Neutrophil profiling illuminates anti-tumor antigen-presenting potency.

Neutrophils, the most abundant and efficient defenders against pathogens, exert opposing functions across cancer types. However, given their short half-life, it remains challenging to explore how neutrophils adopt specific fates in cancer. Here, we generated and integrated single-cell neutrophil transcriptomes from 17 cancer types (225 samples from 143 patients). Neutrophils exhibited extraordinary complexity, with 10 distinct states including inflammation, angiogenesis, and antigen presentation. Notably, the antigen-presenting program was associated with favorable survival in most cancers and could be evoked by leucine metabolism and subsequent histone H3K27ac modification. These neutrophils could further invoke both (neo)antigen-specific and antigen-independent T cell responses. Neutrophil delivery or a leucine diet fine-tuned the immune balance to enhance anti-PD-1 therapy in various murine cancer models. In summary, these data not only indicate the neutrophil divergence across cancers but also suggest therapeutic opportunities such as antigen-presenting neutrophil delivery.

Environmental Evaluation on Toxicity, Toxic Mechanism, and Hydrolysis Behavior of Potential Acethydrazide Fungicide Candidates.

The evaluation of toxicity and environmental behavior of bioactive lead molecules is helpful in providing theoretical support for the development of agrochemicals, in line with the sustainable development of the ecological environment. In previous work, some acethydrazide structures have been demonstrated to exhibit excellent and broad-spectrum fungicidal activity; however, its environmental compatibility needs to be further elucidated if it is to be identified as a potential fungicide. In this project, the toxicity of fungicidal acethydrazide lead compounds F51, F58, F72, and F75 to zebrafish was determined at 10 µg mL-1 and 1 µg mL-1. Subsequently, the toxic mechanism of compound F58 was preliminarily explored by histologic section and TEM observations, which revealed that the gallbladder volume of common carp treated with compound F58 increased, accompanied by a deepened bile color, damaged plasma membrane, and atrophied mitochondria in gallbladder cells. Approximately, F58-treated hepatocytes exhibited cytoplasmic heterogeneity, with partial cellular vacuolation and mitochondrial membrane rupture. Metabolomics analysis further indicated that differential metabolites were enriched in the bile formation-associated steroid biosynthesis, primary bile acid biosynthesis, and taurine and hypotaurine metabolism pathways, as well as in the membrane function-related glycerophospholipid metabolism, linolenic acid metabolism, α-linolenic acid metabolism, and arachidonic acid metabolism pathways, suggesting that the acethydrazide F58 may have acute liver toxicity to common carp. Finally, the hydrolysis dynamics of F58 was investigated, with the obtained half-life of 5.82 days. The above results provide important guiding significance for the development of new green fungicides.

Inhibition of Gpx4-mediated ferroptosis alleviates cisplatin-induced hearing loss in C57BL/6 mice.

Cisplatin-induced hearing loss is a common side effect of cancer chemotherapy in clinics; however, the mechanism of cisplatin-induced ototoxicity is still not completely clarified. Cisplatin-induced ototoxicity is mainly associated with the production of reactive oxygen species, activation of apoptosis, and accumulation of intracellular lipid peroxidation, which also is involved in ferroptosis induction. In this study, the expression of TfR1, a ferroptosis biomarker, was upregulated in the outer hair cells of cisplatin-treated mice. Moreover, several key ferroptosis regulator genes were altered in cisplatin-damaged cochlear explants based on RNA sequencing, implying the induction of ferroptosis. Ferroptosis-related Gpx4 and Fsp1 knockout mice were established to investigate the specific mechanisms associated with ferroptosis in cochleae. Severe outer hair cell loss and progressive damage of synapses in inner hair cells were observed in Atoh1-Gpx4-/- mice. However, Fsp1-/- mice showed no significant hearing phenotype, demonstrating that Gpx4, but not Fsp1, may play an important role in the functional maintenance of HCs. Moreover, findings showed that FDA-approved luteolin could specifically inhibit ferroptosis and alleviate cisplatin-induced ototoxicity through decreased expression of transferrin and intracellular concentration of ferrous ions. This study indicated that ferroptosis inhibition through the reduction of intracellular ferrous ions might be a potential strategy to prevent cisplatin-induced hearing loss.

Discovery of Fungicidal Hydrazide Lead Compounds Derived from Sinapic Acid and Mycophenolic Acid.

Structure optimization based on natural products has become an effective way to develop new green fungicides. In this project, thirty-two novel NPs-derived hydrazide compounds were designed and synthesized by introducing the bioactive hydrazide substructure into sinapic acid and mycophenolic acid. The fungicidal bioassays indicated that the obtained hydrazide compounds showed excellent and selective fungicidal activity against specific pathogens, especially compounds C8, D7, and D8 with EC50 values of 0.63, 0.56, and 0.43 µg mL-1 against M. oryzae, respectively. SAR indicated that the introduction of 4-fluoro, 4-chloro, and 2,4-difluoro groups was conducive to improving the fungicidal activity, while the extension of the hydrazide bridge would affect the selectivity for inhibitory activity. Subsequently, the effects of hydrazide compounds on rice seedling and zebrafish growth were also investigated. The fungicidal mechanism implied that treatment with compound B4 would cause significant changes in metabolites of plasma membrane-related linolenic acid metabolism, arachidonic acid metabolism, and α-linolenic acid metabolism pathways, which further led to the wrinkled hyphae and the blurred plasma membrane and cytoplasm. Finally, the frontier molecular orbitals and charge distribution were calculated to analyze the differences in bioactivity from a structural perspective. These results provide important guidance for the development and practical application of novel fungicides.

SARS-CoV-2 Nsp15 suppresses type I interferon production by inhibiting IRF3 phosphorylation and nuclear translocation.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes 2019 coronavirus disease (COVID-19), poses a significant threat to global public health security. Like other coronaviruses, SARS-CoV-2 has developed various strategies to inhibit the production of interferon (IFN). Here, we have discovered that SARS-CoV-2 Nsp15 obviously reduces the expression of IFN-ß and IFN-stimulated genes (ISG56, CXCL10), and also inhibits IRF3 phosphorylation and nuclear translocation by antagonizing the RLR-mediated antiviral signaling pathway. Mechanically, we found that the poly-U-specific endonuclease domain (EndoU) of Nsp15 directly associates with the kinase domain (KD) of TBK1 to interfere TBK1 interacting with IRF3 and the flowing TBK1-mediated IRF3 phosphorylation. Furthermore, Nsp15 also prevented nuclear translocation of phosphorylated IRF3 via binding to the nuclear import adaptor karyopherin α1 (KPNA1) and promoting it autophagy-dependent degradation. These findings collectively reveal a novel mechanism by which Nsp15 antagonizes host's innate immune response.

Twisted moiré photonic crystal enabled optical vortex generation through bound states in the continuum.

The twisted stacking of two layered crystals has led to the emerging moiré physics as well as intriguing chiral phenomena such as chiral phonon and photon generation. In this work, we identified and theoretically formulated a non-trivial twist-enabled coupling mechanism in twisted bilayer photonic crystal (TBPC), which connects the bound state in the continuum (BIC) mode to the free space through the twist-enabled channel. Moreover, the radiation from TBPC hosts an optical vortex in the far field with both odd and even topological orders. We quantitatively analyzed the twist-enabled coupling between the BIC mode and other non-local modes in the photonic crystals, giving rise to radiation carrying orbital angular momentum. The optical vortex generation is robust against geometric disturbance, making TBPC a promising platform for well-defined vortex generation. As a result, TBPCs not only provide a new approach to manipulating the angular momentum of photons, but may also enable novel applications in integrated optical information processing and optical tweezers. Our work broadens the field of moiré photonics and paves the way toward the novel application of moiré physics.

Natural Alkaloid Waltherione F-Derived Hydrazide Compounds Evaluated in an Agricultural Fungicidal Field.

In this project, quinoline and quinolone-containing hydrazide compounds were designed and synthesized by introducing a bioactive hydrazide group into the skeleton of waltherione F. The fungicidal activity revealed that some hydrazide compounds exhibited excellent and broad-spectrum fungicidal activity; especially, compounds E8, E12, and E16 showed more than 90% or even 100% inhibition rates against most pathogens at 50 µg·mL-1. The fungicidal mechanism indicated that compound E8 may affect the normal function of the plasma membrane, further generating changes in the morphology and subcellular structure of mycelia. Simultaneously, Fusarium graminearum may resist the E8-treated stress through the metabolic pathways related to l-glutamate, l-glutamine, and glutathione. Finally, the effect of compound E8 on wheat seedling's growth and the toxicity to zebrafish were accomplished. These results will provide important guidance to discover novel fungicidal lead compounds and explore new targets, which are effective ways to alleviate the increasingly severe drug resistance.

The p65-LOC727924-miR-26a/KPNA3-p65 regulatory loop mediates vasoactive intestinal peptide effects on osteoarthritis chondrocytes.

Loss and dysfunction of articular chondrocytes, which disrupt the homeostasis of extracellular matrix formation and breakdown, promote the onset of osteoarthritis (OA). Targeting inflammatory pathways is an important therapeutic strategy for OA. Vasoactive intestinal peptide (VIP) is an immunosuppressive neuropeptide with potent anti-inflammatory effects; however, its role and mechanism in OA remain unclear. In this study, microarray expression profiling from the Gene Expression Omnibus database and integrative bioinformatics analyses were performed to identify differentially expressed lncRNAs in OA samples. qRT-PCR validation of the top ten different expressed lncRNAs indicated that the expression level of intergenic non-protein coding RNA 2203 (LINC02203, also named LOC727924) was the highest in OA cartilage compared to normal cartilage. Hence, the LOC727924 function was further investigated. LOC727924 was upregulated in OA chondrocytes, with a dominant sub-localization in the cytoplasm. In OA chondrocytes, LOC727924 knockdown boosted cell viability, suppressed cell apoptosis, reactive oxygen species (ROS) accumulation, increased aggrecan and collagen II, decreased matrix metallopeptidase (MMP)-3/13 and ADAM metallopeptidase with thrombospondin type 1 motif (ADAMTS)-4/5 levels, and reduced the levels of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1ß), and interleukin 6 (IL-6). LOC727924 could interact with the microRNA 26a (miR-26a)/ karyopherin subunit alpha 3 (KPNA3) axis by competitively targeting miR-26a for KPNA3 binding, therefore down-regulating miR-26a and upregulating KPNA3; in OA chondrocytes, miR-26a inhibition partially abolished LOC727924 knockdown effects on chondrocytes. miR-26a inhibited the nuclear translocation of p65 through targeting KPNA3 and p65 transcriptionally activated LOC727924, forming a p65-LOC727924-miR-26a/KPNA3-p65 regulatory loop to modulate OA chondrocyte phenotypes. In vitro, VIP improved OA chondrocyte proliferation and functions, down-regulated LOC727924, KPNA3, and p65 expression, and upregulated miR-26a expression; in vivo, VIP ameliorated destabilization of the medial meniscus (DMM)-induced damages on the mouse knee joint, down-regulated KPNA3, inhibited the nuclear translocation of p65. In conclusion, the p65-LOC727924-miR-26a/KPNA3-p65 regulatory loop modulates OA chondrocyte apoptosis, ROS accumulation, extracellular matrix (ECM) deposition, and inflammatory response in vitro and OA development in vivo, being one of the mechanisms mediating VIP ameliorating OA.

Relevance of PUFA-derived metabolites in seminal plasma to male infertility.

Aim: This study aims to investigate the biological effects of polyunsaturated fatty acid (PUFA)-derived metabolites in seminal plasma on male fertility and to evaluate the potential of PUFA as a biomarker for normozoospermic male infertility. Methods: From September 2011 to April 2012, We collected semen samples from 564 men aged 18 to 50 years old (mean=32.28 years old)ch., residing in the Sandu County, Guizhou Province, China. The donors included 376 men with normozoospermia (fertile: n=267; infertile: n=109) and 188 men with oligoasthenozoospermia (fertile: n=121; infertile: n=67). The samples thus obtained were then analyzed by liquid chromatography-mass spectrometry (LC-MS) to detect the levels of PUFA-derived metabolites in April 2013. Data were analyzed from December 1, 2020, to May 15, 2022. Results: Our analysis of propensity score-matched cohorts revealed that the concentrations of 9/26 and 7/26 metabolites differed significantly between fertile and infertile men with normozoospermia and oligoasthenozoospermia, respectively (FDR < 0.05). In men with normozoospermia, higher levels of 7(R)-MaR1 (HR: 0.4 (95% CI [0.24, 0.64]) and 11,12-DHET (0.36 (95% CI [0.21, 0.58]) were significantly associated with a decreased risk of infertility, while higher levels of 17(S)-HDHA (HR: 2.32 (95% CI [1.44, 3.79]), LXA5 (HR: 8.38 (95% CI [4.81, 15.24]), 15d-PGJ2 (HR: 1.71 (95% CI [1.06, 2.76]), and PGJ2 (HR: 2.28 (95% CI [1.42, 3.7]) correlated with an increased risk of infertility. Our ROC model using the differentially expressed metabolites showed the value of the area under the curve to be 0.744. Conclusion: The PUFA-derived metabolites 7(R)-MaR1, 11,12-DHET, 17(S)-HDHA, LXA5, and PGJ2 might be considered as potential diagnostic biomarkers of infertility in normozoospermic men.

Single-pixel reconstructive mid-infrared micro-spectrometer.

Miniaturized spectrometers in the mid-infrared (MIR) are critical in developing next-generation portable electronics for advanced sensing and analysis. The bulky gratings or detector/filter arrays in conventional micro-spectrometers set a physical limitation to their miniaturization. In this work, we demonstrate a single-pixel MIR micro-spectrometer that reconstructs the sample transmission spectrum by a spectrally dispersed light source instead of spatially grated light beams. The spectrally tunable MIR light source is realized based on the thermal emissivity engineered via the metal-insulator phase transition of vanadium dioxide (VO2). We validate the performance by showing that the transmission spectrum of a magnesium fluoride (MgF2) sample can be computationally reconstructed from sensor responses at varied light source temperatures. With potentially minimum footprint due to the array-free design, our work opens the possibility where compact MIR spectrometers are integrated into portable electronic systems for versatile applications.

A Comprehensive Investigation of Hydrazide and Its Derived Structures in the Agricultural Fungicidal Field.

Hydrazides are present in many bioactive molecules and exhibit a variety of biological activities, such as insecticidal, herbicidal, antifungal, antitumor, and antiviral effects. In this Review, we review the application of hydrazide and its derived structures in the agricultural fungicidal field, including monohydrazides, diacylhydrazines, hydrazide-hydrazones, and sulfonyl hydrazides. In addition, the antifungal mechanism of action of the hydrazide derivatives was analyzed and summarized, mainly involving succinate dehydrogenase inhibitors, laccase inhibitors, and targeting plasma membranes. Finally, based on the structural analysis of the novel fungicidal lead compounds, the structure-activity relationship of the hydrazide derivatives was constructed and the development trend of hydrazide structures in fungicidal applications was prospected. It is hoped that this Review can provide some significant guidance for the development of new hydrazide fungicides in the future.

Dosimetric properties of PASSAG polymer gel dosimeter in electron beam radiotherapy using magnetic resonance imaging.

BACKGROUND: Several physical factors such as photon beam energy, electron beam energy, and dose rate may affect the dosimetric properties of polymer gel dosimeters. The photon beam energy and dose rate dependence of PASSAG gel dosimeter were previously evaluated. OBJECTIVE: This study aims to assess the dosimetric properties of the optimized PASSAG gel samples in various electron beam energies. METHODS: The optimized PASSAG gel samples are first fabricated and irradiated to various electron energies (5, 7, 10 and 12 MeV). Then, the response (R2) and sensitivity of gel samples are analyzed by magnetic resonance imaging technique at a dose range of 0 to 10 Gy, scanning room temperature range of 15 to 22 °C, and post-irradiation time range of 1 to 30 days. RESULTS: The R2-dose response and sensitivity of gel samples do not change under the evaluated electron beam energies (the differences are less than 5%). Furthermore, a dose resolution range of 11 to 38 cGy is obtained for the gel samples irradiated to different electron beam energies. Moreover, the findings show that the R2-dose response and sensitivity dependence of gel samples on electron beam energy varies over different scanning room temperatures and post-irradiation times. CONCLUSION: The dosimetric assessment of the optimized PASSAG gel samples provides the promising data for this dosimeter during electron beam radiotherapy.

Neutrophils promote tumor invasion via FAM3C-mediated epithelial-to-mesenchymal transition in gastric cancer.

In gastric cancer, lymph node metastasis (LNM) is the major metastasis route, and lymphatic invasion is the precursor of LNM. Tumor-associated neutrophils (TANs) promote LNM. However, the molecular mechanisms underlying TANs-mediated lymphatic invasion and/or LNM remain unclear. Herein, we revealed that high level of TANs was the independent risk factor for lymphatic invasion and LNM respectively, and lymphatic tumor cell-neutrophil clusters were positively correlated with LNM. Crosstalk between neutrophils and tumor cells was required for enhanced tumor cell invasiveness, endowing neutrophils to boost epithelial-to-mesenchymal transition (EMT) of tumor cells and in turn promoting LNM. Mechanically, tumor cells educated neutrophils via TGFß1 to produce more FAM3C through Smad2/3 signaling activation, and FAM3C promoted tumor cell EMT through JNK-ZEB1/Snail signaling pathway. The crosstalk enhanced the affinity of neutrophils with tumor cells through interaction of integrins α6ß1 and α6ß4 with CD151. Furthermore, studies using tumor-bearing mice demonstrated that neutrophils were the important driver for gastric cancer tumorigenesis and invasiveness. The study clearly identifies the functional roles of TANs in promoting tumor invasion, and facilitates a better understanding of novel mechanisms responsible for LNM of gastric cancer, which provides potential targets for developing new strategies to prevent or treat LNM in gastric cancer.

Bispecific antibodies targeting immunomodulatory checkpoints for cancer therapy.

Advances in antibody engineering have led to the generation of more innovative antibody drugs, such as bispecific antibodies (bsAbs). Following the success associated with blinatumomab, bsAbs have attracted enormous interest in the field of cancer immunotherapy. By specifically targeting two different antigens, bsAbs reduce the distance between tumor and immune cells, thereby enhancing tumor killing directly. There are several mechanisms of action upon which bsAbs have been exploited. Accumulating experience on checkpoint-based therapy has promoted the clinical transformation of bsAbs targeting immunomodulatory checkpoints. Cadonilimab (PD-1 × CTLA-4) is the first approved bsAb targeting dual inhibitory checkpoints, which confirms the feasibility of bsAbs in immunotherapy. In this review we analyzed the mechanisms by which bsAbs targeting immunomodulatory checkpoints and their emerging applications in cancer immunotherapy.

Influences of point defects on electron transport of two-dimensional gep semiconductor device.

The quantum transport properties of defective two-dimensional (2D) GeP semiconductor nanodevice consisting of typical point defects, such as antisite defect, substitutional defect, and Schottky defect, have been studied by using density functional theory combined with non-equilibrium Green's function calculation. The antisite defect has indistinctive influences on electron transport. However, both substitutional and Schottky defect have introduced promising defect state at the Fermi level, indicating the possibility of improvement on the carrier transport. Our quantitative quantum transport calculations ofI-Vbbehavior have revealed that the electrical characters are enhanced. Moreover, the P atom vacancy could induce significant negative differential resistance phenomenon, and the physical mechanism is unveiled by detailed analysis. The transfer characteristic properties could be prominently improved by substitutional defect and vacancy defect. Most importantly, we have proposed a computational design of GeP-based electronic device with improved electrical performance by introducing vacancy defect. Our findings could be helpful to the practical application of novel 2D GeP semiconductor nanodevice in future.

Simulation of the nonlinear Kerr and Raman effect with a parallel local time-stepping DGTD solver.

In this paper, an efficient discontinuous Galerkin time-domain (DGTD) method is proposed to solve Maxwell's equations for nonlinear Kerr or Raman media. Based on our previous work, an arbitrary high-order derivatives DGTD method with a local time-stepping scheme is introduced for simulating dynamic optical responses in nonlinear dispersive media such that the nonlinear effects do not impose constraints on the stability conditions for linear subdomains. Therefore, the scheme enables the simulations in the nonlinear and linear media regions with independent time-stepping increments, which greatly improves the efficiency of the time-domain analysis. Moreover, by applying an iteration solution scheme, the proposed method preserves the intrinsic local features, which is favorable for the realization of highly parallelized algorithms. Numerical examples demonstrate the accuracy and the efficiency of our proposed method. We believe the proposed method provides an effective tool for numerical analysis of nonlinear optical phenomena.

Effect of advanced paternal age on reproductive outcomes in IVF cycles of non-male-factor infertility: a retrospective cohort study.

Advanced paternal age has been overlooked, and its effect on fertility remains controversial. Previous studies have focused mainly on intracytoplasmic sperm injection (ICSI) cycles in men with oligozoospermia. However, few studies have reported on men with semen parameters within reference ranges. Therefore, we conducted a retrospective cohort study analyzing the reproductive outcomes of couples with non-male-factor infertility undergoing in vitro fertilization (IVF) cycles. In total, 381 cycles included were subgrouped according to paternal age (<35-year-old, 35-39-year-old, or ≥40-year-old), and maternal age was limited to under 35 years. Data on embryo quality and clinical outcomes were analyzed. The results showed that fertilization and high-quality embryo rates were not significantly different (all P > 0.05). The pregnancy rate was not significantly different in the 35-39-year-old group (42.0%; P > 0.05), but was significantly lower in the ≥40-year-old group (26.1%; P < 0.05) than that in the <35-year-old group (40.3%). Similarly, the implantation rate significantly decreased in the ≥40-year-old group (18.8%) compared with that in the <35-year-old group (31.1%) and 35-39-year-old group (30.0%) (both P < 0.05). The live birth rate (30.6%, 21.7%, and 19.6%) was not significantly different across the paternal age subgroups (<35-year-old, 35-39-year-old, and ≥40-year-old, respectively; all P > 0.05), but showed a declining trend. The miscarriage rate significantly increased in the 35-39-year-old group (44.8%) compared with that in the <35-year-old group (21.0%; P < 0.05). No abnormality in newborn birth weight was found. The results indicated that paternal age over 40 years is a key risk factor that influences the assisted reproductive technology success rate even with good semen parameters, although it has no impact on embryo development.

Discovery of Aryloxy-, Arylthio-, and Arylamino-Containing Acethydrazides as Fungicidal Agents.

The development of new green fungicides is an effective way to solve the resistance of agricultural pathogens and plays an important role in promoting high-quality and sustainable development of modern agriculture. In this project, a series of aryloxy-, arylthio-, and arylamino-containing acethydrazide derivatives were designed, synthesized, and characterized by 1H nuclear magnetic resonance (NMR), 13C NMR, and high-resolution mass spectrometry (HRMS). The fungicidal bioassays indicated that some compounds showed excellent and broad-spectrum fungicidal activity, and the structure-activity relationship was discussed. The in vivo fungicidal activity demonstrated that compounds C4 and D8 exhibited good preventative effects against Fusarium graminearum infecting wheat leaves, of which the preventative activity of compound D8 was almost equal to that of the positive agents. Transmission electron microscopy (TEM) observation revealed that the plasma membrane in the C4-treated F. graminearum hyphal cells was severely contracted and separated with the cell wall, coupling with the visible lysosomes and the disappeared cytoplasm and organelles, which may be the reasons for the shriveled and even ruptured hyphae observed by scanning electron microscopy (SEM). Subsequently, transcriptomics and metabolomics were performed to further elucidate the fungicidal mechanism. The regulatory networks of differential genes and metabolites in plasma membrane-related sphingolipid metabolism, linoleic acid metabolism, α-linoleic acid metabolism, and arachidonic acid metabolism were constructed and elaborated. Additionally, preliminary investigation of seeding growth suggested that compounds C4 and D8 may have different degrees of influence on the growth indicators of wheat seedlings; however, this effect may be negligible as the plant grows.

Potential categories of health risk behaviors of college students in Wuling Mountain Area and its association with campus bullying / 中国学校卫生

Objective@#To understand the potential categories of harmful behaviors of college students in Wuling Mountain Area and its relationship with campus bullying, so as to provide a theoretical basis for promoting the development of college students physical and mental health.@*Methods@#The stratified random cluster sampling method was used to select 3 042 college students from six universities in Wuling Mountain Area from October to December, 2022. The "Chinese Youth Health Related/Risk Behaviors Questionnaire" (University Edition) compiled by the National Youth Health Related/Risk Behaviors Survey Group was used to investigate the health risk behaviors. The potential category analysis method was used to analyze the food preference, insecurity, fighting, loneliness, depression, insomnia, heartbreak, suicidal ideation, smoking, drinking, game addiction, Internet addiction of health risk behaviors were used to further analyze the relationship between different categories and campus bullying by using multi category Logistic regression method.@*Results@#College students in Wuling Mountain Area were classified into low risk group of category 1 (44.2%), category 2 (5.4%) substance dependent group, category 3(50.4%) emotional disorder group. The distribution of potential categories of health risk behaviors among college students was statistically significant by gender( χ 2=31.44, 11.69， P < 0.05 ). Logistic regression analysis showed that after controlling demographic variables, campus bullying was the risk factor of category 3 emotional disorder group( OR =1.88, P <0.01).@*Conclusion@#bullying. Colleges and universities should attach great importance to the occurrence of campus bullying, formulate intervention programs for different categories of health hazard behaviors, and promote the healthy development of college students physical and mental health.

Immune Modulatory Effects of Molecularly Targeted Therapy and Its Repurposed Usage in Cancer Immunotherapy.

The fast evolution of anti-tumor agents embodies a deeper understanding of cancer pathogenesis. To date, chemotherapy, targeted therapy, and immunotherapy are three pillars of the paradigm for cancer treatment. The success of immune checkpoint inhibitors (ICIs) implies that reinstatement of immunity can efficiently control tumor growth, invasion, and metastasis. However, only a fraction of patients benefit from ICI therapy, which turns the spotlight on developing safe therapeutic strategies to overcome the problem of an unsatisfactory response. Molecular-targeted agents were designed to eliminate cancer cells with oncogenic mutations or transcriptional targets. Intriguingly, accumulating shreds of evidence demonstrate the immunostimulatory or immunosuppressive capacity of targeted agents. By virtue of the high attrition rate and cost of new immunotherapy exploration, drug repurposing may be a promising approach to discovering combination strategies to improve response to immunotherapy. Indeed, many clinical trials investigating the safety and efficacy of the combination of targeted agents and immunotherapy have been completed. Here, we review and discuss the effects of targeted anticancer agents on the tumor immune microenvironment and explore their potential repurposed usage in cancer immunotherapy.