Search

An abstract of the research paper "Highly expression of Tim-3 on HIV-specific T cells associated with disease progression and T-cell exhaustion in HIV-1 infected Chinese," by Z. Liu and colleagues is presented.

An abstract of the conference paper "Human leukocyte antigen class I supertypes and viral control in HIV-1 infected former plasma donors from China," by J. Hao and colleagues is presented.

Background: Men who have sex with men (MSM) are much more likely to be infected with HIV than the general population. China has a sizable population of MSM, including gay, bisexual men, money boys and some rural workers. So reducing HIV infection in this population is an important component of the national HIV/AIDS prevention and control program.Methods: We develop a mathematical model using a sex-role-preference framework to predict HIV infection in the MSM population and to evaluate different intervention strategies.Results: An analytic formula for the basic reproduction ratio R0 was obtained; this yields R0 = 3.9296 in the current situation, so HIV will spread very fast in the MSM population if no intervention measure is implemented in a timely fashion. The persistence of HIV infection and the existence of disease equilibrium (or equilibria) are also shown. We utilized our model to simulate possible outcomes of antiretroviral therapy and vaccination for the MSM population. We compared the effects of these intervention measures under different assumptions about MSM behaviour. We also found that R0 is a decreasing function of the death rate of HIV-infected individuals, following a power law at least asymptotically.Conclusion: HIV will spread very fast in the MSM population unless intervention measures are implemented urgently. Antiretroviral therapy can have substantial impact on the reduction of HIV among the MSM population, even if disinhibition is considered. The effect of protected sexual behaviour on controlling the epidemic in the MSM population largely depends on the sex-ratio preference of different sub-populations. [ABSTRACT FROM AUTHOR]

Background: Extrachromosomal circular DNA (eccDNA), a novel class of DNA with a circular topological structure, is present in a variety of cancer cells and tissues and may play broad roles in processes ranging from aging to cancer cell heterogeneity through multiple mechanisms. EccDNA has been characterized by profile, structure and function in several prominent studies but its effect on hydroquinone (HQ)-induced malignantly transformed cells (TK6-HQ) is still elusive., Methods: Circle-seq was applied to determine the eccDNA counts and characteristics of TK6-HQ cells. DNA-fluorescence in situ hybridization was used to measure the abundance of eccDNA&#95;DTX1. Differential gene expression analysis was carried out by RNA-seq. Gene expression was quantified by wertern blot and qPCR. Decircularization of eccDNA&#95;DTX1 was achieved by CRISPR/Cas9. Tumorigenicity was evaluated by xenograft assay in BALB/c nude mice., Results: In this study, we characterized the structure of eccDNAs and the function of DTX1-containing eccDNA (eccDNA&#95;DTX1) in TK6-HQ cells. A total of 669,179 eccDNAs were identified, including 901 eccDNAs with different counts. Most of the eccDNAs were < 1000 bp in length and were enriched in four periodic peaks starting at 186 bp with an interval of ~ 180 bp. The genomic distribution of eccDNAs confirmed that eccDNAs could be observed across all chromosomes and had greater enrichment on chromosomes 17, 19, 20, and 22, with abundant Alu repeat elements, introns and CpG islands. By combining the results of the integrated circle-seq analysis of eccDNAs with those from the RNA-seq analysis (differentially expressed genes, 1064 upregulated and 427 downregulated), the authors showed that the transcription of 20 potential coding genes might be driven by eccDNAs. Finally, the knockdown of eccDNA&#95;DTX1 by CRISPR/Cas9 inhibited the growth of TK6-HQ cells in vitro and in vivo by inhibiting the transcription of DTX1 and promoting ferroptosis, and ferroptosis inhibior, Ferrostatin-1, abrogated the proliferation inhibition of eccDNA&#95;DTX1 knockdown., Conclusions: EccDNA&#95;DTX1 promotes cell growth in hydroquinone-induced malignantly transformed cells by regulating the transcription of DTX1 and ferroptosis. This study profiles eccDNA characteristics and defines the role and mechanism of eccDNA&#95;DTX1 for the first time, shedding new light on the relationship between eccDNAs and carcinogenesis., Competing Interests: Declarations. Ethics approval and consent to participate: Humans were not included in this study. The animal study was approved by the Animal Welfare and Ethics Committee of Guangdong Medical University (GDY2204004). The animal experiments were carried out according to the 3Rs principle. Consent for publication: Not Applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Air pollution is a major environmental risk factor. Hypertension is one of the most important modifiable risk factors for cardiovascular diseases. However, few studies have evaluated the impact of exposure to ambient air pollution on hypertension hospitalizations., Objective: This study aims to explore the correlation between exposure to air pollution and hospital admissions for hypertension, to evaluate the short-term effects of air pollution on hypertension hospitalizations and its lag effects., Methods: We collected air pollution concentration and hypertension hospitalization data from 2013 to 2020. Distributed lag non-linear models were employed to assess the impact of air pollution on hypertension hospitalizations in Lanzhou City. We also performed subgroup analyses and sensitivity analyses., Results: A total of 47,884 cases of hypertension hospitalizations were included. Short-term exposure to NO 2 and CO increased the risk of hypertension hospitalization. For each 10 µg/m 3 increase in NO 2 and each 1 mg/m 3 increase in CO, the relative risk (RR) for hypertension hospitalization were highest at lag0-3 (RR: 1.0427; 95% CI: 1.0196, 1.0663) and lag3 (RR: 1.0986; 95% CI: 1.0350, 1.1661), respectively. SO 2 at different lag structures showed opposite effects on hypertension hospitalization. O 3 was significantly negatively associated with hypertension hospitalization. No correlation was observed between PM 2.5 and PM 10 and hypertension hospitalization. Females and individuals aged ≥ 65 were more susceptible to air pollution. The harmful effects of air pollution are greater in the cold season., Conclusion: Short-term exposure to ambient air pollution increases risk of hypertension hospitalization., Competing Interests: Declarations. Ethics approval and consent to participate: The Institutional Review Board (IRB) at School of Public Health, Lanzhou University has waived the ethics approval and the informed consent for the study. The study adhered to the guidelines and regulations outlined in the Declaration of Helsinki. This exemption is due to the fact that the data used in the study was provided by government agencies and consented for use in this research. The data did not involve any direct or indirect identification of hospital patients’ personal information. And the waiver of informed consent has been reviewed and approved by the research ethics committee. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Plant-soil feedback arises from microbial legacies left by plants in the soil. Grafting is a common technique used to prevent yield declines in monocultures. Yet, our understanding of how grafting alters the composition of soil microbiota and how these changes affect subsequent crop performance remains limited. Our experiment involved monoculturing ungrafted and grafted watermelons to obtain conditioned soils, followed by growing the watermelons on the conditioned soils to investigate plant-soil feedback effects., Results: Ungrafted plants grew better in soil previously conditioned by a different plant (heterospecific soil) while grafted plants grew better in soil conditioned by the same plant (conspecific soil). We demonstrated experimentally that these differences in growth were linked to changes in microorganisms. Using a supervised machine learning algorithm, we showed that differences in the relative abundance of certain genera, such as Rhizobium, Chryseobacterium, Fusarium, and Aspergillus, significantly influenced the conspecific plant-soil feedback. Metabolomic analyses revealed that ungrafted plants in heterospecific soil enriched arginine biosynthesis, whereas grafted plants in conspecific soil increased sphingolipid metabolism. Elsewhere, the metagenome-assembled genomes (MAGs) of ungrafted plants identified in heterospecific soil include Chryseobacterium and Lysobacter, microorganisms having been prominently identified in earlier research as contributors to plant growth. Metabolic reconstruction revealed the putative ability of Chryseobacterium to convert D-glucono-1,5-lactone to gluconic acid, pointing to distinct disease-suppressive mechanisms and hence distinct microbial functional legacies between grafted and ungrafted plants., Conclusions: Our findings show a deep impact of the soil microbial reservoir on plant growth and suggest the necessity to protect and improve this microbial community in agricultural soils. The work also suggests possibilities of optimizing microbiota-mediated benefits through grafting herein, a way that "engineered" soil microbial communities for better plant growth. Video Abstract., Competing Interests: Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests., (© 2024. The Author(s).)

Background: This study aimed to evaluate the prognostic value of the newly revised International Association for the Study of Lung Cancer (IASLC) grading system (2020) on the 5-year overall survival (OS) and recurrence-free survival (RFS) in patients with lung adenocarcinoma (LADC)., Methods: Clinical studies that investigated the prognostic value of revised IASLC staging system in patients with LADC were retrieved from the PubMed, Web of Science, ScienceDirect, and Cochrane Library databases. This study was conducted in accordance to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and checklists., Results: Based on inclusion and exclusion criteria, we included 12 studies for analysis. The grade of LADC was assessed by revised IASLC system, which included three grades. Compared to Grade 3 LADC, grade 1 (total [95% CI]: 1.38 [1.19, 1.60]) and grade 2 (total [95% CI]: 1.29 [1.15, 1.44]) LADC had higher 5-year OS rates. Similarly, Grade 1 (total [95% CI]: 1.76 [1.42, 2.18]) and Grade 2 (total [95% CI]: 1.51 [1.28, 1.77]) had higher 5-year RFS rates Grade 3 LADC. However, 5-year OS and RFS had no significant difference between Grade 1 and Grade 2 patients., Conclusion: This systematic review and meta-analysis provides evidence that the newly revised IASLC grading system is significantly associated with the prognosis of patients with LADC, where Grade 3 indicated unfavorable prognosis., Competing Interests: Declarations Ethics approval and consent to participate This study was approved by the Ethics Committee of The First People’s Hospital of Jiande. Written informed consent was obtained from all the participants. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: The study focuses on the effect of temperature and relative humidity on hospitalization for acute lower respiratory tract infections (LRTI) in children, respectively., Methods: In this study, the Distributed Lag Nonlinear Model (DLNM) based on quasi-Poisson distribution was used to investigate the effect of temperature and relative humidity on LRTI hospitalization in children, and subgroup analyses were conducted to identify sensitive populations by gender and age., Results: A total of 43,951 children were hospitalized for LRTI from 1 January 2014 to 31 December 2019 in Lanzhou. The mean temperature during the study period was 11.34 °C and the mean relative humidity was 51.03%. With reference to the median temperature of 12.7 °C during the study period, both low (-4.1 °C) and high (25.43 °C) temperature had a detrimental effect on LRTI hospitalization, and the maximum effect was reached at lag0-10 and lag0-9, respectively, with RR values of 1.645 (95%CI: 1.533, 1.764) and 1.098 (95%CI: 1.018, 1.184). With a reference to the median relative humidity of 51.17% during the study period, both low relative humidity (26.71%) and high relative humidity (76.70%, P95) had a detrimental effect on LRTI hospitalization, and the maximum effect was reached at lag0-21 and lag21, respectively, with RR values of 1.235 (95% CI: 1.163, 1.311) and 1.044 (95% CI: 1.036, 1.051). The results of subgroup analyses showed that changes in meteorological factors had a stronger effect on Female and children aged 5-14 years., Conclusions: The meteorological factors all have different degrees of influence on LRTI hospitalization in children. Girls and the children aged 5-14 years are more sensitive. Attention to these meteorological risks can inform targeted interventions., Competing Interests: Declarations Ethics approval and consent to participate The present study was considered exempt from institutional review board approval since the data used was collected for administrative purpose without any personal identifiers. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Tuberculosis (TB), induced by Mycobacterium tuberculosis (Mtb) infection, remains a major public health issue worldwide. Mtb has developed complicated strategies to inhibit the immunological clearance of host cells, which significantly promote TB epidemic and weaken the anti-TB treatments. Host-directed therapy (HDT) is a novel approach in the field of anti-infection for overcoming antimicrobial resistance by enhancing the antimicrobial activities of phagocytes through phagosomal maturation, autophagy and antimicrobial peptides. Autophagy, a highly conserved cellular event within eukaryotic cells that is effective against a variety of bacterial infections, has been shown to play a protective role in host defense against Mtb. In recent decades, the introduction of nanomaterials into medical fields open up a new scene for novel therapeutics with enhanced efficiency and safety against different diseases. The active modification of nanomaterials not only allows their attractive targeting effects against the host cells, but also introduce the potential to regulate the host anti-TB immunological mechanisms, such as apoptosis, autophagy or macrophage polarization. In this review, we introduced the mechanisms of host cell autophagy for intracellular Mtb clearance, and how functional nanomaterials regulate autophagy for disease treatment. Moreover, we summarized the recent advances of nanomaterials for autophagy regulations as novel HDT strategies for anti-TB treatment, which may benefit the development of more effective anti-TB treatments., (© 2024. The Author(s).)

Colorectal cancer (CRC) is a common malignant tumor with the third and second highest incidence and mortality rates among various malignant tumors. Despite significant advancements in the present therapy for CRC, the majority of CRC cases feature proficient mismatch repair/microsatellite stability and have no response to immunotherapy. Therefore, the search for new treatment options holds immense importance in the diagnosis and treatment of CRC. In recent years, clinical research on immunotherapy combined with epigenetic therapy has gradually increased, which may bring hope for these patients. This review explores the role of epigenetic regulation in exerting antitumor effects through its action on immune cell function and highlights the potential of certain epigenetic genes that can be used as markers of immunotherapy to predict therapeutic efficacy. We also discuss the application of epigenetic drug sensitization immunotherapy to develop new treatment options combining epigenetic therapy and immunotherapy., (© 2024. The Author(s).)

Background: With the backdrop of global climate change, the impact of climate change on respiratory diseases like asthma is receiving increasing attention. However, the effects of temperature and diurnal temperature range (DTR) on asthma are complex, and understanding these effects across different seasons, age groups, and sex is of utmost importance., Methods: This study utilized asthma hospitalization data from Lanzhou, China, and implemented a distributed lag nonlinear model (DLNM) to investigate the relationship between temperature and DTR and asthma hospitalizations. It considered differences in the effects across various seasons and population subgroups., Results: The study revealed that low temperatures immediately increase the risk of asthma hospitalization (RR = 1.2010, 95% CI: 1.1464, 1.2580), and this risk persists for a period of time. Meanwhile, both high and low DTR were associated with an increased risk of asthma hospitalization. Lower temperatures (RR = 2.9798, 95% CI: 1.1154, 7.9606) were associated with higher asthma risk in the warm season, while in the cold season, the risk significantly rose for the general population (RR = 3.6867, 95% CI: 1.7494, 7.7696), females (RR = 7.2417, 95% CI: 2.7171, 19.3003), and older individuals (RR = 18.5425, 95% CI: 5.1436, 66.8458). In the warm season, low DTR conditions exhibited a significant association with asthma hospitalization risk in males (RR = 7.2547, 95% CI: 1.2612, 41.7295) and adults aged 15-64 (RR = 9.9494, 95% CI: 2.2723, 43.5643). Children also exhibited noticeable risk within specific DTR ranges. In the cold season, lower DTR increases the risk of asthma hospitalization for the general population (RR = 3.1257, 95% CI: 1.4004, 6.9767). High DTR significantly increases the risk of asthma hospitalization in adults (RR = 5.2563, 95% CI: 2.4131, 11.4498)., Conclusion: This study provides crucial insights into the complex relationship between temperature, DTR, and asthma hospitalization, highlighting the variations in asthma risk across different seasons and population subgroups., (© 2024. The Author(s).)

The activation of ferroptosis presents a versatile strategy for enhancing the antitumor immune responses in cancer therapy. However, developing ferroptosis inducers that combine high biocompatibility and therapeutic efficiency remains challenging. In this study, we propose a novel approach using biological nanoparticles derived from outer membrane vesicles (OMVs) of Escherichia coli for tumor treatment, aiming to activate ferroptosis and stimulate the immune responses. Specifically, we functionalize the OMVs by anchoring them with ferrous ions via electrostatic interactions and loading them with the STING agonist-4, followed by tumor-targeting DSPE-PEG-FA decoration, henceforth referred to as OMV/SaFeFA. The anchoring of ferrous ions endows the OMVs with peroxidase-like activity, capable of inducing cellular lipid peroxidation by catalyzing H 2 O 2 to • OH. Furthermore, OMV/SaFeFA exhibits pH-responsive release of ferrous ions and the agonist, along with tumor-targeting capabilities, enabling tumor-specific therapy while minimizing side effects. Notably, the concurrent activation of the STING pathway and ferroptosis elicits robust antitumor responses in colon tumor-bearing mouse models, leading to exceptional therapeutic efficacy and prolonged survival. Importantly, no acute toxicity was observed in mice receiving OMV/SaFeFA treatments, underscoring its potential for future tumor therapy and clinical translation., (© 2024. The Author(s).)

Myofibroblast buildup and prostatic fibrosis play a crucial role in the development of benign prostatic hyperplasia (BPH). Treatments specifically targeting myofibroblasts could be a promising approach for treating BPH. Tadalafil, a phosphodiesterase type 5 (PDE5) inhibitor, holds the potential to intervene in this biological process. This study employs prostatic stromal fibroblasts to induce myofibroblast differentiation through TGFβ1 stimulation. As a result, tadalafil significantly inhibited prostatic stromal fibroblast proliferation and fibrosis process, compared to the control group. Furthermore, our transcriptome sequencing results revealed that tadalafil inhibited FGF9 secretion and simultaneously improved miR-3126-3p expression via TGFβ1 suppression. Overall, TGFβ1 can trigger pro-fibrotic signaling through miR-3126-3p in the prostatic stroma, and the use of tadalafil can inhibit this process., (© 2024. The Author(s).)

Background: This study aimed to evaluate the impact of preoperative inflammatory indices and postoperative pneumonia (POP) on postoperative atrial fibrillation (POAF) in non-small cell lung cancer (NSCLC) patients., Methods: All consecutive patients who underwent pulmonary resection at our hospital (January 2016-October 2019) were enrolled. Preoperative inflammatory indices, demographic data, surgical details, and postoperative conditions were analyzed. Univariate and multivariate analyses of risk factors associated with POAF were also conducted., Results: Among the 382 patients included in the study, 32 (8.38%) developed POAF. Compared to non-POAF patients, POAF patients had greater incidence of POP (P = 0.09). Approximately 31 patients (96.9%) developed atrial fibrillation within three days after surgery. The POAF group had a significantly greater mean age (68.94 years) than did the non-POAF group (63 years) (P = 0.002). Additionally, compared to non-POAF patients, POAF patients exhibited an increased number of resected mediastinal lymph nodes (P < 0.001) and mediastinal lymph node stations (P < 0.001).The POAF group also had a greater intraoperative blood volume (P = 0.006), longer surgical duration (P = 0.022), and greater drainage volume (P = 0.003). IA/B stage (P < 0.001) and IIIA/B stage(P < 0.001), and lobectomy resection (P = 0.008) and wedge resection (P = 0.023) were also associated with POAF. Compared to those in the non-POAF group, the POAF group had longer postoperative hospital stays (10.54 days vs. 9 days; P = 0.001) and longer drainage times (7 days vs. 5 days; P = 0.004). Multivariate analysis revealed age, POP, and stage IIIA/B as independent influencing factors of POAF in NSCLC patients., Conclusion: Preoperative inflammatory indices were not significantly associated with POAF, but age, POP, and stage IIIA/B were identified as independent influencing factors. Advanced-stage NSCLC patients may have a greater susceptibility to POAF than early-stage patients, although further validation is needed. Additionally, POAF was linked to a longer postoperative hospital stay., (© 2024. The Author(s).)

Background: Angina is a crucial risk signal for cardiovascular disease. However, few studies have evaluated the effects of ambient air pollution exposure on angina., Objective: We aimed to explore the short-term effects of air pollution on hospitalization for angina and its lag effects., Methods: We collected data on air pollutant concentrations and angina hospitalizations from 2013 to 2020. Distributed lag nonlinear model (DLNM) was used to evaluate the short-term effects of air pollutants on angina hospitalization under different lag structures. Stratified analysis by sex, age and season was obtained., Results: A total of 39,110 cases of angina hospitalization were included in the study. The results showed a significant positive correlation between PM 2.5 , SO 2 , NO 2 , and CO and angina hospitalization. Their maximum harmful effects were observed at lag0-7 (RR = 1.042; 95% CI: 1.017, 1.068), lag0-3 (RR = 1.067; 95% CI: 1.005, 1.133), lag0-6 (RR = 1.078; 95% CI: 1.041, 1.117), and lag0-6 (RR = 1.244; 95% CI: 1.109, 1.397), respectively. PM 10 did not have an overall risk effect on angina hospitalization, but it did have a risk effect on women and the elderly. O 3 was significantly negatively correlated with angina hospitalization, with the most pronounced effect observed at lag0-6 (RR = 0.960; 95% CI: 0.940, 0.982). Stratified analysis results showed that women and the elderly were more susceptible to pollutants, and the adverse effects of pollutants were stronger in the cold season., Conclusion: Short-term exposure to PM 2.5 , SO 2 , NO 2 , and CO increases the risk of hospitalization for angina., (© 2024. The Author(s).)

Background: Optimum moisture in straw and grain at maturity is important for timely harvesting of wheat. Grain harvested at the right time has reduced chance of being affected by adverse weather conditions which is important to maintain grain quality and end use functionality. Wheat varieties with a short dry down period could help in timely harvest of the crop. However, measuring single kernel moisture in wheat and other small grain crops is a phenotyping bottleneck which requires characterising moisture content of the developing kernel at physiological maturity., Results: Here we report developing a pin-based probe to detect moisture in a developing wheat kernel required for determining physiological maturity. An in-house designed pin-based probe was used with different commercially available electronic moisture meters to assess the moisture content of the individual kernels in spikes with high accuracy (R 2  = 0.73 to 0.94, P < 0.001) compared with a reference method of oven drying. The average moisture values varied among different electronic moisture meters and the oven-dry method and differences in values were minimized at low kernel moisture content (< 50%). The single kernel moisture probe was evaluated in the field to predict the physiological maturity in wheat using 38% moisture content as the reference and visible notes on kernel stage., Conclusion: The pin-based moisture probe is a reliable tool for wheat physiologists and breeders to conveniently and accurately measure moisture content in developing grain that will aid in identifying wheat germplasm with fast dry-down characteristics., (© 2024. His Majesty the King in Right of Canada as represented by the Minister of Agriculture and Agri-Food Canada.)

Background: Plant microbiota contributes to plant growth and health, including enhancing plant resistance to various diseases. Despite remarkable progress in understanding diseases resistance in plants, the precise role of rhizosphere microbiota in enhancing watermelon resistance against soil-borne diseases remains unclear. Here, we constructed a synthetic community (SynCom) of 16 core bacterial strains obtained from the rhizosphere of grafted watermelon plants. We further simplified SynCom and investigated the role of bacteria with synergistic interactions in promoting plant growth through a simple synthetic community., Results: Our results demonstrated that the SynCom significantly enhanced the growth and disease resistance of ungrafted watermelon grown in non-sterile soil. Furthermore, analysis of the amplicon and metagenome data revealed the pivotal role of Pseudomonas in enhancing plant health, as evidenced by a significant increase in the relative abundance and biofilm-forming pathways of Pseudomonas post-SynCom inoculation. Based on in vitro co-culture experiments and bacterial metabolomic analysis, we selected Pseudomonas along with seven other members of the SynCom that exhibited synergistic effects with Pseudomonas. It enabled us to further refine the initially constructed SynCom into a simplified SynCom comprising the eight selected bacterial species. Notably, the plant-promoting effects of simplified SynCom were similar to those of the initial SynCom. Furthermore, the simplified SynCom protected plants through synergistic effects of bacteria., Conclusions: Our findings suggest that the SynCom proliferate in the rhizosphere and mitigate soil-borne diseases through microbial synergistic interactions, highlighting the potential of synergistic effects between microorganisms in enhancing plant health. This study provides a novel insight into using the functional SynCom as a promising solution for sustainable agriculture. Video Abstract., (© 2024. The Author(s).)

Background: Tripartite motif-containing 26 (TRIM26), a member of the TRIM protein family, exerts dual function in several types of cancer. Nevertheless, the precise role of TRIM26 in clear cell renal cell carcinoma (ccRCC) has not been investigated., Methods: The expression of TRIM26 in ccRCC tissues and cell lines were examined through the use of public resources and experimental validation. The impacts of TRIM26 on cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) process were determined via CCK-8, colony formation, EdU incorporation, wound healing, Transwell invasion, Western blot, and Immunofluorescence assays. RNA-seq followed by bioinformatic analyses were used to identify the downstream pathway of TRIM26. The interaction between TRIM26 and ETK was assessed by co-immunoprecipitation, qRT-PCR, Western blot, cycloheximide (CHX) chase, and in vivo ubiquitination assays., Results: We have shown that TRIM26 exhibits a downregulation in both ccRCC tissues and cell lines. Furthermore, this decreased expression of TRIM26 is closely linked to unfavorable overall survival and diseases-free survival outcomes among ccRCC patients. Gain- and loss-of-function experiments demonstrated that increasing the expression of TRIM26 suppressed the proliferation, migration, invasion, and EMT process of ccRCC cells. Conversely, reducing the expression of TRIM26 had the opposite effects. RNA sequencing, coupled with bioinformatic analysis, revealed a significant enrichment of the mTOR signaling pathway in the control group compared to the group with TRIM26 overexpression. This finding was then confirmed by a western blot assay. Subsequent examination revealed that TRMI26 had a direct interaction with ETK, a non-receptor tyrosine kinase. This interaction facilitated the ubiquitination and degradation of ETK, resulting in the deactivation of the AKT/mTOR signaling pathway in ccRCC. ETK overexpression counteracted the inhibitory effects of TRIM26 overexpression on cell proliferation, migration, and invasion., Conclusion: Our results have shown a novel mechanism by which TRIM26 hinders the advancement of ccRCC by binding to and destabilizing ETK, thus leading to the deactivation of AKT/mTOR signaling. TRIM26 shows promise as both a therapeutic target and prognostic biomarker for ccRCC patients., (© 2024. The Author(s).)

Background: Neoadjuvant immunochemotherapy (NICT) plus esophagectomy has emerged as a promising treatment option for locally advanced esophageal squamous cell carcinoma (LA-ESCC). Pathologic complete response (pCR) is a key indicator associated with great efficacy and overall survival (OS). However, there are insufficient indicators for the reliable assessment of pCR., Methods: 192 patients with LA-ESCC treated with NICT from December 2019 to October 2023 were recruited. According to pCR status, patients were categorized into pCR group (22.92%) and non-pCR group (77.08%). Radiological features of pretreatment and preoperative CT images were extracted. Logistic and COX regressions were trained to predict pathological response and prognosis, respectively., Results: Four of the selected radiological features were combined to construct an ESCC preoperative imaging score (ECPI-Score). Logistic models revealed independent associations of ECPI-Score and vascular sign with pCR, with AUC of 0.918 in the training set and 0.862 in the validation set, respectively. After grouping by ECPI-Score, a higher proportion of pCR was observed among the high-ECPI group and negative vascular sign. Kaplan Meier analysis demonstrated that recurrence-free survival (RFS) with negative vascular sign was significantly better than those with positive (P = 0.038), but not for OS (P = 0.310)., Conclusions: This study demonstrates dynamic radiological features are independent predictors of pCR for LA-ESCC treated with NICT. It will guide clinicians to make accurate treatment plans., (© 2024. The Author(s).)

Background: Patients with functional dyspepsia (FD) cannot be assessed for their mental health using a suitable and practical measure. The purpose of the study is to investigate the usefulness of several anxiety and depression scales in patients with FD, offering recommendations for clinical identification and therapy., Methods: From September 2021 to September 2022, patients were sought and selected. The psychological symptoms were assessed using ten depression or anxiety questionnaires. The receiver operating characteristic (ROC) curve, Spearman analysis, Pearson correlation analysis, and single factor analysis were applied., Results: Prospective analysis was performed on 142 healthy individuals and 113 patients with FD. In the case group, anxiety and depression symptoms were more common than in the control group, and the 10 scales showed strong validity and reliability. HAMD had the strongest connection with the PHQ-9 score on the depression scale (0.83). The score correlation between SAS and HAMA on the anxiety analysis scale was the greatest at 0.77. The PHQ-9, SAS, HAMD, and HAMA measures performed exceptionally well in detecting FD with anxiety or depression symptoms (AUC = 0.72, 0.70, 0.70, 0.77, and 0.77, respectively)., Conclusions: PHQ-9, SAS, HAMD, and HAMA scales have good application performance in FD patients. They can assist gastroenterologists in evaluating anxiety and depression symptoms, and provide reference and guidance for subsequent treatment., (© 2024. The Author(s).)

In recent years, there has been an increase in the incidence and mortality rates of prostate cancer (PCa). However, the specific molecular mechanisms underlying its occurrence and development remain unclear, necessitating the identification of new therapeutic targets. Through bioinformatics analysis, we discovered a previously unstudied differential gene called HIST3H2A in prostate cancer. Our study revealed that HIST3H2A is highly expressed in PCa tissues, as confirmed by analysis of both the GEO and UALCAN databases. Further analysis using the KEGG database demonstrated that HIST3H2A regulates the pathway of programmed necroptosis in cells. Additionally, we observed significant up-regulation of HIST3H2A in PCa tissues and cell lines. HIST3H2A was found to regulate cell proliferation, migration, invasion, and the epithelial-mesenchymal transition (EMT) process in tumors. Notably, HIST3H2A's role in regulating programmed necroptosis in prostate cancer cells differs from its role in apoptosis. In vitro and in vivo experiments collectively support the key role of HIST3H2A in promoting the development of prostate cancer, highlighting its potential as a therapeutic target for patients with PCa., (© 2024. The Author(s).)

Background: Activation of VDR pathway was a promising anti-tumor therapy strategy. However, numerous clinical studies have demonstrated the effect of activating VDR is limited, which indicates that VDR plays a complex role in vivos., Methods: We analyzed the TCGA database to examine the association between VDR expression and immune cell infiltration in pancreatic adenocarcinoma (PAAD). Western blot, ELISA, ChIP, and dual-luciferase reporter assays were performed to determine the mechanism of VDR regulating CCL20. Migration assay and immunofluorescence were used to investigate the role of CCL20 in M2 macrophage polarization and recruitment. We employed multiplexed immunohistochemical staining and mouse models to validate the correlation of VDR on macrophages infiltration in PAAD. Flow cytometry analysis of M2/M1 ratio in subcutaneous graft tumors., Results: VDR is extensively expressed in PAAD, and patients with elevated VDR levels exhibited a significantly reduced overall survival. VDR expression in PAAD tissues was associated with increased M2 macrophages infiltration. PAAD cells overexpressing VDR promote macrophages polarization towards M2 phenotype and recruitment in vitro and vivo. Mechanistically, VDR binds to the CCL20 promoter and up-regulates its transcription. The effects of polarization and recruitment on macrophages can be rescued by blocking CCL20. Finally, the relationship between VDR and M2 macrophages infiltration was evaluated using clinical cohort and subcutaneous graft tumors. A positive correlation was demonstrated between VDR/CCL20/CD163 in PAAD tissues and mouse models., Conclusion: High expression of VDR in PAAD promotes M2 macrophage polarization and recruitment through the secretion of CCL20, which activates tumor progression. This finding suggests that the combination of anti-macrophage therapy may improve the efficacy of VDR activation therapy in PAAD., (© 2024. The Author(s).)

Aim: To investigate the differences in gut microbiota composition among nonpregnant women of reproductive age, healthy pregnant women, and gestational diabetes (GD) patients., Methods: A total of 45 outpatients were enrolled and divided into three groups: nonpregnant women of reproductive age (control group, n = 23), healthy pregnant women (normal group, n = 10), and GD patients (GD group, n = 12). Faecal samples were collected and sequenced using 16S rRNA gene sequencing to analyse the microbial composition., Results: (1) Pregnant patients exhibited an increase in the abundance of Streptococcus (P normal  = 0.01286, P GD  = 0.002965) and Blautia (P normal  = 0.0003924, P GD  = 0.000246) but a decrease in the abundance of Roseburia (P normal  = 0.0361, P GD  = 0.007075), Phascolarctobacterium (P normal  = 0.0003906, P GD  = 0.02499) and Lachnoclostridium (P normal  = 0.0003906, P GD  = 0.03866). (2) Compared with healthy pregnant women, GD patients had an excessive increase in Streptococcus abundance and decrease in Roseburia abundance. The increase in Blautia abundance and the decrease in Phascolarctobacterium and Lachnoclostridium abundance in GD patients were less than those in healthy pregnant women. (3) The abundance of Faecalibacterium prausnitzii decreased significantly in GD patients (P GD  = 0.02985) but not in healthy pregnant patients (P normal  = 0.1643)., Conclusions: Abnormal increases and decreases in the abundances of gut microbiota components, especially Faecalibacterium prausnitzii, were observed in GD patients., Trial Registration: The cross-sectional research was conducted in accordance with the Declaration of Helsinki, and approved by Sir Run Run Shaw Hospital Clinical Trials and Biomedical Ethics Committee. The study has been registered in the Chinese Clinical Trial Registry (ChiCTR1900026164, 24/09/2019, http://www.chictr.org.cn/showproj.aspx?proj=43,455 )., (© 2024. The Author(s).)

Background: Bladder cancer (BC) is the most common urinary tract malignancy. Aurora kinase B (AURKB), a component of the chromosomal passenger protein complex, affects chromosomal segregation during cell division. Mitotic arrest-deficient 2-like protein 2 (MAD2L2) interacts with various proteins and contributes to genomic integrity. Both AURKB and MAD2L2 are overexpressed in various human cancers and have synergistic oncogenic effects; therefore, they are regarded as emerging therapeutic targets for cancer. However, the relationship between these factors and the mechanisms underlying their oncogenic activity in BC remains largely unknown. The present study aimed to explore the interactions between AURKB and MAD2L2 and how they affect BC progression via the DNA damage response (DDR) pathway., Methods: Bioinformatics was used to analyze the expression, prognostic value, and pro-tumoral function of AURKB in patients with BC. CCK-8 assay, colony-forming assay, flow cytometry, SA-β-gal staining, wound healing assay, and transwell chamber experiments were performed to test the viability, cell cycle progression, senescence, and migration and invasion abilities of BC cells in vitro. A nude mouse xenograft assay was performed to test the tumorigenesis ability of BC cells in vivo. The expression and interaction of proteins and the occurrence of the senescence-associated secretory phenotype were detected using western blot analysis, co-immunoprecipitation assay, and RT-qPCR., Results: AURKB was highly expressed and associated with prognosis in patients with BC. AURKB expression was positively correlated with MAD2L2 expression. We confirmed that AURKB interacts with, and modulates the expression of, MAD2L2 in BC cells. AURKB knockdown suppressed the proliferation, migration, and invasion abilities of, and cell cycle progression in, BC cells, inducing senescence in these cells. The effects of AURKB knockdown were rescued by MAD2L2 overexpression in vitro and in vivo. The effects of MAD2L2 knockdown were similar to those of AURKB knockdown. Furthermore, p53 ablation rescued the MAD2L2 knockdown-induced suppression of BC cell proliferation and cell cycle arrest and senescence in BC cells., Conclusions: AURKB activates MAD2L2 expression to downregulate the p53 DDR pathway, thereby promoting BC progression. Thus, AURKB may serve as a potential molecular marker and a novel anticancer therapeutic target for BC., (© 2024. The Author(s).)

Background: Fusarium head blight (FHB) infection results in Fusarium damaged kernels (FDK) and deoxynivalenol (DON) contamination that are downgrading factors at the Canadian elevators. Durum wheat (Triticum turgidum L. var. durum Desf.) is particularly susceptible to FHB and most of the adapted Canadian durum wheat cultivars are susceptible to moderately susceptible to this disease. However, the durum line DT696 is less susceptible to FHB than commercially grown cultivars. Little is known about genetic variation for durum wheat ability to resist FDK infection and DON accumulation. This study was undertaken to map genetic loci conferring resistance to DON and FDK resistance using a SNP high-density genetic map of a DT707/DT696 DH population and to identify SNP markers useful in marker-assisted breeding. One hundred twenty lines were grown in corn spawn inoculated nurseries near Morden, MB in 2015, 2016 and 2017 and the harvested seeds were evaluated for DON. The genetic map of the population was used in quantitative trait locus analysis performed with MapQTL.6® software., Results: Four DON accumulation resistance QTL detected in two of the three years were identified on chromosomes 1 A, 5 A (2 loci) and 7 A and two FDK resistance QTL were identified on chromosomes 5 and 7 A in single environments. Although not declared significant due to marginal LOD values, the QTL for FDK on the 5 and 7 A were showing in other years suggesting their effects were real. DT696 contributed the favourable alleles for low DON and FDK on all the chromosomes. Although no resistance loci contributed by DT707, transgressive segregant lines were identified resulting in greater resistance than DT696. Breeder-friendly KASP markers were developed for two of the DON and FDK QTL detected on chromosomes 5 and 7 A. Markers flanking each QTL were physically mapped against the durum wheat reference sequence and candidate genes which might be involved in FDK and DON resistance were identified within the QTL intervals., Conclusions: The DH lines harboring the desired resistance QTL will serve as useful resources in breeding for FDK and DON resistance in durum wheat. Furthermore, breeder-friendly KASP markers developed during this study will be useful for the selection of durum wheat varieties with low FDK and DON levels in durum wheat breeding programs., (© 2024. Crown.)

Background: Pyroptosis has been demonstrated being closely associated with the inflammatory progression in chronic rhinosinusitis (CRS). However, platycodon D (PLD) has emerged as a key anti-inflammatory mediator in the inflammatory progression of various respiratory diseases. This study aims at investigating whether PLD could reduce inflammatory progression of CRS by inhibiting pyroptosis., Methods: Nasal mucosal tissues from patients with CRS and the control group (simple nasal septal deviation) were analyzed for morphological difference using hematoxylin & eosin staining and for the expression of pyroptosis-related makers by immunofluorescence (IF). Human nasal epithelial cells (HNEpCs) were cultured and co-stimulated with lipopolysaccharide (LPS)/adenosine triphosphate (ATP) to construct an in vitro cellular model simulating CRS. After pretreatment with PLD, EthD-I staining, TUNEL staining, transmission electron microscopy (TEM), and GSDMD-NT detection were performed to evaluate pyroptosis markers. The NLRP3 inflammasome was detected by IF and western blotting (WB). Reactive oxygen species (ROS) were detected by H2DCFDA staining, and mitochondrial membrane potential was evaluated by JC-1 staining. Mitochondrial morphology and structure were observed using TEM. The Nrf2/HO-1 antioxidant signaling pathway was detected using WB., Results: The nasal mucosa structure of patients with CRS exhibited significant damage, with a marked increase in the expression of pyroptosis-related proteins compared with the control group. LPS/ATP co-stimulation resulted in an increased expression of IL-18 and IL-1β in HNEpCs, causing significant damage to nuclear and cell membranes, GSDMD-NT accumulation around the cell membrane, and intracellular NLRP3 inflammasome activation. Furthermore, it led to increased ROS expression, significantly decreased mitochondrial membrane potential, and damaged mitochondrial structure. However, pretreatment with PLD significantly reversed the aforementioned trends and activated the Nrf2/HO-1 antioxidant signaling pathway., Conclusions: The results of this study confirm that NLRP3-mediated pyroptosis plays a crucial role in the pathological process of nasal mucosal impairment in patients with CRS. PLD inhibits NLRP3-mediated pyroptosis, preventing inflammatory damage in HNEpCs of patients with CRS by activating the Nrf2/HO-1 antioxidant signaling pathway, which in turn reduces ROS production and ameliorates mitochondrial damage., (© 2024. The Author(s).)

Background: Cesarean scar pregnancy (CSP) is a long-term complication of cesarean section characterized by the localization of a subsequent gestational sac within the scar area or niche developed as a result of a previous cesarean section. Its incidence has increased substantially because of the high global cesarean section rate in recent decades. Several surgical and drug treatments exist for this condition; however, there is currently no optimal treatment. This study compared the effectiveness of direct hysteroscopic removal of the gestational tissue and hysteroscopy combined with vacuum suction for the treatment of CSP., Methods: From 2017 to 2023, 521 patients were diagnosed with CSP at our hospital. Of these patients, 45 underwent hysteroscopy. Among them, 28 underwent direct hysteroscopic removal (hysteroscopic removal group) and 17 underwent hysteroscopy combined with vacuum suction (hysteroscopic suction group). The clinical characteristics and outcomes of the hysteroscopic removal group and hysteroscopic suction group were analyzed., Results: Among the 45 patients, the amount of bleeding and hospitalization cost were significantly higher in the hysteroscopic removal group than in the hysteroscopic suction group (33.8 mL vs. 9.9 mL, P < 0.001; and 8744.0 yuan vs. 5473.8 yuan, P < 0.001; respectively). The operation time and duration of hospitalization were significantly longer in the hysteroscopic removal group than in the hysteroscopic suction group (61.4 min vs. 28.2 min, P < 0.001; and 3.8 days vs. 2.4 days, P = 0.026; respectively). Three patients in the hysteroscopic removal group had uterine perforation and received laparoscopic repair during operation. No complications occurred in the hysteroscopic suction group. One patient in the hysteroscopic removal group received ultrasound-guided suction curettage due to postoperative moderate vaginal bleeding, and one patient in the hysteroscopic suction group received ultrasound-guided suction curettage due to postoperative gestational residue and elevated serum beta-human chorionic gonadotropin levels. Reproductive function was preserved in all patients., Conclusions: Hysteroscopy is an effective method for treating CSP. Compared with direct hysteroscopic removal, hysteroscopy combined with vacuum suction is more suitable for CSP. However, multicenter prospective studies with large sample sizes are required for verification of these findings., (© 2024. The Author(s).)

Background: Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) plays a pivotal role in inducing metabolic inflammation in diabetes. Additionally, the NOD1 ligand disrupts the equilibrium of bone marrow-derived hematopoietic stem/progenitor cells, a process that has immense significance in the development of diabetic retinopathy (DR). We hypothesized that NOD1 depletion impedes the advancement of DR by resolving bone marrow dysfunction., Methods: We generated NOD1 -/- -Akita double-mutant mice and chimeric mice with hematopoietic-specific NOD1 depletion to study the role of NOD1 in the bone marrow-retina axis., Results: Elevated circulating NOD1 activators were observed in Akita mice after 6 months of diabetes. NOD1 depletion partially restored diabetes-induced structural changes and retinal electrical responses in NOD1 -/- -Akita mice. Loss of NOD1 significantly ameliorated the progression of diabetic retinal vascular degeneration, as determined by acellular capillary quantification. The preventive effect of NOD1 depletion on DR is linked to bone marrow phenotype alterations, including a restored HSC pool and a shift in hematopoiesis toward myelopoiesis. We also generated chimeric mice with hematopoietic-specific NOD1 ablation, and the results further indicated that NOD1 had a protective effect against DR. Mechanistically, loss of hematopoietic NOD1 resulted in reduced bone marrow-derived macrophage infiltration and decreased CXCL1 and CXCL2 secretion within the retina, subsequently leading to diminished neutrophil chemoattraction and NETosis., Conclusions: The results of our study unveil, for the first time, the critical role of NOD1 as a trigger for a hematopoietic imbalance toward myelopoiesis and local retinal inflammation, culminating in DR progression. Targeting NOD1 in bone marrow may be a potential strategy for the prevention and treatment of DR., (© 2024. The Author(s).)

Background: The phenotypic traits of leaves are the direct reflection of the agronomic traits in the growth process of leafy vegetables, which plays a vital role in the selection of high-quality leafy vegetable varieties. The current image-based phenotypic traits extraction research mainly focuses on the morphological and structural traits of plants or leaves, and there are few studies on the phenotypes of physiological traits of leaves. The current research has developed a deep learning model aimed at predicting the total chlorophyll of greenhouse lettuce directly from the full spectrum of hyperspectral images., Results: A CNN-based one-dimensional deep learning model with spectral attention module was utilized for the estimate of the total chlorophyll of greenhouse lettuce from the full spectrum of hyperspectral images. Experimental results demonstrate that the deep neural network with spectral attention module outperformed the existing standard approaches, including partial least squares regression (PLSR) and random forest (RF), with an average R 2 of 0.746 and an average RMSE of 2.018., Conclusions: This study unveils the capability of leveraging deep attention networks and hyperspectral imaging for estimating lettuce chlorophyll levels. This approach offers a convenient, non-destructive, and effective estimation method for the automatic monitoring and production management of leafy vegetables., (© 2024. The Author(s).)

Background: This study explores the effectiveness of Photobiomodulation Therapy (PBMT) in enhancing orthodontic tooth movement (OTM), osteogenesis, and angiogenesis through a comprehensive series of in vitro and in vivo investigations. The in vitro experiments involved co-culturing MC3T3-E1 and HUVEC cells to assess PBMT's impact on cell proliferation, osteogenesis, angiogenesis, and associated gene expression. Simultaneously, an in vivo experiment utilized an OTM rat model subjected to laser irradiation at specific energy densities., Methods: In vitro experiments involved co-culturing MC3T3-E1 and HUVEC cells treated with PBMT, enabling a comprehensive assessment of cell proliferation, osteogenesis, angiogenesis, and gene expression. In vivo, an OTM rat model was subjected to laser irradiation at specified energy densities. Statistical analyses were performed to evaluate the significance of observed differences., Results: The results revealed a significant increase in blood vessel formation and new bone generation within the PBMT-treated group compared to the control group. In vitro, PBMT demonstrated positive effects on cell proliferation, osteogenesis, angiogenesis, and gene expression in the co-culture model. In vivo, laser irradiation at specific energy densities significantly enhanced OTM, angiogenesis, and osteogenesis., Conclusions: This study highlights the substantial potential of PBMT in improving post-orthodontic bone quality. The observed enhancements in angiogenesis and osteogenesis suggest a pivotal role for PBMT in optimizing treatment outcomes in orthodontic practices. The findings position PBMT as a promising therapeutic intervention that could be seamlessly integrated into orthodontic protocols, offering a novel dimension to enhance overall treatment efficacy. Beyond the laboratory, these results suggest practical significance for PBMT in clinical scenarios, emphasizing its potential to contribute to the advancement of orthodontic treatments. Further exploration of PBMT in orthodontic practices is warranted to unlock its full therapeutic potential., (© 2024. The Author(s).)

Background: Cancer-associated fibroblasts (CAFs) are heterogeneous and can influence the progression of prostate cancer in multiple ways; however, their capacity to present and process antigens in PRAD has not been investigated. In this study, antigen presentation and process-related CAFs (APPCAFs) were identified using bioinformatics, and the clinical implications of APPCAF-related signatures in PRAD were investigated., Methods: SMART technology was used to sequence the transcriptome of primary CAFs isolated from patients undergoing different treatments. Differential expression gene (DEG) screening was conducted. A CD4 + T-cell early activation assay was used to assess the activation degree of CD4 + T cells. The datasets of PRAD were obtained from The Cancer Genome Atlas (TCGA) database and NCBI Gene Expression Omnibus (GEO), and the list of 431 antigen presentation and process-related genes was obtained from the InnateDB database. Subsequently, APP-related CAFs were identified by nonnegative matrix factorization (NMF) based on a single-cell seq (scRNA) matrix. GSVA functional enrichment analyses were performed to depict the biological functions. A risk signature based on APPCAF-related genes (APPCAFRS) was developed by least absolute shrinkage and selection operator (LASSO) regression analysis, and the independence of the risk score as a prognostic factor was evaluated by univariate and multivariate Cox regression analyses. Furthermore, a biochemical recurrence-free survival (BCRFS)-related nomogram was established, and immune-related characteristics were assessed using the ssGSEA function. The immune treatment response in PRAD was further analyzed by the Tumor Immune Dysfunction and Exclusion (TIDE) tool. The expression levels of hub genes in APPCAFRS were verified in cell models., Results: There were 134 upregulated and 147 downregulated genes, totaling 281 differentially expressed genes among the primary CAFs. The functions and pathways of 147 downregulated DEGs were significantly enriched in antigen processing and presentation processes, MHC class II protein complex and transport vesicle, MHC class II protein complex binding, and intestinal immune network for IgA production. Androgen withdrawal diminished the activation effect of CAFs on T cells. NMF clustering of CAFs was performed by APPRGs, and pseudotime analysis yielded the antigen presentation and process-related CAF subtype CTSK + MRC2 + CAF-C1. CTSK + MRC2 + CAF-C1 cells exhibited ligand‒receptor connections with epithelial cells and T cells. Additionally, we found a strong association between CTSK + MRC2 + CAF-C1 cells and inflammatory CAFs. Through differential gene expression analysis of the CTSK + MRC2 + CAF-C1 and NoneAPP-CAF-C2 subgroups, 55 significant DEGs were identified, namely, APPCAFRGs. Based on the expression profiles of APPCAFRGs, we divided the TCGA-PRAD cohort into two clusters using NMF consistent cluster analysis, with the genetic coefficient serving as the evaluation index. Four APPCAFRGs, THBS2, DPT, COL5A1, and MARCKS, were used to develop a prognostic signature capable of predicting BCR occurrence in PRAD patients. Subsequently, a nomogram with stability and accuracy in predicting BCR was constructed based on Gleason grade (p = n.s.), PSA (p < 0.001), T stage (p < 0.05), and risk score (p < 0.01). The analysis of immune infiltration showed a positive correlation between the abundance of resting memory CD4 + T cells, M1 macrophages, resting dendritic cells, and the risk score. In addition, the mRNA expression levels of THBS2, DPT, COL5A1, and MARCKS in the cell models were consistent with the results of the bioinformatics analysis., Conclusions: APPCAFRS based on four potential APPCAFRGs was developed, and their interaction with the immune microenvironment may play a crucial role in the progression to castration resistance of PRAD. This novel approach provides valuable insights into the pathogenesis of PRAD and offers unexplored targets for future research., (© 2024. The Author(s).)

Objectives: To evaluate the prevention efficacy of scaling up HIV/AIDS antiretroviral therapy (ART) on HIV transmission at the population level and determine associated factors of HIV secondary transmission., Methods: We used HIV longitudinal molecular networks to assess the genetic linkage between baseline and newly diagnosed cases. A generalized estimating equation was applied to determine the associations between demographic, clinical characteristics and HIV transmission., Results: Patients on ART had a 32% lower risk of HIV transmission than those not on ART. A 36% reduction in risk was also seen if ART-patients maintained their HIV viral load lower than 50 copies/mL. A 71% lower risk occurred when patients sustained ART for at least 3 years and kept HIV viral load less than 50 copies/mL. Patients who discontinued ART had a similar HIV transmission risk as those not on ART. Patients who were older, male, non-Han, not single, retired, infected via a heterosexual route of transmission and those who possessed higher CD4 counts had a higher risk of HIV transmission. HIV-1 subtype of CRF01&#95;AE was less transmissible than other subtypes., Conclusions: The efficacy of ART in a real-world setting was supported by this longitudinal molecular network study. Promoting adherence to ART is crucial to reduce HIV transmission., (© 2023. The Author(s).)

Introduction: Primary breast lymphoma (PBL) is rare, and most cases occur in female patients, with few reported cases in male patients. The clinical presentation is similar to that of breast cancer, but the condition needs to be well understood, as treatment options and clinical course vary. Hence, we provide a relatively rare case of primary breast diffuse large B cell lymphoma (PB-DLBCL) in a male, including its complete clinicopathological features, radiological findings, genomic mutational profiles, and clinical course., Case Presentation: A 45-year-old male presented with a lump in his right breast for 1 week and was pathologically diagnosed with breast malignancy after a breast puncture biopsy at the local hospital. He came to our hospital for further treatment and underwent breast ultrasound and systemic positron emission tomography/computed tomography (PET/CT) imaging, followed by right mastectomy and sentinel lymph node biopsy. Histomorphology showed diffuse hyperplasia of tumor cells with clear boundaries and surrounding normal breast ducts. The adhesion of tumor cells was poor with obvious atypia. Immunohistochemical results showed that the tumor cells were positive for CD20, Bcl6, and MUM-1 but negative for CK (AE1/AE3), ER, PR, CD3, and CD10. Forty percent of the tumor cells were positive for c-Myc, and 80% of tumor cells were positive for Bcl2. The Ki-67 proliferation index was up to 80%. The tumor cells were negative for MYC and BCL2 rearrangements but positive for BCL6 rearrangement by fluorescent in situ hybridization. No abnormality was found in the pathological examination of bone marrow aspiration. Therefore, the male was diagnosed with PB-DLBCL, nongerminal center (non-GCB) phenotype, dual-expression type. The sample were sequenced by a target panel of 121 genes related to lymphoma. Next-generation sequencing revealed six tumor-specific mutated genes (IGH/BCL6, TNFAIP3, PRDM1, CREBBP, DTX1, and FOXO1). The patient was given six cycles of orelabrutinib plus R-CHOP chemotherapy and two cycles of intrathecal injection of cytarabine. The last follow-up was on April 13, 2023 (17 months). No recurrence or metastasis was found in laboratory and imaging examinations., Conclusion: We reported a relatively rare PB-DLBCL in a male, non-GBC phenotype, dual-expression type. It is worth mentioning that this case had IgH/BCL6 fusion, nonsense mutations in TNFAIP3, frameshift mutations in PRDM1, and missense mutations in CREBBP, DTX1, and FOXO1. To the best of our knowledge, this case is the first report of genomic mutational profiles of PB-DLBCL in males., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) infection, is still one of the top killers worldwide among infectious diseases. The escape of Mtb from immunological clearance and the low targeting effects of anti-TB drugs remain the substantial challenges for TB control. Iron is particularly required for Mtb growth but also toxic for Mtb in high dosages, which makes iron an ideal toxic decoy for the 'iron-tropic' Mtb. Here, a macrophage-targeted iron oxide nanoparticles (IONPs)-derived IONPs-PAA-PEG-MAN nanodecoy is designed to augment innate immunological and drug killings against intracellular Mtb. IONPs-PAA-PEG-MAN nanodecoy exhibits preferential uptake in macrophages to significantly increase drug uptake with sustained high drug contents in host cells. Moreover, it can serve as a specific nanodecoy for the 'iron-tropic' Mtb to realize the localization of Mtb contained phagosomes surrounding the drug encapsulated nanodecoys and co-localization of Mtb with the drug encapsulated nanodecoys in lysosomes, where the incorporated rifampicin (Rif) can be readily released under acidic lysosomal condition for enhanced Mtb killing. This drug encapsulated nanodecoy can also polarize Mtb infected macrophages into anti-mycobacterial M1 phenotype and enhance M1 macrophage associated pro-inflammatory cytokine (TNF-α) production to trigger innate immunological responses against Mtb. Collectively, Rif@IONPs-PAA-PEG-MAN nanodecoy can synergistically enhance the killing efficiency of intracellular Mtb in in vitro macrophages and ex vivo monocyte-derived macrophages, and also significantly reduce the mycobacterial burdens in the lung of infected mice with alleviated pathology. These results indicate that Rif@IONPs-PAA-PEG-MAN nanodecoy may have a potential for the development of more effective therapeutic strategy against TB by manipulating augmented innate immunity and drug killings., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) are the most common types of leukemia in adults with an overall poor prognosis. PD-1 alone or combined with other immune checkpoint blockade is a promising research direction for the treatment of acute leukemia (AL) patients. However, clinical Implications of aberrant PD-1 expression in peripheral CD4+ and CD8+ T lymphocytes of AML and ALL patients in assessing the prognosis of diseases, remains inconclusive., Methods: In the present study, we used flow cytometry to evaluate PD-1 expression on the surface of CD4+ and CD8+ T lymphocytes in the peripheral circulation of AML and ALL patients and its clinical significance. A total of 53 AML patients, 44 ALL patients and 28 healthy controls were enrolled in this study and peripheral blood specimens were detected by flow cytometry., Results: Our results indicated that percentages of CD4+ PD1+ and CD8+ PD1+ T lymphocytes in newly diagnosed and non-remission groups were significantly higher than healthy control both in AML and ALL patients. The high level of CD4+ PD1+ and CD8+ PD1+ T lymphocytes were respectively poor prognostic indicators of AML patients and ALL patients but had no significant correlation with most common clinical risks., Conclusions: Our findings show that aberrant PD-1 expression correlates with the prognosis of AL patient and may thus serve as poor prognostic indicators. Immunotherapy using PD-1 inhibitors may be a promising strategy for AML and ALL patients with peripheral circulating CD4+ PD1+ and CD8+ PD1+ T lymphocytes positively expressed, respectively., (© 2023. The Author(s).)

Background: Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignancy with a poor prognosis. The underlying functions and mechanisms of circular RNA and SUMOylation in the development of ICC remain poorly understood., Methods: Circular RNA hsa&#95;circ&#95;0001681 (termed Circ-RAPGEF5 hereafter) was identified by circular RNA sequencing from 19 pairs of ICC and adjacent tissue samples. The biological function of Circ-RAPGEF5 in tumor proliferation and metastasis was examined by a series of in vitro assays. A preclinical model was used to validate the therapeutic effect of targeting Circ-RAPGEF5. RNA pull-down and dual-luciferase reporter assays were used to access the RNA interactions. Western blot and Co-IP assays were used to detect SUMOylation levels., Results: Circ-RAPGEF5, which is generated from exons 2 to 6 of the host gene RAPGEF5, was upregulated in ICC. In vitro and in vivo assays showed that Circ-RAPGEF5 promoted ICC tumor proliferation and metastasis, and inhibited apoptosis. Additionally, high Circ-RAPGEF5 expression was significantly correlated with a poor prognosis. Further investigation showed that SAE1, a potential target of Circ-RAPGEF5, was also associated with poor oncological outcomes. RNA pull-down and dual-luciferase reporter assays showed an interaction of miR-3185 with Circ-RAPGEF5 and SAE1. Co-IP and western blot assays showed that Circ-RAPGEF5 is capable of regulating SUMOylation., Conclusion: Circ-RAPGEF5 promotes ICC tumor progression and SUMOylation by acting as a sponge for miR-3185 to stabilize SAE1. Targeting Circ-RAPGEF5 or SAE1 might be a novel diagnostic and therapeutic strategy in ICC., (© 2023. Italian National Cancer Institute ‘Regina Elena’.)

Background: Short-term exposure to air pollution is associated with acute lower respiratory infections (ALRI) in children. We investigated the relationship between hospitalization for ALRI in children and air pollutant concentrations from January 1, 2014 to December 31, 2020 in Lanzhou City., Methods: We collected data on air pollutant concentrations and children's hospitalization data during the study period. A time series regression analysis was used to assess the short-term effects of air pollutants on ALRI in children, and subgroup analyses and sensitivity analyses were performed., Results: A total of 51,206 children with ALRI were studied, including 40,126 cases of pneumonia and 11,080 cases of bronchiolitis. The results of the study revealed that PM 2.5 , PM 10 , SO 2 and NO 2 were significantly associated with hospitalization for ALRI in children aged 0-14 years. For each 10 µg/m 3 increase in air pollutant concentration in lag0-7, the relative risk of ALRI hospitalization in children due to PM 2.5 , PM 10 , SO 2 and NO 2 increased by 1.089 (95%CI:1.075, 1.103), 1.018 (95%CI:1.014, 1.021), 1.186 (95%CI:1.154. 1.219) and 1.149 (95%CI:1.130, 1.168), respectively., Conclusions: PM 2.5 , PM 10 , SO 2 and NO 2 short-term exposures were positively associated with ALRI, pneumonia and bronchiolitis hospitalizations in Lanzhou, China. Local governments should make efforts to improve urban ambient air quality conditions to reduce hospitalization rates for childhood respiratory diseases., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Urothelial carcinoma is a major subtype of bladder cancer and small cell carcinoma (SCC) is a rare type of cancer in clinical practice. Pathologic collision of urinary bladder urothelial carcinoma with SCC is not common in clinical settings., Case Presentation: Here, we report a patient with high-grade papillary carcinoma which changed to collision tumor with SCC. The patient underwent radical cystectomy; however, neck and mediastinum lymph nodes metastases were detected 11 months after the operation. The lymph nodes were diagnosed pathologically as SCC. Chemoradiotherapy was subsequently prescribed. Unfortunately, this patient died of COVID-19 in early 2023., Discussion: We hypothesized the mechanism underlying this pathological transformation. For patients with urothelial bladder cancer, pathological analysis should be conducted to allow standardized and persistent treatment. Moreover, drugs should be selected depending on the type of pathology, especially for patients who develop relapse, since collision tumor or other pathological tumors may be present., Conclusions: We recommend that radical cystectomy be performed early enough for patients with non-muscle invasive bladder cancer, who are at a high risk of tumor recurrence. However, this conclusion needs to be validated in a larger number of patients., (© 2023. The Author(s).)

Background: Inflammatory bowel disease (IBD) is a heterogeneous group of disorders associated with environmental triggers and dysregulated immune responses resulting in chronic, recurrent intestinal inflammation. Very early-onset IBD (VEO-IBD) refers to patients with symptoms or diagnosis before the age of 6 years and is widely thought to be associated with monogenic mutations. Traditional drug therapy is often ineffective in this patient population, while hematopoietic stem cell transplantation (HSCT) represents the definitive cure for patients with gene mutations., Case Presentation: We report a case of VEO-IBD associated with a monogenic mutation in a 2-year-old girl presenting mainly with gastrointestinal symptoms, including recurrent hematochezia and abdominal pain for more than 3 months. A gastroscopy revealed erosive gastritis and bulbar duodenitis, while a colonoscopy indicated erosive colitis. Abnormal results were obtained from the dihydrohodamine (DHR) assay and immunoglobulin testing. Whole-exome sequencing identified a heterozygous and de novo nonsense mutation (c.388 C > T; p.R130X) in the CYBB gene leading to deficiency of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) (encoded by CYBB), a critical component of phagocytes. HSCT was performed successfully, and the DHR assay showed that normal neutrophil function was restored. Six months after HSCT, clinical remission was observed, and a repeat colonoscopy revealed intestinal mucosal healing was attained., Conclusions: Patients with CYBB mutations often develop recurrent or severe bacterial or fungal infections, mostly in the lungs, skin, lymph nodes, and liver. Here, we report on a young female child with CYBB mutations presenting predominantly with gastrointestinal symptoms. This study explores the mechanisms of inflammatory bowel disease caused by a monogenic mutation in CYBB to improve early diagnosis and effective treatment rates of this patient population., (© 2023. The Author(s).)

Background: Prostate cancer (PCa) is a prevalent malignant disease affecting a significant number of males globally. Elevated expression of the Bloom's syndrome protein (BLM) helicase has emerged as a promising cancer biomarker, being associated with the onset and progression of PCa. Nevertheless, the precise molecular mechanisms governing BLM regulation in PCa remain elusive., Methods: The expression of BLM in human specimens was analyzed using immnohistochemistry (IHC). A 5'-biotin-labeled DNA probe containing the promoter region of BLM was synthesized to pull down BLM promoter-binding proteins. Functional studies were conducted using a range of assays, including CCK-8, EdU incorporation, clone formation, wound scratch, transwell migration, alkaline comet assay, xenograft mouse model, and H&E staining. Mechanistic studies were carried out using various techniques, including streptavidin-agarose-mediated DNA pull-down, mass spectrometry (MS), immunofluorescence (IF), dual luciferase reporter assay system, RT-qPCR, ChIP-qPCR, co-immunoprecipitation (co-IP), and western blot., Results: The results revealed significant upregulation of BLM in human PCa tissues, and its overexpression was associated with an unfavorable prognosis in PCa patients. Increased BLM expression showed significant correlations with advanced clinical stage (P = 0.022) and Gleason grade (P = 0.006). In vitro experiments demonstrated that BLM knockdown exerted inhibitory effects on cell proliferation, clone formation, invasion, and migration. Furthermore, PARP1 (poly (ADP-ribose) polymerase 1) was identified as a BLM promoter-binding protein. Further investigations revealed that the downregulation of PARP1 led to increased BLM promoter activity and expression, while the overexpression of PARP1 exerted opposite effects. Through mechanistic studies, we elucidated that the interaction between PARP1 and HSP90AB1 (heat shock protein alpha family class B) enhanced the transcriptional regulation of BLM by counteracting the inhibitory influence of PARP1 on BLM. Furthermore, the combination treatment of olaparib with ML216 demonstrated enhanced inhibitory effects on cell proliferation, clone formation, invasion, and migration. It also induced more severe DNA damage in vitro and exhibited superior inhibitory effects on the proliferation of PC3 xenograft tumors in vivo., Conclusions: The results of this study underscore the significance of BLM overexpression as a prognostic biomarker for PCa, while also demonstrating the negative regulatory impact of PARP1 on BLM transcription. The concurrent targeting of BLM and PARP1 emerges as a promising therapeutic approach for PCa treatment, holding potential clinical significance., (© 2023. The Author(s).)

Background: Peritoneal catheter related infection is one of the main complications and the major cause of technical failure of peritoneal dialysis (PD) treatment. However, PD catheter tunnel infection can be difficult to diagnosis and resolve. We presented a rare case in which a granuloma formation after repeated episodes of peritoneal dialysis catheter-related infection., Case Presentation: A 53-year-old female patient with kidney failure due to chronic glomerulonephritis treated with peritoneal dialysis for 7 years. The patient had repeated exit-site and tunnel inflammation, and repeated suboptimal courses of antibiotics. She switched to hemodialysis after 6 years in a local hospital without the peritoneal dialysis catheter being removed. The patient complained of an abdominal wall mass that lasted for several months. She was admitted to the Department of surgery to undergo mass resection. The resected tissue of the abdominal wall mass was sent for pathological examination. The result showed foreign body granuloma with necrosis and abscess formation. After the surgery, the infection did not recur., Conclusions: The following key points can be learned from this case: 1. It is important to strengthen patient follow-up. 2.The PD catheter should be removed as early as possible in patients who do not need long-term PD, especially in patients with a history of exit-site and tunnel infections. 3. For patients presenting abnormal subcutaneous mass, attention should be paid to the possibility of the granuloma formation of infected Dacron cuffs of the PD catheter. If catheter infection occurs repeatedly, catheter removal and debridement should be considered., (© 2023. The Author(s).)

Background & Aims: The individual effect of working schedule on survival in the hypertensive population has not been adequately studied. Shiftworkers are also prone to unhealthy lifestyles like pro-inflammatory diet. Therefore, we assessed the effect of shift work and its joint association with dietary inflammatory potential on mortality risk among the large US nationally representative sample of adult hypertensive population., Methods: Data were from a nationally representative prospective cohort among US hypertensive population (n = 3680; weighted population, 54,192,988). The participants were linked to the 2019 public-access linked mortality archives. The working schedule were self-reported using the Occupation Questionnaire Section. Dietary inflammatory index (DII) scores were equally calculated using the 24-hour dietary recall (24 h) interviews. Multivariable Cox proportional hazards regression models were used to estimate hazard ratio and 95% confidence intervals (95%CI) for survival of hypertension individuals by work schedule and dietary inflammatory potential. The joint effect of work schedule and dietary inflammatory potential was then examined., Results: Among the 3680 hypertension individuals (39.89% female [n = 1479] and 71.42% white [n = 1707]; weighted mean [SE] age, 47.35 [0.32] years), 592 individuals reported shift work status. 474 (10.76%) reported shift work status with pro-inflammatory dietary pattern (DII scores > 0). 118 (3.06%) reported shift work status with anti-inflammatory dietary pattern (DII scores < 0). 646 (19.64%) reported a non-shift working schedule with anti-inflammatory dietary pattern, while 2442 (66.54%) reported non-shift working schedule with pro-inflammatory dietary pattern. After a median follow-up of 11.67 years (140 months), 317 deaths (cardiovascular diseases (CVD), 65; cancer, 104) were registered. Cox regression analysis showed that shift work was associated with higher risk of all-cause mortality (hazard ratio [HR], 1.48; 95% CI, 1.07-2.06) compared with non-shift workers. In the joint analysis, shift work status combined with pro-inflammatory dietary pattern was associated with the highest all-cause mortality risk. Moreover, adopting the anti-inflammatory diet significantly attenuates the deleterious effect of shift work on mortality risk., Conclusions: In this large representative sample of adults with hypertension in the U.S., the combination of shift work status with pro-inflammatory dietary pattern was highly prevalent and was associated with the highest risks of death from all causes., (© 2023. The Author(s).)

Background: Both low-carbohydrate (LC) and calorie-restricted (CR) diets have been shown to have metabolic benefits. However, the two regimens have yet to be thoroughly compared. We conducted a 12-week randomized trial to compare the effects of these diets separately and in combination on both weight loss and metabolic risk factors in overweight/obese individuals., Methods: A total of 302 participants were randomized to LC diet (n = 76), CR diet (n = 75), LC + CR diet (n = 76), or normal control (NC) diet (n = 75) using a computer-based random number generator. The primary outcome was the change in body mass index (BMI). The secondary outcomes included body weight, waist circumference, waist-to-hip ratio, body fat, and metabolic risk factors. All participants attended health education sessions during the trial., Results: A total of 298 participants were analyzed. BMI change over 12 weeks was - 0.6 (95% CI, - 0.8 to - 0.3) kg/m 2 in NC, - 1.3 (95% CI, - 1.5 to - 1.1) kg/m 2 in CR, - 2.3 (95% CI, - 2.6 to - 2.1) kg/m 2 in LC, and - 2.9 (95% CI, - 3.2 to - 2.6) kg/m 2 in LC + CR. LC + CR diet was more effective than LC or CR diet alone at reducing BMI (P = 0.001 and P < 0.001, respectively). Furthermore, compared with the CR diet, the LC + CR diet and LC diet further reduced body weight, waist circumference, and body fat. Serum triglycerides were significantly reduced in the LC + CR diet group compared with the LC or CR diet alone. Plasma glucose, homeostasis model assessment of insulin resistance, and cholesterol concentrations (total, LDL, and HDL) did not change significantly between the groups during the 12-week intervention., Conclusions: The reduction of carbohydrate intake without restricting caloric intake is more potent to achieve weight loss over 12 weeks when compared to a calorie-restricted diet in overweight/obese adults. The combination of restricting carbohydrate and total calorie intake may augment the beneficial effects of reducing BMI, body weight, and metabolic risk factors among overweight/obese individuals., Trial Registration: The study was approved by the institutional review board of Zhujiang Hospital of Southern Medical University and registered at the China Clinical Trial Registration Center (registration number: ChiCTR1800015156)., (© 2023. The Author(s).)

Background: Cervical cancer is an important public health problem. Conventional colposcopy is inefficient in the diagnosis of cervical lesions and massive biopsies result in trauma. There is an urgent need for a new clinical strategy to triage women with abnormal cervical screening results immediately and effectively. In this study, the high-resolution microendoscopy combined with methylene blue cell staining technology was used to perform real-time in vivo imaging of the cervix for the first time., Methods: A total of 41 patients were enrolled in the study. All patients underwent routine colposcopy and cervical biopsy, and high-resolution images of methylene blue-stained cervical lesions were obtained in vivo using microendoscopy. The cell morphological features of benign and neoplastic cervical lesions stained with methylene blue under microendoscopy were analyzed and summarized. The microendoscopy and histopathology findings of the high-grade squamous intraepithelial lesion (HSIL) and more severe lesions were compared., Results: The overall consistency of microendoscopy diagnosis with pathological diagnosis was 95.12% (39/41). Diagnostic cell morphological features of cervicitis, low-grade squamous intraepithelial lesion (LSIL), HSIL, adenocarcinoma in situ, and invasive cancer were clearly demonstrated in methylene blue stained microendoscopic images. In HSIL and more severe lesions, microendoscopic methylene blue cell staining technology can show the microscopic diagnostic features consistent with histopathology., Conclusions: This study was an initial exercise in the application of the microendoscopy imaging system combined with methylene blue cell staining technology to cervical precancerous lesions and cervical cancer screening. The results provided the basis for a novel clinical strategy for triage of women with abnormal cervical screening results using in vivo non-invasive optical diagnosis technology., (© 2023. The Author(s).)

Background: Previous studies have not clearly demonstrated the impact of behavioral and emotional problems (BEDs) on treatment outcomes among HIV-infected children on antiretroviral therapy (ART). This study aimed to describe the prevalence of BEDs among this population and identify the factors associated with HIV treatment outcomes., Methods: This cross-sectional study was conducted in Guangxi, China, between July and August 2021. HIV-infected children answered questionnaires about BEDs, physical health, social support, and whether they have missed doses in the past month. BEDs were assessed using the Chinese version of the self-reported Strengths and Difficulties Questionnaire (SDQ-C). The self-reported survey data were linked to participants' HIV care information that was obtained from the national surveillance database. Univariate and multivariate logistic regression models were used to identify factors that were associated with missed doses in the past month and virological failure., Results: The study sample was 325 HIV-infected children. HIV-infected children had a higher proportion of abnormal scores on SDQ-C total difficulties compared to their peers in the general population (16.9 vs 10.0%; P = 0.002). An abnormal SDQ-C total difficulties score (AOR = 2.06, 95%CI: 1.10-3.88) and infrequency of receiving assistance and support from parents over the past 3 months (AOR = 1.85, 95%CI: 1.12-3.06) were significantly associated with missed doses in the past month. Between the ages of 14-17 years (AOR = 2.66, 95% CI: 1.37-5.16), female (AOR = 2.21, 95% CI: 1.20-4.08), and suboptimal adherence (AOR = 2.45, 95% CI: 1.32-4.57) were significantly associated with virological failure., Conclusions: Children's mental health plays a role in HIV treatment outcomes. Psychological interventions should be promoted in pediatric HIV care clinics to improve children's mental health status and HIV treatment outcomes., (© 2023. The Author(s).)

Objective: Studies have shown that obesity has a significant impact on poor surgical outcomes. However, the relationship between obesity and pediatric epilepsy surgery has not been reported. This study aimed to explore the relationship between obesity and complications of pediatric epilepsy surgery and the effect of obesity on the outcome of pediatric epilepsy surgery, and to provide a reference for weight management of children with epilepsy., Methods: A single-center retrospective analysis of complications in children undergoing epilepsy surgery was conducted. Body mass index (BMI) percentiles were adjusted by age and used as a criterion for assessing obesity in children. According to the adjusted BMI value, the children were divided into the obese group (n = 16) and nonobese group (n = 20). The intraoperative blood loss, operation time, and postoperative fever were compared between the two groups., Results: A total of 36 children were included in the study, including 20 girls and 16 boys. The mean age of the children was 8.0 years old, ranging from 0.8 to 16.9 years old. The mean BMI was 18.1 kg/m2 , ranging from 12.4 kg/m2 to 28.3 kg/m2 . Sixteen of them were overweight or obese (44.4%). Obesity was associated with higher intraoperative blood loss in children with epilepsy (p = 0.04), and there was no correlation between obesity and operation time (p = 0.21). Obese children had a greater risk of postoperative fever (56.3%) than nonobese children (55.0%), but this was statistically nonsignificant (p = 0.61). The long-term follow-up outcomes showed that 23 patients (63.9%) were seizure-free (Engel grade I), 6 patients (16.7%) had Engel grade II, and 7 patients (19.4%) had Engel grade III. There was no difference in long-term seizure control outcomes between obese and nonobese groups (p = 0.682). There were no permanent neurological complications after surgery., Conclusion: Compared with nonobese children with epilepsy, obese children with epilepsy had a higher intraoperative blood loss. It is necessary to conduct early weight management of children with epilepsy as long as possible., (© 2023. The Author(s).)

Background: Inflammasome activation has a pathogenic role in Parkinson's disease (PD). Up-regulated expressions of inflammasome adaptor apoptosis-associated speck-like protein containing a CARD (ASC) and assembly of ASC specks have been observed in postmortems of human PD brains and experimental PD models. Extracellular ASC specks behave like danger signals and sustain prolonged inflammasome activation. However, the contribution of ASC specks in propagation of inflammasome activation and pathological progression in PD has not been fully established., Methods: Herein, we used human A53T mutant α-synuclein preformed fibrils (PFFs)-stimulated microglia in vitro and unilateral striatal stereotaxic injection of PFFs-induced mice model of PD in vivo, to investigate the significance of ASC specks in PD pathological progression. Rotarod and open-field tests were performed to measure motor behaviors of indicated mice. Changes in the molecular expression were evaluated by immunofluorescence and immunoblotting (IB). Intracellular knockdown of the ASC in BV2 cells was performed using si-RNA. Microglial and neuronal cells were co-cultured in a trans-well system to determine the effects of ASC knockdown on cytoprotection., Results: We observed a direct relationship between levels of ASC protein and misfolded α‑synuclein aggregates in PD mice brains. ASC specks amplified NLRP3 inflammasome activation driven by α-synuclein PFFs stimulation, which aggravated reactive microgliosis and accelerated α‑synuclein pathology, dopaminergic neurodegeneration and motor deficits. Endogenous ASC knockdown suppressed microglial inflammasome activation and neuronal α‑synuclein aggregation., Conclusions: In conclusion, our study elucidated that ASC specks contribute to the propagation of inflammasome activation-associated α‑synuclein pathology in PD, which forms the basis for targeting ASC as a potential therapy for PD., (© 2023. The Author(s).)

Background: Cadmium (Cd) is a highly toxic element for plant growth. In plants, hydrogen sulfide (H 2 S) and methylglyoxal (MG) have emerged as vital signaling molecules that regulate plant growth processes under Cd stress. However, the effects of sodium hydrosulfide (NaHS, a donor of H 2 S) and MG on Cd uptake, physiological responses, and gene expression patterns of Salix to Cd toxicity have been poorly understood. Here, Salix matsudana Koidz. seedlings were planted in plastic pot with applications of MG (108 mg kg - 1 ) and NaHS (50 mg kg - 1 ) under Cd (150 mg kg - 1 ) stress., Results: Cd treatment significantly increased the reactive oxygen species (ROS) levels and malondialdehyde (MDA) content, but decreased the growth parameters in S. matsudana. However, NaHS and MG supplementation significantly decreased Cd concentration, ROS levels, and MDA content, and finally enhanced the growth parameters. Cd stress accelerated the activities of antioxidative enzymes and the relative expression levels of stress-related genes, which were further improved by NaHS and MG supplementation. However, the activities of monodehydroascorbate reductase (MDHAR), and dehydroascorbate reductase (DHAR) were sharply decreased under Cd stress. Conversely, NaHS and MG applications restored the MDHAR and DHAR activities compared with Cd-treated seedlings. Furthermore, Cd stress decreased the ratios of GSH/GSSG and AsA/DHA but considerably increased the H 2 S and MG levels and glyoxalase I-II system in S. matsudana, while the applications of MG and NaHS restored the redox status of AsA and GSH and further improved glyoxalase II activity. In addition, compared with AsA, GSH showed a more sensitive response to exogenous applications of MG and NaHS and plays more important role in the detoxification of Cd., Conclusions: The present study illustrated the crucial roles of H 2 S and MG in reducing ROS-mediated oxidative damage to S. matsudana and revealed the vital role of GSH metabolism in regulating Cd-induced stress., (© 2023. The Author(s).)