± 9.59)°, (107.30 ± 9.96)°, (27.59 ± 10.96)°, (13.27 ± 5.69) mm, and (2.24 ± 0.21) cm (P < 0.05). Postoperative detrusor muscle thickness, bladder neck movement, residual urine volume, and bladder rotation angle (4.48 ± 0.82) mm, (0.64 ± 0.17) cm, (12.82 ± 2.69) ml, (12.11 ± 2.43)° were significantly higher than those of preoperative (3.70 ± 0.64) mm, (0.43 ± 0.18) cm, (4.83 ± 1.07) ml, (4.30 - 1.19)° (P < 0.05). The scores of emotional function, psychological function, social function, and physiological function were (2.35 ± 0.75) points, (2.45 ± 0.66) points, (2.30 ± 0.77) points, and (2.19 ± 0.71) points, significantly higher than those of (1.01 ± 0.50) points, (1.25 ± 0.54) points, and (1.00 ± 0.57) points before surgery, (1.05 ± 0.46) (P < 0.05). Conclusions: The application of pelvic floor ultrasonography to detect pelvic floor dysfunction after total hysterectomy can clearly display the anatomical structure of the pelvic floor, which is conducive to disease prevention and treatment. Four-dimensional pelvic floor ultrasound can clearly show the postoperative pelvic floor function, which is worthy of clinical promotion and reference.

Analysis of two naval pilots' ejection injuries: Two case reports.

BACKGROUND: Recently, two naval pilots in a two-seat trainer jet were forced to eject urgently due to sudden mechanical failure during night-time training. They were both successfully rescued and sent to the hospital for emergency treatment. In this study, we investigate their ejection injuries and recovery process. CASE SUMMARY: We analyzed the clinical data of the traumatic condition and recovery process from ejection injuries of two pilots who ejected from a failed trainer jet and survived. After being successfully rescued and sent to the hospital, they were diagnosed with multiple ejection injuries, including eye trauma, limb bone and joint injury, rib and spine injury, and so on. Both cases underwent fluid replacement, acid suppression, nutritional support, hemostasis, bone metabolism improvement, phlegm elimination, psychological measurement, blood circulation promotion and detumescence, physical therapy, and external fixation with braces for 1 mo before being discharged from hospital. They then recuperated in a sanatorium for 2 mo, and the related laboratory tests and supplementary examinations show that they recovered from all the above injuries. After successfully passing the psychological test and physical examination, they returned to flight duty 3 mo after ejection. CONCLUSION: The causes and conditions of ejection injury in the pilots were very complex. Although they finally recovered quickly and were released, it also serves as a reminder that attention should be paid to pilots' ejection and parachute training in order to significantly reduce ejection injury and improve the ejection success rate. In addition, air defense support personnel should strengthen search and rescue and on-site emergency measures, and locate and rescue pilots in distress as early as possible to reduce subsequent injuries.

Transvaginal natural orifice transluminal endoscopic surgery in gynecological procedure: Experience of a Women's and Children's Medical Center from China.

OBJECTIVE: To review of our hospital's experiences in transvaginal natural orifice transluminal endoscopic surgery (vNOTES) and challenges we encountered in performance of the procedure, so as to provide help to medical institutions who are preparing to carry out vNOTES. METHODS: We retrospectively analyzed the data of all patients receiving vNOTES in our hospital from April 2018 to May 2021. Data we collected cover the general characteristics, perioperative outcomes, and complications of the patients. RESULTS: A total of 1147 patients underwent vNOTES in the past 3 years at our hospital. The total numbers of adnexal surgery, myomectomy, hysterectomy, pelvic floor reconstruction surgery, and malignant tumor surgery performed via vNOTES were 902, 98, 82, 51, and 14, respectively. Eighteen patients were converted to transabdominal laparoscopic surgery. A total of 38 patients had complications according to Clavien-Dindo classification, and the total complication rate was 3.31%. Among these cases of complications, 27 were Grade I, 4 were Grade II, and 7 were Grade III. No complications of Grade IV or V were reported. CONCLUSION: The application of vNOTES is safe and feasible for most gynecological surgeries. Moreover, hospitals with traditional laparoscopic equipment are advised to try this technique as there is no need to purchase additional expensive equipment. However, since vNOTES represents a novel approach, the long-term complications and efficacy associated with this technique are pending to be verified through large-scale prospective multicenter randomized controlled studies.

Targeting PERK mediated endoplasmic reticulum stress attenuates neuroinflammation and alleviates lipopolysaccharide-induced depressive-like behavior in male mice.

Neuroinflammation plays a key role in the development of depression-like behaviors.Endoplasmic reticulum (ER) stress,defined as accumulation of unfolded proteins in the ER,is suggested tocollaboratewithinflammation process to drive sustained neuroinflammation. Protein kinase R-like endoplasmic reticulum kinase (PERK) is ofparticularly attractive target because it plays key rolein the regulation of ER stress-induced neuroinflammation, however, little isknown whether PERKmediatedER stress is implicated in LPS-induced depression-like behaviors.Thus, we aimed to evaluate the induction of PERK pathwayin mice with depression-like behaviors induced by LPS, as well as the alterations in depression-like behaviorsfollowing the blocking of PERK pathway.We found that LPS challenges resulted in enhanced PERK in the hippocampus, with no alteration in the prefrontal cortex. Importantly, we found that PERKinhibitorISRIB reducedthe proinflammatory responsesof microglia in the context of acute LPS-induced brain inflammation, and subsequent the preserved hippocampal neurogenesis, and improvement in depression-like behavioroutcomes following LPS challenges.It was also worth mentioning thatISRIB treatmentreduced the peripheral pro-inflammatory cytokines includingIL-1ß, IL-6 and IL-18. Thus, targetingPERK mediated Endoplasmic reticulum stress may be a promising antidepressant and anti-inflammatory candidate drug for the alleviation of neuroinflammationmediated depression, and PERKinhibitorISRIBmay havebenefits for combating major depressive disorder.

Clinical diagnosis, treatment, and medical identification of specific pulmonary infection in naval pilots: Four case reports.

BACKGROUND: Specific pulmonary infection could seriously threaten the health of pilots and their companions. The consequences are serious. We investigated the clinical diagnosis, treatment, and medical identification of specific pulmonary infections in naval pilots. CASE SUMMARY: We analyzed the medical waiver and clinical data of four pilots with specific pulmonary infections, who had accepted treatment at the Naval Medical Center of Chinese People's Liberation Army between January 2020 and November 2021, including three cases of tuberculosis and one of cryptococcal pneumonia. All cases underwent a series of comprehensive treatment courses. Three cases successfully obtained medical waiver for flight after being cured, while one was grounded after reaching the maximum flight life after being cured. CONCLUSION: Chest computed tomography scanning should be used instead of chest radiography in pilots' physical examination. Most pilots with specific pulmonary infection can be cured and return to flight.

Silencing GmBIR1 in Soybean Results in Activated Defense Responses.

Receptor-like kinases (RLKs) are a large group of pattern recognition receptors (PRRs) and play a critical role in recognizing pathogens, transducing defense signals, and mediating the activation of immune defense responses. Although extensively studied in the model plant Arabidopsis, studies of RLKs in crops, including soybean, are limited. When a BAK1-interacting receptor-like kinase (BIR1) homolog (referred to as GmBIR1 hereafter) was silenced by the BPMV (Bean pod mottle virus)-induced gene silencing (BPMV-VIGS), it resulted in phenotypes that were reminiscent of constitutively activated defense responses, including a significantly stunted stature with observable cell death on the leaves of the silenced plants. In addition, both SA and H2O2 were over-accumulated in the leaves of the GmBIR1-silenced plants. Consistent with this autoimmune phenotype, GmBIR1-silenced plants exhibited significantly enhanced resistance to both Pseudomonas syringae pv. glycinea (Psg) and Soybean mosaic virus (SMV), two different types of pathogens, compared to the vector control plants. Together, our results indicated that GmBIR1 is a negative regulator of immunity in soybean and the function of BIR1 homologs is conserved in different plant species.