CYP2E1 deficit mediates cholic acid-induced malignant growth in hepatocellular carcinoma cells.

BACKGROUND: Increased level of serum cholic acid (CA) is often accompanied with decreased CYP2E1 expression in hepatocellular carcinoma (HCC) patients. However, the roles of CA and CYP2E1 in hepatocarcinogenesis have not been elucidated. This study aimed to investigate the roles and the underlying mechanisms of CYP2E1 and CA in HCC cell growth. METHODS: The proteomic analysis of liver tumors from DEN-induced male SD rats with CA administration was used to reveal the changes of protein expression in the CA treated group. The growth of CA-treated HCC cells was examined by colony formation assays. Autophagic flux was assessed with immunofluorescence and confocal microscopy. Western blot analysis was used to examine the expression of CYP2E1, mTOR, AKT, p62, and LC3II/I. A xenograft tumor model in nude mice was used to examine the role of CYP2E1 in CA-induced hepatocellular carcinogenesis. The samples from HCC patients were used to evaluate the clinical value of CYP2E1 expression. RESULTS: CA treatment significantly increased the growth of HCC cells and promoted xenograft tumors accompanied by a decrease of CYP2E1 expression. Further studies revealed that both in vitro and in vivo, upregulated CYP2E1 expression inhibited the growth of HCC cells, blocked autophagic flux, decreased AKT phosphorylation, and increased mTOR phosphorylation. CYP2E1 was involved in CA-activated autophagy through the AKT/mTOR signaling. Finally, decreased CYP2E1 expression was observed in the tumor tissues of HCC patients and its expression level in tumors was negatively correlated with the serum level of total bile acids (TBA) and gamma-glutamyltransferase (GGT). CONCLUSIONS: CYP2E1 downregulation contributes to CA-induced HCC development presumably through autophagy regulation. Thus, CYP2E1 may serve as a potential target for HCC drug development.

Fabrication of lignosulfonate-derived porous carbon via pH-tunable self-assembly strategy for efficient atrazine removal.

Herein, a straightforward protocol was developed for the one-pot synthesis of N-doped lignosulfonate-derived carbons (NLDCs) with a tunable porous structure using natural amino acids-templated self-assembly strategy. Specifically, histidine was employed as a template reagent, leading to the preparation of 10-NLDC-21 with remarkable characteristics, including the large specific surface area (SBET = 1844.5 m2/g), pore volume (Vmes = 1.22 cm3/g) and efficient adsorption for atrazine (ATZ) removal. The adsorption behavior of ATZ by NLDCs followed the Langmuir and pseudo-second-order models, suggesting a monolayer chemisorption nature of ATZ adsorption with the maximum adsorption capacity reached up to 265.77 mg/g. Furthermore, NLDCs exhibited excellent environmental adaptability and recycling performance. The robust affinity could be attributed to multi-interactions including pore filling, electrostatic attraction, hydrogen bonding and π-π stacking between the adsorbents and ATZ molecules. This approach offers a practical method for exploring innovative bio-carbon materials for sewage treatment.

Risk factors and a predictive model for the occurrence of adverse outcomes in patients with new-onset refractory status epilepsy.

Objectives: To determine risk factors for the occurrence of adverse outcomes in patients with new-onset refractory status epilepsy (NORSE) and to construct a concomitant nomogram. Methods: Seventy-six adult patients with NORSE who were admitted to the Department of Neurology, First Affiliated Hospital of Sun Yat-sen University between January 2016 and December 2022 were enrolled for the study. Participants were divided into two-those with good and poor functional outcomes-and their pertinent data was obtained from the hospital medical recording system. Univariate analysis was used to identify potential causes of poor outcomes in both groups and a multivariate logistic regression model was used to identify risk factors for the occurrence of poor outcomes. Using the R programming language RMS package, a nomogram was created to predict the occurrence of poor outcomes. Results: The NORSE risk of adverse outcome nomogram model included four predictors, namely duration of mechanical ventilation (OR = 4.370, 95% CI 1.221-15.640, p = 0.023), antiviral therapy (OR = 0.045, 95% CI 0.005-0.399, p = 0.005), number of anesthetics (OR = 13.428, 95% CI 2.16-83.48, p = 0.005) and neutrophil count/lymphocyte count ratio (NLR) (OR = 5.248, 95% CI 1.509-18.252, p = 0.009). The nomogram had good consistency and discrimination in predicting risk and can thus assist clinical care providers to assess outcomes for NORSE patients. Through ordinary bootstrap analyses, the results of the original set prediction were confirmed as consistent with those of the test set. Conclusion: The nomogram model of risk of adverse outcomes in NORSE adult patients developed in this study can facilitate clinicians to predict the risk of adverse outcomes in NORSE patients and make timely and reasonable interventions for patients at high risk of adverse outcomes.

Research on the Effect Mechanism of Re on Interface Dislocation Networks of Ni-Based Single Crystal Alloys.

The effect of interface dislocation networks on the mechanical properties of new Ni-based single crystal alloys containing Rhenium (Re) is very large. Because the interface dislocations are microscopic in the nano-scale range, this has not been investigated, and it is very difficult to prepare new Ni-based single crystal alloys containing Re. Therefore, six kinds of new Ni-based single crystal alloys containing Re were prepared, and the hardness tests and nonlinear ultrasonic lamb wave tests were performed on the samples. It was found that the density of interface dislocation networks increases with the increase in the content of Re, which improves the blocking ability of matrix phase dislocation cutting into precipitated phase and enhances the inhibition of dislocation movement. The nonlinear ultrasonic lamb wave tests showed that the materials exhibit better mechanical properties when the density of the interface dislocation networks increases. Meanwhile, a new molecular dynamics model which is closer to the real state of an Ni-based single crystal alloy was constructed to reveal the evolution mechanism of interface dislocation networks. The results showed that the potential energy of Re atoms at the interface is the lowest, which affects the reduction of the potential energy of other atoms at the interface, and thus the stability of the model is improved. In addition, according to the change in the total length of dislocation loops in the model system, with the increase in the content of Re atoms, the inhibition of dislocation movement by dislocation networks at the interface is strengthened.

GADD45B in the ventral hippocampal CA1 modulates aversive memory acquisition and spatial cognition.

AIMS: This study was designed to investigate the role of growth arrest and DNA damage-inducible ß (GADD45B) in modulating fear memory acquisition and elucidate its underlying mechanisms. MAIN METHODS: Adeno-associated virus (AAV) that knockdown or overexpression GADD45B were injected into ventral hippocampal CA1 (vCA1) by stereotactic, and verified by fluorescence and Western blot. The contextual fear conditioning paradigm was employed to examine the involvement of GADD45B in modulating aversive memory acquisition. The Y-maze and novel location recognition (NLR) tests were used to examine non-aversive cognition. The synaptic plasticity and electrophysiological properties of neurons were measured by slice patch clamp. KEY FINDINGS: Knockdown of GADD45B in the vCA1 significantly enhanced fear memory acquisition, accompanied by an upregulation of long-term potentiation (LTP) expression and intrinsic excitability of vCA1 pyramidal neurons (PNs). Conversely, overexpression of GADD45B produced the opposite effects. Notably, silencing the activity of vCA1 neurons abolished the impact of GADD45B knockdown on fear memory development. Moreover, mice with vCA1 GADD45B overexpression exhibited impaired spatial cognition, whereas mice with GADD45B knockdown did not display such impairment. SIGNIFICANCE: These results provided compelling evidence for the crucial involvement of GADD45B in the formation of aversive memory and spatial cognition.

Photocatalyzed Aerobic Cross-Dehydrogenative Coupling of Diarylphosphine Oxides with Alcohols and Phenols.

A photocatalytic cross-dehydrogenative coupling of diarylphosphine oxides with alcohols and phenols has been developed. Using organic dye Rose Bengal as the photocatalyst and air as the oxidant, the reaction proceeded smoothly at room temperature. Both alcohols and phenols were feasible, affording various organophosphinates in high yields. The absence of a halogenating reagent, the absence of a transition-metal catalyst, a green oxidant, and mild conditions make this strategy environmentally benign and sustainable. Mechanistic studies indicated that the reaction is enabled by the cooperation of photoredox catalysis and photosensitization.

Hyperuricemia research progress in model construction and traditional Chinese medicine interventions.

Hyperuricemia (HUA), a severe metabolic disease derived from purine metabolism disorder, will lead to abnormally increased serum uric acid (SUA) levels in the body. Studies have shown that HUA is highly related to gout, hypertension, diabetes, coronary heart disease, chronic kidney diseases, and so on. Traditional Chinese medicine (TCM) shows excellent results in treating HUA because of its unique advantages of multi-metabolites and multi-targets. This article reports on the use of TCM components for uric acid (UA)-lowering activity with excellent efficacy and low side effects based on established HUA models. This work summarizes the advantages and limitations of various HUA disease models for efficacy evaluation. Applications of TCM in HUA treatment have also been discussed in detail. This paper reveals recent research progress on HUA in constructing evaluation models and systematic TCM interventions. It will provide a scientific reference for establishing the HUA model and suggest future TCM-related HUA studies.

Thymoma-associated autoimmune encephalitis with myasthenia gravis: Case series and literature review.

OBJECTIVES: This comprehensive review aimed to compile cases of patients with thymoma diagnosed with both autoimmune encephalitis (AE) and myasthenia gravis (MG), and describe their clinical characteristics. METHODS: Clinical records of 3 AE patients in the first affiliated hospital of Sun Yat-sen University were reviewed. All of them were diagnosed with AE between 1 November 2021 and 1 March 2022, and clinical evidence about thymoma and MG was found. All published case reports were searched for comprehensive literature from January 1990 to June 2022. RESULTS: A total of 18 cases diagnosed with thymoma-associated autoimmune encephalitis (TAAE) and thymoma-associated myasthenia gravis (TAMG) were included in this complication, wherein 3 cases were in the first affiliated hospital of Sun Yat-sen University and the other 15 were published case reports. 5/18 patients had alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antibody (AMPAR-Ab) in their serum and cerebrospinal fluid (CSF). All of them had positive anti-acetylcholine receptor antibody (AChR-Ab). And 12/18 patients showed a positive response to thymectomy and immunotherapy. Besides, thymoma recurrences were detected because of AE onset. And the shortest interval between operation and AE onset was 2 years in patients with thymoma recurrence. CONCLUSIONS: There was no significant difference in the clinical manifestations between these patients and others with only TAMG or TAAE. TAAE was commonly associated with AMPAR2-Ab. Significantly, AE more commonly heralded thymoma recurrences than MG onset. And the intervals of thymectomy and MG or AE onset had different meanings for thymoma recurrence and prognoses of patients.

Advances in the role of the GADD45 family in neurodevelopmental, neurodegenerative, and neuropsychiatric disorders.

The growth arrest and DNA damage inducible protein 45 (GADD45) family comprises stress-induced nuclear proteins that interact with DNA demethylases to facilitate DNA demethylation, thereby regulating diverse cellular processes including oxidative stress, DNA damage repair, apoptosis, proliferation, differentiation, inflammation, and neuroplasticity by modulating the expression patterns of specific genes. Widely expressed in the central nervous system, the GADD45 family plays a pivotal role in various neurological disorders, rendering it a potential therapeutic target for central nervous system diseases. This review presented a comprehensive overview of the expression patterns and potential mechanisms of action associated with each member of GADD45 family (GADD45α, GADD45ß, and GADD45γ) in neurodevelopmental, neurodegenerative, and neuropsychiatric disorders, while also explored strategies to harness these mechanisms for intervention and treatment. Future research should prioritize the development of effective modulators targeting the GADD45 family for clinical trials aimed at treating central nervous system diseases.

Inflammation mechanism and anti-inflammatory therapy of dry eye.

Dry eye is a widespread chronic inflammatory disease that causes fatigue, tingling, burning, and other symptoms. Dry eye is attributed to rheumatic diseases, diabetes, hormone disorders, and contact lenses, which activate inflammatory pathways: mitogen-activated protein kinases (MAPK) and nuclear factor-B (NF-κB), promote macrophage inflammatory cell and T cell activation, and inflammation factors. Clinicians use a combination of anti-inflammatory drugs to manage different symptoms of dry eye; some of these anti-inflammatory drugs are being developed. This review introduces the dry eye inflammation mechanisms and the involved inflammatory factors. We also elucidate the anti-inflammatory drug mechanism and the detection limits.

Photoredox Catalytic Phosphine-Mediated Deoxygenative Hydroacylation of Azobenzenes with Carboxylic Acids.

The convenient and precise preparation of N,N'-diarylhydrazides, especially from readily available raw materials, remains highly challenging. Here, a photoredox catalytic phosphine-mediated deoxygenative hydroacylation of azobenzenes with abundant and readily available carboxylic acids has been developed. With Ir[dF(CF3)ppy]2(dtbbpy)PF6 as the photocatalyst, the reactions proceeded smoothly in the presence of PPh3 under visible light irradiation, delivering various N,N'-diarylhydrazides in up to 92% yields. Mechanistic studies revealed that the reaction proceeds via photoredox catalysis and phosphoranyl-radical-mediated C-O bond cleavage of carboxylic acids.

Liver organoids and their application in liver cancer research.

Liver cancer, a common and intractable liver-related disease, is a malignant tumor with a high morbidity, which needs a high treatment cost but still lacks perfect clinical treatment methods. Looking for an effective platform for liver cancer study and drug screening is urgent and important. Traditional analytical methods for liver disease studies mainly rely on the 2D cell culture and animal experiments, which both cannot fully recapitulate physiological and pathological processes of human liver. For example, cell culture can only show basic functions of cells in vitro, while animal models always hold the problem of species divergence. The organoids, a 3D invitro culture system emerged in recent years, is a cell-bound body with different cell types and has partial tissue functions. The organoid technology can reveal the growth state, structure, function and characteristics of the tissue or organ, and plays an important role in reconstructing invitro experimental models that can truly simulate the human liver. In this paper, we will give a brief introduction of liver organoids and review their applications in liver cancer research, especially in liver cancer pathogenesis, drug screening, precision medicine, regenerative medicine, and other fields. We have also discussed advantages and disadvantages of organoids, as well as future directions and perspectives towards liver organoids.

The Relationship between Complements and Age-Related Macular Degeneration and Its Pathogenesis.

Age-related macular degeneration is a retinal disease that causes permanent loss of central vision in people over the age of 65. Its pathogenesis may be related to mitochondrial dysfunction, inflammation, apoptosis, autophagy, complement, intestinal flora, and lipid disorders. In addition, the patient's genes, age, gender, cardiovascular disease, unhealthy diet, and living habits may also be risk factors for this disease. Complement proteins are widely distributed in serum and tissue fluid. In the early 21st century, a connection was found between the complement cascade and age-related macular degeneration. However, little is known about the effect of complement factors on the pathogenesis of age-related macular degeneration. This article reviews the factors associated with age-related macular degeneration, the relationship between each factor and complement, the related functions, and variants and provides new ideas for the treatment of this disease.

Fe single atoms encapsulated in N, P-codoped carbon nanosheets with enhanced peroxidase-like activity for colorimetric detection of methimazole.

Excessive use of antithyroid drug methimazole (MMI) in pharmaceutical samples can cause hypothyroidism and symptoms of metabolic decline. Hence, it is urgent to develop rapid, low cost and accurate colorimetric method with peroxidase-like nanozymes for determination of MMI in medical, nutrition and pharmaceutical studies. Herein, Fe single atoms were facilely encapsulated into N, P-codoped carbon nanosheets (Fe SAs/NP-CSs) by a simple pyrolysis strategy, as certified by a series of characterizations. UV-vis absorption spectroscopy was employed to illustrate the high peroxidase-mimicking activity of the resultant Fe SAs/NP-CSs nanozyme through the typical catalysis of 3,3',5,5'-tetramethylbenzidine (TMB) oxidation. The catalytic mechanism was scrutionously investigated by the fluorescence spectroscopy and electron paramagnetic resonance (EPR) tests. Additionally, the introduced MMI had the ability to reduce the oxidation of TMB (termed oxTMB) as a peroxidase inhibitor, coupled by fading the blue color. By virtue of the above findings, a visual colorimetric sensor was established for dual detection of methimazole (MMI) with a linear scope of 5-50 mM and a LOD of 1.57 mM, coupled by assay of H2O2 at a linear range of 3-50 mM. According to the irreversible oxidation of the drug, its screening with acceptable results was achieved on the sensing platform even in commercial tablets The Fe SAs/NP-CSs nanozyme holds great potential for clinical diagnosis and drug analysis.

Recent advances in the involvement of epigenetics in the pathogenesis of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a typical systemic autoimmune disease that manifests as skin rash, arthritis, lymphadenopathy, and multiple organ lesions. Epigenetics, including DNA methylation, histone modification, and non-coding RNA regulation, mainly affect the function and characteristics of cells through the regulation of gene transcription or translation. Increasing evidence indicates that there are a variety of complex epigenetic effects in patients with SLE, which interfere with the differentiation and function of T, and B lymphocytes, monocytes, and neutrophils, and enhance the expression of SLE-associated pathogenic genes. This paper summarizes our currently knowledge regarding pathogenesis of SLE, and introduces current advances in the epigenetic regulation of SLE from three aspects: immune function, inflammatory response, and lupus complications. We propose that epigenetic changes could be used as potential biomarkers and therapeutic targets of SLE.

Effect of percutaneous cerebral oximetry-guided anaesthetic management on postoperative delirium in older adults undergoing off-pump coronary artery bypass grafting: study protocol for a single-centre prospective randomised controlled trial in a tertiary academic hospital in China.

INTRODUCTION: Postoperative delirium is a prominent and clinically important complication in older adults after coronary artery bypass grafting (CABG) surgery, resulting in prolonged hospital stay, long-term cognitive impairment and increased morbidity and mortality. Many studies have shown that cerebral desaturation is associated with increased risk of postoperative delirium during on-pump cardiac surgery. However, few studies have focused on the effect of optimising regional cerebral oxygen saturation (rSO2) on postoperative delirium during off-pump CABG. The purpose of this study is to investigate whether intraoperative anaesthetic management based on percutaneous cerebral oximetry monitoring decreases the incidence of postoperative delirium in older adults undergoing off-pump CABG. METHODS: This single-centre randomised controlled trial will randomly assign 200 patients to the intervention group or the control group at a ratio of 1:1. The patients in the intervention group will be observed by percutaneous cerebral oximetry monitoring that the desaturation (a drop of more than 20% from baseline value or rSO2 less than 55% for >60 consecutive seconds at either probe) during the procedure triggered the intervention strategies, while the cerebral oximetry data of the control group will be hidden from the clinical team and patients will be anaesthetised by the usual anaesthetic management. The primary outcome will be the incidence of postoperative delirium during the first 7 days after off-pump CABG. Delirium will be comprehensively evaluated by the combination of the Richmond Agitation Sedation Scale and the Confusion Assessment Method for the intensive care unit. The secondary outcomes will include the incidence of postoperative acute kidney injury and myocardial infarction during the hospital stay, as well as the intensive care unit and hospital length of stay. ETHICS AND DISSEMINATION: This study was approved by the Ethics Committee of the Chinese Academy of Medical Sciences, Fuwai Hospital (No 2022-1824). Written informed consent will be obtained from each patient or their legal representatives before enrolment. The results of this trial will be published in an international peer-reviewed scientific journal. TRIAL REGISTRATION NUMBER: ChiCTR2300068537.

Hybrid endovenous laser ablation reduces the recurrence of varicose veins below the knee compared with radiofrequency ablation: a real-world study.

Introduction: This study aimed to investigate the outcome of hybrid endovenous laser ablation (EVLA, 1470 nm) and radiofrequency ablation (RFA) procedures for varicose veins (VVs). Material and methods: We retrospectively analysed the clinical data of patients from July 2019 to December 2020. Eighty-four patients (121 limbs) underwent a hybrid EVLA procedure, and 108 patients (151 limbs) underwent an RFA procedure. The outcomes, venous clinical severity score (VCSS), chronic venous disease quality-of-life questionnaire (CIVIQ-20) score, and recurrence at 1, 6, and 12 months were collected. Results: No differences in complications or 24-h pain scores were noted between the 2 procedures, but a lower dosage of foam sclerosant was used in the EVLA procedure than in the RFA procedure (p < 0.02). The postoperative VCSS and CIVIQ-20 scores in the 2 groups were significantly decreased compared with the scores before the procedure, and no differences in scores were noted between the 2 procedures at 1 month. However, the VCSS and CIVIQ-20 scores for the EVLA procedure were significantly better than those for the RFA procedure at 6 and 12 months (p < 0.05). Both procedures showed a similar great saphenous vein closure rate at 12 months. The EVLA procedure showed lower rates of overall recurrence (4.96% vs. 14.57%, OR = 3.27, 95% CI: 1.33-8.00, p = 0.01) and recurrence below the knee (4.13% vs. 11.92%, OR = 3.14; 95% CI: 1.18-8.35, p = 0.02). Moreover, the patient satisfaction score was greater for the EVLA procedure than for the RFA procedure (p < 0.02). Conclusions: The hybrid EVLA (1470 nm) procedure reduces VV recurrence below the knee and results in better quality-of-life scores.

The Role of PKM2 in Multiple Signaling Pathways Related to Neurological Diseases.

Pyruvate kinase M2 (PKM2) is a key rate-limiting enzyme in glycolysis. It is well known that PKM2 plays a vital role in the proliferation of tumor cells. However, PKM2 can also exert its biological functions by mediating multiple signaling pathways in neurological diseases, such as Alzheimer's disease (AD), cognitive dysfunction, ischemic stroke, post-stroke depression, cerebral small-vessel disease, hypoxic-ischemic encephalopathy, traumatic brain injury, spinal cord injury, Parkinson's disease (PD), epilepsy, neuropathic pain, and autoimmune diseases. In these diseases, PKM2 can exert various biological functions, including regulation of glycolysis, inflammatory responses, apoptosis, proliferation of cells, oxidative stress, mitochondrial dysfunction, or pathological autoimmune responses. Moreover, the complexity of PKM2's biological characteristics determines the diversity of its biological functions. However, the role of PKM2 is not entirely the same in different diseases or cells, which is related to its oligomerization, subcellular localization, and post-translational modifications. This article will focus on the biological characteristics of PKM2, the regulation of PKM2 expression, and the biological role of PKM2 in neurological diseases. With this review, we hope to have a better understanding of the molecular mechanisms of PKM2, which may help researchers develop therapeutic strategies in clinic.

Role of Oxidative Stress in the Occurrence and Development of Cognitive Dysfunction in Patients with Obstructive Sleep Apnea Syndrome.

Obstructive sleep apnea syndrome (OSAS) causes recurrent apnea and intermittent hypoxia at night, leading to several complications such as cognitive dysfunction. However, the molecular mechanisms underlying cognitive dysfunction in OSAS are unclear, and oxidative stress mediated by intermittent hypoxia is an important mechanism. In addition, the improvement of cognitive dysfunction in patients with OSAS varies by different treatment regimens; among them, continuous positive airway pressure therapy (CPAP) is mostly recognized for improving cognitive dysfunction. In this review, we discuss the potential mechanisms of oxidative stress in OSAS, the common factors of affecting oxidative stress and the Links between oxidative stress and inflammation in OSAS, focusing on the potential links between oxidative stress and cognitive dysfunction in OSAS and the potential therapies for neurocognitive dysfunction in patients with OSAS mediated by oxidative stress. Therefore, further analysis on the relationship between oxidative stress and cognitive dysfunction in patients with OSAS will help to clarify the etiology and discover new treatment options, which will be of great significance for early clinical intervention.

A broad-spectrum pneumococcal vaccine induces mucosal immunity and protects against lethal Streptococcus pneumoniae challenge.

Pneumococcal disease is a major threat to public health globally, impacting individuals across all age groups, particularly infants and elderly individuals. The use of current vaccines has led to unintended consequences, including serotype replacement, leading to a need for a new approach to combat pneumococcal disease. A promising solution is the development of a broad-spectrum pneumococcal vaccine. In this study, we present the development of a broad-spectrum protein-based pneumococcal vaccine that contains three pneumococcal virulence factors: rlipo-PsaA (lipidated form), rPspAΔC (truncated form), and rPspCΔC (truncated form). Intranasal immunization with rlipo-PsaA, rPspAΔC, and rPspCΔC (LAAC) resulted in significantly higher IgG titres than those induced by administration of nonlipidated rPsaA, rPspAΔC, and rPspCΔC (AAC). Furthermore, LAAC immunization induced the production of higher IgA titres in vaginal washes, feces, and sera in mice, indicating that LAAC can induce systemic mucosal immunity. In addition, administration of LAAC also induced Th1/Th17-biased immune responses and promoted opsonic phagocytosis of Streptococcus pneumoniae strains of various serotypes, implying that the immunogenicity of LAAC immunization provides a protective effect against pneumococcal infection. Importantly, challenge data showed that the LAAC-immunized mice had a reduced bacterial load not only for several serotypes of the 13-valent conjugate pneumococcal vaccine (PCV13) but also for selected non-PCV13 serotypes. Consistently, LAAC immunization increased the survival rate of mice after bacterial challenge with both PCV13 and non-PCV13 serotypes. In conclusion, our protein-based pneumococcal vaccine provides protective effects against a broad spectrum of Streptococcus pneumoniae serotypes.