The internalization H. pylori into gastric epithelial cells may play a critical role in pathogenicity and evasion of antibacterial agents. However, many issues remain elusive. This review aimed to summarize the researches on H. pylori internalization and its associated intervention strategies. This descriptive review systematically analyzed studies in this field. BabA and SabA mediate H. pylori internalization, correlating with invasion into normal and inflammatory/neoplastic tissues, respectively. H. pylori invades gastric epithelial cells via zipper-like (spiral strains) and trigger (coccoid strains) pathways, rather than the single zipper-like mechanism conventionally recognized. Post-internalization, H. pylori reside in autophagosomes containing large and small vacuoles, distinct from the intracellular localization of Listeria monocytogenes and Salmonella spp. It proliferates within 12-24 h independent of virulence factors and is subsequently cleared. VacA⁺ strains exhibit lower intracellular clearance rates and a linear decline compared with VacA⁻ strains. Multiple toxins and molecular targets cooperatively mediate autophagy suppression via multipathway regulation. Probiotics, natural medicines, polymeric compounds and sonodynamic therapy represent promising interventions with translational potential. Critical knowledge gaps remain regarding the direct association between H. pylori internalization and eradication failure, invasion into non-gastric cancer cells, and the undefined intracellular survival time window of wild-type strains. Unlike other bacteria, H. pylori invades gastric epithelial cells via two pathways and evades intracellular immunity through specific toxins. However, knowledge gaps persist. Future research should focus on these gaps and promote the translational application of potential interventions. The invasion of gastric epithelial cells by H. pylori has been increasingly observed, suggesting that the invasion rate may have been underestimated previously. Current knowledge gaps include: insufficient direct evidence linking H. pylori internalization to eradication failure, limited real-world evidence for invasion of non-gastric cancer cells and an undefined intracellular survival time window of wild-type strains.Adhesins BabA (in normal gastric tissue) and SabA (in inflammatory/neoplastic tissues) mediate the internalization process, with no other adhesins confirmed to date. Contrary to previous understanding, H. pylori employs two distinct internalization pathways into gastric epithelial cells: the zipper-like (spiral strains) and trigger mechanism (coccoid strains).Probiotics, natural products, polymeric compounds and sonodynamic therapy may reduce adhesion or attenuate H. pylori-mediated autophagy inhibition, thereby lowering intracellular bacterial load. Several of these strategies hold translational potential.
Retroperitoneal sarcoma (RPS) is a type of malignant tumour arising from mesenchymal tissues within the retroperitoneal space. RPSs tend to develop covertly and are often undiscovered when they have already grown significantly and invaded surrounding tissues and organs. These malignancies demonstrate high recurrence rates, present surgical challenges and exhibit limited responsiveness to radiotherapy and chemotherapy. Serum-derived molecules are known to play critical roles in tumourigenesis and tumour progression. However, the serum molecular profile of RPS patients remains unclear. We performed multi-omics analysis of serum samples from patients with retroperitoneal dedifferentiated liposarcoma. Prolactin concentrations were quantified using Enzyme-Linked Immunosorbent Assay (ELISA). RNA-seq facilitated the identification of candidate signalling pathways, while gene expression was validated through quantitative polymerase chain reaction, immunohistochemistry and western blot analyses. Molecular mechanisms underlying transcriptional regulation were investigated through Chromatin Immunoprecipitation-qPCR (ChIP-qPCR) and dual-luciferase reporter gene assays. Integrative multi-omics profiling identified significant perturbations in galactose metabolism coupled with marked elevation of prolactin (PRL) levels in Retroperitoneal Liposarcoma (RLPS) patients. Further screening of serum prolactin levels in 100 patients with retroperitoneal tumours revealed that 90% of the cases exhibited hyperprolactinaemia in our research cohort, encompassing both malignant sarcomas and benign tumours. Studies at the clinical sample, cellular and animal levels have found that abnormally elevated prolactin in the serum can originate from sarcoma tissues. Mechanistic investigations identified SRY-box transcription factor 4 (SOX4) as a previously unrecognised transcriptional regulator of PRL. Functionally, PRL not only enhanced liposarcoma cell and fibrosarcoma cell proliferation but also conferred resistance to MDM2 inhibitors. Signalling pathway analysis revealed that PRL activates the Janus Kinase-Signal Transducer and Activator of Transcription Pathway (JAK-STAT) signalling pathway and up-regulates c-MYC expression. This study indicates that PRL can serve as an oncogenic driver and therapeutic target. The identification of SOX4-PRL-c-MYC signalling axis provides actionable insights for developing novel therapeutic strategies against this malignancy. Retroperitoneal sarcoma cells can secrete prolactin into the bloodstream, inducing hyperprolactinaemia, which subsequently triggers metabolic reprogramming, such as glucose metabolism. SOX4 can function as a transcription factor that facilitates PRL transcription. PRL can activate the JAK-STAT signalling pathway by binding to PRLR on sarcoma cells, leading to the up-regulation of c-MYC.
Anopheles stephensi is a major malaria vector mainly present in southern Asia and the Arabian Peninsula. Since 2012 it has invaded several countries of eastern Africa, stimulating urgent efforts to develop more efficient strategies for vector control such as CRISPR/Cas9-based homing gene drives. Target site resistance due to end-joining repair is a significant challenge to the deployment of these systems. The use of multiple sgRNAs has the potential to solve this issue. Here we perform experimental crosses to assess the homing and cutting efficiency of both classical (e.g. four adjacent sgRNAs all in one construct) and additive (e.g. separate constructs each expressing a single sgRNA) multiplexing strategies targeting the cardinal locus, in the presence and absence of a resistance allele. We find resistance alleles at one sgRNA target site can be mitigated by the presence of the additional sgRNAs with either strategy, and do not significantly reduce the homing efficiency for either strategy, validating their effectiveness. Further modelling using parameters derived from the strains generated indicates that while both strategies can overcome resistance allele formation, the fitness of the drive-carrying alleles is a critical factor in determining the overall performance and persistence of a split drive.
Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity lung disease triggered by sensitization to Aspergillus fumigatus or other Aspergillus species, with 1.0%-3.5% incidence in asthma patients and 7%-15% incidence in cystic fibrosis patients. It is more common in patients with asthma or cystic fibrosis. Clinical manifestations include recurrent bronchial obstruction, cough, pulmonary infiltrates, and bronchiectasis. However, its actual incidence is likely underestimated due to complex diagnostic criteria and insufficient clinical awareness. To standardize the integrated traditional Chinese and western medicine practice for ABPA, exert the advantage of synergistic efficacy of Chinese and western medicine, and improve the comprehensive diagnostic and therapeutic level, the Professional Committee of Allergy of the Chinese Association of Integrated Traditional and western Medicine organized multidisciplinary experts to formulate this consensus. This consensus defines diagnostic criteria, clinical classification and long-term management plans of ABPA, emphasizes the importance of environmental control and screening in high-risk populations, and systematically outlines an integrated diagnosis and treatment strategy combining western and traditional Chinese medicine. Western medicine is based on corticosteroids and antifungal agents, with biologics such as omalizumab representing an emerging option, while traditional Chinese medicine contributes through syndrome differentiation and treatment-addressing patterns such as "wind invading the lung" and "phlegm-stasis binding"-combined with proprietary Chinese medicines and acupuncture to enhance efficacy, with the aim of providing standardized guidance for clinical practice. 变应性支气管肺曲霉病（ABPA）是一种由烟曲霉或其他曲霉属真菌致敏引发的变态反应性肺部疾病，其患病率在哮喘患者中为1.0%~3.5%，囊性纤维化患者中达7%~15%，多见于哮喘或囊性纤维化患者，临床表现为反复支气管阻塞、咳嗽、肺部浸润及支气管扩张，但因诊断标准复杂且临床认识不足，实际发病率可能被低估。为了规范ABPA的中西医结合诊疗实践，发挥中西医协同增效的优势，提升综合诊疗水平，中国中西医结合学会变态反应专业委员会组织多学科专家撰写本共识。本共识明确了ABPA的诊断标准、临床分类及长期管理方案，强调环境控制与高风险人群筛查的重要性，并系统阐述了ABPA的中西医结合治疗策略，西医以糖皮质激素和抗真菌药物为基础，生物制剂如奥马珠单抗为新兴选择，中医则通过辨证论治如风邪袭肺、痰瘀互结等证型联合中成药及针灸等特色疗法协同增效，以期为临床提供规范化指导。.
Fissureless lobectomy has been shown to prevent air leaks in patients with fused or incomplete interlobar fissures or emphysema. The technique is also beneficial in advanced lung cancers involving adjacent lobes, where interlobar manipulation is technically difficult. Although this technique is widely used in standard lobectomies, reports on bilobectomy remain scarce. A 57-year-old woman with left-sided tongue cancer (pT2N0M0, Stage II) underwent subtotal glossectomy followed by postoperative concurrent chemoradiotherapy. Eighteen months after the surgery, imaging revealed a mass in the right lower lobe. Bronchoscopy confirmed squamous cell carcinoma, and the patient was referred to our department with suspected pulmonary metastasis. Over the 3 weeks following initial presentation, the lung tumor enlarged rapidly. The tumor was centered in the lower lobe with invasion of the middle and upper lobes, and the distal lung parenchyma was complicated by obstructive pneumonia. Although antibiotics were administered, the fever and inflammatory markers persisted; thus, we decided to proceed with surgery for infection control. Due to the presence of incomplete lung fissure and the lower lobe tumor invading the other lobes, pneumonectomy was the initial option. However, to preserve lung capacity, we decided to perform a fissure-last right middle and lower bilobectomy with division of the interlobar pulmonary artery prior to resection of the bronchus. The patient was discharged 16 days after surgery without complications. We report a case of bilobectomy using a modified fissureless technique and describe the technical details of how we dissect the pulmonary artery prior to resection of the bronchus. Being familiar with the fissureless bilobectomy technique is an important option for avoiding right pneumonectomy.
Plants utilize receptor-like proteins and receptor-like kinases (RLPs/RLKs) to perceive and respond to a wide variety of invading pathogens and insect herbivores. While the strategies employed by microbial pathogens to suppress plant immunity have been well characterized, it remains unclear how herbivorous insects counteract receptor-mediated defenses. Here, we show that salivary effectors evolve independently in whiteflies and planthoppers to dampen RLP4-mediated plant immunity. RLP4, as a leucine-rich repeat RLP (LRR-RLP), confers plant resistance against herbivorous insects by forming the RLP4/SOBIR1 complexes. In the whitefly Bemisia tabaci, BtRDP, the Aleyrodidae-specific salivary sheath protein, interacts with RLP4 from multiple plant species and promotes its ubiquitin-dependent degradation. Overexpression of NtRLP4 in transgenic plants exerts a detrimental effect on B. tabaci by exploiting the crosstalk between the salicylic acid and jasmonic acid pathways. Conversely, overexpression of BtRDP or silencing of NtRLP4 effectively alleviates such negative effects. In planthopper Nilaparvata lugens, the Delphacidae-restricted salivary protein NlSP104 also targets and promotes the degradation of OsRLP4 from rice plants. These findings reveal convergent evolution of salivary proteins in insects and underscore the complex interactions between plants and herbivorous insects. Plants cannot escape from insects, so they rely on their own defense systems. One key strategy involves proteins on the cell surface that act as sensors. These sensors detect insect attacks and trigger protective responses within the plant. Scientists have long known that microbes can disable these sensors, thereby weakening plant defences. However, it has been unclear whether plant-eating insects use similar tactics. Many insects feed by inserting needle-like mouthparts (stylets) into plants and releasing saliva, which contains proteins capable of altering plant responses. To investigate this, Wang et al. studied two major crop pests: the whitefly Bemisia tabaci and the brown planthopper Nilaparvata lugens. They focused on a plant sensor called RLP4, a surface protein that helps plants recognize insect attack and activate defenses. The researchers found that both insects produce salivary proteins that bind to RLP4 and trigger its breakdown inside plant cells. This weakens the plant’s defenses and makes feeding easier for the insects. Experiments in tobacco and rice plants showed that increasing RLP4 levels improved resistance to these pests. In contrast, reducing RLP4 levels or introducing the insect salivary proteins made plants more susceptible. Although the two insect proteins are unrelated, they perform the same function, suggesting that different insects have independently evolved similar strategies to overcome plant defenses. These findings reveal a shared mechanism used by plant-eating insects and provide new insight into plant–insect interactions. In the future, this knowledge could help guide the development of crops with improved resistance to insect pests. However, further research is needed to determine how widespread this mechanism is and how it can be effectively applied in agriculture.
Salmonella enterica infection remains a major threat to poultry health and food safety, largely due to its ability to invade the intestinal epithelium, modulate host immunity, and persist intracellularly. Curcumin, a bioactive phytochemical, has shown promising antimicrobial and immunomodulatory potential; however, its precise molecular interplay with host and pathogen systems remains unclear. An integrated computational pipeline was applied, combining target prediction, host immune network construction, Salmonella virulence interaction analysis, STRING-based PPI mapping, KEGG/GO enrichment, and molecular docking validation. Host immune hub genes and Salmonella virulence regulators were identified, followed by docking of curcumin to key host (AKT1, STAT3, TNF) and pathogen proteins (invA, phoP, ssrB). Host network analysis revealed enrichment in the PI3K-AKT, NF-κB, FoxO, and IL-10 signaling pathways, indicating roles in epithelial protection, immune regulation, inflammation suppression, and antioxidant defense. Salmonella virulence hubs were primarily associated with epithelial invasion, Type III secretion, intracellular survival, and global virulence reg-ulation. Docking analysis demonstrated a strong binding affinity of curcumin toward AKT1 (-7.4 kcal/mol), STAT3 (-6.5 kcal/mol) and TNF (-5.8 kcal/mol), supporting host immunomodulation and epithelial protection. Simultaneously, curcumin showed notable affinity for phoP (-6.8 kcal/mol), invA (-6.3 kcal/mol), and ssrB (-5.8 kcal/mol), suggesting the potential suppression of virulence signaling, invasion machinery, and intracellular persistence. This integrated host-pathogen systems analysis demonstrates that curcumin exerts a dual regulatory effect by enhancing host immune protection while concurrently disrupting Salmonella virulence mechanisms. These findings provide mechanistic insight supporting curcumin as a promising natural therapeutic candidate for controlling Salmonella infection in broilers.
Phytolacca acinosa Roxb., a perennial herb native to East Asia, is increasingly naturalizing in Europe, yet its reproductive ecology in the secondary range remains poorly understood. This study evaluated seed productivity across central and edge populations in the secondary range, fruit and seed morphometrics, and germination responses to cold storage, acid scarification (simulating bird endozoochory), and light exposure. Fruit production per raceme was influenced by an interaction between insolation and range position: reduced insolation increased fruit set in central populations but decreased it at the range edge. Raceme number per shoot was lower in spontaneous plants compared to cultivated ones. Fresh seeds exhibited strong dormancy with no germination without scarification. Acid scarification significantly enhanced germination, particularly with light exposure, reaching up to 55%. Cold storage did not increase germination percentage but accelerated germination of scarified seeds under light, reducing median germination time from 24 to 21 days. Compared to the congeneric P. americana, P. acinosa shows more stringent dormancy requirements. We conclude that P. acinosa retains deep seed dormancy in its secondary range and relies on bird-mediated endozoochory for both dispersal and dormancy release. At the northern range edge, reduced plant vigor and lower raceme numbers are partially offset by increased flower production per raceme, though fruit set remains constrained. The species does not exhibit the simplified germination requirements often associated with successful invaders; instead, its invasion success appears driven by a bet-hedging strategy combining persistent seed banks with specific dormancy-breaking cues.
U.S. Navy ships have not engaged in heavy combat operations since World War II. Although naval warfare and navy ships have advanced technologically since that time, the fundamental violence of combat and resultant human factors of war have not. This article discusses how the Navy is not fully prepared for the expected large number of combat stress casualties likely to occur in any maritime large-scale combat operations (LSCO) such as the threat by China to invade Taiwan by 2027. U.S. Naval Surface Forces began assigning mental health providers to support Navy surface combatant ships in 2019. These mental health professionals provide psychological support to shipboard Sailors but do not deploy with these ships. Rather, Navy surface combatant ships are supported by a single Independent Duty Corpsman (IDC) paraprofessional with limited training in mental health. Therefore, in any LSCO scenario, the acute psychological needs of these shipboard Sailors will be provided by these medical assets. The article discusses how U.S. Naval Surface Forces is preparing shipboard Sailors for combat stress reactions as well as training organic shipboard resources (i.e. IDCs, chaplains) in applying psychological first aid and legacy combat psychiatry principles (i.e. PIES - Proximity to the frontline, Immediacy of treatment, Expectancy of recovery, Simple interventions). The article concludes with a discussion of future directions for closing the current gaps in training needed to enhance psychological support to Naval Surface Forces ships/Sailors in preparation for future LSCO scenarios.
Ecosystems worldwide face growing impacts from non-native species invasions. However, little is known about how soil microbial communities respond to the addition of non-native plants, and whether these responses differ along a successional gradient. To address these knowledge gaps, we collected soil samples, recorded plant species cover and measured the traits of the plant species in lava flow vegetation and lowland rainforest (representing early and late successional stages) on La Réunion Island. Our results show that non-native plant cover drives variation in plant species diversity, community composition, functional composition (community-weighted means of vegetative height and leaf area) and functional diversity (mean pairwise trait distance among species), with these effects being stronger in early than in late successional stage. Non-native plant cover did not affect the diversity or community composition of soil fungi and bacteria. Instead, the functional diversity of plant communities associated with non-native plant addition explained the variation in soil microbial community composition and co-occurrence network structure. These results suggest that while non-native plant cover is a good indicator of variation in plant community composition, the functional diversity of the plant community is more useful for describing shifts in soil microbial communities of invaded habitats along primary succession.
While Yersinia ruckeri is known for causing systemic vascular damage, its potential to invade the central nervous system remains poorly understood. This study investigated the spatiotemporal distribution, pathological progression, antimicrobial resistance (AMR), and biochemical alterations associated with Y. ruckeri across 12 commercial rainbow trout farms in Türkiye. Advanced diagnostics using MALDI-TOF MS enabled rapid and accurate identification of the pathogen. Disease prevalence peaked in farms experiencing thermal stress (18 °C) and high biomass density. Histopathological examination revealed inflammatory alterations suggestive of neural involvement, including perivascular cuffing, neuronal degeneration, and focal neuroinflammation. In addition, Y. ruckeri was isolated from brain tissue in 15 infected fish and confirmed by MALDI-TOF MS, supporting the possibility of central nervous system involvement during systemic infection. Furthermore, the observation of neuroinflammation and perivascular cuffing suggests that the pathogenesis of Y. ruckeri is not limited to systemic vascular damage but also involves the central nervous system, which may explain the distinct behavioral changes and complex clinical progression of the disease. Antimicrobial susceptibility testing showed consistent multidrug resistance to amoxicillin, gentamicin, netilmicin, erythromycin, and sulfisoxazole. Serum biochemical analysis confirmed significantly elevated ALT levels, with ROC analysis identifying ALT as an excellent early biomarker (AUC = 0.956), having an optimal cut-off value of 71.4 U/L with high sensitivity (91.8%) and specificity (92.5%). The identified ALT threshold may provide a practical biomarker for the early detection and monitoring of ERM under field conditions. Collectively, this study provides new insights into ERM pathogenesis and highlights the need for improved antimicrobial stewardship and environmental risk management in aquaculture.
This article presents a 60-year-old woman presented with a one-year history of abdominal distension, which acutely worsened over four days prior to admission. Imaging revealed a large retroperitoneal liposarcoma. Exploratory laparotomy identified a massive tumor (approximately 45×40×13 cm, weighing 8 kg) invading the left kidney, adrenal gland, adnexa, left hemicolon, and mesentery. En bloc resection was performed. Postoperative pathology combined with fluorescence in situ hybridization (FISH) testing demonstrated MDM2/CDK4 amplification, confirming dedifferentiated liposarcoma (DDLPS). The patient recovered well postoperatively and was discharged following adjuvant radiotherapy (IMRT; 50 Gy in 25 fractions), chemotherapy (AD regimen), and immunotherapy (sintilimab).Through this case, we mainly understand the characteristics of the disease onset, special diagnosis, and main treatment methods.
Background/Objectives: Cryptosporidium parvum is a major causative agent of cryptosporidiosis; however, progress in anti-cryptosporidial drug discovery has been hindered by the lack of robust and reproducible in vitro evaluation systems. In this study, we developed and optimized a luciferase-based in vitro assay to quantitatively monitor C. parvum growth in HCT-8 cells. Methods: Key experimental parameters affecting infection efficiency were systematically examined, including sodium taurocholate treatment, timing of medium replacement, and serum concentration. Results: Sodium taurocholate significantly enhanced parasite infectivity, and removal of non-invaded parasites at 3 h post-infection (hpi) resulted in approximately 2-fold and 3.7-fold increase in luciferase activity at 24 and 48 hpi, respectively, compared with untreated controls. In contrast, removal at 24 hpi led to only an approximately 2.5-fold increase at 48 hpi, consistent with stage-dependent differences in parasite development. Morphological analyses confirmed parasite differentiation from trophozoites to meronts, followed by progression toward sexual stages. Using the optimized assay system, we evaluated several anticoccidial compounds and demonstrated potent in vitro activity of monensin and its structural analog kijimicin, whereas diclazuril and toltrazuril exhibited limited efficacy. Conclusions: Collectively, this luciferase-based platform provides a reliable and quantitative tool for anti-cryptosporidial drug screening and will facilitate future therapeutic development against C. parvum.
Vaccinia virus (VACV) and monkeypox virus (MPXV) are closely related members of the family Poxviridae, genus Orthopoxvirus, both capable of causing systemic infections with potential neurological complications. Although live, replication-competent VACV strains were historically used in smallpox vaccination, their clinical use was associated with rare but severe central nervous system (CNS)-related adverse events. Despite this, the mechanisms underlying VACV-induced CNS pathology, particularly olfactory dysfunction, remain poorly characterized. In this study, we found VACV-VR1354, a tissue culture-adapted derivative of the neurovirulent Western Reserve strain, can invade the CNS via the olfactory route and induce olfactory impairment. By using an intranasal infection model in two inbred mouse strains-C57BL/6N and BALB/c, we demonstrate that VACV-VR1354 efficiently disseminates from the nasal mucosa to the brain, as evidenced by a spatiotemporal gradient of viral DNA load (nasal mucosa > olfactory bulb > cerebrum > cerebellum). Evans blue extravasation assays indicated a transient increase in blood-brain barrier (BBB) permeability in the olfactory bulb, peaking at 7 days post-infection (dpi) and resolving by 14 dpi, with more pronounced effects in C57BL/6N mice. Neuroinvasion was accompanied by robust microglial and astrocytic activation, as well as injury to mature olfactory sensory neurons, particularly at 7 dpi. Transcriptomic profiling of the olfactory bulb revealed significant downregulation of olfactory receptor (OR) genes, with the downregulated genes significantly enriched in olfactory transduction pathways. Concurrently, strong upregulation of proinflammatory cytokines, chemokines, and interferon-stimulated genes (ISGs) was detected in the olfactory bulb tissue, indicative of intense neuroinflammation. Behaviorally, infected C57BL/6N mice exhibited impaired aversion to camphor odor between 14 and 49 dpi, with full functional recovery observed by 56 dpi. Collectively, our findings showed that intranasal infection of mice with VACV-VR1354 leads to a transient increase BBB permeability, neuroinflammation, and reversible olfactory/chemosensory impairment. This murine model recapitulates key features of post-viral olfactory loss and establishes a valuable platform for mechanistic studies of orthopoxvirus neuropathogenesis and therapeutic evaluation of interventions targeting viral neuroinvasion and sensory recovery.
Toxoplasmosis is a cosmopolitan zoonosis that particularly threatens pregnant women, their fetuses and immunocompromised individuals. Among people living with HIV, Toxoplasma gondii may invade the central nervous system, producing neuropathological effects associated with mental and psychiatric disorders. We assessed the seroprevalence of anti-T. gondii IgG in HIV-infected and HIV-uninfected residents of Iquitos, Peru, and evaluated an in-house ELISA based on total lysate antigen (TLA) and recombinant GRA1 (rGRA1), with ELISA-TLA compared against a commercial kit. In this observational cross-sectional study, 151 participants were enrolled: 92 HIV-positive and 59 HIV-negative. ELISA-TLA showed a seroprevalence of 88.08% (133/151), reaching 91.30% (84/92) in the HIV-positive group and 83.05% (49/59) in the HIV-negative group. ELISA-rGRA1 showed a similar epidemiological pattern but lower overall seroprevalence, 81.46% (123/151), with 84.78% (78/92) in HIV-positive and 74.58% (44/59) in HIV-negative participants. Taken together, both TLA and rGRA1-based ELISAs showed similar epidemiological patterns, supporting the consistency of the serological findings. These results also indicate very high exposure to T. gondii in Iquitos, particularly among HIV-positive individuals, in whom prior exposure is clinically relevant because of the risk of reactivation under immunosuppression. Serological screening and preventive counseling may therefore be warranted in high-burden Amazonian communities.
Reexpansion pulmonary edema following pulmonary and mediastinal surgery presents a complex clinical challenge. Independent lung ventilation (ILV), which facilitates the application of distinct positive end-expiratory pressures (PEEP) and tidal volumes to each lung, may serve as an alternative therapeutic approach for managing reexpansion pulmonary edema. A 58-year-old female patient presented with a giant space-occupying lesion measuring 17.1*11.2*19.2 cm in the left lung and underwent mediastinal tumor resection under general anesthesia. Intraoperatively, following the resection of the tumor and the invaded upper lobe of the left lung, the left lung was manually reopened, resulting in the development of reexpansion pulmonary edema (RPE). To prevent exudate from the left lung from infiltrating the right lung and to avoid barotrauma to the right lung due to excessive airway pressure, a dual ventilator mechanical ventilation strategy was employed. This approach utilized a double-lumen endotracheal tube, allowing for differential ventilation modes tailored to each lung. The mechanical ventilation treatment involving double-lumen bronchial intubation with various ventilation modes serves as an effective ventilatory support for managing reexpansion pulmonary edema.
A painful retroareolar mass in a male patient may initially suggest a primary breast process, but in rare cases it may reflect contiguous spread from an intrathoracic malignancy. Distinguishing between these possibilities is essential because delayed recognition may affect staging, resectability, and treatment planning. We present the case of a 50-year-old man with a history of tobacco use who presented with a progressively enlarging and painful right retroareolar mass. Physical examination revealed a firm, fixed, tender subareolar lesion measuring approximately 5 cm. CT of the chest demonstrated a heterogeneous soft tissue mass involving the right anterior chest wall, with extension through the intercostal space and intrathoracic involvement. Surgical exploration revealed a tumor extending through the chest wall deep to the pectoralis major muscle, with contiguous growth into the subareolar region. Debulking and biopsy were performed. Frozen section analysis was suspicious for squamous cell carcinoma, and final histopathologic evaluation demonstrated non-small cell lung carcinoma (NSCLC) with immunophenotypic features of hepatoid differentiation. The lesion was deemed unresectable because of extensive local invasion into surrounding structures. A permanent venous access port was placed, and the patient was referred for systemic platinum-based chemotherapy with immunotherapy after multidisciplinary staging and oncology evaluation. This case highlights a rare clinical presentation of lung malignancy manifesting as a retroareolar mass in a male patient and emphasizes the importance of maintaining a broad differential diagnosis when evaluating fixed, painful chest wall and breast-region lesions.
Microorganisms with dozens, hundreds, or thousands of proteins invade hosts. Whether the hosts simultaneously recognize all or a part of them is unknown. A total of 68 Escherichia coli recombinant outer membrane (OM) proteins were pooled to immunize mice, and the resulting antisera were analyzed using a protein microarray. Proteins recognized in each cycle were removed, and the remaining proteins were re-pooled for subsequent immunizations. Bioinformatics analysis of B cell epitope scores and GO functional categories was performed across the identified immunogen hierarchies. Among the 68 OM proteins, only 18 were recognized to generate antibodies, designated as the first hierarchy of immunogens. When the other 50 proteins were grouped to immunize mice, 15 were detected to have their corresponding antibodies, designated as the second hierarchy of immunogens. This procedure was repeated four times, leading to the identification of 16 and eight proteins as the third and the fourth hierarchy of immunogens, respectively, and 11 residual proteins as the fifth hierarchy of immunogens. Bioinformatics analysis showed a negative correlation of B cell epitope score with increasing hierarchies, suggesting that the score plays an essential role in hierarchy recognition. In addition, more proteins with transport and fewer proteins with metabolic process were found in the combination of the first, second, and third than the combination of the fourth and fifth hierarchies of immunogens. The host's immune system hierarchically recognizes antigens to mount antibody responses. This finding highlights the way in understanding differentially neutralizing antibodies during infections caused by different microorganisms.
Lymphatic cyst with infection is caused by interruption of lymphatic vessels during para-aortic lymphnode dissection in patients with gynecological malignancies. It is generally considered that the infection is caused by bacteria invading through the lower limb and perineal wound, but the pathogenic factors of most lymphatic cysts are not clear. Our literature search revealed no previously reported cases similar to ours, in which a lymphatic cyst infection resulted from a co-infection with Streptococcus mitis/oralis (S. mitis/oralis) and Klebsiella pneumoniae (K. pneumoniae). A woman of 61 years of age, was diagnosed in endometrial cancer, carcinosarcoma FIGO grade 3, stage IIIC of the FIGO system. During the third postoperative pelvic replacement and drainage procedure, the patient developed a fever with a peak temperature of 39.2°C on the second day after the removal of the drainage tube. Empiric broad-spectrum antibiotics were started upon hospital readmission, but the patient showed poor response to therapy, with persistent and recurrent lower abdominal tenderness, raising concern for ongoing intra-abdominal or pelvic infection. As a result, it is important to identify pathogenic bacteria associated with lymphatic cyst infections and determine antimicrobial regimens. We further investigated the pathogenicity and antibiotic resistance of S. mitis/oralis, formulated an appropriate anti-infective treatment strategies. Consequently, the patient recovered and was discharged.
Anti-CRISPRs (Acrs) are diverse proteins or RNAs that protect invading phages and plasmids from host CRISPR-Cas immunity. Most Acrs neutralize their cognate Cas proteins via direct physical interaction. Here we describe CasPRs, a particularly widespread family of DNA-binding Acrs that recognize specific sequence motifs within cas gene coding regions, thereby blocking RNA polymerase and silencing transcription. We demonstrate that eight diverse CasPRs bind to the cas8b gene to repress the type I-B CRISPR-Cas system in its native host, Listeria seeligeri . Meanwhile, a CasPR from Streptococcus dysgalactiae silences type II-A CRISPR-Cas immunity by binding to the cas9 coding sequence. We found that one CasPR is required to inhibit CRISPR immunity during lysogeny by its host prophage. Taken together, our results indicate that members of the CasPR family have diverged to silence completely unrelated CRISPR types, and suggest transcriptional repression is a common mode of phage-mediated immune antagonism.