Limited Clinical Efficacy with Potential Adverse Events in a Pilot Study of Autologous Adoptive Cell Therapy in Canine Oral Malignant Melanoma.

Adoptive cell therapy (ACT) has been studied in several human and canine cancers with some promising clinical outcomes but not in canine oral malignant melanoma (OMM). Our manuscript aimed to explore one kind of ACT, the ex vivo-expanded autologous immune cell infusion in canine OMM, as this tumor remains a treatment dilemma. The study recruited dogs with histopathological diagnoses of oral malignant melanoma, generated their peripheral blood mononuclear cells, expanded them into predominantly non-B non-T cells via stimulations of IL-15, IL-2, and IL-21, and then re-infused the cells into tumor-bearing dogs. Ten dogs were enrolled; three dogs did not report any adverse events; three had a mildly altered appetite; one had a mildly increased liver index, while the other three developed suspected anaphylaxis at different levels. The median progression-free interval was 49 days. Dogs with progressive disease during treatment had a shorter survival. This pilot study indicates limited efficacy with potential adverse events of this ACT. Most recruited patients were in a later stage and had macroscopic disease, which might affect the treatment efficacy. Further exploration of this cell therapy in an adjuvant setting, with adequate protocol modification and standardization, could still be considered.

miR-199a-5p modulates choroidal neovascularization by regulating Wnt7b/Wnt/ß-catenin signaling pathway.

Choroidal neovascularization (CNV) can be seen in many fundus diseases, and lead to fundus exudation, bleeding, or vision loss. miRNAs are vital regulator in CNV. miR-199a-5p has been proved to be involved in regulating vascular formation of endothelial cells, but its role in CNV remains unclear. This study aims to study the role of miR-199a-5p in CNV. Laser irradiation was used to induce CNV model. The lesion area of CNV was calculated by high-resolution angiography with fluorescein isothiocyanate-dextran. Wnt family member 7b (Wnt7b), ß-catenin, and Wnt pathway proteins was measured by western blot. Immunofluorescence was performed to test Wnt7b, ß-catenin, CD31, and p-p65. miR-199a-5p and Wnt7b mRNA were tested by reverse transcription real-time polymerase chain reaction. Cell count kit-8, wound healing, Transwell, tube formation, and flow cytometry were used to detect the function of miR-199a-5p and Wnt7b on human retinal microvascular endothelial cells (HRMEC). TargetScan database and dual-luciferase reporter assay verified the interaction between miR-199a-5p and Wnt7b. The results revealed that Wnt7b increased in CNV rats. Knocking down Wnt7b repressed cell proliferation, migration, invasion, and angiogenesis, and accelerated cell apoptosis of HRMEC. Dual-luciferase reporter assay verified that miR-199a-5p targeted Wnt7b. Overexpression of miR-199a-5p inhibited the angiogenesis of HRMEC and promoted cell apoptosis by inhibiting Wbt7b. In vivo experiment found that Wnt7b rescued the promotion of miR-199a-5p inhibition on CNV lesion of rats. In addition, Wnt7b positively regulated Wnt/ß-catenin signaling pathway and promoted the angiogenesis of HRMEC. In conclusion, overexpression of miR-199a-5p inhibited the angiogenesis of HRMEC by regulating Wnt7b/Wnt/ß-catenin signaling pathway, which may serve as a promising therapy target of CNV.

Assessing the efficacy of aluminum metal clusters Al13 and Al15 in mitigating NO2 and SO2 pollutants: a DFT investigation.

The present investigation delves into the adverse environmental impact of atmospheric pollutant gases, specifically nitrogen dioxide (NO2) and sulfur dioxide (SO2), which necessitates the identification and implementation of effective control measures. The central objective of this study is to explore the eradication of these pollutants through the utilization of aluminum Al13 and Al15 metal clusters, distinguished by their unique properties. The comprehensive evaluation of gas/cluster interactions is undertaken employing density functional theory (DFT). Geometric optimization calculations for all structures are executed using the ωB97XD functional and the Def2-svp basis set. To probe various interaction modalities, gas molecule distribution around the metal clusters is sampled using the bee colony algorithm. Frequency calculations employing identical model chemistry validate the precision of the optimization calculations. The quantum theory of atoms in molecules (QTAIM) and natural bond orbital (NBO) methodologies are applied for the analysis of intermolecular interactions. This research establishes the robust formation of van der Waals attractions between the investigated gas molecules, affirming aluminum metal clusters as viable candidates for the removal and control of these gases.

Trends in prevalence of hearing loss in adults in the USA 1999-2018: a cross-sectional study.

BACKGROUND: A better understanding of how the prevalence of hearing loss and its associated factors change over time could help in developing an appropriate program to prevent the development of hearing loss. METHODS: Population-representative cross-sectional data from the United States National Health and Nutrition Examination Survey (NHANES) were used to estimate the trends in the prevalence of hearing loss among adults in the USA over the period 1999-2018. A total of 15,498 adult participants aged 20 years or older had complete audiometric examination data. Logistic regression was employed to evaluate the trend in hearing loss; weighted Rao-Scott χ2 tests and univariate logistic regression analyses were used to examine the association between hearing loss and relevant factors. RESULTS: The overall hearing loss prevalence in 1999-2018 was 19.1% 19.1 (95% CI, 18.0-20.2%). The prevalence of hearing loss decreased in cycles (P for trend < 0.001). For participants aged 20-69 years, the prevalence decreased from 15.6% (95% CI, 12.9-18.4%) in 1999-2000 to 14.9% (95% CI, 13.2- 16.6%) in 2015-2016; for participants aged > 70 years the prevalence decreased from 79.9% (95% CI, 76.1-83.8%) in 2005-2006 to 64.5% (95% CI, 58.8-70.2%) in 2017-2018. Participants with hearing loss were likely to be older, male, non-Hispanic white, and to have not completed high school. Mild hearing loss was more prevalent among those aged 20-79 years; in those aged over 80 years the prevalence of moderate hearing loss exceeded that of mild loss. Among all otologically normal participants, hearing thresholds increased with age across the entire frequency range. CONCLUSIONS: The prevalence of hearing loss in USA adults changed over the period 1999-2018. The trends observed provide valuable insight for making public health plans and allocating resources to hearing care. Further investigation is necessary to monitor hearing loss and its potential risk factors.

Immediate effect of kinesiology taping on muscle strength, static balance and proprioception after eccentric muscle fatigue on ankle: a randomized cross-over trial.

BACKGROUND: Kinesiology Taping(KT) is commonly used as a physical therapy to prevent exercise-induced fatigue. This study aims to evaluate the immediate effects of KT on muscle strength, static balance, and proprioception after eccentric muscle fatigue on ankle. METHODS: Twenty healthy male university students were recruited. The experimental protocol was structured into four sessions, each separated by a one-week washout period to prevent carryover effects. Participants were randomly allocated to one of four intervention conditions in each session, ensuring no participant received the same intervention twice. These conditions were: no taping(NT),sham taping(ST),athletic taping(AT),and kinesiology taping(KT).Taping was applied immediately following an eccentric muscle fatigue protocol targeting the ankle, and assessments were conducted in the order of proprioception, muscle strength and static balance. Isometric muscle strength and proprioception were evaluated using the Biodex isokinetic system. Static balance was measured using the TecnoBody balance platform. RESULTS: KT had a significantly higher plantarflexion/dorsiflexion peak torque, dorsiflexion average peak torque, and plantarflexion/dorsiflexion average power at 60°/s compared with NT and ST in terms of isometric muscle strength (p < 0.05).Furthermore, the plantarflexion peak torque of KT was significantly greater than AT at 60°/s[p = 0.005,95% confidence interval(CI) = 3.39 to 18.20] and 180°/s[p = 0.006,95%CI(2.62,21.98)]. In terms of proprioception, KT showed a lower absolute error in 25° plantarflexion and 10° dorsiflexion compared to NT, ST and AT. For static balance with eyes-open and eyes-closed conditions, AT and KT had a lower total sway area than NT and ST (p < 0.05). Additionally, a significant difference in total sway length with eyes-open condition was observed between AT and KT[p < 0.001,95%CI(-431.81,-168.25)];total sway area and the center of pressure(COP) velocity in the mediolateral(ML) and anteroposterior(AP) directions with eyes-closed condition were significantly lower in AT compared to KT. CONCLUSION: This study suggests that KT is more effective than other taping conditions in improving muscle strength and proprioception after eccentric muscle fatigue on ankle. However, AT is more helpful in increasing static postural control ability after ankle muscle fatigue than KT. TRIAL REGISTRATION: This study was registered with www.chictr.org.cn (registration number: ChiCTR2300068278) on 13/2/2023.

Effects of Astragaloside IV on Hearing, Inflammatory Factors, and Intestinal Flora in Mice Exposed to Noise.

Long-term exposure to noise can cause irreversible hearing loss. Considering that there is no effective drug treatment, it is important to seek preventive treatment for noise-induced hearing loss (NIHL). Although astragaloside IV (AS-IV) protects against NIHL by reducing serum inflammatory factors, there is scarce information on the regulation of inflammatory factors by AS-IV to prevent NIHL. We investigated the hearing thresholds and relationship between the serum levels of inflammatory cytokines and intestinal microbiota of c57bl/6j mice exposed to noise (103 dB SPL 4 h·d-1) for 7 days, treated with or without AS-IV. Our results revealed a lower hearing threshold and lower serum levels of TNF-α, TNF-γ, IL-6, IL-1ß, and IFN-γ in the mice treated with AS-IV. Additionally, AS-IV increased the abundance levels of the phylum Firmicutes, class Bacillus, order Lactobacillus, and family Lactobacillus (p < 0.05), and decreased those of the phylum Bacteroidetes and order Bacteroidales (p < 0.05). Lactobacillus and Bacilli negatively correlated with TNF-α, TNF-γ, and IL-1ß; Erysipelotrichaceae negatively correlated with INF-γ; and Clostridiales positively correlated with IL-1ß. In conclusion, AS-IV reduces the elevation of hearing thresholds in mice, preventing hearing loss in mice exposed to noise, and under the intervention of AS-IV, changes in the levels of inflammatory factors correlate with intestinal flora. We suggest that AS-IV improves intestinal flora and reduces inflammation levels in c57bl/6j mice exposed to noise.

Association between Homologous Recombination Repair Defect Status and Long-Term Prognosis of Early HER2-Low Breast Cancer: A Retrospective Cohort Study.

BACKGROUND: As a newly identified subtype of HER2-negative tumors associated with a less favorable prognosis, it remains crucial to evaluate potential prognostic and predictive factors, particularly non-invasive biomarkers, for individuals with human epidermal growth factor 2 (HER2) low early-stage breast cancer (EBC). Multiple investigations have highlighted that HER2-negative patients with EBC exhibiting high homologous recombination deficiency (HRD) scores display lower rates of pathological complete response (PCR) to neoadjuvant chemotherapy (NAC). Nevertheless, no study to date has explored the correlation between HRD and the long-term prognosis in HER2-low patients with EBC. PATIENTS AND METHODS: This retrospective observational study focuses on primary EBC sourced from The Cancer Genome Atlas dataset (TCGA). It reveals the gene mutation landscape in EBC with low HER2 expression and elucidates the tumor immune landscape across different HRD states. Utilizing bioinformatics analysis and Cox proportional models, along with the Kaplan-Meier method, the study assesses the correlation between HRD status and disease-specific survival (DSS), disease-free interval (DFI), and progression-free interval (PFI). Subgroup analyses were conducted to identify potential variations in the association between HRD and prognosis. RESULTS: In the patients with HER2-low breast cancer, patients with homologous recombination related genes (HRRGs) defects had an HRD score about twice that of those without related genes mutations, and were at higher risk of acquiring ARID1A, ATM, and BRCA2 mutations. We also found that most immune cell abundances were significantly higher in EBC tumors with high HRD than in EBC tumors with low HRD or HRD-medium, particularly plasma B-cell abundance, CD8 T-cell abundance, and M1 macrophages. In addition, these tumors with HRD-high also appear to have significantly higher tumor immune scores and lower interstitial scores. Then, we analyzed the relationship between different HRD status and prognosis. There was statistical significance (P = .036 and P = .046, respectively) in DSS and PFI between the HRD-low and HRD-high groups, and patients with HRD-high EBC showed relatively poor survival outcomes. A medium HRD score (hazard ratio, HR = 2.15, 95% CI: 1.04-4.41, P = .038) was a significant risk factor for PFI. Hormone receptor positivity is an important factor in obtaining medium-high HRD score and poor prognosis. CONCLUSION: Higher HRD scores were associated with poorer PFI outcomes, particularly in people with HR+/HER2-low. Varied HRD states exhibited distinctions in HRRGs and the tumor immune landscape. These insights have the potential to assist clinicians in promptly identifying high-risk groups and tailoring personalized treatments for patients with HER2-low EBC, aiming to enhance long-term outcomes.

Selective biosynthesis of a rhamnosyl nosiheptide by a novel bacterial rhamnosyltransferase.

Nosiheptide (NOS) is a thiopeptide antibiotic produced by the bacterium Streptomyces actuosus. The hydroxyl group of 3-hydroxypyridine in NOS has been identified as a promising site for modification, which we therefore aimed to rhamnosylate. After screening, Streptomyces sp. 147326 was found to regioselectively attach a rhamnosyl unit to the 3-hydroxypyridine site in NOS, resulting in the formation of a derivative named NOS-R at a productivity of 24.6%. In comparison with NOS, NOS-R exhibited a 17.6-fold increase in aqueous solubility and a new protective effect against MRSA infection in mice, while maintaining a similar in vitro activity. Subsequently, SrGT822 was identified as the rhamnosyltransferase in Streptomyces sp. 147326 responsible for the biosynthesis of NOS-R using dTDP-L-rhamnose. SrGT822 demonstrated an optimal reaction pH of 10.0 and temperature of 55°C, which resulted in a NOS-R yield of 74.9%. Based on the catalytic properties and evolutionary analysis, SrGT822 is anticipated to be a potential rhamnosyltransferase for use in the modification of various complex scaffolds.

ZDHHC5-mediated S-palmitoylation of FAK promotes its membrane localization and epithelial-mesenchymal transition in glioma.

BACKGROUND: Abnormal activation of FAK is associated with tumor development and metastasis. Through interactions with other intracellular signalling molecules, FAK influences cytoskeletal remodelling, modulation of adhesion signalling, and activation of transcription factors, promoting migration and invasion of tumor cells. However, the exact mechanism that regulates these processes remains unresolved. Herein, our findings indicate that the S-palmitoylation of FAK is crucial for both its membrane localization and activation. METHODS: The palmitoylation of FAK in U251 and T98G cells was assessed by an acyl-PEG exchange (APE) assay and a metabolic incorporation assay. Cellular palmitoylation was inhibited using 2-bromopalmitate, and the palmitoylation status and cellular localization of FAK were determined. A metabolic incorporation assay was used to identify the potential palmitoyl acyltransferase and the palmitoylation site of FAK. Cell Counting Kit-8 (CCK8) assays, colony formation assays, and Transwell assays were conducted to assess the impact of ZDHHC5 in GBM. Additionally, intracranial GBM xenografts were utilized to investigate the effects of genetically silencing ZDHHC5 on tumor growth. RESULTS: Inhibiting FAK palmitoylation leads to its redistribution from the membrane to the cytoplasm and a decrease in its phosphorylation. Moreover, ZDHHC5, a protein-acyl-transferase (PAT), catalyzes this key modification of FAK at C456. Knockdown of ZDHHC5 abrogates the S-palmitoylation and membrane distribution of FAK and impairs cell proliferation, invasion, and epithelial-mesenchymal transition (EMT). Taken together, our research reveals the crucial role of ZDHHC5 as a PAT responsible for FAK S-palmitoylation, membrane localization, and activation. CONCLUSIONS: These results imply that targeting the ZDHHC5/FAK axis has the potential to be a promising strategy for therapeutic interventions for glioblastoma (GBM). Video Abstract.

An inflammatory response-related gene signature can predict the prognosis and impact the immune infiltration of multiple myeloma.

Multiple myeloma (MM) is a highly heterogeneous and incurable disease. Inflammation plays a vital role in cancer genesis and progression. However, the relationship between inflammatory response-related genes (IRRGs) and the prognosis of MM patients remains unknown. We constructed a IRRGs prognosis model by least absolute shrinkage and selection operator regression analysis. Moreover, clinical multivariate regression was performed to identify clinical implications. Gene set enrichment analysis was implemented to conduct its biological properties. CIBERSORT deconvolution algorithm was utilized to calculate the immune cell infiltration in different risk groups. The flow cytometry was utilized to perform protein expression of prognostic gene. A Six-IRRGs (VCAM1, RGS1, KIT, CD81, BLNK, and BIRC3) prognostic risk model was successfully constructed and validated. The risk model was an independent predictor for overall survival. Enrichment analysis revealed autophagy and PI3K-Akt signaling pathways were enriched in the high-risk group. Furthermore, we found CD81 widely impacted on the infiltration of immune cells, especially on monocytes and macrophages2. At last, the role of CD81 in MM was confirmed to be an adverse prognostic factor in clinical. Our study explores the potential application value of IRRGs in MM. These findings may provide new insights into the treatment for MM patients.

Association of FTH1-Expressing Circulating Tumor Cells With Efficacy of Neoadjuvant Chemotherapy for Patients With Breast Cancer: A Prospective Cohort Study.

BACKGROUND: The association between different phenotypes and genotypes of circulating tumor cells (CTCs) and efficacy of neoadjuvant chemotherapy (NAC) remains uncertain. This study was conducted to evaluate the relationship of FTH1 gene-associated CTCs (F-CTC) with/without epithelial-mesenchymal transition (EMT) markers, or their dynamic changes with the efficacy of NAC in patients with non-metastatic breast cancer. PATIENTS AND METHODS: This study enrolled 120 patients with non-metastatic breast cancer who planned to undergo NAC. The FTH1 gene and EMT markers in CTCs were detected before NAC (T0), after 2 cycles of chemotherapy (T1), and before surgery (T2). The associations of these different types of CTCs with rates of pathological complete response (pCR) and breast-conserving surgery (BCS) were evaluated using the binary logistic regression analysis. RESULTS: F-CTC in peripheral blood ≥1 at T0 was an independent factor for pCR rate in patients with HER2-positive (odds ratio [OR]=0.08, 95% confidence interval [CI], 0.01-0.98, P = .048). The reduction in the number of F-CTC at T2 was an independent factor for BCS rate (OR = 4.54, 95% CI, 1.14-18.08, P = .03). CONCLUSIONS: The number of F-CTC prior to NAC was related to poor response to NAC. Monitoring of F-CTC may help clinicians formulate personalized NAC regimens and implement BCS for patients with non-metastatic breast cancer.

Dynamic alterations of locomotor activity and the microbiota in zebrafish larvae with low concentrations of lead exposure.

Lead (Pb) is a ubiquitous heavy metal associated with developmental and behavioral disorders. The establishment of pioneer microbiota overlaps with the development of the brain during early life, and Pb-induced developmental neurotoxicity may be partially caused by early-life microbiota dysbiosis. This study investigated the locomotor activity and the microbiota in developing zebrafish at multiple developmental time points (five days post fertilization [5 dpf], 6 dpf, and 7 dpf) under exposure to low concentrations of lead (0.05 mg/L). Time-dependent reductions in the number of activities and the average movement distance of larvae compared to the control were observed following Pb exposure. Furthermore, Pb exposure significantly altered the composition of the gut microbiota of zebrafish larvae. At the phylum level, the abundance of Proteobacteria decreased from 5 to 7 dpf, while that of Actinobacteria increased in the control groups. At the class level, the proportion of Alphaproteobacteria decreased, while that of Actinobacteria increased in the control groups. Notably, all showed the opposite trend in Pb groups. A correlation analysis between indices of locomotor activity and microbial communities revealed genus-level features that were clearly linked to the neurobehavioral performance of zebrafish. Seven genera were significantly correlated with the two performance indicators of the locomotion analysis, namely Rhodococcus, Deinococcus, Bacillus, Bosea, Bradyrhizobium, Staphylococcus, and Rhizobium. Rhizobium was dominant in zebrafish and increased in the Pb groups in a time-dependent manner. In addition, the expression levels of bdnf, trkb1, trkb2, and p75ntr changed in zebrafish from 5 to 7 dpf under Pb exposure. Collectively, these results suggest that Pb-induced neurotoxicity could potentially be treated by targeting the gut microbiota.

Insight into the fate of nitrogen during char thermal conversion and the influence mechanism of potassium: A theoretical research.

Nitrogen oxides (NOₓ) are primary pollutants produced during biomass combustion. During the devolatilization stage, char nitrogen (char(N)) is formed. In the subsequent char combustion stage, char(N) can decompose directly into NOx precursors or engage in heterogeneous reactions with O2 or NO to form NO and N2. Nonetheless, a comprehensive understanding of the reaction mechanisms and competitiveness of char(N) migration, especially the influence of the alkali metal potassium (K) present in biomass, remains incomplete. Building on the Zigzag char(N) models, the present study delves into the migration reactions of char(N), assessing their competitive dynamics through the integration of density functional theory, electronic structure analysis, and conventional transition state theory. Furthermore, it examines the impact of K on char(N) conversion. The competitiveness of the heterogeneous reactions follows the sequence: heterogeneous reduction of NO to N2 > heterogeneous oxidation of char(N) to NO > decomposition of char(N) to NOx precursors. Moreover, the formation of HCN is more favorable than NH3 production. The successive conversion from char(N) to NO and then to N2 is the predominant migration route for char(N), with NO generation as the pivotal step. The less preferred char(N) migration route involves decomposition to NH3/HCN, followed by oxidation to NOx within the main combustion zone, which cannot be mitigated by char. K can accelerate NO generation and sustain the primacy of the heterogeneous NO reduction, consequently enhancing the oxidation-reduction process of char(N). As a result, K plays a constructive role in managing NOx emissions during the thermal conversion of char.

Luteolin Attenuates Oxidative Stress and Colonic Hypermobility in Water Avoidance Stress Rats by Activating the Nrf2 Signaling Pathway.

SCOPE: Irritable bowel syndrome (IBS) is an intestinal disorder, whose symptoms can be alleviated by certain dietary phytochemicals. This study explores the role and potential mechanisms of a natural flavonoid luteolin (LUT) in alleviating the excessive motility of colonic smooth muscles and reducing oxidative stress in IBS with diarrhea (IBS-D) rats. METHODS AND RESULTS: LUT reduces excessive intestinal motility and lowers reactive oxygen species (ROS) levels in a water avoidance stress (WAS) rat model. Moreover, LUT increases the protein expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), activates the nuclear translocation of Nrf2, and greatly reduces the hydrogen peroxide (H2 O2 )-induced oxidative damage in intestinal epithelial cells. CONCLUSIONS: LUT, a phyto-active component, protects against excessive intestinal motility and diarrhea by regulating the Nrf2 signaling pathway and effectively reduces oxidative stress damage in the colon.

On-Off Switching of a Photocatalytic Overall Reaction through Dynamic Spin-State Transition in a Hofmann Clathrate System.

Spin-state transition is a vital factor that dominates catalytic processes, but unveiling its mechanism still faces the great challenge of the lack of catalyst model systems. Herein, we propose that the {Fe-Pt} Hofmann clathrates, whose dynamic spin-state transition of metal centers can be chemically manipulated through iodine treatment, can serve as model systems in the spin-related structural-catalytic relationship study. Taking the photocatalytic synthesis of H2O2 as the basic catalytic reaction, when the spin state of Fe(II) in the clathrate is high spin (HS), sacrificial agents are indispensable to the photosynthesis of H2O2 because only the photocatalytic oxygen reduction reaction (ORR) occurs; when it is low spin (LS), both the ORR and water oxidation reaction (WOR) can take place, enabling a high H2O2 photosynthesis rate of 66 000 µM g-1 h-1 under visible-light irradiation. In situ characterizations combined with density functional theory calculations confirmed that, compared with the HS-state counterpart, the LS state can induce strong charge transfer between the LS Fe(II) and the iodide-coordinating Pt(IV) in the polymer and reduce the energy barriers for both the ORR and WOR processes, dominating the on-off switching upon the photosynthesis of H2O2 in O2-saturated water. What's more, the one-pot tandem reactions were conducted to utilize the synthesized H2O2 for transforming the low-value-added sodium alkenesulfonates into value-added bromohydrin products with decent conversion rates. This work provides a pioneering investigation into on-off switching the photocatalytic overall reaction through manipulating the metallic spin-state transition in spin-crossover systems.

Association between human herpesvirus infection and cervical carcinoma: a systematic review and meta-analysis.

BACKGROUND: Cervical cancer (CC) is one of the most common gynecologic tumors among women around the world. Although the etiological role of human papillomavirus (HPV) in CC is well established, other factors in CC carcinogenesis remains unclear. Here, we performed a systematic review and meta-analysis to explore the association between infections of human herpesvirus (HHVs) and CC risk. METHODS: Embase and PubMed databases were utilized to search the relevant studies. The revised JBI Critical Appraisal Tool was used to assess the quality of the included studies. Prevalence and odds ratios (ORs) with 95% confidence intervals (CI) were calculated to evaluate the association between viral infection and CC or precancerous cervical lesions (PCL). RESULTS: Totally 67 eligible studies involving 7 different HHVs were included in meta-analysis. We found an increased risk of CC or PCL that was associated with the overall infection of HHVs (CC, OR = 2.74, 95% CI 2.13-3.53; PCL, OR = 1.95, 95% CI 1.58-2.41). Subgroup analysis showed a trend towards positive correlations between herpes simplex virus type 2 (HSV-2) infection and CC (OR = 3.01, 95% CI 2.24 to 4.04) or PCL (OR = 2.14, 95% CI 1.55 to 2.96), and the same is true between Epstein-Barr virus (EBV) infection and CC (OR = 4.89, 95% CI 2.18 to 10.96) or PCL (OR = 3.55, 95% CI 2.52 to 5.00). However, for HSV-1 and cytomegalovirus (HCMV), there was no association between viral infection and CC or PCL. By contrast, the roles of HHV-6, HHV-7, and Kaposi sarcoma-associated herpesvirus (KSHV) in cervical lesions were unclear due to the limited number of studies. CONCLUSIONS: This study provided evidence that HHVs infection as a whole increase the risk of CC incidence. In addition, some types of HHVs such as EBV and HSV-2 may serve as potential targets in the development of new interventions or therapeutic strategies for cervical lesions.

Single-cell transcriptomic atlas throughout anti-BCMA CAR-T therapy in patients with multiple myeloma.

Introduction: The emergence of chimeric antigen receptor (CAR)-T therapy targeting B cell maturation antigen (BCMA) has improved the prognosis of patients with multiple myeloma (MM); however, the majority of patients eventually experience relapse. Methods: In this study, employing the latest single-cell RNA sequencing technology, we examined 24 bone marrow or peripheral blood samples collected throughout the course of anti-BCMA CAR-T therapy, analyzing a total of 59,725 bone marrow cells and 72,479 peripheral blood cells. Results: Our findings reveal that tumor cells in relapsed patient exhibit higher expression levels of HSP90B1 and HSPA5, and demonstrate significantly enriched pathways regarding endoplasmic reticulum stress and unfolded protein response. In the analysis of T cells, we observed that patient with impaired effector function and increased expression of immune checkpoints in endogenous T cell are more susceptible to relapse. Notably, T cells from both the bone marrow microenvironment and peripheral blood share highly similar biological characteristics. Discussion: Overall, this study provides a comprehensive atlas of endogenous immune cells, particularly in the relatively long term, after CAR-T therapy. It offers clinical evidence for a deeper understanding of the internal environment post CAR-T treatment and for identifying mechanisms underlying relapse.

Effect of Air Pollutants and Meteorological Factors on Daily Outpatient Visits of Allergic Rhinitis in Hohhot, China.

Objective: There is limited evidence that atmospheric pollutants are associated with the number of allergic rhinitis (AR) visits. This study aimed to investigate the relationship between atmospheric pollutants and meteorological factors and the number of daily visits for AR in Hohhot City, providing a theoretical basis for further research on the effects of atmospheric pollutants on AR. Methods: Microsoft Excel 2016 was used to collect and organize the AR outpatient consultation data, air pollution and meteorological data in Hohhot City during 2018-2020, and the data were descriptively analyzed and Spearman correlation test was performed using SPSS22.0; A generalized additive model was built in R4.2.3 to analyze the effect of air pollution on the number of AR visits and its lagged and cumulative effects, while the robustness of the model was tested using a two-pollutant analysis. Finally, we analyzed the effects of the interaction of temperature, relative humidity and pollutants on the number of AR visits. Results: The daily average concentrations of PM2.5, PM10, SO2, NO2, CO, and O3 in Hohhot during 2018-2020 were 38.1 µg/m3, 83.3 µg/m3, 36.1 µg/m3, 15.1 µg/m3, 14.2 mg/m3, and 99.95 µg/m3, respectively, with the concentrations of PM2.5 and PM10 exceeding the secondary limit of the national standard. The results of the generalized additive model analysis showed that the RR and 95% CI of the effect of each 10 µg/m3 increase in pollutant concentration (1 mg/m3 increase in CO) on the number of AR outpatient clinics were 1.008 (1.001-1.016), 1.002 (1-1.005), 1.072 (1.033-1.113), 1.020 (1007-1.034), 1.033 (1.014-1.052), 0.987 (0.9804-0.9936). Conclusion: Short-term exposure to PM2.5, PM10, SO2, NO2, and CO was significantly associated with an increase in AR clinic visits, and short-term exposure to O3 was significantly associated with a decrease in allergic rhinitis clinic visits.

Homodimer-mediated phosphorylation of C/EBPα-p42 S16 modulates acute myeloid leukaemia differentiation through liquid-liquid phase separation.

CCAAT/enhancer binding protein α (C/EBPα) regulates myeloid differentiation, and its dysregulation contributes to acute myeloid leukaemia (AML) progress. Clarifying its functional implementation mechanism is of great significance for its further clinical application. Here, we show that C/EBPα regulates AML cell differentiation through liquid-liquid phase separation (LLPS), which can be disrupted by C/EBPα-p30. Considering that C/EBPα-p30 inhibits the functions of C/EBPα through the LZ region, a small peptide TAT-LZ that could instantaneously interfere with the homodimerization of C/EBPα-p42 was constructed, and dynamic inhibition of C/EBPα phase separation was observed, demonstrating the importance of C/EBPα-p42 homodimers for its LLPS. Mechanistically, homodimerization of C/EBPα-p42 mediated its phosphorylation at the novel phosphorylation site S16, which promoted LLPS and subsequent AML cell differentiation. Finally, decreasing the endogenous C/EBPα-p30/C/EBPα-p42 ratio rescued the phase separation of C/EBPα in AML cells, which provided a new insight for the treatment of the AML.

Relationship Between Outdoor Air Pollutant Exposure and Premature Delivery in China- Systematic Review and Meta-Analysis.

Objective: Preterm birth (PTB) is considered as a public health problem and one of the main risk factors related to the global disease burden. The purpose of this study aims to explore the influence of exposure to major air pollutants at different pregnancies on PTB. Methods: The relationship between air pollutants and PTB in China was collected from cohort studies and case-control studies published before 30 April 2022. Meta-analysis was carried out with STATA 15.0 software. Results: A total of 2,115 papers were retrieved, of which 18 papers met the inclusion criteria. The comprehensive effect of pollutant exposure and PTB were calculated. PM2.5 during entire pregnancy and O3 exposure during third trimester were positively associated with preterm birth. Every 10 µg/m3 increase in the average concentration of PM2.5 during the whole pregnancy will increase the risk of premature delivery by 4%, and every 10 µg/m3 increase in the average concentration of O3 in the third trimester will increase the risk of premature delivery by 1%. Conclusion: Exposure to PM2.5 entire prenatal pregnancy and O3 in third trimester is associated with an increased risk of preterm birth occurrence.