UBE2S facilitates glioblastoma progression through activation of the NF-κB pathway via attenuating K11-linked ubiquitination of AKIP1.

BACKGROUND: Rapid proliferation is a hallmark of glioblastoma multiforme (GBM) and a major contributor to its recurrence. Aberrant ubiquitination has been implicated in various diseases, including cancer. In our preliminary studies, we identified Ubiquitin-conjugating enzyme E2S (UBE2S) as a potential glioma biomarker, exhibiting close associations with glioma grade and protein phosphatase 1, regulatory subunit 105 (Ki67) expression levels. However, the underlying molecular mechanisms remained elusive. NF-κB is an important signaling pathway that promotes GBM proliferation. Direct intervention targeting NF-κB has not yielded the expected results, prompting the exploration of new molecules for regulating NF-κB as a new direction. METHODS: This study employed methods including yeast two-hybrid and immunoprecipitation to uncover the interaction between UBE2S and A kinase interacting protein 1 (AKIP1). Laser confocal microscopy was used to observe the localization of UBE2S and AKIP1. Dual luciferase reporter genes were utilized to observe the activation of NF-κB. RESULTS: Our findings demonstrate that UBE2S deficiency significantly impedes GBM progression, both in vitro and in vivo. Mechanistically, UBE2S plays a crucial role in recruiting Ubiquitin Specific Peptidase 15 (USP15), facilitating the removal of K11-linked ubiquitination on AKIP1. This action enhances AKIP1 stability within the GBM context. The resulting increase in AKIP1 levels further augments nuclear factor kappa-B (NF-κB) transcriptional activity, leading to the upregulation of downstream genes regulated by the NF-κB pathway, thereby promoting GBM progression. CONCLUSIONS: In summary, our findings reveal the role of the UBE2S/AKIP1-NF-κB axis in regulating GBM progression and provide novel evidence supporting UBE2S as a potential drug target for GBM.

Immunotherapy for small cell lung cancer: the current state and future trajectories.

Small cell lung cancer (SCLC) constitutes approximately 10% to 15% of all lung cancer diagnoses and represents a pressing global public health challenge due to its high mortality rates. The efficacy of conventional treatments for SCLC is suboptimal, characterized by limited anti-tumoral effects and frequent relapses. In this context, emerging research has pivoted towards immunotherapy combined with chemotherapy, a rapidly advancing field that has shown promise in ameliorating the clinical outcomes of SCLC patients. Through originally developed for non-small cell lung cancer (NSCLC), these therapies have extended new treatment avenues for SCLC. Currently, a nexus of emerging hot-spot treatments has demonstrated significant therapeutic efficacy. Based on the amalgamation of chemotherapy and immunotherapy, and the development of new immunotherapy agents, the treatment of SCLC has seen the hoping future. Progress has been achieved in enhancing the tumor immune microenvironment through the concomitant use of chemotherapy, immunotherapy, and tyrosine kinase inhibitors (TKI), as evinced by emerging clinical trial data. Moreover, a tripartite approach involving immunotherapy, targeted therapy, and chemotherapy appears auspicious for future clinical applications. Overcoming resistance to post-immunotherapy regimens remains an urgent area of exploration. Finally, bispecific antibodies, adoptive cell transfer (ACT), oncolytic virus, monotherapy, including Delta-like ligand 3 (DLL3) and T cell immunoreceptor with Ig and ITIM domains (TIGIT), as well as precision medicine, may present a prospective route towards achieving curative outcomes in SCLC. This review aims to synthesize extant literature and highlight future directions in SCLC treatment, acknowledging the persistent challenges in the field. Furthermore, the continual development of novel therapeutic agents and technologies renders the future of SCLC treatment increasingly optimistic.

Cold atmospheric plasma enhances SLC7A11-mediated ferroptosis in non-small cell lung cancer by regulating PCAF mediated HOXB9 acetylation.

Lung cancer is a leading cause of cancer death worldwide, with high incidence and poor survival rates. Cold atmospheric plasma (CAP) technology has emerged as a promising therapeutic approach for cancer treatment, inducing oxidative stress in malignant tissues without causing thermal damage. However, the role of CAP in regulating lung cancer cell ferroptosis remains unclear. Here, we observed that CAP effectively suppressed the growth and migration abilities of lung cancer cells, with significantly increased ferroptotic cell death, lipid peroxidation, and decreased mitochondrial membrane potential. Mechanistically, CAP regulates SLC7A11-mediated cell ferroptosis by modulating HOXB9. SLC7A11, a potent ferroptosis suppressor, was markedly reduced by HOXB9 knockdown, while it was enhanced by overexpressing HOXB9. The luciferase and ChIP assays confirmed that HOXB9 can directly target SLC7A11 and regulate its gene transcription. Additionally, CAP enhanced the acetylation modification level of HOXB9 by promoting its interaction with acetyltransferase p300/CBP-associated factor (PCAF). Acetylated HOXB9 affects its protein ubiquitination modification level, which in turn affects its protein stability. Notably, the upregulation of SLC7A11 and HOXB9 mitigated the suppressive effects of CAP on ferroptosis status, cell proliferation, invasion, and migration in lung cancer cells. Furthermore, animal models have also confirmed that CAP can inhibit the progression of lung cancer in vivo. Overall, this study highlights the significance of the downregulation of the HOXB9/SLC7A11 axis by CAP treatment in inhibiting lung cancer, offering novel insights into the potential mechanisms and therapeutic strategies of CAP for lung cancer.

NOP2 facilitates EZH2-mediated epithelial-mesenchymal transition by enhancing EZH2 mRNA stability via m5C methylation in lung cancer progression.

NOP2, a member of the NOL1/NOP2/SUN domain (NSUN) family, is responsible for catalyzing the posttranscriptional modification of RNA through 5-methylcytosine (m5C). Dysregulation of m5C modification has been linked to the pathogenesis of various malignant tumors. Herein, we investigated the expression of NOP2 in lung adenocarcinoma (LUAD) tissues and cells, and found that it was significantly upregulated. Moreover, lentivirus-mediated overexpression of NOP2 in vitro resulted in enhanced migration and invasion capabilities of lung cancer cells, while in vivo experiments demonstrated its ability to promote the growth and metastasis of xenograft tumors. In contrast, knockdown of NOP2 effectively inhibited the growth and metastasis of lung cancer cells. RNA-sequencing was conducted to ascertain the downstream targets of NOP2, and the findings revealed a significant upregulation in EZH2 mRNA expression upon overexpression of NOP2. Subsequent validation experiments demonstrated that NOP2 exerted an m5C-dependent influence on the stability of EZH2 mRNA. Additionally, our investigations revealed a co-regulatory relationship between NOP2 and the m5C reader protein ALYREF in modulating the stability of EZH2 mRNA. Notably, the NOP2/EZH2 axis facilitated the malignant phenotype of lung cancer cells by inducing epithelial-mesenchymal transition (EMT) both in vitro and in vivo. Mechanistically, ChIP analysis proved that EZH2 counteracted the impact of NOP2 on the occupancy capacity of EZH2 and H3K27me3 in the promoter regions of E-cadherin, a gene crucial for regulating EMT. In a word, our research highlights the significant role of NOP2 in LUAD and offers novel mechanistic insights into the NOP2/ALYREF/EZH2 axis, which holds promise as a potential target for lung cancer therapy.

Construction and application of fetal loss risk model in systemic lupus erythematosus patients with mild disease severity.

BACKGROUND: This dynamic nomogram model was developed to predict the probability of fetal loss in pregnant patients with systemic lupus erythematosus (SLE) with mild disease severity before conception. METHODS: An analysis was conducted on 314 pregnancy records of patients with SLE who were hospitalized between January 2015 and January 2022 at Shenzhen People's Hospital, and the Longhua Branch of Shenzhen People's Hospital. Data from the Longhua Branch of the Shenzhen People's Hospital were utilized as an independent external validation cohort. The nomogram, a widely used statistical visualization tool to predict disease onset, progression, prognosis, and survival, was created after feature selection using multivariate logistic regression analysis. To evaluate the model prediction performance, we employed the receiver operating characteristic curve, calibration curve, and decision curve analysis. RESULTS: Lupus nephritis, complement 3, immunoglobulin G, serum albumin, C-reactive protein, and hydroxychloroquine were all included in the nomogram model. The model demonstrated good calibration and discriminatory power, with an area under the curve of 0.867 (95% confidence interval: 0.787-0.947). According to decision curve analysis, the nomogram model exhibited clinical importance when the probability of fetal loss in patients with SLE ranged between 10 and 70%. The predictive ability of the model was demonstrated through external validation. CONCLUSION: The predictive nomogram approach may facilitate precise management of pregnant patients with SLE with mild disease severity before conception.

Fully exposed Pt clusters for efficient catalysis of multi-step hydrogenation reactions.

For di-nitroaromatics hydrogenation, it is a challenge to achieve the multi-step hydrogenation with high activity and selectivity due to the complexity of the process involving two nitro groups. Consequently, many precious metal catalysts suffer from low activity for this multi-step hydrogenation reaction. Herein, we employ a fully exposed Pt clusters catalyst consisting of an average of four Pt atoms on nanodiamond@graphene (Ptn/ND@G), demonstrating excellent catalytic performance for the multi-step hydrogenation of 2,4-dinitrotoluene. The TOF (40647 h-1) of Ptn/ND@G is significantly superior to that of single Pt atoms catalyst, Pt nanoparticles catalyst, and even all the known catalysts. Density functional theory calculations and absorption experiments reveal that the synergetic interaction between the multiple active sites of Ptn/ND@G facilitate the co-adsorption/activation of reactants and H2, as well as the desorption of intermediates/products, which is the key for the higher catalytic activity than single Pt atoms catalyst and Pt nanoparticles catalyst.

Amino Group-Driven Adsorption of Sodium p-Perfluorous Nonenoxybenzene Sulfonate in Water by the Modified Graphene Oxide.

Sodium p-perfluorous nonenoxybenzene sulfonate (OBS) is one of the key alternatives to perfluoroalkyl substances (PFASs). Its widespread tendency has increased extensive contamination in the aquatic environment. However, the present treatment technology for OBS exhibited insignificant adsorption capacity and long adsorption time. In this study, three proportions (1:5, 3:5, and 10:1) of chitosan-modified amino-driven graphene oxide (CS-GO) were innovated to strengthen the OBS adsorption capacity, compared with graphene oxide (GO) and graphene (GH). Through the characterization of SEM, BET, and FTIR, it was discovered that CS was synthetized on GO surfaces successfully with a low specific surface area. Subsequently, batch single influence factor studies on OBS removal from simulated wastewater were investigated. The optimum removal efficiency of OBS could be achieved up to 95.4% within 2 h when the adsorbent was selected as CS-GO (10:1), the dosage was 2 mg, and the pH was 3. The addition of inorganic ions could promote the adsorption efficiency of OBS. In addition, CS-GO presented the maximum adsorption energy due to additional functional groups of -NH3, and electrostatic interaction was the foremost motive for improving the adsorption efficiency of OBS. Moreover, OBS exhibited the fastest diffusion coefficient in the CS-GO-OBS solution, which is consistent with the fitting results of adsorption kinetics.

RNA methylation-related inhibitors: Biological basis and therapeutic potential for cancer therapy.

RNA methylation is widespread in nature. Abnormal expression of proteins associated with RNA methylation is strongly associated with a number of human diseases including cancer. Increasing evidence suggests that targeting RNA methylation holds promise for cancer treatment. This review specifically describes several common RNA modifications, such as the relatively well-studied N6-methyladenosine, as well as 5-methylcytosine and pseudouridine (Ψ). The regulatory factors involved in these modifications and their roles in RNA are also comprehensively discussed. We summarise the diverse regulatory functions of these modifications across different types of RNAs. Furthermore, we elucidate the structural characteristics of these modifications along with the development of specific inhibitors targeting them. Additionally, recent advancements in small molecule inhibitors targeting RNA modifications are presented to underscore their immense potential and clinical significance in enhancing therapeutic efficacy against cancer. KEY POINTS: In this paper, several important types of RNA modifications and their related regulatory factors are systematically summarised. Several regulatory factors related to RNA modification types were associated with cancer progression, and their relationships with cancer cell migration, invasion, drug resistance and immune environment were summarised. In this paper, the inhibitors targeting different regulators that have been proposed in recent studies are summarised in detail, which is of great significance for the development of RNA modification regulators and cancer treatment in the future.

African swine fever virus pB318L, a trans-geranylgeranyl-diphosphate synthase, negatively regulates cGAS-STING and IFNAR-JAK-STAT signaling pathways.

African swine fever (ASF) is an acute, hemorrhagic, and severe infectious disease caused by the ASF virus (ASFV). ASFV has evolved multiple strategies to escape host antiviral immune responses. Here, we reported that ASFV pB318L, a trans-geranylgeranyl-diphosphate synthase, reduced the expression of type I interferon (IFN-I) and IFN-stimulated genes (ISGs). Mechanically, pB318L not only interacted with STING to reduce the translocation of STING from the endoplasmic reticulum to the Golgi apparatus but also interacted with IFN receptors to reduce the interaction of IFNAR1/TYK2 and IFNAR2/JAK1. Of note, ASFV with interruption of B318L gene (ASFV-intB318L) infected PAMs produces more IFN-I and ISGs than that in PAMs infected with its parental ASFV HLJ/18 at the late stage of infection. Consistently, the pathogenicity of ASFV-intB318L is attenuated in piglets compared with its parental virus. Taken together, our data reveal that B318L gene may partially affect ASFV pathogenicity by reducing the production of IFN-I and ISGs. This study provides a clue to design antiviral agents or live attenuated vaccines to prevent and control ASF.

A causal association between amyotrophic lateral sclerosis and atrial fibrillation: a two-sample Mendelian randomization study.

Objectives: To look into the connection between amyotrophic lateral sclerosis (ALS) and atrial fibrillation (AF) using Mendelian randomization (MR). Methods: Two-sample MR was performed using genetic information from genome-wide association studies (GWAS). Genetic variants robustly associated with ALS and AF were used as instrumental variables. GWAS genetic data for ALS (n = 138,086, ncase = 27,205) and AF (n = 1,030,836, ncase = 60,620), publicly available from IEU Open. The specific MR protocols were Inverse variance-weighted (IVW), Simple mode, MR Egger, Weighted mode, and Weight median estimator (WME). Subsequently, the MR-Egger intercept and Cochran Q examine were used to evaluate instrumental variables (IVs)' heterogeneity and multiplicative effects (IVs). In addition, MR-PRESSO analysis was conducted to exclude any potential pleiotropy. Results: The IVW method demonstrated that ALS positively affected AF [OR: 1.062, 95% CI (1.004-1.122); P = 0.035]. Indeed, other MR methods were in accordance with the tendency of the IVW method (all OR > 1), and sensitivity testing verified the reliability of this MR result. Conclusions: This MR study proves a positive causal connection between ALS and atrial fibrillation. Further studies are warranted to elucidate the mechanisms linking ALS and AF.

Impaired meningeal lymphatic drainage in Listeria monocytogenes infection.

Previous studies have demonstrated an association between lymphatic vessels and diseases caused by bacterial infections. Listeria monocytogenes (LM) bacterial infection can affect multiple organs, including the intestine, brain, liver and spleen, which can be fatal. However, the impacts of LM infection on morphological and functional changes of lymphatic vessels remain unexplored. In this study, we found that LM infection not only induces meningeal and mesenteric lymphangiogenesis in mice, but also impairs meningeal lymphatic vessels (MLVs)-mediated macromolecules drainage. Interestingly, we found that the genes associated with lymphatic vessel development and function, such as Gata2 and Foxc2, were downregulated, suggesting that LM infection may affect cellular polarization and valve development. On the other hand, photodynamic ablation of MLVs exacerbated inflammation and bacterial load in the brain of mice with LM infection. Overall, our findings indicate that LM infection induces lymphangiogenesis and may affect cell polarization, cavity formation, and valve development during lymphangiogenesis, ultimately impairing MLVs drainage.

[The experience on the construction of the cluster prevention and control system for COVID-19 infection in designated hospitals during the period of "Category B infectious disease treated as Category A"].

The COVID-19 epidemic has spread to the whole world for three years and has had a serious impact on human life, health and economic activities. China's epidemic prevention and control has gone through the following stages: emergency unconventional stage, emergency normalization stage, and the transitional stage from the emergency normalization to the "Category B infectious disease treated as Category B" normalization, and achieved a major and decisive victory. The designated hospitals for prevention and control of COVID-19 epidemic in Tianjin has successfully completed its tasks in all stages of epidemic prevention and control, and has accumulated valuable experience. This article summarizes the experience of constructing a hospital infection prevention and control system during the "Category B infectious disease treated as Category A" period in designated hospital. The experience is summarized as the "Cluster" hospital infection prevention and control system, namely "three rings" outside, middle and inside, "three districts" of green, orange and red, "three things" before, during and after the event, "two-day pre-purification" and "two-director system", and "one zone" management. In emergency situations, we adopt a simplified version of the cluster hospital infection prevention and control system. In emergency situations, a simplified version of the "Cluster" hospital infection prevention and control system can be adopted. This system has the following characteristics: firstly, the system emphasizes the characteristics of "cluster" and the overall management of key measures to avoid any shortcomings. The second, it emphasizes the transformation of infection control concepts to maximize the safety of medical services through infection control. The third, it emphasizes the optimization of the process. The prevention and control measures should be comprehensive and focused, while also preventing excessive use. The measures emphasize the use of the least resources to achieve the best infection control effect. The fourth, it emphasizes the quality control work of infection control, pays attention to the importance of the process, and advocates the concept of "system slimming, process fattening". Fifthly, it emphasizes that the future development depends on artificial intelligence, in order to improve the quality and efficiency of prevention and control to the greatest extent. Sixth, hospitals need to strengthen continuous training and retraining. We utilize diverse training methods, including artificial intelligence, to ensure that infection control policies and procedures are simple. We have established an evaluation and feedback mechanism to ensure that medical personnel are in an emergency state at all times.

Loss of UBE2S causes meiosis I arrest with normal spindle assembly checkpoint dynamics in mouse oocytes.

The timely degradation of proteins that regulate the cell cycle is essential for oocyte maturation. Oocytes are equipped to degrade proteins via the ubiquitin-proteasome system. In meiosis, anaphase promoting complex/cyclosome (APC/C), an E3 ubiquitin-ligase, is responsible for the degradation of proteins. Ubiquitin-conjugating enzyme E2 S (UBE2S), an E2 ubiquitin-conjugating enzyme, delivers ubiquitin to APC/C. APC/C has been extensively studied, but the functions of UBE2S in oocyte maturation and mouse fertility are not clear. In this study, we used Ube2s knockout mice to explore the role of UBE2S in mouse oocytes. Ube2s-deleted oocytes were characterized by meiosis I arrest with normal spindle assembly and spindle assembly checkpoint dynamics. However, the absence of UBE2S affected the activity of APC/C. Cyclin B1 and securin are two substrates of APC/C, and their levels were consistently high, resulting in the failure of homologous chromosome separation. Unexpectedly, the oocytes arrested in meiosis I could be fertilized and the embryos could become implanted normally, but died before embryonic day 10.5. In conclusion, our findings reveal an indispensable regulatory role of UBE2S in mouse oocyte meiosis and female fertility.

Increased antibody titers but induced T cell AICD and apoptosis response in COVID-19 convalescents by inactivated vaccine booster.

It is urgently needed to evaluate the necessity and benefits of booster vaccination against the coronavirus 2 of the severe acute respiratory syndrome (SARS-CoV-2) Omicron to facilitate clinical decision-making for 2019 coronavirus disease (COVID-19) convalescents. We conducted a multicenter, prospective clinical trial (registration number: ChiCTR2100045810) in the first patients with COVID-19 from 28 January 2020 to 20 February 2020 to assess the long-term durability of neutralizing antibodies against live Omicron BA.5 and further assess the efficiency and safety of CoronaVac in the convalescent group. A total of 96 COVID-19 convalescents were enrolled in this study. Neutralizing antibody titers in convalescents were significantly reduced in 9-10 months. A dose-refreshing vaccination in 28 convalescents with an antibody titer below 96 significantly induced neutralizing antibodies against live Omicron by 4.84-fold. Meanwhile, the abundance of naive T cells increased dramatically, and TEMRA and TEM cells gradually decreased after vaccination. Activation-induced cell death and apoptosis-related genes were significantly elevated after vaccination in all T-cell subtypes. One-dose booster vaccination was effective in inducing a robust antibody response against SARS-CoV-2 Omicron in COVID-19 convalescents with low antibody titers. However, vaccine-mediated T-cell consumption and regeneration patterns may be detrimental to the antiviral response.IMPORTANCEThe globally dominant coronavirus 2 of the severe acute respiratory syndrome (SARS-CoV-2) Omicron variant raises the possibility of repeat infections among 2019 coronavirus disease (COVID-19) convalescents with low neutralizing antibody titers. The importance of this multicenter study lies in its evaluation of the long-term durability of neutralizing antibodies in COVID-19 convalescents and the efficacy of a booster vaccination against the live Omicron. The findings suggest that a one-dose booster vaccination is effective in inducing a robust antibody response against SARS-CoV-2 Omicron in convalescents with low antibody titers. However, the study also highlights the potential detrimental effects on the antiviral response due to vaccine-mediated T-cell consumption and regeneration patterns. These results are crucial for facilitating clinical decision-making for COVID-19 convalescents and informing public health policies regarding booster vaccinations.

5-Methylcytosine transferase NSUN2 drives NRF2-mediated ferroptosis resistance in non-small cell lung cancer.

RNA 5-methylcytosine (m5C) is an abundant chemical modification in mammalian RNAs and plays crucial roles in regulating vital physiological and pathological processes, especially in cancer. However, the dysregulation of m5C and its underlying mechanisms in non-small cell lung cancer (NSCLC) remain unclear. Here we identified that NSUN2, a key RNA m5C methyltransferase, is highly expressed in NSCLC tumor tissue. We found elevated NSUN2 expression levels strongly correlate with tumor grade and size, predicting poor outcomes for NSCLC patients. Furthermore, RNA-seq and subsequent confirmation studies revealed the antioxidant-promoting transcription factor NRF2 is a target of NSUN2, and depleting NSUN2 decreases the expression of NRF2 and increases the sensitivity of NSCLC cells to ferroptosis activators both in vitro and in vivo. Intriguingly, the methylated-RIP-qPCR assay results indicated that NRF2 mRNA has a higher m5C level when NSUN2 is overexpressed in NSCLC cells but shows no significant changes in the NSUN2 methyltransferase-deficient group. Mechanistically, we confirmed that NSUN2 upregulates the expression of NRF2 by enhancing the stability of NRF2 mRNA through the m5C modification within its 5'UTR region recognized by the specific m5C reader protein YBX1, rather than influencing its translation. In subsequent rescue experiments, we show knocking down NRF2 diminished the proliferation, migration, and ferroptosis tolerance mediated by NSUN2 overexpression. In conclusion, our study unveils a novel regulatory mechanism in which NSUN2 sustains NRF2 expression through an m5C-YBX1-axis, suggesting that targeting NSUN2 and its regulated ferroptosis pathway might offer promising therapeutic strategies for NSCLC patients.

African swine fever virus pH240R enhances viral replication via inhibition of the type I IFN signaling pathway.

African swine fever (ASF) is an acute, hemorrhagic, and severe infectious disease caused by ASF virus (ASFV) infection. At present, there are still no safe and effective drugs and vaccines to prevent ASF. Mining the important proteins encoded by ASFV that affect the virulence and replication of ASFV is the key to developing effective vaccines and drugs. In this study, ASFV pH240R, a capsid protein of ASFV, was found to inhibit the type I interferon (IFN) signaling pathway. Mechanistically, pH240R interacted with IFNAR1 and IFNAR2 to disrupt the interaction of IFNAR1-TYK2 and IFNAR2-JAK1. Additionally, pH240R inhibited the phosphorylation of IFNAR1, TYK2, and JAK1 induced by IFN-α, resulting in the suppression of the nuclear import of STAT1 and STAT2 and the expression of IFN-stimulated genes (ISGs). Consistent with these results, H240R-deficient ASFV (ASFV-∆H240R) infection induced more ISGs in porcine alveolar macrophages compared with its parental ASFV HLJ/18. We also found that pH240R enhanced viral replication via inhibition of ISGs expression. Taken together, our results clarify that pH240R enhances ASFV replication by inhibiting the JAK-STAT signaling pathway, which highlights the possibility of pH240R as a potential drug target.IMPORTANCEThe innate immune response is the host's first line of defense against pathogen infection, which has been reported to affect the replication and virulence of African swine fever virus (ASFV) isolates. Identification of ASFV-encoded proteins that affect the virulence and replication of ASFV is the key step in developing more effective vaccines and drugs. In this study, we found that pH240R interacted with IFNAR1 and IFNAR2 by disrupting the interaction of IFNAR1-TYK2 and IFNAR2-JAK1, resulting in the suppression of the expression of interferon (IFN)-stimulated genes (ISGs). Consistent with these results, H240R-deficient ASFV (ASFV-∆H240R) infection induces more ISGs' expression compared with its parental ASFV HLJ/18. We also found that pH240R enhanced viral replication via inhibition of ISGs' expression. Taken together, our findings showed that pH240R enhances ASFV replication by inhibiting the IFN-JAK-STAT axis, which highlights the possibility of pH240R as a potential drug target.

Single-Atom Site SERS Chip for Rapid, Ultrasensitive, and Reproducible Direct-Monitoring of RNA Binding.

Ribonucleic acids (RNA) play active roles within cells or viruses by catalyzing biological reactions, controlling gene expression, and communicating responses to cellular signals. Rapid monitoring RNA variation has become extremely important for appropriate clinical decisions and frontier biological research. However, the most widely used method for RNA detection, nucleic acid amplification, is restricted by a mandatory temperature cycling period of ≈1 h required to reach target detection criteria. Herein, a direct detection approach via single-atom site integrated surface-enhanced Raman scattering (SERS) monitoring nucleic acid pairing reaction, can be completed within 3 min and reaches high sensitivity and extreme reproducibility for COVID-19 and two other influenza viruses' detection. The mechanism is that a single-atom site on SERS chip, enabled by positioning a single-atom oxide coordinated with a specific complementary RNA probe on chip nanostructure hotspots, can effectively bind target RNA analytes to enrich them at designed sites so that the binding reaction can be detected through Raman signal variation. This ultrafast, sensitive, and reproducible single-atom site SERS chip approach paves the route for an alternative technique of immediate RNA detection. Moreover, single-atom site SERS is a novel surface enrichment strategy for SERS active sites for other analytes at ultralow concentrations.

Plasma proteome profiling reveals the therapeutic effects of the PPAR pan-agonist chiglitazar on insulin sensitivity, lipid metabolism, and inflammation in type 2 diabetes.

Chiglitazar is a novel peroxisome proliferator-activated receptor (PPAR) pan-agonist, which passed phase III clinical trials and was newly approved in China for use as an adjunct to diet and exercise in glycemic control in adult patients with Type 2 Diabetes (T2D). To explore the circulating protein signatures associated with the administration of chiglitazar in T2D patients, we conducted a comparative longitudinal study using plasma proteome profiling. Of the 157 T2D patients included in the study, we administered chiglitazar to a specific group, while the controls were given either placebo or sitagliptin. The plasma proteomes were profiled at baseline and 12 and 24 weeks post-treatment using data-independent acquisition mass spectrometry (DIA-MS). Our study indicated that 13 proteins were associated with chiglitazar treatment in T2D patients, including 10 up-regulated proteins (SHBG, TF, APOA2, APOD, GSN, MBL2, CFD, PGLYRP2, A2M, and APOA1) and 3 down-regulated proteins (PRG4, FETUB, and C2) after treatment, which were implicated in the regulation of insulin sensitivity, lipid metabolism, and inflammation response. Our study provides insight into the response of chiglitazar treatment from a proteome perspective and demonstrates the multi-faceted effects of chiglitazar in T2D patients, which will help the clinical application of chiglitazar and further study of its action mechanism.

A modified single-needle continuous suture of duct-to-mucosa pancreaticojejunostomy in pancreaticoduodenectomy.

Background: The pancreatic reconstruction technique decides the incidence of postoperative pancreatic fistulas (POPF) in pancreaticoduodenectomy (PD). This study aims to evaluate the safety of modified single-needle continuous suture (SNCS) of duct-to-mucosa and compare the efficacy with double-layer continuous suture (DLCS) of duct-mucosa pancreaticojejunostomy (PJ) in open PD (OPD). Methods: A total of 266 patients that received PD between January 2019 and May 2023 were retrospectively analyzed. Among them, 130 patients underwent DLCS, and 136 patients underwent SNCS [73 OPD and 63 laparoscopic PD (LPD)]. The primary outcome was clinically relevant POPF (CR-POPF) according to the definition of the revised 2016 International Study Group of Pancreatic Fistula (ISGPF). Propensity score matching (PSM) was conducted to reduce confounding bias. Results: A total of 66 pairs were successfully matched using PSM in OPD. No significant difference was observed in the occurrence of CR-POPF between the two groups (9.1% vs. 21.2%, P=0.052). However, the median duration of operation and PJ was shorter in the SNCS group. The incidence of CR-POPF in LPD was 9.5%. Furthermore, regarding the alternative fistula risk score (a-FRS), the CR-POPF rate were 2.1%, 10.5%, and 15.6% in low-, intermediate-, and high-risk groups (P=0.067). Conclusions: The SNCS is a facile, safe, and effective PJ technique and does not increase the incidence of POPF, regardless of a-FRS stratification, pancreatic texture, and main pancreatic duct (MPD) size.

Cyberbullying and its effect on health risk behaviors among secondary vocational school students / 中国学校卫生

Objective@#To investigate the current situation of cyberbullying and health risk behaviors among secondary vocational school students, to explore the effects of cyberbullying on health risk behaviors, so as to provide a reference for formulating intervention strategies to promote adolescent health related behaviors.@*Methods@#From March to April 2023, a field survey was conducted on 1 184 students from one secondary vocational school each in Jilin City and Yanji City by random cluster sampling method. The data was analyzed using Chi square tests and generalized linear models.@*Results@#Among secondary vocational school students, 839 individuals (70.9%) experienced the cyberbullying, and 1 036 individuals (87.5%) had one and more health risk behavior group. There was a positive correlation between cyberbullying and health risk behaviors ( r=0.60, P <0.01). The generalized linear model analysis showed that female and no Internet addiction were negatively correlated with the health risk behaviors of secondary vocational students ( β =-2.75, -8.90), and the single parent families and peer pressure was positively correlated with the health behaviors of secondary vocational students ( β =2.56, 4.82)( P ＜0.05). Secondary vocational students experienced cyberbullying who from single parent families, peer pressure and social oriented internet usage were more likely to engage in health risk behaviors ( β= 3.41, 4.88, 2.20, P <0.05).@*Conclusions@#The incidence of cyberbullying and health risk behaviors among secondary vocational school students is relatively high, and cyberbullying can influence the occurrence of health risk behaviors. It is important to focus on and implement guidance for internet use and health behavior education for secondary vocational students from multiple perspectives, including the family, school, and society. Corresponding intervention strategies should be taken to promote the healthy development of adolescents.