HLA-A*23 Is Associated With Lower Odds of Acute Retroviral Syndrome in Human Immunodeficiency Virus Type 1 Infection: A Multicenter Sub-Saharan African Study.

The role of human leukocyte antigen (HLA) class I and killer immunoglobulin-like receptor molecules in mediating acute retroviral syndrome (ARS) during human immunodeficiency virus type 1 (HIV-1) infection is unclear. Among 72 sub-Saharan African adults, HLA-A*23 was associated with lower odds of ARS (adjusted odds ratio, 0.10 [95% confidence interval, .01-.48]; P = .009), which warrants further studies to explore its role on HIV-1-specific immunopathogenesis.

Annexin A2 combined with TTK accelerates esophageal cancer progression via the Akt/mTOR signaling pathway.

Annexin A2 (ANXA2) is a widely reported oncogene. However, the mechanism of ANXA2 in esophageal cancer is not fully understood. In this study, we provided evidence that ANXA2 promotes the progression of esophageal squamous cell carcinoma (ESCC) through the downstream target threonine tyrosine kinase (TTK). These results are consistent with the up-regulation of ANXA2 and TTK in ESCC. In vitro experiments by knockdown and overexpression of ANXA2 revealed that ANXA2 promotes the progression of ESCC by enhancing cancer cell proliferation, migration, and invasion. Subsequently, animal models also confirmed the role of ANXA2 in promoting the proliferation and metastasis of ESCC. Mechanistically, the ANXA2/TTK complex activates the Akt/mTOR signaling pathway and accelerates epithelial-mesenchymal transition (EMT), thereby promoting the invasion and metastasis of ESCC. Furthermore, we identified that TTK overexpression can reverse the inhibition of ESCC invasion after ANXA2 knockdown. Overall, these data indicate that the combination of ANXA2 and TTK regulates the activation of the Akt/mTOR pathway and accelerates the progression of ESCC. Therefore, the ANXA2/TTK/Akt/mTOR axis is a potential therapeutic target for ESCC.

Bibliometric analysis of photodynamic therapy and immune response from 1989-2023.

Objective: Photodynamic therapy (PDT) is a minimally invasive treatment approach for precancerous and cancerous lesions, known for its ability to activate the host immune response. This study conducted a bibliometric analysis to identify the research trends and hotspots related to the immune response in PDT. Methods: We analyzed articles and reviews published from 1989 to 2023, retrieved from the Web of Science database. Using Citespace and VOSviewer, we visualized the distribution patterns of these studies in time and space. Results: The analysis revealed a substantial increase in the number of publications on PDT-related immune response since 1989. A total of 1,688 articles from 1,701 institutions were included in this analysis. Among thei nstitutions, the Chinese Academy of Sciences demonstrated exceptional productivity and a willingness to collaborate with others. Additionally, 8,567 authors contributed to the field, with Mladen Korbelik, Michael R. Hamblin, and Wei R. Chen being the most prolific contributors. The current research focus revolves around novel strategies to enhance antitumor immunity in PDT, including PDT-based dendritic cell vaccines, combination therapies with immune checkpoint inhibitors (ICIs), and the use of nanoparticles for photosensitizer delivery. Furthermore, genes such as CD8A, TNF, CD4, IFNG, CD274, IL6, IL10, CALR, HMGB1, and CTLA4 have been evaluated in the context of PDT-related immunity. Conclusion: PDT not only achieves tumor ablation but also stimulates the immune response, bolstering antitumor immunity. This study highlights the emerging hotspots in PDT-related immune response research and provides valuable insights for future investigations aimed at further enhancing antitumor immunity.

Unilateral parotid gland Simultaneously primary two different pathological tumors: a case report and literature review / 口腔疾病防治

Objective@#To explore the clinical manifestations, histopathological characteristics, diagnosis, treatment, and prognosis of simultaneous unilateral primary tumors of different pathological types in the parotid gland.@*Methods@#A case of simultaneous unilateral primary parotid gland tumors, i.e., adenolymphoma and basal cell adenoma, was reviewed and analyzed in combination with the literature.@*Results@#The patient discovered a lump in the right parotid gland area one month prior to presentation, and a tumor was palpated in the shallow lobe of the right parotid gland before surgery. According to MR images, the initial diagnoses were tumors of the shallow and deep lobes of the right parotid gland. The tumors of the deep and shallow lobes were excised with part of the gland, and the facial nerves were dissected under general anesthesia. Postoperative pathology revealed an adenolymphoma in the shallow lobe of the right parotid gland and a basal cell adenoma with cystic transformation in the deep lobe. The surgical effect was good, with no complications, and there was no recurrence after 1 year of follow-up. A review of the relevant literature showed that multiple primary tumors of the parotid gland can manifest as the simultaneous presence of two or more types of tumors on both sides or on one side, and the disease is mainly treated with surgery.@*Conclusion@#Multiple unilateral primary parotid gland tumors are rare. Imaging examinations need to be combined with clinical evaluations to prevent missed diagnoses. Surgery is the first treatment option, and patients with benign tumors have a good prognosis.

Analyzing Peak-to-Average Power Ratio Characteristics in Multi-Channel Intensity Modulation and Direct Detection Flexible Transceivers Deploying Inverse Fast Fourier Transform/Fast Fourier Transform-Based Processing.

Cascaded inverse fast Fourier transform/fast Fourier transform (IFFT/FFT)-based multi-channel aggregation/de-aggregation offers a promising solution in constructing highly desirable flexible optical transceivers for considerably improving optical networks' elasticity, flexibility, and adaptability. However, the multi-channel aggregation operation unavoidably results in generated signals having high peak-to-average power ratios (PAPRs). To solve this technical challenge, this paper first explores the PAPR characteristics of the corresponding flexible transceivers in optical back-to-back (B2B) and 20 km intensity modulation and direct detection (IMDD) transmission systems, and then numerically investigates the feasibility and effectiveness of utilizing the conventional clipping techniques in reducing their PAPR reductions. The results show that the last IFFT operation size is the primary factor determining the PAPRs rather than the channel count and modulation format. For a given last IFFT operation size, the optimal clipping ratio can be identified, which is independent of channel count. With the identified optimal clipping ratio, when the channel count is >4, every two-channel increase in the channel count can only lead to <1.2 Gb/s decreases in the maximum aggregated signal transmission capacity.

Highly discriminative and adaptive feature extraction method based on NMF-MFCC for event recognition of Φ-OTDR.

To enhance the capability of phase-sensitive optical time domain reflectometers (Φ-OTDR) to recognize disturbance events, an improved adaptive feature extraction method based on NMF-MFCC is proposed, which replaces the fixed filter bank used in the traditional method to extract the mel-frequency cepstral coefficient (MFCC) features by a spectral structure obtained from the Φ-OTDR signal spectrum using nonnegative matrix factorization (NMF). Three typical events on fences are set as recognition targets in our experiments, and the results show that the NMF-MFCC features have higher distinguishability, with the corresponding recognition accuracy reaching 98.47%, which is 7% higher than that using the traditional MFCC features.

Global burden and trends of ectopic pregnancy: An observational trend study from 1990 to 2019.

BACKGROUND: Ectopic pregnancy (EP) is one of the leading causes of death in women in early pregnancy, and the mortality of EP have gradually decreased over time in developed countries such as the United Kingdom and the United States. However, epidemiological information on EP has been lacking in recent years, so we analyzed EP data over a thirty-year period from 1990-2019 with the help of Global Burden of Disease study (GBD) data to fill this gap. METHODS: According to the EP data in GBD for the three decades from 1990 to 2019, we used estimated annual percentage changes (EAPC) to assess the trend of age-standardized incidence rate (ASIR), age-standardized death rate (ASDR) and age-standardized disability adjusted life years (AS-DALYs) trends in EP and to explore the correlation between socio-demographic index (SDI) stratification, age stratification and EP. RESULTS: Global ASIR, ASDR, AS-DALYs for EP in 2019 are 170.33/100,000 persons (95% UI: 133.18 to 218.49), 0.16/100,000 persons (95% UI, 0.14 to 0.19) and 9.69/100,000 persons (95% UI, 8.27 to 11.31), respectively. At the overall level, ASDR is significantly negatively correlated with SDI values (R = -0.699, p < 0.001). Besides that, ASDR and AS-DALYs have basically the same pattern. In addition, iron deficiency is one of the risk factors for EP. CONCLUSIONS: In the past three decades, the morbidity, mortality and disease burden of EP have gradually decreased. It is noteworthy that some economically disadvantaged areas are still experiencing an increase in all indicators, therefore, it is more important to strengthen the protection of women from ethnic minorities and low-income groups.

Analysis of proteome and post-translational modifications of 2-hydroxyisobutyrylation reveals the glycolysis pathway in oral adenoid cystic carcinoma.

PURPOSE: Oral adenoid cystic carcinoma (OACC) has high rates of both local-regional recurrence and distant metastasis. The objective of this study is to investigate the impact of Khib on OACC and its potential as a targeted therapeutic intervention. EXPERIMENTAL DESIGN: We investigated the DEPs (differentially expressed proteins) and DHMPs between OACC-T and OACC-N using LC-MS/MS-based quantitative proteomics and using several bioinformatics methods, including GO enrichment analysis, KEGG pathway analysis, subcellular localization prediction, MEA (motif enrichment analysis), and PPI (protein-protein interaction networks) to illustrate how Khib modification interfere with OACC evolution. RESULTS: Compared OACC-tumor samples (OACC-T) with the adjacent normal samples (OACC-N), there were 3243 of the DEPs and 2011 Khib sites were identified on 764 proteins (DHMPs). DEPs and DHMPs were strongly associated to glycolysis pathway. GAPDH of K254, ENO of K228, and PGK1 of K323 were modified by Khib in OACC-T. Khib may increase the catalytic efficiency to promote glycolysis pathway and favor OACC progression. CONCLUSIONS AND CLINICAL RELEVANCE: Khib may play a significant role in the mechanism of OACC progression by influencing the enzyme activity of the glycolysis pathway. These findings may provide new therapeutic options of OACC.

Early diagnosis for the onset of peri-implantitis based on artificial neural network.

The aim of this study is to construct an artificial neural network (ANN) based on bioinformatic analysis to enable early diagnosis of peri-implantitis (PI). PI-related datasets were retrieved from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and functional enrichment analyses were performed between PI and the control group. Furthermore, the infiltration of 22 immune cells in PI was analyzed using CIBERSORT. Hub genes were identified with random forest (RF) classification. The ANN model was then constructed for early diagnosis of PI. A total of 1,380 DEGs were identified. Enrichment analysis revealed the involvement of neutrophil-mediated immunity and the NF-kappa B signaling pathway in PI. Additionally, higher proportion of naive B cells, activated memory CD4 T cells, activated NK cells, M0 macrophages, M1 macrophages, and neutrophils were observed in the soft tissues surrounding PI. From the RF analysis, 13 hub genes (ST6GALNAC4, MTMR11, SKAP2, AKR1B1, PTGS2, CHP2, CPEB2, SYT17, GRIP1, IL10, RAB8B, ABHD5, and IGSF6) were selected. Subsequently, the ANN model for early diagnosis of PI was constructed with high performance. We identified 13 hub genes and developed an ANN model that accurately enables early diagnosis of PI.

CDK2-activated TRIM32 phosphorylation and nuclear translocation promotes radioresistance in triple-negative breast cancer.

INTRODUCTION: Despite radiotherapy being one of the major treatments for triple-negative breast cancer (TNBC), new molecular targets for its treatment are still required due to radioresistance. CDK2 plays a critical role in TNBC. However, the mechanism by which CDK2 promotes TNBC radioresistance remains to be clearly elucidated. OBJECTIVES: We aimed to elucidate the relationship between CDK2 and TRIM32 and the regulation mechanism in TNBC. METHODS: We performed immunohistochemical staining to detect nuclear TRIM32, CDK2 and STAT3 on TNBC tissues. Western blot assays and PCR were used to detect the protein and mRNA level changes. CRISPR/Cas9 used to knock out CDK2. shRNA-knockdown and transfection assays also used to knock out target genes. GST pull-down analysis, immunoprecipitation (IP) assay and in vitro isomerization analysis also used. Tumorigenesis studies also used to verify the results in vitro. RESULTS: Herein, tripartite motif-containing protein 32 (TRIM32) is revealed as a substrate of CDK2. Radiotherapy promotes the binding of CDK2 and TRIM32, thus leading to increased CDK2-dependent phosphorylation of TRIM32 at serines 328 and 339. This causes the recruitment of PIN1, involved in cis-trans isomerization of TRIM32, resulting in importin α3 binding to TRIM32 and contributing to its nuclear translocation. Nuclear TRIM32 inhibits TC45-dephosphorylated STAT3, Leading to increased transcription of STAT3 and radioresistance in TNBC. These results were validated by clinical prognosis confirmed by the correlative expressions of the critical components of the CDK2/TRIM32/STAT3 signaling pathway. CONCLUSIONS: Our findings demonstrate that regulating the CDK2/TRIM32/STAT3 pathway is a promising strategy for reducing radioresistance in TNBC.

Sex difference and risk factors in burden of urogenital congenital anomalies from 1990 to 2019.

Urogenital congenital anomalies (UCAs) is defined as "any live-birth with a urinary or genital condition" and affects millions of men and women worldwide. However, sex differences and related environmental risk factors in UCAs burden on a global scale have not been assessed. Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we estimated prevalence, incidence, mortality and disability-adjusted life years (DALYs) of UCAs from 1990 to 2019 by sex, region, and socio-demographic Index (SDI) in 204 countries and territories. The disease burden of UCAs was also estimated attributable to each risk factor were estimated according to risk exposure. In 2019, UCAs caused 10,200 all-ages deaths (95% UI 7550-13,400). The combined global incidence rate was 8.38 per 1000 (95% UI 5.88-12.0) live births. The ASIR increased slightly, while the ASDR decreased from 1990 to 2019.The UCAs burden varies greatly depending on the development level and geographical location. The UCAs burden was significantly higher in men than in women, and the sex differences showed an enlarging trend. Health risks and issues, including pollution, child and maternal malnutrition, diet habits, unsafe sanitation and water source, were detected to be positively related to UCAs burden. Albeit the age-standardised prevalence, mortality, incidence, and DALYs of UCAs have decreased, they still cause a public health challenge worldwide. The high deaths and DALYs rates in low and low-middle SDI countries highlight the urgent need for improved preventive, diagnostic, and therapeutic measures. Global strategies for enhancing water safety, reducing pollution, and healthy diets are crucial steps in reducing the burden of UCAs.

Chitin-based hydrogel loaded with bFGF and SDF-1 for inducing endogenous mesenchymal stem cells homing to improve stress urinary incontinence.

Nonoperative treatments for Stress Urinary Incontinence (SUI) represent an ideal treatment method. Mesenchymal stem cell (MSCs) treatment is a new modality, but there is a lack of research in the field of gynecological pelvic floor and no good method to induce internal MSC homing to improve SUI. Herein, we develop an injectable and self-healing hydrogel derived from ß-chitin which consists of an amino group of quaternized ß-chitin (QC) and an aldehyde group of oxidized dextran (OD) between the dynamic Schiff base linkage.it can carry bFGF and SDF-1a and be injected into the vaginal forearm of mice in a non-invasive manner. It provides sling-like physical support to the anterior vaginal wall in the early stages. In the later stage, it slowly releasing factors and promoting the homing of MSCs in vivo, which can improve the local microenvironment, increase collagen deposition, repair the tissue around urethra and finally improve SUI (Scheme 1). This is the first bold attempt in the field of pelvic floor using hydrogel mechanical support combined with MSCs homing and the first application of chitin hydrogel in gynecology. We think the regenerative medicine approach based on bFGF/SDF-1/chitin hydrogel may be an effective non-surgical approach to combat clinical SUI.

Single-Nucleus Transcriptome Profiling of Locally Advanced Cervical Squamous Cell Cancer Identifies Neural-Like Progenitor Program Associated with the Efficacy of Radiotherapy.

Radiotherapy is the first-line treatment for locally advanced cervical squamous cell cancer (CSCC). However, ≈50% of patients fail to respond to therapy and, in some cases, tumors progress after radical radiotherapy. Here, single-nucleus RNA-seq is performed to construct high-resolution molecular landscapes of various cell types in CSCC before and during radiotherapy, to better understand radiotherapy related molecular responses within tumor microenvironment. The results show that expression levels of a neural-like progenitor (NRP) program in tumor cells are significantly higher after radiotherapy and these are enriched in the tumors of nonresponding patients. The enrichment of the NRP program in malignant cells from the tumors of nonresponders in an independent cohort analyzed by bulk RNA-seq is validated. In addition, an analysis of The Cancer Genome Atlas dataset shows that NRP expression is associated with poor prognosis in CSCC patients. In vitro experiments on the CSCC cell line demonstrate that downregulation of neuregulin 1 (NRG1), a key gene from NRP program, is associated with decreased cell growth and increased sensitivity to radiation. Immunohistochemistry staining in cohort 3 validated key genes, NRG1 and immediate early response 3 from immunomodulatory program, as radiosensitivity regulators. The findings reveal that the expression of NRP in CSCC can be used to predict the efficacy of radiotherapy.

STNM1 in human cancers: role, function and potential therapy sensitizer.

STMN1 belongs to the stathmin gene family, it encodes a cytoplasmic phosphorylated protein, stathmin1, which is commonly observed in vertebrate cells. STMN1 is a structural microtubule-associated protein (MAP) that binds to microtubule protein dimers rather than microtubules, with each STMN1 binding two microtubule protein dimers and preventing their aggregation, leading to microtubule instability. STMN1 expression is elevated in a number of malignancies, and inhibition of its expression can interfere with tumor cell division. Its expression can change the division of tumor cells, thereby arresting cell growth in the G2/M phase. Moreover, STMN1 expression affects tumor cell sensitivity to anti-microtubule drug analogs, including vincristine and paclitaxel. The research on MAPs is limited, and new insights on the mechanism of STMN1 in different cancers are emerging. The effective application of STMN1 in cancer prognosis and treatment requires further understanding of this protein. Here, we summarize the general characteristics of STMN1 and outline how STMN1 plays a role in cancer development, targeting multiple signaling networks and acting as a downstream target for multiple microRNAs, circRNAs, and lincRNAs. We also summarize recent findings on the function role of STMN1 in tumor resistance and as a therapeutic target for cancer.

Post-translational modifications of histones: Mechanisms, biological functions, and therapeutic targets.

Histones are DNA-binding basic proteins found in chromosomes. After the histone translation, its amino tail undergoes various modifications, such as methylation, acetylation, phosphorylation, ubiquitination, malonylation, propionylation, butyrylation, crotonylation, and lactylation, which together constitute the "histone code." The relationship between their combination and biological function can be used as an important epigenetic marker. Methylation and demethylation of the same histone residue, acetylation and deacetylation, phosphorylation and dephosphorylation, and even methylation and acetylation between different histone residues cooperate or antagonize with each other, forming a complex network. Histone-modifying enzymes, which cause numerous histone codes, have become a hot topic in the research on cancer therapeutic targets. Therefore, a thorough understanding of the role of histone post-translational modifications (PTMs) in cell life activities is very important for preventing and treating human diseases. In this review, several most thoroughly studied and newly discovered histone PTMs are introduced. Furthermore, we focus on the histone-modifying enzymes with carcinogenic potential, their abnormal modification sites in various tumors, and multiple essential molecular regulation mechanism. Finally, we summarize the missing areas of the current research and point out the direction of future research. We hope to provide a comprehensive understanding and promote further research in this field.

KAT7 promotes radioresistance through upregulating PI3K/AKT signaling in breast cancer.

Chromatin-modifying enzymes are commonly altered in cancers, but the molecular mechanism by which they regulate cancers remains poorly understood. Herein, we demonstrated that Lysine acetyltransferase 7 (KAT7) was upregulated in breast cancer. KAT7 expression negatively correlated with the survival of breast cancer patients, and KAT7 silencing suppressed breast cancer radioresistance in vitro. Mechanistically, KAT7 activated Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) transcription, leading to enhanced PI3K/AKT signaling and radioresistance. Overexpression of AKT or PIK3CA restored radioresistance suppression induced by KAT7 inhibition. Moreover, overexpression of KAT7, but not KAT7 acetyltransferase activity-deficient mutants promoted AKT phosphorylation at the Ser473 site, PIK3CA expression and radioresistance suppression due to KAT7 inhibition. In conclusion, KAT7 has huge prospects for clinical application as a new target for predicting radioresistance in breast cancer patients.

LncRNA MCM3AP-AS1 enhances cell invasion, migration and tumor formation in non-small cell lung cancer cells by epigenetic inhibition of miR-34a.

BACKGROUND: The function of long non-coding RNA (lncRNA) MCM3AP-AS1 has been reported in several types of cancer, while its involvement in non-small cell lung cancer (NSCLC) is unknown. OBJECTIVE: This study aimed to investigate the function of MCM3AP-AS1 in NSCLC. METHODS: Silencing or overexpression of MCM3AP-AS1 was achieved in tumor cells to construct a tumor-bearing mice model to evaluate the effects of MCM3AP-AS1 on tumor growth. RESULTS: The results showed that MCM3AP-AS1 was upregulated in NSCLC and associated with worse survival. In NSCLC tissues, MCM3AP-AS1 was inversely correlated with microRNA (miR)-34a. MCM3AP-AS1 led to enhanced NSCLC cell movement and proliferation. Overexpression of miR-34a rescued the effect of overexpression of MCM3AP-AS1 on cell movement. Xenograft experiments showed tumor weight and volume in the si­MCM3AP-AS1 group and the miR-34a group to be significantly reduced. MCM3AP-AS1 increased tumor weight and volume, and miR-34a partially attenuated MCM3AP-AS1-induced promotion of tumor growth. CONCLUSION: MCM3AP-AS1 may enhance cell invasion, migration, and tumor formation capacity by regulating miR-34a in NSCLC cells.

Bidirectional association between polycystic ovary syndrome and periodontal diseases.

Polycystic ovary syndrome (PCOS) and periodontal disease (PDD) share common risk factors. The bidirectional interaction between PCOS and PDD has been reported, but until now, the underlying molecular mechanisms remain unclear. Endocrine disorders including hyperandrogenism (HA) and insulin resistance (IR) in PCOS disturb the oral microbial composition and increase the abundance of periodontal pathogens. Additionally, PCOS has a detrimental effect on the periodontal supportive tissues, including gingiva, periodontal ligament, and alveolar bone. Systemic low-grade inflammation status, especially obesity, persistent immune imbalance, and oxidative stress induced by PCOS exacerbate the progression of PDD. Simultaneously, PDD might increase the risk of PCOS through disturbing the gut microbiota composition and inducing low-grade inflammation and oxidative stress. In addition, genetic or epigenetic predisposition and lower socioeconomic status are the common risk factors for both diseases. In this review, we will present the latest evidence of the bidirectional association between PCOS and PDD from epidemiological, mechanistic, and interventional studies. A deep understanding on their bidirectional association will be beneficial to provide novel strategies for the treatment of PCOS and PDD.

Cohort-Specific Peptide Reagents Broaden Depth and Breadth Estimates of the CD8 T Cell Response to HIV-1 Gag Potential T Cell Epitopes.

An effective HIV vaccine will need to stimulate immune responses against the sequence diversity presented in circulating virus strains. In this study, we evaluate breadth and depth estimates of potential T-cell epitopes (PTEs) in transmitted founder virus sequence-derived cohort-specific peptide reagents against reagents representative of consensus and global sequences. CD8 T-cells from twenty-six HIV-1+ PBMC donor samples, obtained at 1-year post estimated date of infection, were evaluated. ELISpot assays compared responses to 15mer consensus (n = 121), multivalent-global (n = 320), and 10mer multivalent cohort-specific (n = 300) PTE peptides, all mapping to the Gag antigen. Responses to 38 consensus, 71 global, and 62 cohort-specific PTEs were confirmed, with sixty percent of common global and cohort-specific PTEs corresponding to consensus sequences. Both global and cohort-specific peptides exhibited broader epitope coverage compared to commonly used consensus reagents, with mean breadth estimates of 3.2 (global), 3.4 (cohort) and 2.2 (consensus) epitopes. Global or cohort peptides each identified unique epitope responses that would not be detected if these peptide pools were used alone. A peptide set designed around specific virologic and immunogenetic characteristics of a target cohort can expand the detection of CD8 T-cell responses to epitopes in circulating viruses, providing a novel way to better define the host response to HIV-1 with implications for vaccine development.