Deciphering the Transcription Factor Landscape in Neuroendocrine Prostate Cancer Progression: A Novel Approach to Understand NE Transdifferentiation.

Background and Objective: Prostate cancer (PCa) is a leading cause of cancer mortality in men, with neuroendocrine prostate cancer (NEPC) representing a particularly resistant subtype. The role of transcription factors (TFs) in the progression from prostatic adenocarcinoma (PRAD) to NEPC is poorly understood. This study aims to identify and analyze lineage-specific TF profiles in PRAD and NEPC and illustrate their dynamic shifts during NE transdifferentiation. Methods: A novel algorithmic approach was developed to evaluate the weighted expression of TFs within patient samples, enabling a nuanced understanding of TF landscapes in PCa progression and TF dynamic shifts during NE transdifferentiation. Results: unveiled TF profiles for PRAD and NEPC, identifying 126 shared TFs, 46 adenocarcinoma-TFs, and 56 NEPC-TFs. Enrichment analysis across multiple clinical cohorts confirmed the lineage specificity and clinical relevance of these lineage-TFs signatures. Functional analysis revealed that lineage-TFs are implicated in pathways critical to cell development, differentiation, and lineage determination. Novel lineage-TF candidates were identified, offering potential targets for therapeutic intervention. Furthermore, our longitudinal study on NE transdifferentiation highlighted dynamic TF expression shifts and delineated a three-phase hypothesis for the process comprised of de-differentiation, dormancy, and re-differentiation. and proposing novel insights into the mechanisms of PCa progression. Conclusion: The lineage-specific TF profiles in PRAD and NEPC reveal a dynamic shift in the TF landscape during PCa progression, highlighting three distinct phases of NE transdifferentiation.

Associations of incident female breast cancer with long-term exposure to PM2.5 and its constituents: Findings from a prospective cohort study in Beijing, China.

This study aimed to investigate the association between long-term exposure to fine particulate matter (PM2.5) and its constituents (black carbon (BC), ammonium (NH4+), nitrate (NO3-), organic matter (OM), inorganic sulfate (SO42-)) and incident female breast cancer in Beijing, China. Data from a prospective cohort comprising 85,504 women enrolled in the National Urban Cancer Screening Program in Beijing (2013-2019) and the Tracking Air Pollution in China dataset are used. Monthly exposures were aggregated to calculate 5-year average concentrations to indicate long-term exposure. Cox models and mixture exposure models (weighted quantile sum, quantile-based g-computation, and explanatory machine learning model) were employed to analyze the associations. Findings indicated increased levels of PM2.5 and its constituents were associated with higher breast cancer risk, with hazard ratios per 1-µg/m3 increase of 1.02 (95% confidence interval (CI): 1.01, 1.03), 1.39 (95% CI: 1.16, 1.65), 1.28 (95% CI: 1.12, 1.46), 1.15 (95% CI: 1.05, 1.24), 1.05 (95% CI: 1.02, 1.08), and 1.15 (95% CI: 1.07, 1.23) for PM2.5, BC, NH4+, NO3-, OM, and SO42-, respectively. Exposure-response curves demonstrated a monotonic risk increase without an evident threshold. Mixture exposure models highlighted BC and SO42- as key factors, underscoring the importance of reducing emissions of these pollutants.

Multiple exposure pathways and health risk assessment of PAHs in Lanzhou city, a semi-arid region in northwest China.

In the sparse studies for multiple pathway exposure, attention has predominantly been directed towards developed regions, thereby overlooking the exposure level and health outcome for the inhabitants of the semi-arid regions in northwest China. However, cities within these regions grapple with myriad challenges, encompassing insufficient sanitation infrastructure and outdated heating. In this study, we analyzed the characteristics and sources of polycyclic aromatic hydrocarbons (PAHs) pollution in PM2.5, water, diet, and dust during different periods in Lanzhou, and estimated corresponding carcinogenic health risk through inhalation, ingestion, and dermal absorption. Our observations revealed the concentrations of PAHs in PM2.5, food, soil, and water are 200.11 ng m-3, 8.67 mg kg-1, 3.91 mg kg-1, and 14.5 ng L-1, respectively, indicating that the Lanzhou area was seriously polluted. Lifetime incremental cancer risk (ILCR) showed a heightened cancer risk to men compared to women, to the younger than the elderly, and during heating period as opposed to non-heating period. Notably, the inhalation was the primary route of PAHs exposure and the risk of exposure by inhalation cannot be ignored. The total environmental exposure assessment of PAHs can achieve accurate prevention and control of PAHs environmental exposure according to local conditions and targets.

Construction and efficacy testing of DNA vaccines containing HLA-A*02:01-restricted SARS-CoV-2 T-cell epitopes predicted by immunoinformatics.

Vaccines play essential roles in the fight against the COVID-19 pandemic. The development and assessment of COVID-19 vaccines have generally focused on the induction and boosting of neutralizing antibodies targeting the SARS-CoV-2 spike (S) protein. Due to rapid and continuous variation in the S protein, such vaccines need to be regularly updated to match newly emerged dominant variants. T-cell vaccines that target MHC I- or II-restricted epitopes in both structural and non-structural viral proteins have the potential to induce broadly cross-protective and long-lasting responses. In this work, the entire proteome encoded by SARS-CoV-2 (Wuhan-hu-1) is subjected to immunoinformatics-based prediction of HLA-A*02:01-restricted epitopes. The immunogenicity of the predicted epitopes is evaluated using peripheral blood mononuclear cells from convalescent Wuhan-hu-1-infected patients. Furthermore, predicted epitopes that are conserved across major SARS-CoV-2 lineages and variants are used to construct DNA vaccines expressing multi-epitope polypeptides. Most importantly, two DNA vaccine constructs induce epitope-specific CD8 + T-cell responses in a mouse model of HLA-A*02:01 restriction and protect immunized mice from challenge with Wuhan-hu-1 virus after hACE2 transduction. These data provide candidate T-cell epitopes useful for the development of T-cell vaccines against SARS-CoV-2 and demonstrate a strategy for quick T-cell vaccine candidate development applicable to other emerging pathogens.

Enhancing cancer therapy: The role of drug delivery systems in STAT3 inhibitor efficacy and safety.

The signal transducer and activator of transcription 3 (STAT3), a member of the STAT family, resides in the nucleus to regulate genes essential for vital cellular functions, including survival, proliferation, self-renewal, angiogenesis, and immune response. However, continuous STAT3 activation in tumor cells promotes their initiation, progression, and metastasis, rendering STAT3 pathway inhibitors a promising avenue for cancer therapy. Nonetheless, these inhibitors frequently encounter challenges such as cytotoxicity and suboptimal biocompatibility in clinical trials. A viable strategy to mitigate these issues involves delivering STAT3 inhibitors via drug delivery systems (DDSs). This review delineates the regulatory mechanisms of the STAT3 signaling pathway and its association with cancer. It offers a comprehensive overview of the current application of DDSs for anti-STAT3 inhibitors and investigates the role of DDSs in cancer treatment. The conclusion posits that DDSs for anti-STAT3 inhibitors exhibit enhanced efficacy and reduced adverse effects in tumor therapy compared to anti-STAT3 inhibitors alone. This paper aims to provide an outline of the ongoing research and future prospects of DDSs for STAT3 inhibitors. Additionally, it presents our insights on the merits and future outlook of DDSs in cancer treatment.

Zebrafish live imaging: a strong weapon in anticancer drug discovery and development.

Developing anticancer drugs is a complex and time-consuming process. The inability of current laboratory models to reflect important aspects of the tumor in vivo limits anticancer medication research. Zebrafish is a rapid, semi-automated in vivo screening platform that enables the use of non-invasive imaging methods to monitor morphology, survival, developmental status, response to drugs, locomotion, or other behaviors. Zebrafish models are widely used in drug discovery and development for anticancer drugs, especially in conjunction with live imaging techniques. Herein, we concentrated on the use of zebrafish live imaging in anticancer therapeutic research, including drug screening, efficacy assessment, toxicity assessment, and mechanism studies. Zebrafish live imaging techniques have been used in numerous studies, but this is the first time that these techniques have been comprehensively summarized and compared side by side. Finally, we discuss the hypothesis of Zebrafish Composite Model, which may provide future directions for zebrafish imaging in the field of cancer research.

Comprehensive pan-cancer analysis identifies the RNA-binding protein LRPPRC as a novel prognostic and immune biomarker.

AIMS: RNA-binding proteins (RBPs) play pivotal roles in carcinogenesis and immunotherapy. Leucine-rich pentapeptide repeat-containing protein (LRPPRC) is crucial for RNA polyadenylation, transport, and stability. Although recent studies have suggested LRPPRC's potential role in tumor progression, its significance in tumor prognosis, diagnosis, and immunology remains unclear. MAIN METHODS: We comprehensively analyzed LRPPRC expression in tumors using various databases, including Human Transcriptome Cell Atlas (HTCA), University of California Santa Cruz (UCSC), Human Protein Atlas (HPA), Sangerbox, TISIDB, GeneMANIA, GSCALite, and CellMiner. We examined the correlation between LRPPRC expression level and prognosis, immune infiltration, immunotherapy, methylation, biological function, and drug sensitivity. Single-cell analysis was performed using Tumor Immune Single Cell Hub (TISCH) and CancerSEA software. Patients with acute myeloid leukemia (AML) were categorized based on LRPPRC levels for functional and immune infiltration analyses. The role of LRPPRC in cancer was validated using in vitro experiments. KEY FINDINGS: Our findings revealed that LRPPRC was highly expressed in almost all cancer types, indicating its significant prognostic and diagnostic potential. Notably, LRPPRC was associated with diverse immune features, such as immune cell infiltration, immune checkpoint genes, tumor mutational burden, and microsatellite instability, suggesting its value in guiding immunotherapy strategies. Within AML, the high-expression group had lower levels of immune cells, including CD8+ T cells. In vitro experiments confirmed the inhibitory effects of LRPPRC knockdown on AML cell proliferation. SIGNIFICANCE: This study highlights LRPPRC as a reliable pan-cancer prognostic and immune biomarker, particularly in AML. It lays the groundwork for future research on LRPPRC-targeted cancer therapies.

Intrahepatic homeobox protein MSX-1 is a novel host restriction factor of hepatitis B virus.

Chronic hepatitis B virus (HBV) infection (CHB) is a risk factor for the development of liver fibrosis, cirrhosis, and hepatocellular carcinoma. Covalently closed circular DNA serves as the sole transcription template for all viral RNAs and viral transcription is driven and enhanced by viral promoter and enhancer elements, respectively. Interactions between transcription factors and these cis-elements regulate their activities and change the production levels of viral RNAs. Here, we report the identification of homeobox protein MSX-1 (MSX1) as a novel host restriction factor of HBV in liver. In both HBV-transfected and HBV-infected cells, MSX1 suppresses viral gene expression and genome replication. Mechanistically, MSX1 downregulates enhancer II/core promoter (EnII/Cp) activity via direct binding to an MSX1 responsive element within EnII/Cp, and such binding competes with hepatocyte nuclear factor 4α binding to EnII/Cp due to partial overlap between their respective binding sites. Furthermore, CHB patients in immune active phase express higher levels of intrahepatic MSX1 but relatively lower levels of serum and intrahepatic HBV markers compared to those in immune tolerant phase. Finally, MSX1 was demonstrated to induce viral clearance in two mouse models of HBV persistence, suggesting possible therapeutic potential for CHB.IMPORTANCECovalently closed circular DNA plays a key role for the persistence of hepatitis B virus (HBV) since it serves as the template for viral transcription. Identification of transcription factors that regulate HBV transcription not only provides insights into molecular mechanisms of viral life cycle regulation but may also provide potential antiviral targets. In this work, we identified host MSX1 as a novel restriction factor of HBV transcription. Meanwhile, we observed higher intrahepatic MSX1 expression in chronic hepatitis B virus (CHB) patients in immune active phase compared to those in immune tolerant phase, suggesting possible involvement of MSX1 in the regulation of HBV activity by the host. Lastly, intrahepatic overexpression of MSX1 delivered by recombinant adenoviruses into two mouse models of HBV persistence demonstrated MSX1-mediated repression of HBV in vivo, and MSX1-induced clearance of intrahepatic HBV DNA in treated mice suggested its potential as a therapeutic target for the treatment of CHB.

Withanolides: Promising candidates for cancer therapy.

Natural products have played a significant role throughout history in the prevention and treatment of numerous diseases, particularly cancers. As a natural product primarily derived from various medicinal plants in the Withania genus, withanolides have been shown in several studies to exhibit potential activities in cancer treatment. Consequently, understanding the molecular mechanism of withanolides could herald the discovery of new anticancer agents. Withanolides have been studied widely, especially in the last 20 years, and attracted the attention of numerous researchers. Currently, over 1200 withanolides have been classified, with approximately a quarter of them having been reported in the literature to be able to modulate the survival and death of cancer cells through multiple avenues. To what extent, though, has the anticancer effects of these compounds been studied? How far are they from being developed into clinical drugs? What are their potential, characteristic features, and challenges? In this review, we elaborate on the current knowledge of natural compounds belonging to this class and provide an overview of their natural sources, anticancer activity, mechanism of action, molecular targets, and implications for anticancer drug research. In addition, direct targets and clinical research to guide the design and implementation of future preclinical and clinical studies to accelerate the application of withanolides have been highlighted.

Ningetinib plus gefitinib in EGFR-mutant non-small-cell lung cancer with MET and AXL dysregulations: A phase 1b clinical trial and biomarker analysis.

BACKGROUND: MET and AXL dysregulations are implicated in acquired resistance to EGFR-TKIs in NSCLC. But consensus on the optimal definition for MET/AXL dysregulations in EGFR-mutant NSCLC is lacking. Here, we investigated the efficacy and tolerability of ningetinib (a MET/AXL inhibitor) plus gefitinib in EGFR-mutant NSCLC, and evaluated the clinical relevance of MET/AXL dysregulations by different definitions. METHODS: Patients in this phase 1b dose-escalation/dose-expansion trial received ningetinib 30 mg/40 mg/60 mg plus gefitinib 250 mg once daily. Primary endpoints were tolerability (dose-escalation) and objective response rate (dose-expansion). MET/AXL status were analyzed using FISH and IHC. RESULTS: Between March 2017 and January 2021, 108 patients were enrolled. The proportion of MET focal amplification, MET polysomy, MET overexpression, AXL amplification and AXL overexpression is 18.1 %, 5.6 %, 55.8 %, 8.1 % and 45.3 %, respectively. 6.8 % patients have concurrent MET amplification and AXL overexpression. ORR is 30.8 % for tumors with MET amplification, 0 % for MET polysomy, 24.1 % for MET overexpression, 20 % for AXL amplification and 27.6 % for AXL overexpression. For patients with concurrent MET amplification and AXL overexpression, ningetinib plus gefitinib provides an ORR of 80 %, DCR of 100 % and median PFS of 4.7 months. Tumors with higher MET copy number and AXL expression tend to have higher likelihood of response. Biomarker analyses show that MET focal amplification and overexpression are complementary in predicting clinical benefit from MET inhibition, while AXL dysregulations defined by an arbitrary level may dilute the efficacy of AXL blockade. CONCLUSIONS: This study demonstrates that combined blockade of MET, AXL and EGFR is a feasible strategy for a subset of EGFR-mutant NSCLC. TRIAL REGISTRATION: Chinadrugtrials.org.cn, CTR20160875.

Feasibility of Simultaneous Bilateral Endoscopic Surgery in Prone Split-Leg Position for Bilateral Upper Urinary Tract Calculi: A Pilot Study.

Introduction We explored the viability of simultaneous bilateral endoscopic surgery (SBES) in the prone split-leg position for managing bilateral calculi. Methods We retrospectively reviewed 72 patients who underwent SBES, with procedures involving ureteroscopy (URS) and contralateral percutaneous nephrolithotomy (PNL) simultaneously, in prone split-leg position. Results Operative times averaged 109.38±30.76 minutes, with an average hospital stay of 7.79±3.78 days. Bilateral stone-free rate (SFR) was 70.83%, while URS and PNL demonstrated comparable unilateral SFR (83.33% and 79.17%, respectively). Receiver operating characteristics (ROC) curves for predicting unilateral residual fragments yielded an area under the curve (AUC) of 0.84 (URS) and 0.81 (PNL) with respective cut-off values of stone diameter of 11.55 mm and 23.52 mm. 57 (79.17%) and 15 (20.83%) patients encountered grade 0-1/2 complications, with no severe complications (grade 3-5) recorded. No significant changes in blood count or renal function were observed post-SBES. Conclusions SBES in the prone split-leg position is a viable option for managing bilateral upper-tract urolithiasis. Larger-scale studies are needed to further assess safety and efficacy in various positions.

Camrelizumab in combination with neoadjuvant chemotherapy in resectable locally advanced esophageal squamous carcinoma cancer: Results from a retrospective study.

This study aimed to evaluate the safety and efficacy of camrelizumab combined with chemotherapy during preoperative neoadjuvant therapy in patients with locally advanced resectable esophageal squamous cell carcinoma (ESCC) of clinical Stages II and III. The patients received camrelizumab plus chemotherapy regimen on Day 1 for up to three to four cycles (3 weeks per cycle). The probabilities of overall survival (OS) were 55.6% at 12 months and 35.6% at 18 months (45 patients). The disease-free survival (DFS) rates were 70.0% at 12 months and 63.3% at 18 months (30 patients). The median OS and DFS were not reached. The proportion of patients at postneoadjuvant pathological tumor stages ypT0, ypT2, and ypT3 were 10 (33.3%), 14 (46.7%), and 6 (20.0%), respectively, and those at stages ypN0 and ypN1 were 19 (63.3%) and 11 (36.7%), respectively. Additionally, the pathological complete response rate was 33.3% (95% confidence interval [CI]: 0.154-0.512), and the major pathologic response rate was 46.7% (95% CI: 0.277-0.656). Grade ≥3 adverse events (AEs) were reported in five patients (11.1%), with vomiting being the most common AE (three patients; 3.3%). Other common AEs of any grade included decreased lymphocyte count (48.9%), reactive capillary endothelial proliferation (46.7%), decreased white blood cell count (40.0%), anemia (31.1%), and vomiting (31.1%). The combination of camrelizumab and neoadjuvant chemotherapy in patients with locally advanced resectable ESCC demonstrated promising efficacy and acceptable safety.

Foxp3-mediated blockage of ryanodine receptor 2 underlies contact-based suppression by regulatory T cells.

The suppression mechanism of Tregs remains an intensely investigated topic. As our focus has shifted toward a model centered on indirect inhibition of DCs, a universally applicable effector mechanism controlled by the transcription factor forkhead box P3 (Foxp3) expression has not been found. Here, we report that Foxp3 blocked the transcription of ER Ca2+-release channel ryanodine receptor 2 (RyR2). Reduced RyR2 shut down basal Ca2+ oscillation in Tregs, which reduced m-calpain activities that are needed for T cells to disengage from DCs, suggesting a persistent blockage of DC antigen presentation. RyR2 deficiency rendered the CD4+ T cell pool immune suppressive and caused it to behave in the same manner as Foxp3+ Tregs in viral infection, asthma, hypersensitivity, colitis, and tumor development. In the absence of Foxp3, Ryr2-deficient CD4+ T cells rescued the systemic autoimmunity associated with scurfy mice. Therefore, Foxp3-mediated Ca2+ signaling inhibition may be a central effector mechanism of Treg immune suppression.

[Ultrasound-guided continuous fascia iliaca compartment block for perioperative pain management in elderly patients undergoing hip fracture surgery].

OBJECTIVE: To study the effect of ultrasound-guided fascia iliaca compartment block on perioperative analgesia and postoperative complications in geriatric patients with hip fractures. METHODS: A total of 127 elderly patients undergoing hip fracture surgery from January 2021 to September 2021 were randomized to receive ultrasound-guided continuous fascia iliaca compartment block(group F) either intravenous analgesia control group(group C). There were 62 cases in group F, including 19 males and 43 females with an average age of (82.4±7.2) years old ranging from 66 to 95 years old, involving 25 femoral neck fractures and 37 femoral intertrochanteric fractures. There were 65 cases in control group, including 18 males and 47 females, with an average age of (81.4±8.7) years old ranging from 65 to 94 years old, involving 29 femoral neck fractures and 36 femoral intertrochanteric fractures. The visual analogue scale(VAS), minimental state examination (MMSE), observer's assessment of alertness/sedation(OAA/S) scale, modified Bromage score, postoperative complications and general conditions during hospitalization in two groups were observed. RESULTS: The resting and exercise VAS at 30 min after block, anesthesia placement and 6, 24 and 48 h after surgery were lower than those in group C(P<0.05). In group F, MMSE scores at 12 h before surgery, and 1, 3 d after surgery and OAA/S scores at 3 d after surgery were higher than those in group C(P<0.05). The incidence of adverse effects and the number requiring additional analgesia were lower than those in group C(P<0.05). Group F had better perioperative analgesia satisfaction and hospital stay than group C(P<0.05). But there was no significant difference regarding Bromage score and 30-day mortality between two group(P>0.05). CONCLUSION: Ultrasound-guided continuous fascia iliacus space block was safe and effective for elderly patients with hip fracture, and could significantly reduce perioperative pain, improve postoperative cognitive function, and reduce postoperative complications, thereby shortening hospital stay and improving the quality of life during hospitalization.

Evaluation of ITGB1 expression as a predictor of the therapeutic effects of immune checkpoint inhibitors in gastric cancer.

BACKGROUND: Gastric cancer (CC) is a disease with high incidence and mortality rate. Immunotherapy is an important method for gastric cancer while lack of effective predictor. Integrins play an important role in the development. We aimed to explore the predictive value of ß1 integrin (ITGB1) as a predictor of immunnotherapy in gastric cancer. METHODS: Differential expression analysis was conducted using the Gene Expression Profiling Interactive Analysis (GEPIA) 2.0 and GEO databases. GEPIA data were used to evaluate the prognostic value of ITGB1 in gastric cancer (GC). Transcriptomic and clinical data of GC and normal tissues were downloaded from The Cancer Genome Atlas database, and the TIMER database was used to evaluate the association between ITGB1 and immune infiltration. Time-dependent receiver operating characteristic (ROC) curve analysis was used to determine the prognostic value of ITGB1. To verify ITGB1 expression at the protein level, immunohistochemical staining was conducted. In addition, to analyze the correlation of ITGB1 with PD-1 and PD-L1, we examined levels of PD-1 and PD-L1 by IHC and determined the predictive value of ITGB1 for anti-PD-1 therapy in GC by ROC curve analysis. RESULTS: Compared with normal tissues, analysis of GEPIA and data at protein levels showed significantly higher expression of ITGB1 in GC. In addition, higher expression of ITGB1 was associated with worse pathological G-staging and tumor T-staging, which suggested that ITGB1 is a risk factor for poor prognosis in GC. The level of ITGB1 expression was positively correlated with CD8 + T cells, neutrophils, macrophages, and dendritic cells. ITGB1 expression was also correlated with PD-L1 expression, and this was further verified at the protein level by immunohistochemical analysis. The area under the ROC curve was 0.808. CONCLUSION: ITGB1 may be a promising prognostic biomarker and effective predictor for anti-PD-1 therapy in GC. TRIAL REGISTRATION: Retrospectively registered.

Biology and morphometric relationship of gall inducers Contarinia sp. and corresponding parasitoids for swollen galls of Nitraria sibirica pall.

Galls function as provide shelter for gall inducers, guarding them against their natural enemies. Previous research has illuminated the interactions between galls, gall inducers, and their corresponding parasitoids within various caltrop plants. However, less is known about these relationships within Nitraria sibirica, particularly regarding the efficacy of parasitism. Therefore, this study aimed to identify the morphometric relationships among the swollen galls, gall inducers, and their parasitoids. Two species of gall inducers and three species of parasitoids were obtained from the swollen galls of N. sibirica. The correlations of the parasitization indexes, the lifespan of gall inhabitants, and temperature and the morphometric relationships between the galls and their inhabitants were analyzed. The dominant gall inducer identified was Contarinia sp. (Diptera: Cecidomyiidae). Furthermore, it was observed that three solitary parasitoids attacked Contarinia sp. in the swollen galls, with only Eupelmus gelechiphagus acting as an idiobiont ectoparasitoid. The dominant parasitoids were Platygaster sp. and Cheiloneurus elegans at sites 1 and 2, respectively, with Platygaster sp. displaying greater abundance than C. elegans in the swollen galls. The lifespan of the gall inhabitants shortened gradually as the temperature increased. Moreover, the optimal number of gall chambers ranged from two to four per swollen gall with maximized fitness, which can be considered the optimal population density for the gall inducer Contarinia sp. Morphometric analysis exhibited a strong linear correlation between gall size and chamber number or the number of gall inhabitants, as well as a weak correlation between gall size and body size of the primary inhabitants of swollen galls. Our results highlight the importance of the biological investigation of parasitoids and gall inducers living in closed galls with multiple chambers and may pave the way for potential application in biological control.

SERPINB5 is a novel serum diagnostic biomarker for gastric high-grade intraepithelial neoplasia and plays a role in regulation of macrophage phenotypes.

BACKGROUND: Gastric cancer (GC) develops from gastric precancerous lesions (GPL), and early diagnosis and treatment at the premalignant stage may achieve a higher benefit‒cost ratio with a reduced necessity for surgery. However, reliable noninvasive screening biomarkers of GPL are currently lacking. METHODS: The marker genes of GPL encoding extracellular proteins were identified by bioinformatics analysis and further verified by immunofluorescence and immunohistochemistry assays. Serum samples were collected to measure the levels of SERPINB5, the diagnostic efficacy of which was assessed by the area under the receiver operating characteristic (ROC) curve (AUC). Finally, the effect of SERPINB5 on the phenotypic conversion of macrophages was verified by public data and in vitro experiments. RESULTS: SERPINB5 was identified as an extracellular biomarker of GPL that had good diagnostic efficacy. High expression of SERPINB5 was observed in the epithelial cells and adjacent extracellular matrix on sections of gastric high-grade intraepithelial neoplasia (HGIN). Importantly, SERPINB5 determined in serum was significantly increased in the HGIN group, and the AUC for discriminating between HGIN and chronic gastritis or low-grade intraepithelial neoplasia was 0.9936 and 0.9750, respectively. Moreover, SERPINB5 expression was positively correlated with macrophage infiltration, and M1 marker NOS2 expression, but negatively correlated with M2 marker CSF1R expression. In THP-1-derived macrophages, SERPINB5 upregulated expression of M1-related cytokines TNF-α and IL-12, and M1 marker CD86, but suppressed production of M2-related cytokines TGF-ß and IL-10. CONCLUSIONS: Our study provides evidence that SERPINB5 may serve as a promising noninvasive serum biomarker for gastric HGIN screening and regulate macrophage phenotype conversion.

Understanding the time-activity pattern to improve the measurement of personal exposure: An exploratory and experimental research.

Although ambient fine particulate matter (PM2.5) concentrations and their components are commonly used as proxies for personal exposure monitoring, developing an accurate and cost-effective method to use these proxies for personal exposure measurement continues to pose a significant challenge. Herein, we propose a scenario-based exposure model to precisely estimate personal exposure level of heavy metal(loid)s (HMs) using scenario HMs concentrations and time-activity patterns. Personal exposure levels and ambient pollution levels for PM2.5 and HMs differed significantly with corresponding personal/ambient ratios of approximately 2, and exposure scenarios could narrow the assessment error gap by 26.1-45.4%. Using a scenario-based exposure model, we assessed the associated health risks of a large sample population and identified that the carcinogenic risk of As exceeded 1 × 10-6, while we observed non-carcinogenic risks from As, Cd, Ni, and Mn in personal exposure to PM2.5. We conclude that the scenario-based exposure model is a preferential alternative for monitoring personal exposure compared to ambient concentrations. This method ensures the feasibility of personal exposure monitoring and health risk assessments in large-scale studies.

Establishment and characterization of a novel reverse genetic system of BK polyomavirus.

BK polyomavirus (BKV) is a small non-enveloped DNA virus. BKV infection or reactivation may cause BKV-associated nephropathy and hemorrhagic cystitis in immunosuppressed transplant recipients. No effective antivirals or prevention strategies are available against BKV infections. The current BKV reverse system employs the transfection of purified full-length linear viral genomes released by enzyme digestion from BKV genomic plasmids. The method is laborious and often results in variable DNA yield and quality, which can affect the efficiency of transfection and subsequent formation of circular viral genomes in cells. In this study, we report the generation of circular viral genomes by Cre-mediated DNA recombination in cells directly transfected with BKV precursor genomic plasmids. The novel system supported efficient viral expression and replication, and produced a higher level of infectious virions compared with the transfection with linear BKV genomes. Furthermore, we successfully constructed recombinant BKV capable of reporter gene expression. In conclusion, the novel BKV reverse genetic system allows for simpler manipulation of BKV genome with better virus yield, providing a tool for the study of BKV life cycle and antiviral screening.