Trabectedin Enhances Oncolytic Virotherapy by Reducing Barriers to Virus Spread and Cytotoxic Immunity in Preclinical Pediatric Bone Sarcoma.

We previously reported that the DNA alkylator and transcriptional-blocking chemotherapeutic agent trabectedin enhances oncolytic herpes simplex viroimmunotherapy in human sarcoma xenograft models, though the mechanism remained to be elucidated. Here we report trabectedin disrupts the intrinsic cellular anti-viral response which increases viral transcript spread throughout the human tumor cells. We also extended our synergy findings to syngeneic murine sarcoma models, which are poorly susceptible to virus infection. In the absence of robust virus replication, we found trabectedin enhanced viroimmunotherapy efficacy by reducing immunosuppressive macrophages and stimulating granzyme expression in infiltrating T and NK cells to cause immune-mediated tumor regressions. Thus, trabectedin enhances both the direct virus-mediated killing of tumor cells and the viral-induced activation of cytotoxic effector lymphocytes to cause tumor regressions across models. Our data provide a strong rationale for clinical translation as both mechanisms should be simultaneously active in human patients.

Clinical significance of abdominal computed tomography and colonoscopy in the evaluation of phlebosclerotic colitis.

Clinical manifestations of phlebosclerotic colitis (PC) exhibit significant variability, necessitating diverse treatment strategies depending on disease severity. However, there is limited research exploring the relationship between imaging findings and disease severity. Hence, this retrospective study aimed to analyze the correlation between computed tomography (CT) findings, colonoscopic features, and disease severity. This study compared the abdominal CT characteristics, colonoscopy findings, and treatment modalities of 45 PC patients. CT images were assessed for the severity of mesenteric venous calcification, maximum colonic wall thickness, number of involved colonic segments, and presence of pericolic inflammation. Colonoscopic images were assessed for dark purple discoloration mucosa, erosive and ulcerative lesions, mucosal edema, luminal narrowing, and the number of involved colonic segments. In addition, patients were categorized into three groups: the observation (n = 15), medical treatment (n = 19), and operation (n = 11) groups. In CT images, a significant difference in pericolic inflammation (p = 0.039) was observed among groups. Further, significant differences in dark purple discoloration mucosa (p = 0.033), erosive or ulcerative lesions (p < 0.001), mucosal edema (p < 0.001), luminal narrowing (p = 0.012), and the number of involved colonic segments (p = 0.001) were observed in colonoscopy. Moreover, we found positive correlations between CT and colonoscopy features. In conclusion, CT manifestations and colonoscopy findings exhibited correlation with disease severity in PC. When limited to one diagnostic tool, observations from that tool can infer potential manifestations of the alternative tool.

HLA-DR genotypes in patients with systemic lupus erythematosus in Taiwan.

BACKGROUND: Different human leukocyte antigen (HLA)-DR genotypes have been known to be associated with the risk of development of systemic lupus erythematosus (SLE) in different populations, although Lu et al. have reported previously that no correlation exists between the HLA-DR genotype and disease manifestation in SLE patients in Taiwan. We investigated the effects different HLA-DR genotypes had on SLE incidence in Taiwanese patients as to whether risk alleles were associated with different clinical manifestations, and the effects risk alleles had on the age of disease onset. METHODS: Two hundred thirty-four SLE patients and 346 healthy controls were enrolled. HLA-DR genotyping was performed with the HLA FluoGene DRDQ kit for each subject. Chi-square tests and t tests were performed for statistical analysis. RESULTS: HLA-DR2 was significantly more frequently found in SLE patients than in controls (odds ratio [OR] = 2.05, 95% CI, 1.44-2.92, p < 0.001). Notably, HLA-DR6 appeared to trend toward negative correlation with SLE, whereas HLA-DR8 appeared to trend toward positive correlation. HLA-DR2 patients had an earlier onset of disease as well as a higher prevalence of oral ulcer, avascular necrosis of bone, and renal involvement (lupus nephritis). CONCLUSION: HLA-DR2 was associated with SLE susceptibility in this Taiwanese population as well as lower age of disease onset and more severe clinical manifestations.

Transition Metal Dichalcogenides Nanoscrolls: Preparation and Applications.

Two-dimensional (2D) transition metal dichalcogenides (TMDCs) nanosheets have shown extensive applications due to their excellent physical and chemical properties. However, the low light absorption efficiency limits their application in optoelectronics. By rolling up 2D TMDCs nanosheets, the one-dimensional (1D) TMDCs nanoscrolls are formed with spiral tubular structure, tunable interlayer spacing, and opening ends. Due to the increased thickness of the scroll structure, the light absorption is enhanced. Meanwhile, the rapid electron transportation is confined along the 1D structure. Therefore, the TMDCs nanoscrolls show improved optoelectronic performance compared to 2D nanosheets. In addition, the high specific surface area and active edge site from the bending strain of the basal plane make them promising materials for catalytic reaction. Thus, the TMDCs nanoscrolls have attracted intensive attention in recent years. In this review, the structure of TMDCs nanoscrolls is first demonstrated and followed by various preparation methods of the TMDCs nanoscrolls. Afterwards, the applications of TMDCs nanoscrolls in the fields of photodetection, hydrogen evolution reaction, and gas sensing are discussed.

Chemotaxis of Meloidogyne incognita Response to Rhizosphere Bacteria.

Rhizosphere microorganisms and the volatile organic compounds (VOCs) produced by them take part in the regulation of the chemotaxis of nematodes. A total of 150 strains of rhizosphere bacteria were screened via a chemotaxis experiment with Meloidogyne incognita. Some isolates affected the behavior of the nematodes, including attraction, randomness, and repulsion. Volatile metabolites produced via the selected bacteria were associated with the chemotaxis of nematodes. M. incognita was highly attracted to decanal. In addition, dimethyl disulfide, 2,5-dimethylpyrazine, pentadecanoic acid, and palmitic acid were found to attract weakly M. incognita. Furthermore, the chemotaxis of M. incognita was tested in a pot experiment. The bacteria Bacillus sp. 1-50, Brevibacillus brevis 2-35, B. cereus 5-14, Chryseobacterium indologens 6-4, and VOC decanal could regulate the movement of M. incognita in the pot with or without plants. The results provide insights into rhizosphere microorganisms and their VOCs and how they regulate the chemotaxis of the nematodes.

Sequential treatment for diabetic foot ulcers in dialysis patients: A case report.

BACKGROUND: Diabetic foot ulcers (DFUs) are common in patients with diabetes, especially those undergoing hemodialysis. In severe cases, these ulcers can cause damage to the lower extremities and lead to amputation. Traditional treatments such as flap transposition and transfemoral amputation are not always applicable in all cases. Therefore, there is a need for alternative treatment methods. CASE SUMMARY: This report describes a 62-year-old female patient who was admitted to the hospital with plantar and heel ulcers on her left foot. The patient had a history of renal failure and was undergoing regular hemodialysis. Digital subtraction angiography showed extensive stenosis and occlusion in the left superficial femoral artery, left peroneal artery and left posterior tibial artery. Following evaluation by a multidisciplinary team, the patient was diagnosed with type 2 DFUs (TEXAS 4D). Traditional treatments were deemed unsuitable, and the patient was treated with endovascular surgery in the affected area, in addition to supportive medical treatment, local debridement, and sequential repair using split-thickness skin and tissue-engineered skin grafts combined with negative pressure treatment. After four months, the wound had completely healed, and the patient was able to walk with a walking aid. CONCLUSION: This study demonstrates a new treatment method for DFUs was successful, using angioplasty, skin grafts, and negative pressure.

Lymphocyte-Rich Hepatocellular Carcinoma with Multiple Lymphadenopathy and Positive Epstein-Barr Virus Encoding Region.

Lymphocyte-rich hepatocellular carcinoma (HCC) represents the rarest subtype among the various subgroups of HCC, and limited clinical data are available for this particular subtype. It is commonly observed as a solitary lesion and tends to present at an early stage. Histopathological examination typically reveals tumor cells infiltrated by a lymphocyte-rich background, leading to its designation as lymphoepithelioma-like HCC. Unlike other lymphoepithelioma-like tumors associated with the Epstein-Barr virus (EBV), lymphocyte-rich HCC is predominantly negative for EBV. This subtype is characterized by more favorable clinical outcomes and prognosis compared to conventional HCC. Here, we present a case of lymphocyte-rich hepatocellular carcinoma (HCC) characterized by the presence of bilateral hepatic tumors and concurrent multiple lymphadenopathy. Interestingly, contrary to previous literature, the examination for the Epstein-Barr virus (EBV) revealed a positive result in this particular case.

The Role of Macrophages in Connective Tissue Disease-Associated Interstitial Lung Disease: Focusing on Molecular Mechanisms and Potential Treatment Strategies.

Connective tissue disease-associated interstitial lung disease (CTD-ILD) is a severe manifestation of CTD that leads to significant morbidity and mortality. Clinically, ILD can occur in diverse CTDs. Pathologically, CTD-ILD is characterized by various histologic patterns, such as nonspecific interstitial pneumonia, organizing pneumonia, and usual interstitial pneumonia. Abnormal immune system responses have traditionally been instrumental in its pathophysiology, and various changes in immune cells have been described, especially in macrophages. This article first briefly overviews the epidemiology, clinical characteristics, impacts, and histopathologic changes associated with CTD-ILD. Next, it summarizes the roles of various signaling pathways in macrophages or products of macrophages in ILD, helped by insights gained from animal models. In the following sections, this review returns to studies of macrophages in CTD-ILD in humans for an overall picture of the current understanding. Finally, we direct attention to potential therapies targeting macrophages in CTD-ILD in investigation or in clinical trials, as well as the future directions regarding macrophages in the context of CTD-ILD. Although the field of macrophages in CTD-ILD is still in its infancy, several lines of evidence suggest the potential of this area.

Positive youth development attributes and cyberbullying victimization among Chinese middle school students: A longitudinal moderated mediation model involving internet gaming disorder and depression.

As an extension of traditional bullying, cyberbullying emerges with the increasing popularity of the internet, and seriously affects the health of students. However, fewer studies have explored the potential influencing mechanisms of cyberbullying victimization from a positive psychology perspective. Therefore, based on the positive youth development theory, this study will explore the potential mediator and moderator in the relationship between positive youth development (PYD) attributes and cyberbullying victimization through a longitudinal design. 719 students (Mage = 15.95 years, SD = 0.76, 45.2% boy) participated in the study and completed self-report questionnaires on relevant variables. The result found that students' level of PYD significantly and negatively predicted the level of cyberbullying victimization. Meanwhile, SEM analysis showed that PYD influenced individuals' cyberbullying victimization by affecting their internet gaming disorder (IGD), while depression levels moderated the relationship between PYD and IGD. This study examines cyberbullying victimization from a positive psychology orientation, with potential prevention and intervention value.

Periosteal distraction for foot preservation contributes to favorable clinical effects and prognosis in a foot ulcer patient with critical limb ischemia after multiple operations.

This paper presents the challenges faced by a patient undergoing limb-sparing treatment due to chronic limb-threatening ischemia (CLTI) complicated with long-standing nonhealing foot ulcer and intense pain. However, after multiple vascular surgeries, the foot wound continued to worsen, which could lead to transfemoral amputation and even death. We report a case of an aged male patient admitted after complaining of "pain and ulceration in his left foot for ten months". The patient was diagnosed with arteriosclerosis obliterans of the lower limbs with critical limb ischemia, which improved little after the drug therapy. This patient had undergone three endovascular procedures with a medical history of myocardial infarction and stenting. The main artery could not be directly connected to the foot by open or endovascular surgery due to severe vascular occlusion below the knee. In addition, foot ulcers made it impossible to walk, which induced angina pectoris. After coordination and discussion, we determined to perform a 2-week lateral tibial periosteum distraction (LTPD). The procedure significantly improved the foot wound and relieved the pain. After the two-week personalized wound management, the wound healed, and the pain disappeared. Consequently, the patient was able to walk independently, without recurrence during the 3-month follow-up period. Periosteal distraction has rarely been reported in previous literature and is mainly used to treat patients with diabetic foot, rather than those who have undergone repeated percutaneous transluminal angioplasty (PTA) for CLTI combined with foot ulcers. As most CLTI patients are suffering from cardiac, cerebral, and renal diseases, their blood vessels are difficult to open, with high re-occlusion and recurrence rates and low limb salvage rate. Therefore, we present our case herein so that the CLTI patients whose inferior genicular arteries cannot be opened due to severe infrapopliteal arterial occlusion complicated with nonhealing foot ulcers or intractable pain can be treated with LTPD, thus providing them with the "last kilometer" bloodstream towards the foot.

Fluorescence Noise Eliminating Fiber-Enhanced Raman Spectroscopy for Simultaneous and Multiprocess Analysis of Intermediate Compositions for C2H2 and H2 Production.

C2H2 and H2, as important chemical and energy raw materials, can be produced effectively and environmentally friendly by the partial oxidation (POX) of CH4. Simultaneous analysis of intermediate gas compositions in the multiprocess (cracking, recovery, degassing, etc) of POX can regulate product generation and improve production efficiency. To overcome the disadvantage of common gas chromatography, we propose a fluorescence noise eliminating fiber-enhanced Raman spectroscopy (FNEFERS) technique for simultaneous and multiprocess analysis of the POX process, in which the fluorescence noise eliminating (FNE) method can effectively eliminate the horizontal and vertical spatial noise to ensure ppm level limits of detection (LOD). The vibration modes of gas compositions related to each POX process such as cracked gas, synthesis gas, and product acetylene are analyzed. Meanwhile, the composition of three-process intermediate sample gases from Sinopec Chongqing SVW Chemical Co., Ltd is quantitatively and qualitatively analyzed simultaneously, along with the ppm level LODs (H2: 11.2 ppm, C2H2: 3.1 ppm, CO2: 9.4 ppm, C2H4: 4.8 ppm, CH4: 1.5 ppm, CO: 17.9 ppm, allene: 1.5 ppm, methyl acetylene: 2.6 ppm, 1,3-butadiene: 2.8 ppm) with a laser power of 180 mW, exposure time of 30 s, and accuracy of higher than 95.2%. This study fully demonstrates the ability of FNEFERS to replace gas chromatography to achieve simultaneous and multiprocess analysis of intermediate compositions for C2H2 and H2 production and to monitor other chemical and energy production processes.

Cavity-Enhanced Raman Spectroscopy for Detection of Trace Gaseous Impurities in Hydrogen for Fuel Cells.

Gaseous impurities contained in hydrogen (H2) profoundly affect the performance of hydrogen proton-exchange membrane fuel cells. We demonstrate the utility of cavity-enhanced Raman spectroscopy as a unique approach for detection of gaseous impurities. A dense-pattern multipass cavity which is composed of four spherical mirrors placed in a Z-shaped configuration is used to enhance the Raman signal by extending the laser-gas interaction length. A total of 85 spots are identified on the 2-inch-diameter front (or rear) mirror, which indicates that 510 beams exist in the cavity. Detection limits of the impurity gases, including oxygen (O2), nitrogen (N2), carbon monoxide (CO), carbon dioxide (CO2), methane (CH4), ammonia (NH3), and hydrogen sulfide (H2S), reach sub-ppm- and ppb-levels at a total pressure of 0.1 and 2.5 MPa, respectively. This satisfies the detection requirements according to the maximum allowable concentration for these gases. Our cavity-enhanced Raman spectroscopy (CERS) apparatus can simultaneously measure multiple gases with high sensitivity and selectivity with no sample destruction. It has excellent application prospects in gaseous impurity analysis for the quality assessment of gaseous energy.

Distilling functional variations for human UGT2B4 upstream region based on selection signals and implications for phenotypes of Neanderthal and Denisovan.

Our previous work identified one region upstream human UGT2B4 (UDP glucuronosyltransferase family 2 member B4) which is associated with breast cancer and under balancing selection. However, the distribution, functional variation and molecular mechanism underlying breast cancer and balancing selection remain unclear. In current study, the two haplotypes with deep divergence are described by analyzing 1000 genomes project data and observed to be with high frequencies in all human populations. Through population genetics analysis and genome annotation, the potential functional region is identified and verified by reporter gene assay. Further mutagenesis indicates that the functional mutations are rs66862535 and rs68096061. Both SNPs can alter the interaction efficiency of transcription factor POU2F1 (POU class 2 homeobox 1). Through chromosome conformation capture, it is identified that the enhancer containing these two SNPs can interact with UGT2B4 promoter. Expression quantitative trait loci analysis indicates that UGT2B4 expression is dependent on the genotype of this locus. The common haplotype in human is lost in four genomes of archaic hominins, which suggests that Neanderthal and Denisovan should present relatively lower UGT2B4 expression and further higher steroid hormone level. This study provides new insight into the contribution of ancient population structure to human phenotypes.

Parental marital conflict and internet gaming disorder among Chinese adolescents: The multiple mediating roles of deviant peer affiliation and teacher-student relationship.

A considerable amount of evidence suggests that parental marital conflict is an important factor in adolescents' internet gaming disorder (IGD). However, the mechanism underlying this relationship remains unclear. Therefore, the purpose of this study is to explore the relationship between parental marital conflict and IGD among Chinese adolescents, and whether this relationship is mediated by deviant peer affiliation and teacher-student relationship. There were 698 Chinese adolescents that took part in the study (51.58% male; Mage = 13.52). They completed self-report questionnaires regarding perception of parental marital conflict, deviant peer affiliation, teacher-student relationship and IGD. Structural equation model (SEM) was used to examine the relationship between parental marital conflict and adolescents' IGD, as well as the mediating roles of deviant peer affiliation and teacher-student relationship. Correlation analysis showed a positive correlation between parental marital conflict, deviant peer affiliation, and IGD, as well as a negative correlation between them and teacher-student relationship. The results of the SEM showed that parental marital conflict not only predicts adolescent IGD directly, but also through the mediation effects of deviant peer affiliation and teacher-student relationship. Additionally, deviant peer affiliation and teacher-student relationship not only play an independent but also a sequential mediating effect in the relationship between parental marital conflict and IGD. The relationship between parental marital conflict and IGD is mediated by deviant peer affiliation and teacher-student relationship, which has potential prevention and intervention value for adolescent IGD.

Alienation from school and cyberbullying among Chinese middle school students: A moderated mediation model involving self-esteem and emotional intelligence.

As an extension of traditional bullying behavior, cyberbullying behavior emerges with the increasing popularity of the internet, and seriously affects the health of middle school students. However, just a few studies have explored the impact of the school factor on cyberbullying and its underlying mechanisms. Therefore, the purpose of this study is to explore the potential mediator (i.e., self-esteem) and potential moderator (i.e., emotional intelligence) of the relationships between alienation from school and cyberbullying. Five hundred and seventy five Chinese middle school students participated in the study (45.74% male) and completed self-report questionnaires regarding alienation from school, cyberbullying, self-esteem, and emotional intelligence. Correlation analysis showed a positive correlation between alienation from school and cyberbullying. Mediation analysis indicated that alienation from school positively predicts individual cyberbullying, and self-esteem partly mediated the association. Meanwhile, emotional intelligence moderated the pathway from alienation from school to cyberbullying. Specifically, the effect of high alienation from school on cyberbullying was weaker for middle school students who reported high emotional intelligence. The findings of this study expose the influence of the school factor and individual factors on cyberbullying, which has potential preventive and intervention value for youth cyberbullying.

Cumulative Family Risk and Cyberbullying Among Chinese Adolescents: The Chain Mediating Role of School Connectedness and Cyber Victimization.

Abundant evidence has demonstrated that cumulative family risk is associated with cyberbullying. However, few studies to date have investigated how cumulative family risk links to cyberbullying. To fill in these gaps, the present study examined the mediating role of school connectedness and cyber victimization in the relation between cumulative family risk and cyberbullying. A sample of 1,804 Chinese adolescents was recruited to complete measures of cumulative family risk, cyberbullying, school connectedness, cyber victimization, and demographic variables through convenience sampling. There were 813 boys and 991 girls, aged from 13 to 18, with an average age of 16 years (SD = 1.71). Correlational analyses and SPSS macro PROCESS (Model 6) were used for major data analysis. Results indicated that cumulative family risk was positively associated with cyberbullying, and this link could be mediated by school connectedness and cyber victimization. The present study identifies the potential underlying mechanism by which cumulative family risk is associated with adolescent cyberbullying, which has important implications for theory and prevention.

Leveraging gene therapy to achieve long-term continuous or controllable expression of biotherapeutics.

T cells redirected to cancer cells either via a chimeric antigen receptor (CAR-T) or a bispecific molecule have been breakthrough technologies; however, CAR-T cells require individualized manufacturing and bispecifics generally require continuous infusions. We created an off-the-shelf, single-dose solution for achieving prolonged systemic serum levels of protein immunotherapeutics via adeno-associated virus (AAV) gene transfer. We demonstrate proof of principle in a CD19+ lymphoma xenograft model using a single intravenous dose of AAV expressing a secreted version of blinatumomab, which could serve as a universal alternative for CD19 CAR-T cell therapy. In addition, we created an inducible version using an exon skipping strategy and achieved repeated, on-demand expression up to at least 36 weeks after AAV injection. Our system could be considered for short-term and/or repeated expression of other transgenes of interest for noncancer applications.

Dense-pattern multi-pass cavity based on spherical mirrors in a Z-shaped configuration for Raman gas sensing.

We report a dense-pattern multi-pass cavity (MPC) based on four spherical mirrors placed in a Z-shaped cavity configuration for improving the Raman signals from gases. The folding structure of the cavity causes dense patterns of spots, and at least 420 beams are reflected in the cavity. Raman spectra of ambient air, methane, and ethylene are recorded to demonstrate the performance of our apparatus. At atmospheric pressure, ppm-level detection limits of the gases are achieved with 10 s of exposure time. The Raman signal intensities of the gases show excellent linearity with the gases' partial pressures, which means that high-accuracy detection is also feasible.

Peer Victimization and Problematic Online Game Use Among Chinese Adolescents: The Dual Mediating Effect of Deviant Peer Affiliation and School Connectedness.

Abundant evidence has proved an association between peer victimization and problematic online game use (POGU). However, the underlying mechanisms of this relation are still under-investigated. Grounded in the ecological system theory, this study examined whether deviant peer affiliation (DPA) and school connectedness mediated the association between peer victimization and adolescent POGU. A sample of 698 Chinese adolescents completed questionnaires regarding peer victimization, problematic online game use, DPA, and school connectedness, of which 51.58% were boys. Path analyses indicated that peer victimization was positively associated with problematic online game use, and this link could be mediated by deviant peer affiliation and school connectedness. The findings identify the potential underlying mechanism by which peer victimization is associated with adolescent problematic online game use, which has important implications for theory and prevention.