SIRT5 exacerbates eosinophilic chronic rhinosinusitis by promoting polarization of M2 macrophage.

BACKGROUND: Previous studies implied that local M2 polarization of macrophage promoted mucosal edema and exacerbated TH2 type inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP). However, the specific pathogenic role of M2 macrophages and the intrinsic regulators in the development of CRS remains elusive. OBJECTIVE: We sought to investigate the regulatory role of SIRT5 in the polarization of M2 macrophages and its potential contribution to the development of CRSwNP. METHODS: Real-time reverse transcription-quantitative PCR and Western blot analyses were performed to examine the expression levels of SIRT5 and markers of M2 macrophages in sinonasal mucosa samples obtained from both CRS and control groups. Wild-type and Sirt5-knockout mice were used to establish a nasal polyp model with TH2 inflammation and to investigate the effects of SIRT5 in macrophage on disease development. Furthermore, in vitro experiments were conducted to elucidate the regulatory role of SIRT5 in polarization of M2 macrophages. RESULTS: Clinical investigations showed that SIRT5 was highly expressed and positively correlated with M2 macrophage markers in eosinophilic polyps. The expression of SIRT5 in M2 macrophages was found to contribute to the development of the disease, which was impaired in Sirt5-deficient mice. Mechanistically, SIRT5 was shown to enhance the alternative polarization of macrophages by promoting glutaminolysis. CONCLUSIONS: SIRT5 plays a crucial role in promoting the development of CRSwNP by supporting alternative polarization of macrophages, thus providing a potential target for CRSwNP interventions.

Exploring gene biomarkers and targeted drugs for ferroptosis and cuproptosis in osteosarcoma: A bioinformatic approach.

Osteosarcoma predominantly affects adolescents and young adults and is characterized as a malignant bone tumor. In recent decades, substantial advancements have been achieved in both diagnosing and treating osteosarcoma. Resulting in enhanced survival rates. Despite these advancements, the intricate relationship between ferroptosis and cuproptosis genes in osteosarcoma remains inadequately understood. Leveraging TARGET and GEO datasets, we conducted Cox regression analysis to select prognostic genes from a cohort of 71 candidates. Subsequently, a novel prognostic model was engineered using the LASSO algorithm. Kaplan-Meier analysis demonstrated that patients stratified as low risk had a substantially better prognosis compared with their high-risk counterparts. The model's validity was corroborated by the area under the receiver operating characteristic (ROC) curve. Additionally, we ascertained independent prognostic indicators, including clinical presentation, metastatic status, and risk scores, and crafted a clinical scoring system via nomograms. The tumor immune microenvironment was appraised through ESTIMATE, CIBERSORT, and single-sample gene set enrichment analysis. Gene expression within the model was authenticated through PCR validation. The prognostic model, refined by Cox regression and the LASSO algorithm, comprised two risk genes. Kaplan-Meier curves confirmed a significantly improved prognosis for the low-risk group in contrast to those identified as high-risk. For the training set, the ROC area under the curve (AUC) values stood at 0.636, 0.695, and 0.729 for the 1-, 3-, and 5-year checkpoints, respectively. Although validation set AUCs were 0.738, 0.668, and 0.596, respectively. Immune microenvironmental analysis indicated potential immune deficiencies in high-risk patients. Additionally, sensitivity to three small molecule drugs was investigated in the high-risk cohort, informing potential immunotherapeutic strategies for osteosarcoma. PCR analysis showed increased mRNA levels of the genes FDX1 and SQLE in osteosarcoma tissues. This study elucidates the interaction of ferroptosis and cuproptosis genes in osteosarcoma and paves the way for more targeted immunotherapy.

Comparative proteomics profiling revealed the involvement of GRB2-ROCK2 axis in Lyme neuroborreliosis caused by Borrelia Burgdorferi.

The zoonotic Lyme neuroborreliosis (LNB) disease is caused by Borrelia burgdorferi, with wide distribution, rapid dissemination and high disability rate. However, the molecular mechanism underlying B. burgdorferi mediated neuroborreliosis remains largely unknown. Here, the frontal cortex from rhesus brains was incubated with B. burgdorferi, and proteomics profiling was evaluated by isobaric tag for relative and absolute quantitation. Proteins were identified and quantified, and differentially expressed proteins (DEPs) were isolated by comparing co-cultured samples and control samples. A total of 43, 164 and 368 DEPs were significantly altered after 6, 12 and 24 h treatment with B. burgdorferi respectively. Gene ontology and KEGG pathway analyses revealed that chemokine biological process was significantly enriched. Two genes in chemokine pathway including GRB2 and ROCK2 were significantly up-regulated after B. burgdorferi co-culturing. By in vitro assay, we confirmed that the expression of GRB2 and ROCK2 was increased after B. burgdorferi infection. In conclusion, our study revealed the involvement of chemokine pathway in the pathogenesis of LNB. GRB2 and ROCK2 may be novel biomarkers and therapeutic targets for LNB.

Circulating small extracellular vesicle-encapsulated SEMA5A-IT1 attenuates myocardial ischemia-reperfusion injury after cardiac surgery with cardiopulmonary bypass.

Cardiomyocyte injury is a common complication during cardiac surgery with cardiopulmonary bypass (CPB). Studies have shown that circulating small extracellular vesicles (sEVs) are involved in the pathological process of cardiovascular diseases via delivering signaling molecules. This study aims to investigate the relationship between circulating sEV-encapsulated long noncoding RNAs (lncRNAs) and cardiac injury after CPB. Here, we found that the expression of sEV SEMA5A-IT1 in serum samples of patients after CPB was higher than that of pre-CPB serum samples. Moreover, serum-derived sEV SEMA5A-IT1 levels were negatively correlated with creatine kinase-MB (CK-MB) levels in patients who underwent CPB operation. Notably, circulating sEVs packaged with SEMA5A-IT1 could be uptaken by cardiomyocyte-like cells AC16 and increased SEMA5A-IT1 expression in AC16 cells. Upregulated SEMA5A-IT1 protected cardiomyocytes against hypoxia/reoxygenation injury, confirmed by increased cell viability, reduced cell apoptosis, and inhibited ferroptosis in AC16 cells. Mechanistically, SEMA5A-IT1 regulated the expression of B-cell CLL/lymphoma 2 (BCL2) and solute carrier family 7 member 11 (SLC7A11) through sponging miR-143-3p. Transfection of miR-143-3p mimics, BCL2, or SLC7A11 knockdown could attenuate the protective effect of SEMA5A-IT1 on cardiomyocytes. In conclusion, we propose that SEMA5A-IT1, which is transported to cardiomyocytes through circulating sEVs, is an important regulatory molecule that protects cardiomyocytes from ischemia-reperfusion injury, providing a target for the prevention and treatment of myocardial ischemia-reperfusion injury.

Analysis and design of a wide-field and large-numerical-aperture compact imaging spectrometer with a freeform surface.

Wide-field-of-view (FoV) Offner imaging spectrometers with freeform surfaces have been studied extensively in recent years. However, a design result with a large numerical aperture (NA) cannot be simultaneously obtained with this layout. We present the concept of a limited system in the tangential direction. Based on this insight, we present a new design method, to the best of our knowledge, based on the decenter anamorphic stop, which can achieve large NA in compact wide-FoV Offner imaging spectrometers with freeform surfaces. Compared to conventional imaging spectrometers with the same parameters, the light-gathering capacity of the decenter anamorphic stop-based imaging spectrometer is increased by more than 40%. In addition, based on the presented method, we design a compact imaging spectrometer with a wide FoV and large NA. The designed imaging spectrometer with a freeform surface has excellent performance. Finally, we fabricate and measure the freeform mirror. The surface irregularity of the freeform mirror is better than 1/30λ (λ=632.8n m). The result shows that the Offner imaging spectrometer with a freeform surface can be fabricated and will play a significant role in the fields of aeronautical and astronautical remote sensing.

Analysis method of the Offner hyperspectral imaging spectrometer based on vector aberration theory.

Compact hyperspectral imaging spectrometers with a wide field of view (FoV) have significant application value. However, the aberration field of such imaging spectrometers is sensitive, and varies for different wavelengths when reducing the spectrometer volume. It is difficult to explain the variation in the aberration field using traditional aberration theory. In this study, we extend the vector aberration theory (VAT) to the Offner imaging spectrometer. We deduce the expression of the aberration field decenter vector of the Offner spectrometer based on the real ray-trace method. Furthermore, we derive the expression of the third-order vector aberration of the system. Subsequently, we explain some common phenomena in the Offner imaging spectrometer. This new analysis method can provide useful guidance for designing a compact wide FoV Offner imaging spectrometer. With this new insight, we designed a compact wide FoV Offner imaging spectrometer with a freeform tertiary mirror. Compared to conventional spectrometers with the same specifications, the total length of the spectrometer decreased by 37%, and the volume by 75%. After the tolerance analysis, the freeform optics satisfied the existing machining technology. The analysis method presented in this paper furthers the designer's understanding of the aberration field of the Offner imaging spectrometer. The method is significant in the design of a compact wide FoV Offner imaging spectrometer with freeform optics.

RASSF10 regulates bone invasion of growth hormone-secreting adenomas via exosomes.

BACKGROUND: Invasion of pituitary growth hormone-secreting adenoma into surrounding tissues poses a challenge for complete resection in surgery, which is the main reason for recurrence of this type of cancer. Studies have shown that abnormal methylation of RASSF10 can promote the expression of MDM2 and regulate the tumor microenvironment by affecting the secretion of exosomes. In the present study, we aim to uncover the specific underlying mechanism of this effect. METHOD: Transwell co-culture assays was performed using GT1.1 cells or exosomes and RAW264.7 cells. RAW264.7 cells were collected for invasion, proliferation and apoptosis assays, RT-qPCR and western blotting. RNA-seq was performed and used to assess the potential molecular pathways of the effect of GT1.1 cell-exosomes on RAW264.7 cells. RESULTS: GT1.1 cells with reduced RASSF10 expression could promote the proliferation and migration of RAW264.7 cells, and promote their expression of osteoclast markers TRAP and CK. The effect of GT1.1 cell exosomes on the RAW264.7-cell phenotype was shown to be achieved through the RASSF10-MDM2 pathway. RNA-seq allowed the identification of PI3K-AKT, MAPK, and calcium signaling as important in this regulation system of RASSF10-MDM2. CONCLUSION: Our results indicate that GT1.1 cells activate PI3K-AKT, MAPK and calcium signaling via the RASSF10-MDM2 pathway, and promote the differentiation of RAW264.7 cells into osteoclasts through exosomes. This study may provide new ideas to aid in early diagnosis, prognostic assessment and treatment of aggressive pituitary adenomas.

NLRP3 inflammasome activation promotes the development of allergic rhinitis via epithelium pyroptosis.

Allergic rhinitis (AR) is a worldwide highly prevalent nasal inflammatory disease with elusive mechanisms about the regulation of innate immune response. The roles and mechanisms of NLRP3, a typical inflammasome, in AR development remain unclear. Here we investigate the roles of NLRP3 inflammasome activation in the development and progression of AR and try to uncover its potential mechanisms underlying. Wildtype and NLRP3 knockout mice were applied to construct the ovalbumin (OVA)-induced AR model. Caspase-1 specific inhibitor Belnacasan and inflammasome activator ATP were used for adjuvant stimulation of AR-model mice respectively. We found that the production of IL-1ß and the activation of inflammasome were increased in both patients and mice with AR. NLRP3 deficiency markedly suppressed AR progression with reduced inflammatory response and epithelium pyroptosis in mice with AR. Furthermore, Caspase-1 inhibitor treatment in vivo ameliorated the development and progression of AR with favorable outcomes. Mechanistically, inflammation augments and nasal mucosa injury during AR were partially due to ASC-specks accumulation and subsequent cell pyroptosis. Our study reveals the previously unknown roles of NLRP3 inflammasome in promoting the development and progression of AR via enhancing inflammatory response and epithelium pyroptosis and thus provides a potential clue for allergic disease interventions.

Design of a compact hyperspectral imaging spectrometer with a freeform surface based on anastigmatism.

Hyperspectral imaging spectrometers with a wide field of view (FoV) have significant application values. However, enhancing the FoV will increase the volume of the imaging spectrometer and reduce the imaging quality, so a wide-FoV spectrometer system is difficult to design. Based on the theory of off-axis astigmatism, we present a method that includes a "prism box," "partial anastigmatism," and a partial differential equation to solve the parameters of a freeform surface. In this method, a compact wide-FoV imaging spectrometer with a freeform surface is designed. The spectrometer is an Offner structure with two curved prisms as the dispersion elements. The primary mirror and tertiary mirror of the Offner spectrometer are an aspheric surface and a freeform surface, respectively, to correct the off-axis aberration of a wide FoV. The ratio of the slit length to the total length of the spectrometer is close to 0.4. In comparison to conventional spectrometers of the same specifications, the total length of the spectrometer is reduced by 40% and the volume by 70%. The compact imaging spectrometer has potential application in the field of space remote sensing. In addition, the design method of the spectrometer provides a reference for the design of other optical systems with freeform surfaces.

Blocking long noncoding RNA MALAT1 restrained the development of laryngeal and hypopharyngeal carcinoma.

PURPOSE: The long non-coding RNA MALAT1 is a predictive marker in several solid tumors with highly conserved sequences. However, the role of non-coding RNA in development of laryngeal or hypopharyngeal cancer remains unclear. METHODS: Tumor tissues and adjacent non-cancer tissues of 24 patients were collected. We detected the expression of MALAT1 in laryngeal cancer tissues and hypopharyngeal cancer tissues. Moreover, we developed a MALAT1 silencing model in human laryngeal tumor cells by transfecting MALAT1 small interfering RNA into human laryngeal carcinoma cell line Hep-2 and pharyngeal carcinoma cell line FaDu with Lipofectamine 2000 system. Cell cycle analysis, Cell Counting Kit-8 assay, Transwell assay, quantitative reverse transcription PCR, and wound-healing assays were performed to evaluate the impact of MALAT1 depletion on laryngeal or hypopharyngeal cancer cell's growth, proliferation, apoptosis, invasion and migration. RESULTS: MALAT1 was significantly up-regulated in laryngeal and hypopharyngeal carcinoma cells. MALAT1 down-regulation induced the increased apoptosis of both cell lines and suppressed cells' proliferation. Cells were arrested in G1/G2 phase and cells of S phase were significantly decreased. Down-regulation of MALAT1 expression can also inhibit the migration and invasion of laryngeal squamous cell carcinoma cell (Hep-2) and hypopharyngeal cancer cell (FaDu). CONCLUSION: In summary, our deactivation model of MALAT1 disentangled the active function of it as a regulator of gene expression governing the hallmarks of laryngeal and hypopharyngeal cancer. Blocking this long non-coding RNA may restrain the development of laryngeal cancer.

Borrelia burgdorferi basic membrane protein A stimulates murine macrophage to secrete specific chemokines.

In this study, we investigated the mechanisms that lead to the production of proinflammatory mediators by the murine macrophage cell line, RAW264.7, when these cells are exposed in vitro to recombinant Borrelia burgdorferi basic membrane protein A (rBmpA). Using antibody protein microarray technology with high-throughput detection ability for detecting 25 chemokines in culture supernatant the RAW264.7 cell culture supernatants at 12 and 24 h post-stimulation with rBmpA, we identified two chemokines, a monocyte chemoattractant protein-5 (MCP-5/CCL12) and a macrophage inflammatory protein-2 (MIP-2/CXCL2), both of which increased significantly after stimulation. We then chose these two chemokines for further study. Enzyme-linked immunosorbent assay and real-time polymerase chain reaction revealed that with the increase of rBmpA concentration, MCP-5/CCL12 and MIP-2/CXCL2 showed concentration-dependent increases (p <0.01).Our results indicate that the rBmpA could stimulate the secretion of several specific chemokines and induce Lyme arthritis.

Off-axis three-mirror freeform telescope with a large linear field of view based on an integration mirror.

We report on the design of an off-axis three-mirror freeform telescope with a large field of view (FOV) based on an integration mirror (IM). This design is the continuation of the authors' previous work. Based on aberration theory, we established a suitable nonrelayed three-mirror-anastigmat initial configuration for integration mirror design. For an optical freeform surface, we analyzed the qualitative aberration correction ability of a x-y polynomial surface that can provide a simple, convenient, and user-friendly relationship between freeform surface term coefficients and aberrations and then applied the x-y polynomial surface on the tertiary mirror to improve the system optimization degrees of freedom. In an example with a focal length of 1200 mm, an F-number of 12, and a FOV of 1°×30°, the tolerance performance was analyzed, and the system presented a good imaging performance. In addition, the IM structure and opto-mechanics support structure were designed and analyzed. The confirmatory design results showed that the integration of the primary mirror and tertiary mirror can improve opto-mechanical properties judged by multiple criteria. In conclusion, the integration of the primary mirror and tertiary mirror not only offers alignment convenience as described previously but also improves system opto-mechanical properties in multiple perspectives. We believe this large linear FOV system based on IM has broad future applications in the optical remote sensing field.

Interfragmentary compression force and fixation stability of lateral tibial plateau fractures in normal and osteoporotic bones.

Lateral platform collapse in fixations of lateral tibial plateau fractures (TPFs) using either double-lag screws fixation (DSF) or locking-plate fixation (LPF) is not rare. This study aimed to explore the effect of enhancing the interfragmentary compression force (IFCF) on fixation stability in lateral TPFs in normal and osteoporotic bones using finite element analysis. Finite element models of DSF in normal bone and LPF in normal and osteoporotic bones were established to simulate the fixations of lateral TPF. After model validation, axial compressive forces of 500, 1000, 1500, and 2500 N to the tibial plateau along with an IFCF of 0, 100, 200, and 300 N were applied. The maximum axial micromotion of the lateral fragment (MAM-LF), maximal translational micromotion of the lateral fragment (MTM-LF), peak von Mises stress (VMS), and peak equivalent elastic strain of the lateral fragment (EES-LF) were evaluated. The MAM-LF showed a decreasing trend as the IFCF increased in all models. For DSF models, the peak VMS of implants increased as the IFCF increased when the axial loads were 500 and 1000 N. The peak EES-LF decreased as the IFCF increased under axial loads of 1000, 1500, and 2500 N. For the normal and osteoporotic LPF models, the peak VMS of the implants decreased as the IFCF increased. Peak EES-LF decreased as IFCF increased. In conclusion, enhancing IFCF was beneficial in improving the fixation stability of lateral TPF. The optimal IFCF for DSF and LPF should be as high as reasonably feasible.

Application of a combined cancellous lag screw enhances the stability of locking plate fixation of osteoporotic lateral tibial plateau fracture by providing interfragmentary compression force.

BACKGROUND: Insufficient interfragmentary compression force (IFCF) frequently leads to unstable fixation of osteoporotic lateral tibial plateau fractures (OLTPFs). A combined cancellous lag screw (CCLS) enhances IFCF; however, its effect on OLTPF fixation stability remains unclear. Therefore, we investigated the effect of CCLS on OLTPF stability using locking plate fixation (LPF). MATERIALS AND METHODS: Twelve synthetic osteoporotic tibial bones were used to simulate OLTPFs, which were fixed using LPF, LPF-AO cancellous lag screws (LPF-AOCLS), and LPF-CCLS. Subsequently, 10,000 cyclic loadings from 30 to 400 N were performed. The initial axial stiffness (IAS), maximal axial micromotion of the lateral fragment (MAM-LF) measured every 1000 cycles, and failure load after 10,000 cycles were tested. The same three fixations for OLTPF were simulated using finite element analysis (FEA). IFCFs of 0, 225, and 300 N were applied to the LPF, LPF-AOCLS, and LPF-CCLS, respectively, with a 1000-N axial compressive force. The MAM-LF, peak von Mises stress (VMS), peak equivalent elastic strain of the lateral fragment (EES-LF), and nodes of EES-LF > 2% (considered bone destruction) were calculated. RESULTS: Biomechanical tests revealed the LPF-AOCLS and LPF-CCLS groups to be superior to the LPF group in terms of the IAS, MAM-LF, and failure load (all p < 0.05). FEA revealed that the MAM-LF, peak VMS, peak EES-LF, and nodes with EES-LF > 2% in the LPF were higher than those in the LPF-AOCLS and LPF-CCLS. CONCLUSION: IFCF was shown to enhance the stability of OLTPFs using LPF. Considering overscrewing, CCLS is preferably recommended, although there were no significant differences between CCLS and AOCLS.

Efficacy and safety of antibiotics for treatment of leptospirosis: a systematic review and network meta-analysis.

BACKGROUND: Leptospirosis, an important zoonotic bacterial disease, commonly affects resource-poor populations and results in significant morbidity and mortality worldwide. The value of antibiotics in leptospirosis remains unclear, as evidenced by the conflicting opinions published. METHODS: We conducted a search in the PubMed, Web of Science, and Cochrane Library databases for studies. These studies included clinical trials and retrospective studies that evaluated the efficacy or safety of antibiotics for leptospirosis treatment. The primary outcomes assessed were defervescence time, mortality rate, and hospital stays. Subgroup analyses were performed based on whether there were cases involving children and whether there were cases of severe jaundice. Safety was defined as the prevalence of adverse events associated with the use of antibiotics. p scores were utilized to rank the efficacy of the antibiotics. RESULTS: There are included 9 randomized controlled trials (RCTs), 1 control trial (CT), and 3 retrospective studies (RS) involving 920 patients and 8 antibiotics. Six antibiotics resulted in significantly shorter defervescence times compared to the control, namely cefotaxime (MD, - 1.88; 95% CI = - 2.60 to - 1.15), azithromycin (MD, - 1.74; 95% CI = - 2.52 to - 0.95), doxycycline (MD, - 1.53; 95% CI = - 2.05 to - 1.00), ceftriaxone (MD, - 1.22; 95% CI = - 1.89 to - 0.55), penicillin (MD, - 1.22; 95% CI = - 1.80 to - 0.64), and penicillin or ampicillin (MD, - 0.08; 95% CI = - 1.01 to - 0.59). The antibiotics were not effective in reducing the mortality and hospital stays. Common adverse reactions to antibiotics included Jarisch-Herxheimer reaction, rash, headache, and digestive reactions (nausea, vomiting, diarrhea, abdominal pain, and others). CONCLUSIONS: Findings recommend that leptospirosis patients be treated with antibiotics, which significantly reduced the leptospirosis defervescence time. Cephalosporins, doxycycline, and penicillin are suggested, and azithromycin may be a suitable alternative for drug-resistant cases. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022354938.

A key protein from Borrelia burgdorferi could stimulate cytokines in human microglial cells and inhibitory effects of Cucurbitacin IIa.

Lyme neuroborreliosis (LNB) is an infectious disease of the nervous system caused by Borrelia burgdorferi (Bb) infection. However, its pathogenesis is not fully understood. We used recombinant BmpA (rBmpA) to stimulate human microglia cell HMC3, then collected the culture supernatant and extracted total RNA from cells, and used the supernatant for cytokine chip, then ELISA and qPCR technology were used to validate the results from cytokine chip. After rBmpA stimulation of microglia, 24 inflammation-related cytokines showed elevated expression. Among them, six cytokines (IL-6, IL-8, CCL2, CCL5, CXCL1, and CXCL10) increased significantly in mRNA transcription, three cytokines (IL-6, IL-8, and CXCL10) concentrations in the cell supernatant increased significantly after the rBmpA stimulation, and CuIIa could inhibit expression of these cytokines. The BmpA can stimulate human microglia to produce large amounts of cytokines, leading to the occurrence of inflammation, which may be closely related to the development of LNB. CuIIa can inhibit BmpA-induced cytokine production in microglia, which may have potential therapeutic effects on LNB.

Seventy years of evidence on the efficacy and safety of drugs for treating leprosy: a network meta-analysis.

OBJECTIVE: The World Health Organization (WHO) recommends multidrug therapy (MDT) with rifampicin, dapsone, and clofazimine for treating leprosy, which is based on very low-quality evidence. Here, we performed a network meta-analysis (NMA) to produce quantitative evidence to strengthen current WHO recommendations. METHOD: All studies were obtained from Embase and PubMed from the date of establishment to October 9, 2021. Data were synthesized with frequentist random-effects network meta-analyses. Outcomes were assessed using odds ratios (ORs), 95% confidence intervals (95% CIs), and P score. RESULTS: Sixty controlled clinical trials and 9256 patients were included. MDT was effective (range of OR: 1.06-1255584.25) for treating leprosy and multibacillary leprosy. Six treatments (Range of OR: 1.199-4.50) were more effective than MDT. Clofazimine (P score=0.9141) and dapsone+rifampicin (P score=0.8785) were effective for treating type 2 leprosy reaction. There were no significant differences in the safety of any of the tested drug regimens. CONCLUSIONS: The WHO MDT is effective for treating leprosy and multibacillary leprosy, but it may not be effective enough. Pefloxacin and ofloxacin may be good adjunct drugs for increasing MDT efficacy. Clofazimine and dapsone+rifampicin can be used in the treatment of a type 2 leprosy reaction. Single-drug regimens are not efficient enough to treat leprosy, multibacillary leprosy, or a type 2 leprosy reaction. AVAILABILITY OF DATA AND MATERIALS: All data generated or analyzed during this study are included in this published article [and its supplementary information files].

The intricate role of CCL5/CCR5 axis in Alzheimer disease.

The morbidity and mortality associated with Alzheimer disease (AD), one of the most common neurodegenerative diseases, are increasing each year. Although both amyloid ß and tau proteins are known to be involved in AD pathology, their detailed functions in the pathogenesis of the disease are not fully understood. There is increasing evidence that neuroinflammation contributes to the development and progression of AD, with astrocytes, microglia, and the cytokines and chemokines they secrete acting coordinately in these processes. Signaling involving chemokine (C-C motif) ligand 5 (CCL5) and its main receptor C-C chemokine receptor 5 (CCR5) plays an important role in normal physiologic processes as well as pathologic conditions such as neurodegeneration. In recent years, many studies have shown that the CCL5/CCR5 axis plays a major effect in the pathogenesis of AD, but there are also a few studies that contradict this. In short, the role of CCL5/CCR5 axis in the pathogenesis of AD is still intricate. This review summarizes the structure, distribution, physiologic functions of the CCL5/CCR5 axis, and the progress in understanding its involvement in the pathogenesis of AD.

Identification of Molecular Subtypes in Head and Neck Squamous Cell Carcinoma Based on Dysregulated Immune LncRNAs.

Long noncoding RNAs (lncRNAs) perform indispensable functions in cancer pathologies and are involved in the onset and progression of multiple cancers. Multiple platforms were performed to comprehensively analyze the head and neck squamous cell carcinoma (HNSCC) for determining molecular subtypes. Molecular subtypes were clustered and analyzed by the "ConsensusClusterPlus" R package. The Limma software was utilized to screen for differentially expressed genes (DEGs). Functional enrichment analyses, including Gene Set Enrichment Analysis (GSEA), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Ontology (GO), were performed on the three database resources. Seventeen lncRNAs were determined as HNSCC-specific immune lncRNAs that were dysregulated. Our research identified and redefined two distinct molecular subtypes, C1 (230 samples) and C2 (269 samples). Moreover, the C1 subtype had a higher survival rate than the C2 subtype in HNSCC samples, as well as a prolonged median survival duration with activated immune response. 1531 DEGs, including 529 upmodulated genes and 1002 downmodulated genes, were identified in the above two subtypes. Functional enrichment analysis revealed that upmodulated genes in C2 were associated with tumorigenesis and development, while downregulated genes in C2 were associated with immune response. By comparing with the existing immunophenotyping group, it found that C1 had more overlaps with the existing Atypical and Basal, and C2 and Classical and Mesenchymal had a high degree of coincidence. On the basis of lncRNA, there were significant differences in the aspect of prognostic and immunological characteristics in the two identified molecular subtypes of HNSCC.

Global seroprevalence and sociodemographic characteristics of Borrelia burgdorferi sensu lato in human populations: a systematic review and meta-analysis.

INTRODUCTION: Borrelia burgdorferi sensu lato (Bb) infection, the most frequent tick-transmitted disease, is distributed worldwide. This study aimed to describe the global seroprevalence and sociodemographic characteristics of Bb in human populations. METHODS: We searched PubMed, Embase, Web of Science and other sources for relevant studies of all study designs through 30 December 2021 with the following keywords: 'Borrelia burgdorferi sensu lato' AND 'infection rate'; and observational studies were included if the results of human Bb antibody seroprevalence surveys were reported, the laboratory serological detection method reported and be published in a peer-reviewed journal. We screened titles/abstracts and full texts of papers and appraised the risk of bias using the Cochrane Collaboration-endorsed Newcastle-Ottawa Quality Assessment Scale. Data were synthesised narratively, stratified by different types of outcomes. We also conducted random effects meta-analysis where we had a minimum of two studies with 95% CIs reported. The study protocol has been registered with PROSPERO (CRD42021261362). RESULTS: Of 4196 studies, 137 were eligible for full-text screening, and 89 (158 287 individuals) were included in meta-analyses. The reported estimated global Bb seroprevalence was 14.5% (95% CI 12.8% to 16.3%), and the top three regions of Bb seroprevalence were Central Europe (20.7%, 95% CI 13.8% to 28.6%), Eastern Asia (15.9%, 95% CI 6.6% to 28.3%) and Western Europe (13.5%, 95% CI 9.5% to 18.0%). Meta-regression analysis showed that after eliminating confounding risk factors, the methods lacked western blotting (WB) confirmation and increased the risk of false-positive Bb antibody detection compared with the methods using WB confirmation (OR 1.9, 95% CI 1.6 to 2.2). Other factors associated with Bb seropositivity include age ≥50 years (12.6%, 95% CI 8.0% to 18.1%), men (7.8%, 95% CI 4.6% to 11.9%), residence of rural area (8.4%, 95% CI 5.0% to 12.6%) and suffering tick bites (18.8%, 95% CI 10.1% to 29.4%). CONCLUSION: The reported estimated global Bb seropositivity is relatively high, with the top three regions as Central Europe, Western Europe and Eastern Asia. Using the WB to confirm Bb serological results could significantly improve the accuracy. More studies are needed to improve the accuracy of global Lyme borreliosis burden estimates. PROSPERO REGISTRATION NUMBER: CRD42021261362.